Abstract

DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm) based biomarkers that reflect the individual aging process. Furthermore, physical fitness is known to relate to the aging process, but its relationship to the gut microbiome has not yet been studied. Here, we examine the relationship among physical fitness, DNAm based biomarkers, and the microbiome in adults aged 33-88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO2max (ρ=0.2, p=6.4E-4, r=0.19, p=1.2E-3), Jumpmax p=0.11, p=5.5E-2, r=0.13 p= 2.8E-2), Gripmax (=ρ=0.17, p=3.5E-3, r=0.16, p=5.6E-3), and HDL levels (ρ=0.18, p=1.95E-3, r=0.19, p=1.1E-3) are associated with better verbal short term memory. In addition, verbal short term memory is associated with decelerated aging assessed with the new DNAm biomarker FitAgeAcceleration (ρ: −0.18, p=0.0017). DNAmFitAge is able to distinguish high fitness individuals from low/medium fitness individuals better than existing DNAm biomarkers and estimates a younger biological age in the high fit males and females (1.5 and 2.0 years younger, respectively). The microbiomal pathways are associated with VO2max, redox balance, and DNAmPhenoAge. PhenoAge Acceleration is influenced by pyruvate producing microbiomal pathways, where higher activity of these pathways lead to suppressed PhenoAge acceleration. Our research shows that regular physical exercise contributes to observable physiological, methylation, and microbiota differences which are beneficial to the aging process. DNAmFitAge emerged as a biological marker of the quality of life.

Abstract

Recent meta-analytic work indicated that guar gum supplementation might improve lipid profile markers in different populations. However, critical methodological limitations such as the use of some unreliable data and the lack of inclusion of several relevant studies, and the scarcity in assessments of regression and dose-specific effects make it difficult to draw meaningful conclusions from the meta-analysis. Therefore, current evidence regarding the effects of guar gum supplementation on lipid profile remains unclear. The present systematic review, meta-regression, and dose-response meta-analysis aimed to examine the effects of guar gum supplementation on lipid profile (total cholesterol [TC], low-density lipoprotein [LDL], triglyceride [TG], and high-density lipoprotein [HDL]) in adults. Relevant studies were obtained by searching the PubMed, SCOPUS, Embase, and Web of Science databases (from inception to September 2021). Weighted mean differences (WMD) and 95% confidence intervals (95% CI) were estimated via a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods. Pooled analysis of 19 randomized controlled trials (RCTs) revealed that guar gum supplementation led to significant reductions in TC (WMD: -19.34 mg/dL, 95% CI: -26.18, -12.49, p<0.001) and LDL (WMD: -16.19 mg/dL, 95% CI: -25.54, -6.83, p=0.001). However, there was no effect on TG and HDL among adults in comparison with control group. Our outcomes suggest that guar gum supplementation lowers TC and LDL in adults. Future large RCTs on various populations are needed to show further beneficial effects of guar gum supplementation on lipid profile and establish guidelines for clinical practice.

Background and Objectives: The virus SARS-CoV2, which causes COVID-19, affects the endocrine system. This study investigated serum concentrations of the thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) in 53 outpatients infected with SARS-CoV2 and 53 non-infected matched participants in Khuzestan Province, Iran. We also examined the possible association of clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4. Materials and Methods: A checklist was applied to collect demographic and clinical data. Blood samples were taken for biochemical analysis of serum concentrations of TSH, T3, and T4. Clinical symptoms of the infected outpatients were monitored weekly for 28 days. Results: Our results indicated that, as the severity of the disease increased, the respiratory and pulse rates raised significantly. Additionally, disease severity was significantly different between genders. Specifically, 79.5% of the asymptomatic/mild, and 38.5% of moderate outpatients were men. We also found significantly lower serum T3 but higher T4 in infected outpatients, compared with controls. However, serum TSH did not significantly differ between the two groups. The generalized estimating equation (GEE) analysis revealed no relationship between clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4 in our study population. Additionally, GEE analysis showed that the odds ratio of neurological symptoms among women was 2.5 times that of men, the odds ratio of neurological symptoms in illiterates was 10 times higher than that of those without a high-school diploma, and the chance of developing pulmonary symptoms in those without high-school diploma was about 21 times higher than illiterates. Conclusion: In conclusion, this study showed that infected outpatients had significantly lower serum T3 but higher T4 than non-infected participants. There was no relation between symptom progression and disease severity with serum concentrations of TSH, T3, and T4, but educational status and sex significantly affected the chance of neurological and pulmonary symptoms occurring over 28 days. Our results may be used to develop potential therapies to treat COVID-19 disease.

Abstract

Exhaustive exercise is known to induce acute renal damage. However, the precise mechanisms remain unclear. We investigated the effects of macrophage depletion on exhaustive exercise-induced acute renal damage. Male C57BL/6 J mice were divided into four groups: sedentary with control liposome (n=8), sedentary with clodronate liposome (n=8), exhaustive exercise with control liposome (n=8), and exhaustive exercise with clodronate liposome (n=8). Mice were treated with clodronate liposomes or control liposomes intraperitoneally for 48 h before undergoing exhaustive exercise. Renal function and renal histology were tested at 24 h. The expression levels of kidney injury molecule (KIM)-1 and inflammatory cytokines in kidney tissues were measured by quantitative RT-PCR, and KIM-1 concentration was semi-quantified by immunostaining. As a result, exhaustive exercise increased macrophage infiltration into the kidney. However, clodronate reduced it. Although exhaustive exercise resulted in an increase in KIM-1 mRNA expression levels and concentration, injection of clodronate liposome reduced it. In addition, TUNEL positive apoptotic cells were increased after exercise, but significantly reduced by clodronate. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the kidney after exhaustive exercise. These results suggest that macrophages play a critical role in increasing renal damage by regulating inflammation.

Background: The impairment of limb function and disability are among the most im portant consequences of stroke. To date, however, little research has been done on the early reha bilitation trial (ERT) after stroke in these patients. The purpose of this study was to evaluate the impact of ERT neuromuscular protocol on motor function soon after hemiparetic stroke. The sample included twelve hemiparetic patients (54.3 ± 15.4 years old) with ischemic stroke (n = 7 control, n = 5 intervention patients). ERTwas started as early as possible after stroke and included passive range of motion exercises, resistance training, assisted standing up, and active exercises of the healthy side of the body, in addition to encouraging voluntary contraction of affected limbs as much as possible. The rehabilitation was progressive and took 3 months, 6 days per week, 2–3 h per session. Fu gle-Meyer Assessment (FMA), Box and Blocks test (BBT) and Timed up and go (TUG) assessments were conducted. There was a significantly greater improvement in the intervention group com pared to control: FMA lower limbs (p = 0.001), total motor function (p = 0.002), but no significant difference in FMA upper limb between groups (p = 0.51). The analysis of data related to BBT showed no significant differences between the experimental and control groups (p = 0.3). However, TUG test showed significant differences between the experimental and control groups (p = 0.004). The most important finding of this study was to spend enough time in training sessions and provide adequate rest time for each person. Our results showed that ERT was associated with improved motor function but not with the upper limbs. This provides a basis for a definitive trial.

New severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, contains 32 mutations that have caused a high incidence of breakthrough infections or re-infections. These mutations have reduced vaccine protection against Omicron and other new emerging variants. This highlights the need to find effective treatment, which is suggested to be stem cell-based therapy. Stem cells could support respiratory epithelial cells and they could restore alveolar bioenergetics. In addition, they can increase the secretion of immunomodulatory cytokines. However, after transplantation, cell survival and growth rate are low because of an inappropriate microenvironment, and stem cells face ischemia, inflammation, and oxidative stress in the transplantation niche which reduces the cells’ survival and growth. Exercise-training can upregulate antioxidant, anti-inflammatory, and anti-apoptotic defense mechanisms and increase growth signaling, thereby improving transplanted cells’ survival and growth. Hence, using athletes’ stem cells may increase stem-cell therapy outcomes in Omicron-affected patients.

The purpose of this study was to systematically review to find if aerobic exercise compared to no exercise or any other intervention affects brain plasticity among people with mild cognitive impairment (MCI). Searches were conducted in the Scopus, SciELO, PubMed, Web of Science, Science Direct, and Google Scholar databases. The included studies were randomized control trials (RCTs) written in English comprising individuals with MCI that evaluated the effects of aerobic training on brain-derived neurotrophic factor (BDNF), brain structures, or brain activity. The quality of trials was evaluated using the PEDro scale for RCTs. Twelve studies with medium to high quality were included, of which five studies focused on brain-derived neurotrophic factor (four articles reported elevation and one article reported no changes in BDNF levels following the aerobic exercise), two studies focused on brain structures (both reported increases in hippocampus volume following the aerobic exercise), and five studies focused on brain activity (four articles reported positive changes, and one article reported no changes in brain activity following the aerobic exercise). Research regarding the effects of aerobic training on brain plasticity in people with MCI is in its infancy. Still, aerobic exercise seems to be a promising therapy in people with MCI.

Research over the past few decades has focused on the use of functional ingredients such as an active lifestyle and proper diet as a treatment for many diseases in the world. Recent studies have shown a variety of health benefits for red beets and their active ingredients such as antioxidant, anti-inflammatory, anti-cancer, blood pressure and fat reduction, anti-diabetic, and anti-obesity effects. This review article examines the effects of exercise and red beet consumption and the effective mechanisms of these two interventions on cellular and molecular pathways in prostate cancer. However, there is a significant relationship between an active lifestyle and proper diet with the incidence of cancer, and the use of these natural interventions for cancer patients in the treatment protocol of avoidance patients. Furthermore, this review article attempts to examine the role and effect of exercise and beetroot nutrition on prostate cancer and provide evidence of the appropriate effects of using natural interventions to prevent, reduce, and even treat cancer in stages. In addition, we examine the molecular mechanisms of the effectiveness of exercise and beetroot consumption. Finally, the use of natural interventions such as exercising and eating beets due to their antioxidant, anti-inflammatory, and anti-cancer properties, due to the lack or low level of side effects, can be considered an important intervention for the prevention and treatment of cancer.

Background: Monitoring physical freshness is essential in assessing athletes’ conditions during training periods, training sessions, or competitions. To date, no single physical freshness scale has been successfully validated against training load variables and widely used scales measuring different facets of physical freshness. Objective: In this study, we develop and test the practical utility of a perceived physical freshness (RPF) scale to monitor the condition of the athletes and to prevent excessive fatigue and insufficient recovery during training sessions or competitions. Methods: Sixteen professional male soccer players (mean ± SD age 26 ± 4 years) were enrolled. Training load (TL), monotony, strain, rate of perceived exertion (RPE), well-being indices (sleep, stress, fatigue, and muscle soreness), total quality recovery (TQR) and RPF were determined each day for two weeks of training, including a week intensified training (IW) and a week taper (TW). The validity of the RPF scale was assessed by measuring the level of agreement of a player’s perceived physical freshness relative to their TL variables, recovery state and well-being indices during each training phase (IW and TW) and during the overall training period (TP). Results: RPF increased during the TW compared to IW (ES = 2.31, p < 0.001, large). For the TP, IW and TW, weekly RPF was related to weekly TL (r = −0.81, r = −0.80, r = −0.69, respectively), well-being (r = −0.91, r = −0.82, r = −0.84, respectively) and TQR (r = 0.76, r = 0.91, r = 0.52, respectively), all p < 0.01. For the TP, IW and TW, daily RPF was related to TL (r = −0.75, r = −0.66, r = −0.70, respectively), well-being (r = −0.84, r = −0.81, r = −0.78, respectively) and TQR (r = 0.82, r = 0.81, r = 0.75, respectively), all p < 0.01. Conclusions: RPF was effective for evaluating the professional soccer players’ physical freshness and may be a strategy for coaches to monitor the physical, psycho-physiological, and psychometric state of the players before training session or matches.

Multiple sclerosis (MS) is a demyelinating disease characterized by plaque formation and neuroinflammation. The plaques can present in various locations, causing a variety of clinical symptoms in patients with MS. Coronavirus disease-2019 (COVID-19) is also associated with systemic inflammation and a cytokine storm which can cause plaque formation in several areas of the brain. These concurring events could exacerbate the disease burden of MS. We review the neuro-invasive properties of SARS-CoV-2 and the possible pathways for the entry of the virus into the central nervous system (CNS). Complications due to this viral infection are similar to those occurring in patients with MS. Conditions related to MS which make patients more susceptible to viral infection include inflammatory status, blood-brain barrier (BBB) permeability, function of CNS cells, and plaque formation. There are also psychoneurological and mood disorders associated with both MS and COVID-19 infections. Finally, we discuss the effects of exercise on peripheral and central inflammation, BBB integrity, glia and neural cells, and remyelination. We conclude that moderate exercise training prior or after infection with SARS-CoV-2 can produce health benefits in patients with MS patients, including reduced mortality and improved physical and mental health of patients with MS.

This study examined the effects of 8-week combined plyometric exercise and high intensity running training (combined training) on the performance fitness in male U17 handball players. Participants were randomly divided between experimental (E; n = 15; age: 16.5 ± 0.4 years) and control (C; n = 13; age: 16.7 ± 0.3 years) groups. The E group performed combined training (4 workshops) twice a week over 8 weeks. Each session lasted approximately 35 min. The C maintained regular in-season training. Before and after the combined training, both groups underwent repeated sprint ability (RSA), sprint performance (5m, 10m, 20m and 30m), change of direction test (Modified change-of-direction T-test (T-half)), vertical jump (squat jump (SJ), counter-movement jump (CMJ), counter-movement jump with aimed arms (CMJA)), horizontal jump (five-jump test (5JT)), strength (1-RM half squat), and 20-meter shuttle run. Group x time interaction showed significant increases on sprint performance ( p < 0.01, 8.6%; p < 0.001, 7.3%; p < 0.05, 6.9%; and p < 0.01, 8.9% over distances of 5m, 10m, 20m and 30m respectively) in E relative to C. The T-half also showed significant gains for E ( p < 0.05, 6.8%), as did vertical jumping ( p < 0.01, 32.7%; p < 0.001, 32.6% and p < 0.001, 23% for SJ, CMJ and CMJA respectively) and horizontal jumping ( p < 0.05, 13.3%) compared to C. Moreover, there were significant improvements of RSA and 20 m shuttle run in E compared to C. However, there were no significant differences in 1-RM half squat between groups. We conclude that the allocation of short periods of a combined training is effective in enhancing performance fitness and thus can be commended to male U17 Handball participants as a potentially useful component of their training.

The aim of this study was to examine the effects of a multicomponent exercise training program on motor function and biochemical markers in patients with Alzheimer’s-type dementia. Twenty patients with Alzheimer disease, divided into the intervention group (IG; aged 84 ± 3.1 years) and the control group (CG; aged 86 ± 2.6 years) were included in this study. The intervention group was enrolled into an exercise training program for three months (two sessions of 60 min per week). The CG was instructed to follow their daily rhythm of life (e.g., rest, reading) without a physical training program. After 3 months of participation in a multicomponent exercise program, gait speed, balance and walking parameters were all improved in the intervention group as measured with the Berg Balance Scale, the Tinetti test, the 6-min walking test and the timed up and go test (p < 0.05 for all; percentage range of improvements: 3.17% to 53.40%), except the walking while talking test, and biochemical parameters were not affected (p > 0.05). Our results demonstrate that exercise improves postural control, aerobic capacity and mobility functions in patients with Alzheimer disease. Physical exercise is a safe and effective method for treating physical disorders in patients with Alzheimer’s disease and can easily be integrated in various programs for the management of Alzheimer disease.

The antioxidant system can be critical in reducing exacerbated inflammation in COVID-19. This study compared the antioxidant and inflammatory responses between COVID-19 outpatients and seemingly healthy individuals. This descriptive-analytical cross-sectional study was conducted on 53 COVID-19 outpatients and 53 healthy individuals as controls. The serum concentrations of amyloid A (SAA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured and compared between COVID-19 patients and controls using the independent sample t-test before and after controlling for dietary supplement use. A generalized estimating equation (GEE) regression model, limited to COVID-19 patients, was used to evaluate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of disease symptoms on days 1, 7, 14, 21, and 28 after the disease onset. Serum concentrations of SOD (p ≤ 0.001) and GPx (p = 0.001) were significantly higher in COVID-19 patients than in controls before adjustment for dietary supplement use. GPx remained significantly higher among COVID-19 patients than in controls after adjustment for all dietary supplements (p = 0.005). Moreover, serum concentrations of GPx (p = 0.003), SOD (p = 0.022), and TAC (p = 0.028) remained significantly higher among COVID-19 patients than in controls after adjustment for vitamin D supplementation. This study showed higher GPx in COVID-19 outpatients than in controls after adjustment for dietary supplement use. Moreover, elevated SOD, GPx, and TAC concentrations were shown in COVID-19 outpatients compared to controls after adjusting for vitamin D supplementation. These results may provide a useful therapeutic target for treating oxidative stress in COVID-19 disease, which may help ameliorate the pandemic.

This study investigated the short-term effects of low-fat chocolate milk (LFCM) consumption on delayed onset muscle soreness (DOMS) and performance in female badminton players. Seven female badminton players (23 ± 1 years; height: 163.8 ± 4.1 cm; body mass: 58.7 ± 0.9 kg) were randomly assigned to 1 week of LFCM (500 mL) or placebo (water, 500 mL) consumption in a crossover design. Participants consumed LFCM or water immediately after each training session during the 1-week intervention. Performance variables (aerobic power, anaerobic power, agility, explosive power, and maximum handgrip strength) were assessed at two separate time points: pre and post-intervention (after 1 week). In addition, the Visual Analogue Scale (VAS) was used to assess DOMS before, immediately after, and at 24 and 48 h after each training session. There were significant time effects for aerobic power, upper body explosive power, minimum anaerobic power, and time to exhaustion (TTE), which significantly increased after LFCM consumption (p < 0.05). Moreover, relative and maximum lower body power significantly (p < 0.05) increased, while rating of perceived exertion (RPE) as well as DOMS in lower extremity muscles immediately after exercise significantly decreased after LFCM consumption compared to placebo (p < 0.05). There were no significant changes in maximum anaerobic power, agility, and maximum handgrip strength (p > 0.05). LFCM, as a post-exercise beverage, may help speed recovery in female badminton players leading to increased aerobic, anaerobic, and strength performance indices, increased TTE, and decreased muscle soreness and RPE.

Abstract

The present study examined the effects of different temperatures of protein-containing drink after exercise on subsequent gastric motility and energy intake in healthy young men. Twelve healthy young men completed three, 1-d trials in a random order. In all trials, the subjects ran on a treadmill for 30 min at 80% of maximum heart rate. In exercise + cold drink (2°C) and exercise + hot drink (60°C) trials, the subjects consumed 300 ml of protein-containing drink (0·34 MJ) at 2°C or 60°C over a 5-min period after exercise. In the exercise (i.e. no preload) trial, the subjects sat on a chair for 5 min after exercise. Then, the subjects sat on a chair for 30 min to measure their gastric motility with an ultrasound imaging system in all trials. Thereafter, the subjects consumed a test meal until they felt comfortably full. Energy intake in the exercise + hot drink trial was 14 % and 15 % higher than the exercise (P = 0·046, 95% CI 4·010, 482·538) trial and exercise + cold drink (P = 0·001, 95% CI 160·089, 517·111) trial, respectively. The frequency of the gastric contractions in the exercise + hot drink trial was higher than the exercise (P = 0·023) trial and exercise + cold drink (P = 0·007) trial. The total frequency of gastric contractions was positively related to energy intake (r = 0·386, P = 0·022). These findings demonstrate that consuming protein-containing drink after exercise at 60°C increases energy intake and that this increase may be related to the modulation of the gastric motility.

This study examined the effects of a resistance-type high-intensity interval training (RHIIT) matched with the lowest velocity that elicited O_2peak (100% vO_2peak) in well-trained kayak sprint athletes. Responses in cardiac structure and function, cardiorespiratory fitness, anaerobic power, exercise performance, muscular strength, and hormonal adaptations were examined. Male kayakers (n = 24, age: 27 ± 4 years) were randomly assigned to one of three 8-wk conditions (N = 8): (RHIIT) resistance training using one-armed cable row at 100% vO_2peak; paddling-based HIIT (PHIIT) six sets of paddling at 100% vO_2peak; or controls (CON) who performed six sessions including 1-h on-water paddling/sessions at 70–80% maximum HR per week. Significant increases (p < 0.05) in O_2peak, vO_2peak, maximal cardiac output, resting stroke volume, left ventricular end-systolic dimension, 500-m paddling performance were seen pre- to post-training in all groups. Change in O_2peak in response to PHIIT was significantly greater (p = 0.03) compared to CON. Also, 500-m paddling performance changes in response to PHIIT and RHIIT were greater (p = 0.02, 0.05, respectively) than that of CON. Compared with pre-training, PHIIT and RHIIT resulted in significant increases in peak and average power output, maximal stroke volume, end-diastolic volume, ejection fraction, total testosterone, testosterone/cortisol ratio, and 1,000-m paddling performance. Also, the change in 1,000-m paddling performance in response to PHIIT was significantly greater (p = 0.02) compared to that of CON. Moreover, maximum strength was significantly enhanced in response to RHIIT pre- to post-training (p < 0.05). Overall, RHIIT and PHIIT similarly improve cardiac structure and hemodynamics, physiological adaptations, and performance of well-trained kayak sprint athletes. Also, RHIIT enhances cardiorespiratory fitness and muscular strength simultaneously.

The effects of exercise on kidney function have been studied for more than three decades. One of the most common health issues among patients with chronic kidney disease (CKD) is a lack of physical activity, which leads to a low exercise capacity in these patients. The majority of maintenance hemodialysis (MHD) patients do not exercise at all. At each stage of dialysis, patients lose 10–12 g of their amino acids through blood sampling. Dialysis also leads to increased cortisol and circadian rhythm sleep disorders in hemodialysis (HD) patients. Studies have also reported higher C-reactive protein levels in HD patients, which causes arterial stiffness. Exercise has a variety of health benefits in these patients, including improved blood pressure control, better sleep, higher physical function, and reduced anxiety and depression. On the other hand, it should be noted that intense exercise has the potential to progress KD, especially when conducted in hot weather with dehydration. This review aimed to investigate the effects of different types of exercise on kidney disease and provide exercise guidelines. In conclusion, moderate-intensity and long-term exercise (for at least a 6-month period), with consideration of the principles of exercise (individualization, intensity, time, etc.), can be used as an adjunctive treatment strategy in patients undergoing dialysis or kidney transplantation.

The 2019 coronavirus (COVID-19) epidemic, has caused unprecedented global social and economic impacts and many deaths. Many risk factors have been identified in the progression of COVID-19 to severe and critical stages, and it is shown that the coronavirus appears more severely in people with cancer. Pro-inflammatory status and weakened immune system due to cancer-related treatments can be determinants in the immune system’s response to the coronavirus in these patients. Higher physical activity levels are associated with lower hospitalization rates and mortality in COVID-19. Also, regular exercise training can improve immune system responses, modulate inflammatory responses, and improve psychological parameters in cancer patients. The interactive effects of nutritional supplements on immune responses and anti-inflammatory status have been shown in some studies. The purpose of this perspective article was to investigate the interaction between dietary supplementation and regular physical exercise in controlling risk factors associated with coronavirus in cancer patients. In addition to appropriate dietary habits, some nutritional supplements, especially vitamin D, have been shown to improve the immune system’s response against COVID-19 and cancer. Using lifestyle strategies such as regular physical activity and intake of functional compounds as supplements can be effective in treatment outcomes, quality of life, and overall survival in cancer patients. We proposed that combining dietary supplements and exercise training in cancer patients can boost immune responses against COVID-19 and probably improve vaccine responses. Angiotensin (ANG)-(1-7) Mas receptor axis can probably activate following exercise training and vitamin D combination. And can prevent pulmonary injury, hematological alterations, and hyperinflammatory state in COVID-19.

Millions of people worldwide are infected with COVID-19, and COVID-19 survivors have been found to suffer from functional disabilities and mental disorders such as depression and anxiety. This is a matter of concern because COVID-19 is still not over. Because reinfection is still possible in COVID-19 survivors, decreased physical function and increased stress and anxiety can lower immune function. However, the optimal exercise intensity and volume appear to remain unknown. Therefore, the current systematic review aimed to evaluate the effect of resistance or aerobic exercises in post-COVID-19 patients after hospital discharge. We conducted searches in the Scopus, SciELO, PubMed, Web of Science, Science Direct, and Google Scholar databases. Studies that met the following criteria were included: (i) English language, (ii) patients with COVID-19 involved with resistance or aerobic exercise programs after hospital discharge. Out of 381 studies reviewed, seven studies met the inclusion criteria. Evidence shows that exercise programs composed of resistance exercise (e.g., 1–2 sets of 8–10 repetitions at 30–80% of 1RM) along with aerobic exercise (e.g., 5 to 30 min at moderate intensity) may improve the functional capacity and quality of life (reduce stress and mental disorders) in post-COVID-19 patients. In addition, only one study reported reinfection of three subjects involved with the exercise program, suggesting that exercise programs may be feasible for the rehabilitation of the patients. A meta-analysis was not conducted because the included studies have methodological heterogeneities, and they did not examine a control group. Consequently, the results should be generalized with caution.

Elite athletes use high-intensity training to maintain their fitness level. However, intense training can harm the immune system, making athletes suspectable to COVID-19 and negatively affecting their performance. In addition, the diet of athletes should be appreciated more as it is another influencer of the immune system, especially during the COVID 19 pandemic. The other important issue elite athletes face currently is vaccination and its possible intervention with their training. The present study attempts to discuss the impact of different training intensities, nutritional strategies, and vaccination on the immune system function in elite athletes. To this end, Scopus, ISC, PubMed, Web of Science, and Google Scholar databases were searched from 1988 to 2021 using the related keywords. The results of our review showed that although high-intensity exercise can suppress the immune system, elite athletes should not stop training in the time of infection but use low- and moderate-intensity training. Moderate-intensity exercise can improve immune function and maintain physical fitness. In addition, it is also better for athletes not to undertake high-intensity training at the time of vaccination, but instead perform moderate to low-intensity training. Furthermore, nutritional strategies can be employed to improve immune function during high-intensity training periods.

Abstract

Purpose

Although acute prolonged strenuous exercise has been shown to increase markers of gastrointestinal permeability and damage, little is known regarding the efficacy of nutritional supplement interventions on the attenuation of exercise-induced gastrointestinal syndrome. This study addressed the effects of oral amino acid supplementation on markers of gastrointestinal permeability and damage in response to exercise.

Methods

Sixteen active men aged 22.7 ± 2.6 years (mean ± standard deviation) completed placebo or cystine and glutamine supplementation trials in random order. Participants received either a placebo or cystine and glutamine supplements, three times a day for 5 days, separated by a 2-week washout period. On day 6, participants took their designated supplements 30 min before running at a speed corresponding to 75% of maximal oxygen uptake for 1 h, followed by a 4-h rest period. Blood samples were collected pre-exercise, immediately post-exercise, 30 min post-exercise, and 1, 2 and 4 h post-exercise on day 6. The plasma lactulose to mannitol ratio (L:M) and plasma intestinal fatty acid-binding protein (I-FABP) were used as markers of gastrointestinal permeability and damage, respectively.

Results

Plasma L:M (linear mixed model, coefficient ± standard error: − 0.011 ± 0.004, P = 0.0090) and changes (i.e., from pre-exercise) in plasma I-FABP (linear mixed model, − 195.3 ± 65.7 coefficient ± standard error (pg/mL), P = 0.0035) were lower in the cystine and glutamine supplementation trial than in the placebo trial.

Conclusion

Oral cystine and glutamine supplementation attenuated the markers of gastrointestinal permeability and damage after 1 h of strenuous running in young men.

Trial registration number

UMIN000026008.

Date of registration

13 December 2018.

Although many studies have reported that a posteriori dietary pattern is associated with metabolic health, there is little evidence of an association between dietary patterns and different metabolic phenotypes. The present study aimed to examine the association between major dietary patterns and different metabolic phenotypes (metabolically healthy non-obese [MHNO], metabolically unhealthy non-obese [MUNO], metabolically healthy obese [MHO], and metabolically unhealthy obese [MUO]) in middle-aged and elderly Japanese adults. This cross-sectional study enrolled 2,170 Japanese adults aged ≥40 years. The four different metabolic phenotypes were determined based on the presence of obesity, abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. The major dietary patterns were determined using principal component analysis based on energy-adjusted food intake. Two dietary patterns were identified: the healthy dietary pattern, which was characterized by a high intake of vegetables, fruits, potatoes, soy products, mushrooms, seaweeds, and fish; and the alcohol dietary pattern, which was characterized by a high intake of alcoholic beverages, liver, chicken, and fish. The healthy dietary pattern was associated with the MHNO and MHO phenotypes (MUNO and MUO as reference groups, respectively), and the multivariate-adjusted odds ratios (ORs) (95% confidence intervals [CIs]) in the highest quartile of healthy dietary pattern score with the lowest quartile as the reference category were 2.10 (1.40–3.15) and 1.86 (1.06–3.25), respectively. Conversely, the alcohol dietary pattern was inversely associated with the MHNO and MHO phenotypes, while the multivariate-adjusted ORs (95% CIs) in the highest quartile of the alcohol dietary pattern score with the lowest quartile as the reference category were 0.63 (0.42–0.94) and 0.45 (0.26–0.76), respectively. There were no significant interactions between sex and healthy/alcohol dietary patterns in the prevalence of the MHNO and MHO phenotypes. In conclusion, the present study's findings suggest that major dietary patterns are associated with different metabolic phenotypes in middle-aged and elderly Japanese adults. These findings provide useful evidence for maintaining metabolic health through diet regardless of obesity status.

Our study examined the effect of 8 weeks of high-intensity interval training (HIIT) and spirulina supplementation on the humoral immunity, cardio-respiratory fitness, and body composition of overweight and obese women. Thirty sedentary women (height: 161.7 ± 2.8 cm, body mass: 75.8 ± 8.4 kg, body mass index [BMI]: 28.8 ± 2.5 kg/m2, age: 25.1 ± 6.7 years) were divided into three groups: placebo with HIIT group, spirulina group (SG), or combined group (CG). Exercise groups performed HIIT for 8 weeks, with three sessions per week and four to seven repetitions in each session of 30 s running and 30 s walking; the intensity was established at 90% of the maximum heart rate. Supplementation groups received 6 g of spirulina powder per day. Fasting blood samples were collected before and after 8 weeks to determine the concentrations of immunoglobulins (IgA and IgG). There was a significant group-by-time interaction for fat free mass (FFM; p = 0.001, f = 8.52, ηp2 = 0.39) and IgA (p = 0.036, f = 3.86, ηp2 = 0.22). The post hoc analysis revealed that CG reduced FFM significantly (p = 0.012, g = −0.55) after training. CG and SG showed significantly greater IgA concentrations after 8 weeks (p = 0.02, g = 0.70 and p = 0.001, g = 0.34, respectively). We conclude that spirulina supplementation with HIIT affects the body composition (lower FFM) but also boosts IgA, which plays an important role in the immune system.

Abstract

Study aim: It is generally accepted that methamphetamine (MA) is a highly addictive psychostimulant which copies functions of certain neurotransmitters in the brain, and emits dopamine and serotonin in the brain. Frequent abuse of methamphetamine damages dopaminergic and serotonergic nerve endings at different sites of brain and also increases the anxiety and depression. Exercise seems to reverse physiological and neurological damages due to previous MA dependents and help to reduce anxiety and depression in this population. The aim is to determine the effect of exercise training on neurotransmitters and rate of depression and anxiety in chronic methamphetamine abusers based on a literature review.

Materials and methods: The present study investigated published articles in five computerized databases including Magiran, Google scholars, SID, PubMed and Scopus from 2011 until 2020. The searched keywords included sports, neurotransmitter, methamphetamine, depression, anxiety and treatment. The obtained results were described using texts, table and figure.

Results: According to the results, physical activity and exercise significantly increased blood serotonin and dopamine levels and significantly decreased the depression and anxiety.

Conclusion: Different evidences suggested that physical activity and exercise as positive responses and adaptations might influence on circulatory levels of two neurotransmitters (serotonin and dopamine) in methamphetamine addicts, decrease anxiety and depression, and improve preparation in previous MA dependents. In the rehabilitation period, the overall improvement in previous MA dependents might significantly increase. Exercise training can improve the physical and mental state of people addicted to methamphetamine as a non-drug therapy to promote health. However, more research is necessary to support this conclusion.

We performed a systematic review and dose–response meta-analysis of observational studies assessing the association between UPF consumption and adult mortality risk. A systematic search was conducted using ISI Web of Science, PubMed/MEDLINE, and Scopus electronic databases from inception to August 2021. Data were extracted from seven cohort studies (totaling 207,291 adults from four countries). Using a random-effects model, hazard ratios (HR) of pooled outcomes were estimated. Our results showed that UPF consumption was related to an enhanced risk of all-cause mortality (HR = 1.21; 95% CI: 1.13, 1.30; I2 = 21.9%; p < 0.001), cardiovascular diseases (CVDs)-cause mortality (HR = 1.50; 95% CI: 1.37, 1.63; I2 = 0.0%; p < 0.001), and heart-cause mortality (HR = 1.66; 95% CI: 1.50, 1.85; I2 = 0.0%; p = 0.022), but not cancer-cause mortality. Furthermore, our findings revealed that each 10% increase in UPF consumption in daily calorie intake was associated with a 15% higher risk of all-cause mortality (OR = 1.15; 95% CI: 1.09, 1.21; I2 = 0.0%; p < 0.001). The dose–response analysis revealed a positive linear association between UPF consumption and all-cause mortality (Pnonlinearity = 0.879, Pdose–response = p < 0.001), CVDs-cause mortality (Pnonlinearity = 0.868, Pdose–response = p < 0.001), and heart-cause mortality (Pnonlinearity = 0.774, Pdose–response = p < 0.001). It seems that higher consumption of UPF is significantly associated with an enhanced risk of adult mortality. Despite this, further experimental studies are necessary to draw a more definite conclusion.

Although exercise-induced humoral factors known as exerkines benefit systemic health, the role of most exerkines has not been investigated. Monocyte chemoattractant protein-1 (MCP-1) is a representative chemokine whose circulating concentrations increase after exercise, and it is one of the exerkines. MCP-1 is a ligand for CC chemokine receptor 2 (CCR2), which is expressed on monocytes, macrophages, and muscle cells. However, there is no information on the role of CCR2 signaling in exercise. Therefore, to investigate the research question, we administrated CCR2 antagonist or PBS to mice to inhibit CCR2 signaling before and after exercise. Our results showed that CCR2 signaling inhibition promoted exercise-induced macrophage infiltration and inflammation 24 h after exercise in muscle. CCR2 signaling inhibition also exacerbated exercise-induced inflammation immediately after exercise in muscle. However, neutrophil infiltration and oxidative stress had no contribution to exercise-induced inflammation by CCR2 signaling inhibition. CCR2 signaling inhibition also exacerbated exercise-induced inflammation immediately after exercise in kidney, liver, and adipose tissues. To summarize, pharmacological inhibition of CCR2 signaling exacerbated exercise-induced inflammation independently of neutrophil infiltration and oxidative stress.

Free radicals are reactive products that have multiple effects on the human body. Endogenous and exogenous antioxidants manage the overproduction of free radicals. However, an imbalance between free radicals and antioxidant factors causes oxidative stress. Exercise and physical activity are factors that increase oxidative stress and disrupts the body’s homeostasis. Intensity and duration of training, training characteristics, and fitness level can have positive or negative effects on oxidative stress. Green tea consumption is recommended for the prevention of a variety of diseases, health maintenance, and weight loss. The effectiveness of green tea is primarily due to the presence of catechins and polyphenols, specifically (–)-epigallocatechin-3-gallate, which has antioxidant and anti-inflammatory properties based on clinical and animal studies. This review investigates the effect of green tea exercise and their interactive effects on free radicals and sports improvement.

Dietary supplements are widely used as a nutritional strategy to improve and maintain performance and achieve faster recovery in sports and exercise. Exercise-induced muscle damage (EIMD) is caused by mechanical stress and subsequent inflammatory responses including reactive oxygen species and cytokine production. Therefore, dietary supplements with anti-inflammatory and antioxidant properties have the potential to prevent and reduce muscle damage and symptoms characterized by loss of muscle strength and delayed-onset muscle soreness (DOMS). However, only a few supplements are considered to be effective at present. This review focuses on the effects of dietary supplements derived from phytochemicals and listed in the International Olympic Committee consensus statement on muscle damage evaluated by blood myofiber damage markers, muscle soreness, performance, and inflammatory and oxidative stress markers. In this review, the effects of dietary supplements are also discussed in terms of study design (i.e., parallel and crossover studies), exercise model, and such subject characteristics as physical fitness level. Future perspectives and considerations for the use of dietary supplements to alleviate EIMD and DOMS are also discussed.

This article focuses on how nutrition may help prevent and/or assist with recovery from the harmful effects of strenuous acute exercise and physical training (decreased immunity, organ injury, inflammation, oxidative stress, and fatigue), with a focus on nutritional supplements. First, the effects of ketogenic diets on metabolism and inflammation are considered. Second, the effects of various supplements on immune function are discussed, including antioxidant defense modulators (vitamin C, sulforaphane, taheebo), and inflammation reducers (colostrum and hyperimmunized milk). Third, how 3-hydroxy-3-methyl butyrate monohydrate (HMB) may offset muscle damage is reviewed. Fourth and finally, the relationship between exercise, nutrition and COVID-19 infection is briefly mentioned. While additional verification of the safety and efficacy of these supplements is still necessary, current evidence suggests that these supplements have potential applications for health promotion and disease prevention among athletes and more diverse populations.

The coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the angiotensin converting enzyme 2 (ACE2) is the cellular receptor of SARS-CoV-2, it has a strong interaction with the renin angiotensin system (RAS). Experimental studies have shown that the higher levels of ACE2 or increasing ACE2/ACE1 ratio improve COVID-19 outcomes through lowering inflammation and death. Aerobic moderate intensity physical exercise fights off infections by two mechanisms, the inhibition of ACE/Ang II/AT1-R pathway and the stimulation of ACE2/Ang-(1–7)/MasR axis. Exercise can also activate the anti-inflammatory response so that it can be a potential therapeutic strategy against COVID-19. Here, we summarize and focus the relation among COVID-19, RAS, and immune system and describe the potential effect of aerobic moderate intensity physical exercise against CoV as a useful complementary tool for providing immune protection against SARS-CoV-2 virus infection, which is a novel intervention that requires further investigation.

Background: We aimed to investigate the effects of an 8-week total-body resistance exercise (TRX) suspension training intervention combined with taurine supplementation on body composition, blood glucose, and lipid markers in T2D females. Methods: Forty T2D middle-aged females (age: 53 ± 5 years, body mass = 84.3 ± 5.1 kg) were randomly assigned to four groups, TRX suspension training + placebo (TP; n = 10), TRX suspension training + taurine supplementation (TT; n = 10), taurine supplementation (T; n = 10), or control (C; n = 10). Body composition (body mass, body mass index (BMI), body fat percentage (BFP)), blood glucose (fasting blood sugar (FBS)), hemoglobin A1c (HbA1c), Insulin, and Insulin resistance (HOMA-IR), and lipid markers (low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC)) were evaluated prior to and after interventions. Results: All three interventions significantly decreased body mass, BMI, and BFP with no changes between them for body mass and BMI; however, BFP changes in the TT group were significantly greater than all other groups. FBS was significantly reduced in TP and TT. Insulin concentrations’ decrement were significantly greater in all experimental groups compared to C; however, no between group differences were observed between TT, TP, and T. In regards to HOMA-IR, decreases in TT were significantly greater than all other groups TG, HbA1c, and LDL were reduced following all interventions. HDL values significantly increased only in the TT group, while TC significantly decreased in TP and TT groups. Changes in HbA1c, TG, HDL, and TC were significantly greater in the TT compared to all other groups. Conclusions: TRX training improved glycemic and lipid profiles, while taurine supplementation alone failed to show hypoglycemic and hypolipidemic properties. Notably, the synergic effects of TRX training and taurine supplementation were shown in HbA1c, HOMA-IR, TG, TC, HDL, and BFP changes. Our outcomes suggest that TRX training + taurine supplementation may be an effective adjuvant therapy in individuals with T2D.

It is well-established that green tea supplementation has antioxidant properties. However, whether green tea supplementation leads to oxidative stress reduction remains unclear, as clinical investigations on this subject have yielded inconsistent outcomes. Consequently, we aimed to determine the effects of green tea supplementation on oxidative stress in adults. A systematic search of English language publications up to 21 August 2021 was carried out in PubMed, Scopus, Embase, and ISI Web of Science, utilizing pertinent keywords. These searches included randomized controlled trials (RCTs) evaluating the relationship between green tea supplementation, malondialdehyde (MDA), and total antioxidant capacity (TAC) in adults. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence intervals (95% CI). Meta-regression and non-linear dose-response analyses were performed to investigate the association between the dosage of green tea (mg/day) and the duration of the intervention (weeks) with pooled effect size. Sixteen RCTs with seventeen arms including 760 participants met the inclusion criteria. Our results indicated that green tea supplementation had significant effects on TAC (weighted mean difference [WMD]: 0.20 mmol/L; 95% CI: 0.09, 0.30, p < 0.001) and significant heterogeneity between studies (I2 = 98.6%, p < 0.001), which was largely related to gender and body mass index (BMI). Subgroup analysis in TAC identified a significant relationship except with low dose supplementation and obese individuals. No relationship between MDA and green tea supplementation was observed in any subgroups; however, meta-regression analysis revealed a linear inverse association between the dosage and significant change in MDA (r = −2117.18, p = 0.017). Our outcomes suggest that green tea supplementation improves TAC and affects MDA based on the dose of the intervention in adults. Future RCTs with longer durations are needed to expand our findings.

Research has shown that both dark chocolate and exercise training may have favorable effects on antioxidant function in obese cohorts. However, their combined effect has not been established. We assessed the influences of six weeks of dark chocolate consumption combined with jump rope exercise on antioxidant markers in adolescent boys with obesity. Fifty adolescent boys with obesity (age = 15 ± 1 years) were randomly assigned into one of four groups; jump rope exercise + white chocolate consumption (JW; n = 13), jump rope exercise + dark chocolate consumption (JD; n = 13), dark chocolate consumption (DC; n = 12), or control (C; n = 12). Two participants dropped out of the study. Participants in JW and JD groups performed jump rope exercise three times per week for six weeks. Participants in the DC and JD groups consumed 30 g of dark chocolate containing 83% of cocoa during the same period. Serum concentrations of superoxide dismutase (SOD), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) were evaluated prior to and after the interventions. All 3 intervention groups noted significant (p < 0.01) increases in serum concentrations of TAC, SOD, and GPx from baseline to post-test. In contrast, all intervention groups showed significantly reduced serum concentrations of TBARS from pre- to post-test (p ≤ 0.01). Bonferroni post hoc analysis revealed that post-test serum concentrations of TAC in the JD group were significantly greater than C (p < 0.001), DC (p = 0.010), and JW (p < 0.001) groups. In addition, post-test serum concentrations of SOD in the JD group were significantly greater than C group (p = 0.001). Post-test serum concentrations of GPx in the JD group were significantly greater than C (p < 0.001), DC (p = 0.021), and JW (p = 0.032) groups. The post-test serum concentrations of TBARS in the JD group was significantly lower than C (p < 0.001). No other significant between-group differences were observed. The current study provides evidence that dark chocolate consumption in combination with jump rope exercise is more efficient in improving antioxidant capacity than dark chocolate consumption or jump rope exercise alone among obese adolescent boys.

Reactive oxygen species (ROS) are strongly reactive chemical entities that include oxygen regulated by enzymatic and non-enzymatic antioxidant defense mechanisms. ROS contribute significantly to cell homeostasis in the heart by regulating cell proliferation, differentiation, and excitation-contraction coupling. When ROS generation surpasses the ability of the antioxidant defense mechanisms to buffer them, oxidative stress develops, resulting in cellular and molecular disorders and eventually in heart failure. Oxidative stress is a critical factor in developing hypoxia- and ischemia-reperfusion-related cardiovascular disorders. This article aimed to discuss the role of oxidative stress in the pathophysiology of cardiac diseases such as hypertension and endothelial dysfunction. This review focuses on the various clinical events and oxidative stress associated with cardiovascular pathophysiology, highlighting the benefits of new experimental treatments such as creatine supplementation, omega-3 fatty acids, microRNAs, and antioxidant supplements in addition to physical exercise

One of the essential injuries caused by moderate to high-intensity and short-duration physical activities is the overproduction of reactive oxygen species (ROS), damaging various body tissues such as skeletal muscle (SM). However, ROS is easily controlled by antioxidant defense systems during low to moderate intensity and long-term exercises. In stressful situations, antioxidant supplements are recommended to prevent ROS damage. We examined the response of SM to ROS generation during exercise using an antioxidant supplement treatment strategy in this study. The findings of this review research are paradoxical due to variances in antioxidant supplements dose and duration, intensity, length, frequency, types of exercise activities, and, in general, the lack of a regular exercise and nutrition strategy. As such, further research in this area is still being felt.

Background and objectives: The purpose of this study was to investigate the influences of oral high-dose genistein (GE) administration on exercise-induced oxidative stress, inflammatory response and tissue damage. Materials and Methods: Thirty-two mice were randomly divided into control group (Con; sedentary/0.5% CMC-Na), GE administrated group (GE; sedentary/GE dosed), exercise group (Ex; exercise/0.5% CMC-Na), or GE administrated plus exercise group (GE + Ex; exercise/GE dosed), mice in the GE and GE + Ex group were given GE orally at the dose of 200 mg/kg weight. Results: Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, liver interleukin (IL)-6, IL-1β, superoxide dismutase 1 (SOD1), catalase (CAT), hemeoxygenase-1 (HO-1) gene expression levels and skeletal muscle IL-6, nuclear factor erythroid 2-related factor (Nrf2), and HO-1 gene expression levels increased immediately after exhaustive exercise. GE supplementation increased liver protein carbonyl concentrations. On the other hand, GE supplementation significantly decreased SOD1, CAT gene expression levels in the liver and Nrf2, and HO-1 gene expression levels in the skeletal muscles. Conclusions: Acute exercise induced organ damage, inflammation, and oxidative stress in skeletal muscles and the liver. However, a single dose of GE supplementation before exercise did not lead to favorable antioxidant and anti-inflammatory effects in this study.

Vitamin D and zinc are important components of nutritional immunity. This study compared the serum concentrations of 25-hydroxyvitamin D (25(OH)D) and zinc in COVID-19 outpatients with those of potentially non-infected participants. The association of clinical symptoms with vitamin D and zinc status was also examined. A checklist and laboratory examination were applied to collect data in a cross-sectional study conducted on 53 infected outpatients with COVID-19 and 53 potentially non-infected participants. Serum concentration of 25(OH)D were not significantly lower in patients with moderate illness (19 ± 12 ng/mL) than patients with asymptomatic or mild illness (29 ± 18 ng/mL), with a trend noted for a lower serum concentration of 25(OH)D in moderate than asymptomatic or mild illness patients (p = 0.054). Infected patients (101 ± 18 µg/dL) showed a lower serum concentration of zinc than potentially non-infected participants (114 ± 13 µg/dL) (p = 0.01). Patients with normal (odds ratio (OR), 0.19; p ≤ 0.001) and insufficient (OR, 0.3; p = 0.007) vitamin D status at the second to seventh days of disease had decreased OR of general symptoms compared to patients with vitamin D deficiency. This study revealed the importance of 25(OH)D measurement to predict the progression of general and pulmonary symptoms and showed that infected patients had significantly lower zinc concentrations than potentially non-infected participants.

(1) Background: Observational studies have established that vitamin D-binding protein (DBP) and 25-hydroxyvitamin D3 (25(OH)D) concentrations are the major factors affecting the bioavailability of 25(OH)D. It has also been shown that poor 25(OH)D bioavailability elevates the risk of obesity and its related cardio-metabolic disorders. However, the relationship between 25(OH)D and DBP concentrations with cardio-metabolic risk factors in overweight and obese cohorts has not been established. Consequently, we evaluated the association between DBP and 25(OH)D concentrations with lipid profile, blood pressure (BP), and body composition in overweight and obese women. (2) Methods: In this cross-sectional study of 236 overweight and obese women, DBP and 25(OH)D concentrations were measured using an enzyme-linked immunosorbent assay. Body composition was assessed via bioelectrical impedance analysis. Lipid profile and BP were assessed by an auto-analyzer and digital BP monitor, respectively. The associations were examined by multivariate logistic regression. (3) Results: The indicated showed an inverse relationship between DBP and high-density lipoprotein (HDL) (p = 0.010) concentrations (where individuals with higher DBP had lower HDL) which, after adjusting for possible cofounders, remained significant (p = 0.006). Moreover, DBP concentration was positively associated with fat mass index (FMI) after adjustment (p = 0.022). No significant relationships were observed among 25(OH)D and target variables. (4) Conclusions: In conclusion, lower concentrations of HDL and higher values of FMI are associated with higher concentrations of DBP in overweight and obese women. These findings present novel awareness regarding the association of DBP with some metabolic and body composition variables in overweight and obese women. However, a two-way causal relationship between DBP and target variables should be considered.

Background: Chronic inflammation associated with breast cancer (BC) poses a major challenge in care management and may be ameliorated by physical activity. This randomized controlled trial assessed the effects of a 12-week high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on inflammatory markers, body composition, and physical fitness in BC survivors (BCS). Methods: Forty BCS (age = 57 ± 1 years; body mass [BM] = 74.8 ± 1.5 kg; VO2peak = 20.8 ± 2.1 mL·kg−1·min−1) were randomly assigned to three groups: HIIT (n = 15), MICT (n = 15), or control (CON; n = 15). The intervention groups (HIIT and MICT) performed their respective exercise protocols on a cycle ergometer 3 days/week for 12 weeks while the CON group maintained their current lifestyle. Baseline and post-intervention assessments included body composition (BM, fat mass (FM), lean mass (LM)), physical fitness (VO2peak, lower body strength (LBS), upper body strength (UBS)), and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), leptin, and adiponectin. Results: Both intervention groups significantly (p < 0.05) decreased BM (HIIT = −1.8 kg, MICT = −0.91 kg), FM (HIIT = −0.81 kg, MICT = −0.18 kg), TNF-α (HIIT = −1.84 pg/mL, MICT = −0.99 pg/mL), IL-6 (HIIT = −0.71 pg/mL, MICT = −0.36 pg/mL), leptin (HIIT = −0.35 pg/mL, MICT = −0.16 pg/mL) and increased VO2peak (HIIT = 0.95 mL·kg−1·min−1, MICT = 0.67 mL·kg−1·min−1), LBS (HIIT = 2.84 kg, MICT = 1.53 kg), UBS (HIIT = 0.53 kg, MICT = 0.53 kg), IL-10 (HIIT = 0.63 pg/mL, MICT = 0.38 pg/mL), and adiponectin (HIIT = 0.23 ng/mL, MICT = 0.1 ng/mL) compared to baseline. The changes in BM, FM, TNF-α, leptin, and LBS were significantly greater in HIIT compared to all other groups. Conclusions: Our findings indicate that compared to the often-recommended MICT, HIIT may be a more beneficial exercise therapy for the improvement of inflammation, body composition and LBS in BCS; and consequently, merits long-term study

Background: The favorable influences of saffron supplementation on metabolic diseases have previously been shown. We aimed to assess the effects of saffron supplementation on blood pressure in adults. Methods: A systematic search was performed in Scopus, Embase, and the Cochrane library databases to find randomized controlled trials (RCTs) related to the effect of saffron supplementation on blood pressure in adults up to March 2021. The primary search yielded 182 publications, of which eight RCTs were eligible. Results: Our results showed that saffron supplementation resulted in a significant decrease in systolic blood pressure (weighted mean difference (WMD): −0.65 mmHg; 95% CI: −1.12 to −0.18, p = 0.006) and diastolic blood pressure (DBP) (WMD: −1.23 mmHg; 95% CI: −1.64 to −0.81, p < 0.001). Moreover, saffron supplementation reduced DBP in a non-linear fashion, based on duration (r = −2.45, p-nonlinearity = 0.008). Conclusions: Saffron supplementation may significantly improve both systolic and diastolic blood pressure in adults. It should be noted that the hypotensive effects of saffron supplementation were small and may not reach clinical importance.

Marine sponge-associated bacteria are known as bio-active compound produce. We have constructed metagenome libraries of the bacteria and developed a metagenomic screening approach. Activity-based screening successfully identified novel genes and novel enzymes; however, the efficiency was only in 1 out of 104 clones. Therefore, in this study, we thought that bioinformatics could help to reduce screening efforts, and combined activity-based screening with database search. Neutrophils play an important role for the immune system to recognize excreted bacterial by-products as chemotactic factors and are recruited to infection sites to kill pathogens via phagocytosis. These excreted by-products are considered critical triggers that engage the immune system to mount a defense against infection, and identifying these factors may guide developments in medicine and diagnostics. We focused on genes encoding amino acid ligase and peptide synthetase and selected from an in-house sponge metagenome database. Cell-free culture medium of each was used in a neutrophil chemiluminescence assay in luminol reaction. The clone showing maximum activity had a genomic sequence expected to produce a molecule like a phospho-N-acetylmuramyl pentapeptide by the metagenome fragment analysis.

Background: The aim of this clinical study was to reveal the relationship between body dehydration and oral mucosa moisture measured by the use of a capacitance sensor for oral epithelial moisture. Methods: The following clinical parameters were recorded from each one of 19 athletes in a one-week period of high-intensity exercise at the U-23 Triathlon Training Camp in summer and winter; body weight, urine specific gravity, oral mucosa moisture, subjective oral thirst, and subjective throat thirst (within 30 min after waking and before breakfast at 7:00 a.m. on Day2 and Day6). Results: There were no significant differences in the mean values of body weight, urine specific gravity, oral mucosa moisture, oral thirst, and throat thirst between Day2 and Day6 in both measurements in summer and winter. The oral mucosa moisture had a moderate negative correlation with urine specific gravity (p < 0.05, r = −0.45). Conclusions: This study suggests that oral mucosal moisture determined using an oral moisture-checking device could be a potential index for assessing dehydration during sports activities.

The purpose of this study was to analyze the intragroup differences in weekly training monotony (TM) and training strain (TS) between starter and non-starter male professional soccer players at accelerometry based variables throughout the periods of a season. TM and TS of different accelerations and decelerations zones for twenty-one players were followed for forty-eight weeks. Regardless of group, players obtained the highest mean TM (starters = 3.3 ± 0.6, non-starters = 2.2 ± 1.1, in arbitrary unit, AU) and TS (starters = 1288.9 ± 265.2, non-starters = 765.4 ± 547.5, AU) scores in the pre-season for accelerations at Zone 1 (<2 m/s2). The results also indicated that both groups exhibited similar TM and TS scores in accelerations at Zones 2 (2 to 4 m/s2) and 3 (>4 m/s2) across the entire season. While the starters showed the highest TM and TS scores at deceleration Zone 1 (<−2 m/s2) in the end-season, the non-starters exhibited the highest scores at the deceleration Zone 1 in pre-season. It seems that in pre-season, coaches applied higher levels of training with greater emphasis on deceleration for non-starters. This tendency was reduced over time for non-starters, while starters presented higher values of deceleration Zone 1. These results highlight the variations in TM and TS across the different periods of a full season according to match starting status among professional soccer players, and the results suggest that non-starter players should receive higher levels of load to compensate for non-participation in matches throughout a soccer season.

<title>Abstract</title>
The association between a dietary pattern characterised by high alcohol intake and dyslipidaemia has not been fully investigated. Therefore, the present study aimed to investigate the association between alcohol dietary patterns and the prevalence of dyslipidaemia and its components. This cross-sectional study enrolled 2,171 men and women aged ≥40 years who were alumni of a Japanese university. To identify dietary patterns, a principal component analysis was performed based on the energy-adjusted food intake estimated by a brief-type self-administered diet history questionnaire. Three dietary patterns were identified, the second of which was named the alcohol dietary pattern and was characterised by a high intake of alcoholic beverages, liver, chicken, and fish. This alcohol dietary pattern was associated with reduced low-density lipoprotein cholesterol (LDL-C) levels. The fully adjusted odds ratios (95% confidence intervals) of high LDL-C for the lowest through highest quartile of alcohol dietary pattern score were 1.00 (reference), 0.83 (0.64–1.08), 0.84 (0.64–1.10), and 0.68 (0.49– 0.94), respectively. Subgroup analysis showed that the alcohol dietary pattern was inversely associated with the prevalence of dyslipidaemia in women, whereas it was positively associated with high triglyceride levels in men. In conclusion, the alcohol dietary pattern, characterised by a high intake of alcoholic beverages, liver, chicken, and fish, was associated with the prevalence of dyslipidaemia and its components. This finding provides useful information for the prevention and treatment of dyslipidaemia by modifying the diet.

Background: There is a growing interest in the considerable benefits of dietary supplementations, such as folic acid, on the glycemic profile. We aimed to investigate the effects of folic acid supplementation on glycemic control markers in adults. Methods: Randomized controlled trials examining the effects of folic acid supplementation on glycemic control markers published up to March 2021 were detected by searching online databases, including Scopus, PubMed, Embase, and ISI web of science, using a combination of related keywords. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the intervention and control groups at follow-up. Meta-regression and non-linear dose-response analysis were conducted to evaluate the association between pooled effect size and folic acid dosage (mg/day) and duration of the intervention (week). From 1814 detected studies, twenty-four studies reported fasting blood glucose (FBG), fasting insulin, hemoglobin A1C (HbA1C), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as an outcome measure. Results: Results revealed significant reductions in FBG (weighted mean difference (WMD): −2.17 mg/dL, 95% CI: −3.69, −0.65, p = 0.005), fasting insulin (WMD: −1.63 pmol/L, 95% CI: −2.53, −0.73, p &lt; 0.001), and HOMA-IR (WMD: −0.40, 95% CI: −0.70, −0.09, p = 0.011) following folic acid supplementation. No significant effect was detected for HbA1C (WMD: −0.27%, 95% CI: −0.73, 0.18, p = 0.246). The dose-response analysis showed that folic acid supplementation significantly changed HOMA-IR (r = −1.30, p-nonlinearity = 0.045) in non-linear fashion. However, meta-regression analysis did not indicate a linear relationship between dose, duration, and absolute changes in FBG, HOMA-IR, and fasting insulin concentrations. Conclusions: Folic acid supplementation significantly reduces some markers of glycemic control in adults. These reductions were small, which may limit clinical applications for adults with type II diabetes. Further research is necessary to confirm our findings.

It has been theorized that folic acid supplementation improves inflammation. However, its proven effects on inflammatory markers are unclear as clinical studies on this topic have produced inconsistent results. To bridge this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of folic acid supplementation on serum concentrations of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Methods: To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, Web of Science, EMBASE, Cochrane databases, and Google Scholar using relevant keywords. A fix or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Twelve RCTs were included in the present meta-analysis. The pooled analysis revealed that serum concentrations of CRP (WMD: −0.59 mg/L, 95% CI −0.85 to −0.33, p &lt; 0.001) were significantly reduced following folic acid supplementation compared to placebo, but did not affect serum concentrations of IL-6 (WMD: −0.12, 95% CI −0.95 to 0.72 pg/mL, p = 0.780) or TNF-α (WMD: −0.18, 95% CI −0.86 to 0.49 pg/mL, p = 0.594). The dose–response analysis demonstrated a significant relationship between an elevated dosage of folic acid supplementation and lower CRP concentrations (p = 0.002). Conclusions: We found that folic acid supplementation may improve inflammation by attenuating serum concentrations of CRP but without significant effects on IL-6 and TNF-α. Future RCTs including a larger number of participants and more diverse populations are needed to confirm and expand our findings.

Previous studies have indicated that curcumin supplementation may be beneficial for cardiometabolic health; however, current evidence regarding the effects of its nanorange formulations, popularly known as “nano-curcumin”, remains unclear. This systematic review and meta-analysis aimed to determine the impact of nano-curcumin supplementation on risk factors for cardiovascular disease. PubMed, Scopus, Embase, and ISI web of science were systematically searched up to May 2021 using relevant keywords. All randomized controlled trials (RCTs) investigating the effects of nano-curcumin supplementation on cardiovascular disease risk factors were included. Meta-analysis was performed using random-effects models, and subgroup analysis was performed to explore variations by dose and baseline risk profiles. According to the results of this study, nano-curcumin supplementation was associated with improvements in the glycemic profile by decreasing fasting blood glucose (FBG) (WMD: −18.14 mg/dL; 95% CI: −29.31 to −6.97; p = 0.001), insulin (WMD: −1.21 mg/dL; 95% CI: −1.43 to −1.00; p &lt; 0.001), and HOMA-IR (WMD: −0.28 mg/dL; 95% CI: −0.33 to −0.23; p &lt; 0.001). Interestingly, nano-curcumin supplementation resulted in increases in high-density lipoprotein (HDL) (WMD: 5.77 mg/dL; 95% CI: 2.90 to 8.64; p &lt; 0.001). In terms of other lipid profile markers (triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL)), subgroup analyses showed that nano-curcumin supplementation had more favorable effects on lipid profiles in individuals with dyslipidemia at baseline. Nano-curcumin supplementation also showed favorable anti-inflammatory effects by decreasing C-reactive protein (CRP) (WMD: −1.29 mg/L; 95% CI: −2.15 to −0.44; p = 0.003) and interleukin-6 (IL-6) (WMD: −2.78 mg/dL; 95% CI: −3.76 to −1.79; p &lt; 0.001). Moreover, our results showed the hypotensive effect of nano-curcumin, evidenced by a decrease in systolic blood pressure (SBP). In conclusion, our meta-analysis suggests that nano-curcumin supplementation may decline cardiovascular disease risk by improving glycemic and lipid profiles, inflammation, and SBP. Future large-scale investigations with longer durations are needed to expand on our findings.

The novel Coronavirus Disease 2019 (COVID-19) crisis is now present in more than 200 countries. It started in December 2019 and has, so far, led to more than 149, 470,968 cases, 3,152,121 deaths, and 127,133,013 survivors recovered by 28 April 2021. COVID-19 has a high morbidity, and mortality of 2%, on average, whereas most people are treated after a period of time. Some people who recover from COVID-19 are left with 20 to 30% decreased lung function. In this context, exercise focused on skeletal muscle with minimal lung involvement could potentially play an important role. Regular exercise protects against diseases associated with chronic low-grade systemic inflammation. This long-term effect of exercise may be ascribed to the anti-inflammatory response elicited by an acute bout of exercise, which is partly mediated by muscle-derived myokines. The isometric training system seems to have this feature, because this system is involved with the skeletal muscle as the target tissue. However, no studies have examined the effect of exercise on the treatment and recovery of COVID-19, and, more importantly, “muscle–lung cross-talk” as a mechanism for COVID-19 treatment. It is suggested that this theoretical construct be examined by researchers.

Previous studies have not investigated the determinants of resting oxidative stress, including physical fitness, as it relates to redox regulation. The present study therefore was aimed at identifying lifestyle and biological factors that determine resting oxidative stress, including objectively measured physical fitness. In 873 middle-aged and elderly men and women, age and anthropometric parameters, lifestyle-related parameters, medication and supplementation status, physical fitness, biochemical parameters, and nutritional intake status, as well as three plasma oxidative stress markers: protein carbonyl (PC), F2-isoprostane (F2-IsoP), and thiobarbituric acid reactive substances (TBARS), were surveyed and measured. The determinants of PC, F2-IsoP, and TBARS in all participants were investigated using stepwise multiple regression analysis. In PC, age (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">
<mi>β</mi>
<mo>=</mo>
<mo>−</mo>
<mn>0.11</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M2">
<mi>P</mi>
<mo>=</mo>
<mn>0.002</mn>
</math>
</inline-formula>), leg extension power (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M3">
<mi>β</mi>
<mo>=</mo>
<mo>−</mo>
<mn>0.12</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M4">
<mi>P</mi>
<mo>=</mo>
<mn>0.008</mn>
</math>
</inline-formula>), BMI (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M5">
<mi>β</mi>
<mo>=</mo>
<mn>0.12</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M6">
<mi>P</mi>
<mo>=</mo>
<mn>0.004</mn>
</math>
</inline-formula>), and HDL-C (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M7">
<mi>β</mi>
<mo>=</mo>
<mn>0.08</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M8">
<mi>P</mi>
<mo>=</mo>
<mn>0.040</mn>
</math>
</inline-formula>) were included in the regression model (adjusted <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M9">
<msup>
<mrow>
<mi>R</mi>
</mrow>
<mrow>
<mn>2</mn>
</mrow>
</msup>
<mo>=</mo>
<mn>0.018</mn>
</math>
</inline-formula>). In the F2-IsoP, smoking status (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M10">
<mi>β</mi>
<mo>=</mo>
<mn>0.07</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M11">
<mi>P</mi>
<mo>=</mo>
<mn>0.060</mn>
</math>
</inline-formula>), BMI (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M12">
<mi>β</mi>
<mo>=</mo>
<mn>0.07</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M13">
<mi>P</mi>
<mo>=</mo>
<mn>0.054</mn>
</math>
</inline-formula>), and HbA1c (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M14">
<mi>β</mi>
<mo>=</mo>
<mo>−</mo>
<mn>0.06</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M15">
<mi>P</mi>
<mo>=</mo>
<mn>0.089</mn>
</math>
</inline-formula>) were included in the regression model (adjusted <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M16">
<msup>
<mrow>
<mi>R</mi>
</mrow>
<mrow>
<mn>2</mn>
</mrow>
</msup>
<mo>=</mo>
<mn>0.006</mn>
</math>
</inline-formula>). In TBARS, glucose (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M17">
<mi>β</mi>
<mo>=</mo>
<mn>0.18</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M18">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.001</mn>
</math>
</inline-formula>), CRF (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M19">
<mi>β</mi>
<mo>=</mo>
<mn>0.16</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M20">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.001</mn>
</math>
</inline-formula>), age (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M21">
<mi>β</mi>
<mo>=</mo>
<mn>0.15</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M22">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.001</mn>
</math>
</inline-formula>), TG (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M23">
<mi>β</mi>
<mo>=</mo>
<mn>0.11</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M24">
<mi>P</mi>
<mo>=</mo>
<mn>0.001</mn>
</math>
</inline-formula>), antioxidant supplementation (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M25">
<mi>β</mi>
<mo>=</mo>
<mn>0.10</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M26">
<mi>P</mi>
<mo>=</mo>
<mn>0.002</mn>
</math>
</inline-formula>), and HbA1c (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M27">
<mi>β</mi>
<mo>=</mo>
<mo>−</mo>
<mn>0.13</mn>
</math>
</inline-formula>, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M28">
<mi>P</mi>
<mo>=</mo>
<mn>0.004</mn>
</math>
</inline-formula>) were included in the regression model (adjusted <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M29">
<msup>
<mrow>
<mi>R</mi>
</mrow>
<mrow>
<mn>2</mn>
</mrow>
</msup>
<mo>=</mo>
<mn>0.071</mn>
</math>
</inline-formula>). In conclusion, the present study showed that age, anthropometric index, lifestyle-related parameters, medication and supplementation status, objectively measured physical fitness, biochemical parameters, and nutritional intake status explain less than 10% of oxidative stress at rest.

Coronavirus (COVID-19) is a dangerous infectious disease that is easily transmitted and which is called an acute respiratory syndrome. With the spread of the coronavirus around the world and its epidemic among humans, we are losing many humans. The long process of treatment in hospitalized patients who are receiving intensive care and medication is associated with physical weakness. It has been suggested that lifelong exercise can create a safe margin for a person that allows them to avoid becoming infected with the virus. The current study was conducted to assess the effects of low-intensity exercise and breathing exercises on cardiorespiratory responses and physical status in an overweight 20-year-old woman infected with COVID-19. The patient was referred to Hazrat Ali Ibn Abitaleb Hospital in Rafsanjan. The patient had initial symptoms of coronavirus including weakness, shortness of breath, fever, and chills, and the initial tests confirmed that the person was infected with the coronavirus. Although COVID-19 reduces respiration and blood oxygen and severely reduces movement and physical activity, low-intensity rehabilitation and breathing exercises along with medication can improve blood oxygen status, resting heart rate, blood pressure, and hand power status in patients and possibly speeding up the healing process. The results of the present study show that low-intensity exercise and breathing exercises in patients with COVID-19, whose disease severity is mild to moderate, can be performed safely under the supervision of their physicians to prevent the disease process.

(1) Background: This systematic review and meta-analysis aimed to assess the effects of folic acid supplementation on oxidative stress markers. (2) Methods: Online database including PubMed, Scopus, Web of Science, and Cochrane were searched up to January 2021, to retrieve randomized controlled trials (RCTs) which examined the effect of folic acid supplementation on markers of oxidative stress. Meta-analyses were carried out using a random-effects model. I2 index was used to evaluate the heterogeneity of RCTs. (3) Results: Among the initial 2322 studies that were identified from electronic databases search, 13 studies involving 1013 participants were eligible. Pooled effect size from 13 studies indicated that folic acid supplementation elicits a significant rise in serum concentrations of glutathione (GSH) (WMD: 219.01 umol/L, 95% CI 59.30 to 378.71, p = 0.007) and total antioxidant capacity (TAC) (WMD: 91.70 umol/L, 95% CI 40.52 to 142.88, p &lt; 0.001) but has no effect on serum concentrations of nitric oxide (NO) (WMD: 2.61 umol/L, 95% CI −3.48 to 8.72, p = 0.400). In addition, folic acid supplementation significantly reduced serum concentrations of malondialdehyde (MDA) (WMD: −0.13 umol/L, 95% CI −0.24 to −0.02, p = 0.020). (4) Conclusions: This meta-analysis study suggests that folic acid supplementation may significantly improve markers within the antioxidative defense system by increasing serum concentrations of GSH and TAC and decreasing serum concentrations of MDA.

Strenuous exercise induces organ damage, inflammation and oxidative stress. To prevent exercise-induced organ damage, inflammation and oxidative stress, rehydrating may be an effective strategy. In the present study, we aimed to examine whether beverage intake after exhaustive exercise to recover from dehydration prevents such disorders. Thirteen male volunteers performed incremental cycling exercise until exhaustion. Immediately after exercise, the subjects drank an electrolyte containing water (rehydrate trial: REH) or did not drink any beverage (control trial: CON). Blood samples were collected before (Pre), immediately (Post), 1 h and 2 h after exercise. Urine samples were also collected before (Pre) and 2 h after exercise. We measured biomarkers of organ damage, inflammation and oxidative stress in blood and urine. Biomarkers of muscle, renal and intestinal damage and inflammation increased in the blood and urine after exercise. However, changes in biomarkers of organ damage and inflammation did not differ between trials (p &gt; 0.05). The biomarker of oxidative stress, thiobarbituric acid reactive substances (TBARS), in plasma, showed different changes between trials (p = 0.027). One hour after exercise, plasma TBARS concentration in REH had a higher trend than that in CON (p = 0.052), but there were no significant differences between Pre and the other time points in each trial. These results suggest that beverage intake after exercise does not attenuate exercise-induced organ damage, inflammation or oxidative stress in healthy males. However, rehydration restores exercise-induced oxidative stress more quickly.

Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.

One of the leading causes of obesity associated with oxidative stress (OS) is excessive consumption of nutrients, especially fast-foods, and a sedentary lifestyle, characterized by the ample accumulation of lipid in adipose tissue (AT). When the body needs energy, the lipid is broken down into glycerol (G) and free fatty acids (FFA) during the lipolysis process and transferred to various tissues in the body. Materials secreted from AT, especially adipocytokines (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)) and reactive oxygen species (ROS), are impressive in causing inflammation and OS of AT. There are several ways to improve obesity, but researchers have highly regarded the use of antioxidant supplements due to their neutralizing properties in removing ROS. In this review, we have examined the AT response to OS to antioxidant supplements focusing on animal studies. The results are inconsistent due to differences in the study duration and diversity in animals (strain, age, and sex). Therefore, there is a need for different studies, especially in humans.

Pain is one of the major problems in haemodialysis patients. Regular resistance exercise (RE), as an effective lifestyle modification, may play a role in reducing pain through changes in blood pressure (BP). Therefore, we aimed to evaluate the effect of RE training on pain, BP, and heart rate. In a randomised controlled trial, eighteen sedentary women completed the study in RE (n=10) or control (n=8) groups. In the exercise group, the patients had a circuit RE program in non-dialysis days, two times a week, for six weeks. The RE protocol consisted of six exercises performing with 10 repetitions at 50-60% of 1-repetition maximum. Resting and intradialytic pain threshold (algometer using a 1 kg pressure load), BP, and heart rate were measured 48 h before and after the intervention. There were no significant differences from pre- to post-intervention, or between the groups regarding pain threshold, systolic and diastolic BP, and heart rate at rest and during the haemodialysis process (P&gt;0.05). Although the 6-week low-intensity RE training in non-dialysis days was safe for chronic haemodialysis women, it could not change resting and intradialytic pain and hemodynamic measures.

Exercise can ameliorate cardiovascular dysfunctions in the diabetes condition, but its precise molecular mechanisms have not been entirely understood. The aim of the present study was to determine the impact of endurance training on expression of angiogenesis-related genes in cardiac tissue of diabetic rats. Thirty adults male Wistar rats were randomly divided into three groups (N = 10) including diabetic training (DT), sedentary diabetes (SD), and sedentary healthy (SH), in which diabetes was induced by a single dose of streptozotocin (50 mg/kg). Endurance training (ET) with moderate-intensity was performed on a motorized treadmill for six weeks. Training duration and treadmill speed were increased during five weeks, but they were kept constant at the final week, and slope was zero at all stages. Real-time polymerase chain reaction (RT-PCR) analysis was used to measure the expression of myocyte enhancer factor-2C (MEF2C), histone deacetylase-4 (HDAC4) and Calmodulin-dependent protein kinase II (CaMKII) in cardiac tissues of the rats. Our results demonstrated that six weeks of ET increased gene expression of MEF2C significantly (p &lt; 0.05), and caused a significant reduction in HDAC4 and CaMKII gene expression in the DT rats compared to the SD rats (p &lt; 0.05). We concluded that moderate-intensity ET could play a critical role in ameliorating cardiovascular dysfunction in a diabetes condition by regulating the expression of some angiogenesis-related genes in cardiac tissues.

Icing is still one of the most common treatments to acute skeletal muscle damage in sports medicine. However, previous studies using rodents reported the detrimental effect of icing on muscle regeneration following injury. This study aimed to elucidate the critical factors governing the impairment of muscle regeneration by icing with a murine model of eccentric contraction-induced muscle damage by electrical stimulation. Because of icing after muscle injury, the infiltration of polynuclear and mononuclear cells into necrotic muscle fibers was retarded and attenuated, leading to the persistent presence of necrotic cellular debris. These phenomena coincided with the delayed emergence and sustained accumulation of Pax7⁺ myogenic cells within the regenerating area. Additionally, due to icing, delayed and/or sustained infiltration of M1 macrophages was noted in accordance with the perturbed expression patterns of inflammation-related factors, including tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). The key myogenic regulatory factors (i.e., MyoD and myogenin) involved in the activation/proliferation and differentiation of myogenic precursor cells were not altered by icing during the regenerative process. A detailed analysis of regenerating myofibers by size distribution at day 14 after muscle damage showed that the ratio of small regenerating fibers to total regenerating fibers was higher in icing-treated animals than in untreated animals. These findings suggest that icing following muscle damage blunts the efficiency of muscle regeneration by perturbing the removal of necrotic myofibers and phenotypic dynamics of macrophages rather than affecting myogenic factors.

Oxidative stress is the result of an imbalance between the generation of reactive oxygen species (ROS) and their elimination by antioxidant mechanisms. ROS degrade biogenic substances such as deoxyribonucleic acid, lipids, and proteins, which in turn may lead to oxidative tissue damage. One of the physiological conditions currently associated with enhanced oxidative stress is exercise. Although a period of intense training may cause oxidative damage to muscle fibers, regular exercise helps increase the cells’ ability to reduce the ROS over-accumulation. Regular moderate-intensity exercise has been shown to increase antioxidant defense. Endogenous antioxidants cannot completely prevent oxidative damage under the physiological and pathological conditions (intense exercise and exercise at altitude). These conditions may disturb the endogenous antioxidant balance and increase oxidative stress. In this case, the use of antioxidant supplements such as creatine can have positive effects on the antioxidant system. Creatine is made up of two essential amino acids, arginine and methionine, and one non-essential amino acid, glycine. The exact action mechanism of creatine as an antioxidant is not known. However, it has been shown to increase the activity of antioxidant enzymes and the capability to eliminate ROS and reactive nitrogen species (RNS). It seems that the antioxidant effects of creatine may be due to various mechanisms such as its indirect (i.e., increased or normalized cell energy status) and direct (i.e., maintaining mitochondrial integrity) mechanisms. Creatine supplement consumption may have a synergistic effect with training, but the intensity and duration of training can play an important role in the antioxidant activity. In this study, the researchers attempted to review the literature on the effects of creatine supplementation and physical exercise on oxidative stress.

Trends relating to specific diets and lifestyle factors like physical (in) activity have formed in recent times [...]

The low-carbohydrate ketogenic diet (LCKD) is a dietary approach characterized by the intake of high amounts of fat, a balanced amount of protein, and low carbohydrates, which is insufficient for metabolic demands. Previous studies have shown that an LCKD alone may contribute to fatty acid oxidation capacity, along with endurance. In the present study, we combined a 10-week LCKD with an 8-week forced treadmill running program to determine whether training in conjunction with LCKD enhanced fatty acid oxidation capacity, as well as whether the maximal exercise capacity would be affected by an LCKD or training in a mice model. We found that the lipid pool and fatty acid oxidation capacity were both enhanced following the 10-week LCKD. Further, key fatty acid oxidation related genes were upregulated. In contrast, the 8-week training regimen had no effect on fatty acid and ketone body oxidation. Key genes involved in carbohydrate utilization were downregulated in the LCKD groups. However, the improved fatty acid oxidation capacity did not translate into an enhanced maximal exercise capacity. In summary, while favoring the fatty acid oxidation system, an LCKD, alone or combined with training, had no beneficial effects in our intensive exercise-evaluation model. Therefore, an LCKD may be promising to improve endurance in low- to moderate-intensity exercise, and may not be an optimal choice for those partaking in high-intensity exercise.

Acute intense exercise causes significant oxidative stress and consequently an increase in total antioxidant capacity; however, the mechanisms and combined effects of intense exercise and smoking on oxidative stress among active and non-active smokers are not clear. The aim of this study was to investigate the effect of acute intense exercise on antioxidant enzyme activity responses in active and non-active individuals exposed to cigarette smoke. The study included 40 subjects who were equally classified as: smokers that did exercise (SE), smokers that did not do exercise (SnE), non-smokers that did exercise (NSE), and non-smokers that did not do exercise (NSnE). The adjusted Astrand test was used to exhaust the subjects. Salivary enzymes of peroxidase (POX), catalase (CAT), and superoxide dismutase (SOD) were measured, by spectrophotometry methods, at 3 different time points: pre-test (TP1), post-test (TP2), and one hour after finishing the test (TP3). Significant (p &lt; 0.05) group x time interactions were found for the three enzymes. Salivary POX, CAT and SOD increased in all groups from TP1 to TP2 and decreased from TP2 to TP3. Only the NSE showed a significant difference between TP1 to TP3 in POX and SOD by +0.011 ± 0.007 and +0.075 ± 0.020 (U/mL), respectively. The NSE showed significantly higher activity of POX, CAT and SOD in TP2 compared to the other groups. Furthermore, NSE and NSnE had higher activity of POX, CAT and SOD in TP1 and TP3 (p &lt; 0.05) compared with SE and SnE. Only in the NSnE, were no differences observed in CAT compared with SE and SnE in TP3. These results showed that the antioxidant activity at rest and in the recovery time after the acute intense exercise was lower in SE and SnE compared with NSE and NSnE, suggesting that smoking habit may reduce the ameliorating effect of regular physical activity on acute exercise-induced oxidative stress.

Fasting is one of the religious rituals of Muslims worldwide who refrain from eating foods and liquids every year during Ramadan. This year (2020), Ramadan is very different from previous years due to the outbreak of a terrible microscopic giant called coronavirus disease 2019 (COVID-19). The pandemic COVID-19 has made Ramadan very important this year because the virus has infected millions of people around the world and killed thousands, especially people with immunodeficiency. In dealing with COVID-19, maintaining good hygiene and supporting the immune system are effective, preventive approaches. Moderate exercise training and proper nutrition are the most important factors to support immune function. Lack of facilities, poor health and many traditions that lead to public community gatherings have made many Islamic countries susceptible to this dangerous virus. In such an unprecedented situation, there are many Muslims who doubt whether they can fast or not. Therefore, the proposal of usable exercise programs and effective nutritional strategies is imperative. In this study, we will look at the proposed health effects of fasting and its impact on the immune system, the effects of Ramadan intermittent fasting on resting values and responses of immunological/antioxidant biomarkers in elite and recreational athletes, together with the important health, nutrition, and exercise advice that fasting people need to follow in the event of a COVID-19 outbreak.

Moderate-intensity exercise is considered to enhance immune function and to be useful for preventing acute upper respiratory infections and similar conditions. Many people practice low-intensity short-duration exercise with the expectation of a beneficial effect on immunocompetency. However, it is difficult to affirm the existence of definite evidence of such a benefit. In this article, we discuss the effects of low-intensity short-duration exercise on cell-mediated immunity, and contrast them to the effects of high-intensity and long-duration exercise. Whereas high-intensity exercise induces inflammation and reduces cell-mediated immune system function, low-intensity exercise does not appear to have a large effect on either inflammation or cell-mediated immune function. Low-intensity exercises such as walking and yoga, which are helpful to relieve stress, cannot be considered as harmful to the immune system. Although yoga was shown to impose fewer restrictions on breathing and physical strain, the evidence that yoga enhances cell-mediated immunity remains insufficient. Therefore, further studies are needed to examine the exercise mode that may be most effective for improvement of immune functions.

Strenuous exercise induces organ damage, inflammation, and oxidative stress. Currently, to monitor or investigate physiological conditions, blood biomarkers are frequently used. However, blood sampling is perceived to be an invasive method and may induce stress. Therefore, it is necessary to establish a non-invasive assessment method that reflects physiological conditions. In the present study, we aimed to search for useful biomarkers of organ damage, inflammation, oxidative stress, and bone turnover in urine following exercise. Ten male runners participated in this study and performed a 3000-m time trial. We measured biomarkers in urine collected before and immediately after exercise. Renal damage markers such as urea protein, albumin, N-acetyl-β-D-glucosaminidase (NAG), and liver-fatty acid binding protein (L-FABP), and an intestinal damage marker, intestine-fatty acid binding protein (I-FABP), increased following exercise (p &lt; 0.05). However, a muscle damage marker, titin N-terminal fragments, did not change (p &gt; 0.05). Inflammation-related factors (IRFs), such as interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, complement (C) 5a, myeloperoxidase (MPO), calprotectin, monocyte chemoattractant protein (MCP)-1, and macrophage colony-stimulating factor (M-CSF), increased whereas IRFs such as IL-4 and IL-10 decreased following exercise (p &lt; 0.05). IRFs such as tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-12p40, and interferon (IFN)-γ did not change (p &gt; 0.05). Oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and nitrotyrosine, did not change following exercise (p &gt; 0.05) whereas 8-hydroxy-2′-deoxyguanosine (8-OHdG) decreased (p &lt; 0.05). Bone resorption markers, such as cross-linked N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), did not change following exercise (p &gt; 0.05). These results suggest that organ damage markers and IRFs in urine have the potential to act as non-invasive indicators to evaluate the effects of exercise on organ functions.

<title>Abstract</title>Discovery of blood biomarkers to evaluate exercise-induced muscle damage have attracted many researchers and coaches. This study aimed to determine changes in circulating myomesin 3 fragments as a novel biomarker for exercise-induced muscle damage. Nine healthy males performed 10 sets of 40 repetitions of one-leg calf-raise exercise by the load corresponding to the half of their body weight. Muscle symptoms were evaluated by a visual analog scale (VAS). Blood samples were collected before and 2, 4, 24, 48, 72, and 96 h post-exercise. Plasma myomesin 3 fragments levels were significantly increased at 96 h after the eccentric exercise. The myomesin 3 fragments levels were correlated with other biomarkers of muscle damage and the muscle symptoms. These results suggest that the circulating myomesin 3 fragments levels are potential biomarkers reflecting eccentric exercise-induced muscle damage.

Accumulation of toxic metals in infants/children is of serious concern worldwide, from the viewpoint of their harmful effects on the normal growth and development. This metallomics study investigates the extent of toxic metal burdens in infants/children and the relationship to those in their mothers for 77 child/mother pair subjects. For mercury, its geometric mean concentration in infants/children was of similar level to that in their mothers, and a high-significant close correlation was observed between infants/children and their mothers (β = 0.758, r = 0.539, p &lt; 0.0001). A significant but less intimate mother/child relationship was observed for arsenic (β = 0.301, r = 0.433), lead (β = 0.444, r = 0.471) and aluminum (β = 0.379, r = 0.451). Remarkably, the burden levels of lead, cadmium and aluminum in infants/children were approximately three times higher than those in their mothers (p &lt; 0.0001), and the burden levels in some individuals were several tens of times higher than in the mothers. In contrast, some essential metal levels such as zinc, magnesium and calcium in infants/children were significantly lower than those in their mothers, and 29 individuals (37.7%) in the child subjects were estimated to be zinc-deficient. In addition, significant inverse correlations were observed between zinc and lead (r = −0.267, p = 0.019), and magnesium and arsenic (r = −0.514, p &lt; 0.0001). These findings suggest that these toxic metal burdens and essential metal deficiencies in infants/children are of serious concern for their neurodevelopment, indicating that the early assessment and intervention are crucial. It is expected that larger epidemiological and intervention studies will provide a reasonable and essential pathway for intervention of neurodevelopment disorders.

<title>Abstract</title>An evolutionarily conserved mechanism, use of non-optimal codons, slows ribosomes during translation to allow proper folding of nascent polypeptides. However, until now, it was unknown whether any eukaryote-specific mechanisms exist for this purpose. Here, we propose that miRNAs slow translating ribosomes to prevent protein misfolding, with little negative effect on protein abundance. To prove this, we bioinformatically analyze ribosome profiling and miRNA binding sites and biochemically confirm that miRNA deficiency causes severe misfolding, which is rescued by slowing translating ribosomes. We demonstrate that non-cleaving shRNAs, targeting regions where elongation rates become faster in miRNA-deficient cells, improve protein folding with minimal effects on protein abundance. These results reveal broader functionality of miRNAs and a previously unknown mechanism to prevent protein misfolding.

<sec><title>One Sentence Summary</title>Eukaryote use of miRNAs prevents protein misfolding in a target-specific manner.

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This study aimed to examine differences between sexes in thermoregulatory responses and exercise time after ice slurry ingestion in a hot environment. Twenty-four healthy adults (male n = 12, body weight (BW) = 65.8 ± 10.3; female n = 12, BW = 58.2 ± 10.0) ingested 7.5 g/kg of either ice slurry at −1 °C (ICE) or control water at 20 °C (CON) before cycling at 55%VO max in a hot environment (controlled at 38 °C, 40% relative humidity). Rectal (Tre) and skin (Tsk) temperature, heart rate, sweat rate, respiratory gases, ratings of thermal sensation (TS), thermal comfort (TC), and rating of perceived exertion (RPE) were measured. Ice slurry did not improve exercise time in both sexes despite Tre was significantly lower in ICE than CON in both sexes. Tre, Tsk, HR, sweat rate and TS did not differ between sexes. TC and RPE in ICE were significantly higher during exercise in males than in females. In conclusion, there were no sex differences in the effects of pre-cooling with ice slurry ingestion; however, pre-cooling with ice slurry may be more effective in mitigating ratings of TC and RPE in females than males. 2

The relationships between cardiorespiratory fitness (CRF) measurements not confounded by adiposity and the prevalence of pre-diabetes mellitus (pre-DM) and diabetes mellitus (DM) are not well known. Thus, we aimed to investigate the associations of visceral fat (VF) and CRF with the prevalence of pre-DM/DM among Japanese adults. The study included 970 individuals (327 women and 643 men) who were 40-87 years old and had complete health examinations, abdominal fat area, and fitness data from WASEDA'S Health Study during 2015-2018. The VF area was measured using magnetic resonance imaging. CRF was measured using a cycle ergometer and was defined as VO2peak divided by fat free mass. The pre-DM/DM was identified based on the questionnaire and fasting blood tests. The odds ratios (ORs) and 95% confidence intervals (CIs) for prevalence of pre-DM/DM were calculated. Seventy-three participants had pre-DM and 48 participants had DM. Compared to the low VF group, the high VF group had a higher prevalence of pre-DM/DM (OR: 1.87, 95% CI: 1.18-2.96), although no significant relationship was observed between CRF and pre-DM/DM prevalence (P for trend = 0.239). The sub-group analyses also revealed no significant relationship between CRF and pre-DM/DM prevalence in the low VF group (P for trend = 0.979), although CRF values were inversely related to the prevalence of pre-DM/DM in the high VF group (P for trend = 0.024). Although CRF was not independently related to the prevalence of pre-DM/DM after adjusting for adiposity, higher VF values were related to a higher prevalence of pre-DM/DM. In addition, CRF levels were inversely associated with the prevalence of pre-DM/DM only among high VF individuals.

Excessive release of inflammatory cytokines and oxidative stress (OS) are triggering factors in the onset of chronic diseases. One of the factors that can ensure health in humans is regular physical activity. This type of activity can enhance immune function and dramatically prevent the spread of the cytokine response and OS. However, if physical activity is done intensely at irregular intervals, it is not only unhealthy but can also lead to muscle damage, OS, and inflammation. In this review, the response of cytokines and OS to exercise is described. In addition, it is focused predominantly on the role of reactive oxygen and nitrogen species (RONS) generated from muscle metabolism and damage during exercise and on the modulatory effects of antioxidant supplements. Furthermore, the influence of factors such as age, sex, and type of exercise protocol (volume, duration, and intensity of training) is analyzed. The effect of antioxidant supplements on improving OS and inflammatory cytokines is somewhat ambiguous. More research is needed to understand this issue, considering in greater detail factors such as level of training, health status, age, sex, disease, and type of exercise protocol.

The prevalence of waterpipe tobacco smoking (WTS), which is also known as ghalyan, shisha or hookah, is increasing rapidly around the world, especially among youth. Growing interest in this form of tobacco smoking can be traced, in part, to the use of flavored tobacco products, social acceptability as a safer option than cigarettes, and its consideration as a relaxation method or entertainment. However, there is a well-established association between WTS and oxidative stress that causes irreversible chronic pathological conditions such as cardiovascular and respiratory problems, as well as different types of cancers, and thus increases the risk of mortality. Clearly, induction of inflammation status through increased reactive oxygen species (ROS), which in turn leads to oxidative stress and harm to lipids, DNA, and proteins, is the most plausible mechanism to explain the potential harmful effects of WTS. Unlike WTS, well-designed exercise training programs increase ROS to the extent that it is beneficial to the body. In this study, we aimed to review available evidence on the impact of exercise training on oxidative stress and inflammation status. We also summarize the effect of acute and chronic WTS on different exercise capacities.

We studied the effects of Ramadan intermittent fasting (RIF) on gut hormones (leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), and ghrelin) in males with obesity. Thirty sedentary males were randomly allocated to either an experimental group (EG, n = 15) or a control group (CG, n = 15). The EG group completed their Ramadan fasting rituals (30 days), whereas the CG continued with their normal daily habits. Blood samples were collected at four time points: 24 h before the start of Ramadan (T0), on the 15th day of Ramadan (T1), the day after the end of Ramadan (T2) and 21 days after Ramadan (T3). There were significant pre-to-post improvements for leptin (p = 0.01, d = 1.52), GLP-1 (p = 0.022, d = 0.75), PYY (p = 0.031, d = 0.69) and CCK (p = 0.027, d = 0.81) in the EG, with no interaction effect for ghrelin (p = 0.74; d = 0.008). No significant changes (p &gt; 0.05) occurred in plasma volume variations (ΔPV) after RIF in both EG (−0.03 ± 0.01%) and CG (0.06 ± 0.07%). RIF represents an effective strategy to modify appetite-regulating hormones, leading to improved body composition indices and reduced obesity.

Cruciferous vegetables hold a myriad of bioactive molecules that are renowned for possessing unique medicinal benefits. Sulforaphane (SFN) is one of the potential nutraceuticals contained within cruciferous vegetables that is useful for improving health and diseased conditions. The objective of this review is to discuss the mechanistic role for SFN in preventing oxidative stress, fatigue, and inflammation. Direct and indirect research evidence is reported to identify the nontoxic dose of SFN for human trials, and effectiveness of SFN to attenuate inflammation and/or oxidative stress. SFN treatment modulates redox balance via activating redox regulator nuclear factor E2 factor-related factor (Nrf2). SFN may play a crucial role in altering the Keap1/Nrf2/ARE pathway (an intricate response to many stimuli or stress), which induces Nrf2 target gene activation to reduce oxidative stress. In addition, SFN reduces inflammation by suppressing centrally involved inflammatory regulator nuclear factor-kappa B (NF-κB), which in turn downregulates the expression of proinflammatory cytokines and mediators. Exercise may induce a significant range of fatigue, inflammation, oxidative stress, and/or organ damage due to producing excessive reactive oxygen species (ROS) and inflammatory cytokines. SFN may play an effective role in preventing such damage via inducing phase 2 enzymes, activating the Nrf2/ARE signaling pathway or suppressing nuclear translocation of NF-κB. In this review, we summarize the integrative role of SFN in preventing fatigue, inflammation, and oxidative stress, and briefly introduce the history of cruciferous vegetables and the bioavailability and pharmacokinetics of SFN reported in previous research. To date, very limited research has been conducted on SFN’s effectiveness in improving exercise endurance or performance. Therefore, more research needs to be carried out to determine the effectiveness of SFN in the field of exercise and lifestyle factors.

Exhaustive exercise induces systemic inflammatory responses, which are associated with exercise-induced tissue/organ damage, but the sources and triggers are not fully understood. Herein, the basics of inflammatory mediator cytokines and research findings on the effects of exercise on systemic inflammation are introduced. Subsequently, the association between inflammatory responses and tissue damage is examined in exercised and overloaded skeletal muscle and other internal organs. Furthermore, an overview of the interactions between oxidative stress and inflammatory mediator cytokines is provided. Particularly, the transcriptional regulation of redox signaling and pro-inflammatory cytokines is described, as the activation of the master regulatory factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved directly or indirectly in controlling pro-inflammatory genes and antioxidant enzymes expression, whilst nuclear factor-kappa B (NF-κB) regulates the pro-inflammatory gene expression. Additionally, preventive countermeasures against the pathogenesis along with the possibility of interventions such as direct and indirect antioxidants and anti-inflammatory agents are described. The aim of this review is to give an overview of studies on the systematic inflammatory responses to exercise, including our own group as well as others. Moreover, the challenges and future directions in understanding the role of exercise and functional foods in relation to inflammation and oxidative stress are discussed.

Prolonged strenuous exercise may induce inflammation, cause changes in gastrointestinal permeability, and lead to other unfavorable biological changes and diseases. Nutritional approaches have been used to prevent exercise-induced inflammatory responses and gastrointestinal disorders. Hyperimmunized milk, obtained by immunizing cows against specific antigens, promotes the development of immunity against pathogens, promotes anti-inflammatory effects, and protects intestinal function. Immune protein (IMP) is a concentrated product of hyperimmunized milk and is a more promising means of supplementation to protect against acute infections and inflammation. To determine whether IMP has protective properties against exercise-induced gastrointestinal dysfunction and inflammation, we examined biochemical markers, intestinal damage markers, and pro-/anti-inflammatory profiles of young male runners using a randomized, placebo controlled, cross-over design. Urine samples were collected and used for measurements of creatinine, N-acetyl-β-d-glucosaminidase, osmotic pressure, and specific gravity. Titin was measured as a muscle damage marker. Further, urine concentrations of complement 5a, calprotectin, fractalkine, myeloperoxidase, macrophage colony-stimulating factor, monocyte chemotactic protein-1, intestinal fatty acid binding protein (I-FABP), interferon (IFN)-γ, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. We demonstrated that urine osmotic pressure, urine specific gravity, I-FABP, IFN-γ, IL-1β, and TNF-α were reduced by 8 weeks of IMP supplementation, indicating that IMP may have potential in preventing strenuous exercise-induced renal dysfunction, increased intestinal permeability, and inflammation. Thus, IMP supplementation may be a feasible nutritional approach for the prevention of unfavorable exercise-induced symptoms.

Regular exercise is beneficial to maintain a healthy lifestyle, but the beneficial effects are lost in the case of acute exhaustive exercise; this causes significant inflammation, oxidative stress along with organ damage. Recently, sulforaphane (SFN), an indirect antioxidant, has drawn special attention for its potential protective effect against inflammation and oxidative stress. However, no studies have been performed regarding acute exhaustive exercise-induced organ damage in association with SFN administration. Therefore, the aim of this study was to investigate the effects of SFN on acute exhaustive exercise-induced organ damage and the mechanisms involved. To perform the study, we divided mice into four groups: Control, SFN, exercise, and SFN plus exercise. The SFN group was administered orally (50 mg/kg body wt) 2 h before the running test. We measured plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), and acute exhaustive exercise significantly increased these biomarkers. In addition, the mRNA expression of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α, were significantly increased in the liver of exercise group. However, the SFN plus exercise group showed a significant reduction in the expression of cytokines and blood biomarkers of tissue damage or cell death. Furthermore, we measured mRNA expression of Nrf2, heme oxygenase (HO)-1, and antioxidant defense enzymes expression, i.e., superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPx1) in the liver. The expression of all these biomarkers was significantly upregulated in the SFN plus exercise group. Collectively, SFN may protect the liver from exhaustive exercise-induced inflammation via inducing antioxidant defense response through the activation of Nrf2/HO-1 signal transduction pathway.

The purpose of this study was to investigate the effects of acacia polyphenol (AP) supplementation on exercise-induced oxidative stress in mouse liver and skeletal muscle. Plasma aspartate aminotransferase (AST), liver and skeletal muscle levels of thiobarbituric acid reactive substance (TBARS), and levels of skeletal muscle protein carbonyls increased immediately after exhaustive exercise. Exhaustive exercise also decreased liver glutathione (GSH). These results suggest that the exhaustive exercise used in this study induced tissue damage and oxidative stress. Contrary to our expectations, AP supplementation increased plasma AST and alanine aminotransferase activities, liver levels of TBARS, and protein carbonyls. Furthermore, AP supplementation decreased glutathione and glutathione peroxidase activity in the liver. On the other hand, AP supplementation decreased TBARS levels in skeletal muscle. These results suggest that oral high-dose AP administration decreased oxidative stress in skeletal muscle but induced oxidative stress in the liver and increased hepatotoxicity.

Postpubescent females may have negative mood or premenstrual syndrome during the menstrual cycle; with the emotional and physical symptoms interfering with their quality of life. Little is known about the relationship of dietary behaviors and dietary antioxidant intake with negative mood or premenstrual syndrome in university students in China; so we explored the relationship between negative mood and dietary behavior in female university students during the three menstrual cycle phases. Random sampling was used to enroll 88 individuals from a university in Guangzhou; China in the study. Data were collected using self-administered questionnaires. Descriptive statistics and multiple logistic regression analyses were performed. During the menstrual phase, tea, black coffee and carbonated beverage intake was higher in the group with a high negative affect scale score than in the low score group (p &lt; 0.05). Likewise; during the premenstrual phase, fresh fruit (banana and red Chinese dates) intake was higher in the group with a high negative affect scale score than in the low-score group (p &lt; 0.05). The logistic regression analysis results showed that negative mood was positively associated with tea, coffee, and carbonated beverage intake during the menstrual phase (β = 0.21, p = 0.0453, odds ratio = 1.23), and negative mood was positively associated with banana and red Chinese dates intake during the premenstrual phase (β = 0.59, p = 0.0172, odds ratio = 1.81). Our results suggest that negative mood may be associated with diet and specific food in university postpubescent females.

This study examined the relationship between a healthy Japanese dietary pattern and micronutrient intake adequacy based on the Dietary Reference Intakes for Japanese 2015 (DRIs-J 2015) in men and women. A cross-sectional study was conducted in 1418 men and 795 women aged 40-87 years, who participated in the Waseda Alumni's Sports, Exercise, Daily Activity, Sedentariness, and Health Study. Dietary patterns were derived from principal component analysis of the consumption of 52 food and beverage items, which were assessed by a validated brief-type self-administered diet history questionnaire. Micronutrient intakes were quantified using the dietary reference intakes score (DRIs-score) for 21 micronutrients (based on DRIs-J 2015). The healthy dietary pattern score was significantly and positively correlated with the intakes of all 21 micronutrients used for constructing the DRIs-score in men and in women (each, p < 0.001). In both sexes, the healthy dietary pattern scores were strongly and positively associated with DRIs-scores (in men: ρ = 0.806, p < 0.001; in women: ρ = 0.868, p < 0.001), and the DRIs-scores reached a plateau around the highest tertile of the healthy dietary pattern score. These results indicate that a healthy Japanese dietary pattern is associated with adequate micronutrient intakes based on the DRIs-J 2015 in both men and women.

MicroRNAs are small regulatory noncoding RNAs that repress gene expression at the posttranscriptional level. Previous studies have reported that the expression of miR-23, miR-27, and miR-24, driven from two miR-23-27-24 clusters, is altered by various pathophysiological conditions. However, their functions in skeletal muscle have not been clarified. To define the roles of the miR-23-27-24 clusters in skeletal muscle, we generated double-knockout (dKO) mice muscle-specifically lacking the miR-23-27-24 clusters. The dKO mice were viable and showed normal growth. The contractile and metabolic features of the muscles, represented by the expression of the myosin heavy chain and the oxidative markers PGC1-alpha and COX IV, were not altered in the dKO mice compared with wild-type mice. The dKO mice showed increased cross-sectional areas of the oxidative fibers. However, this dKO did not induce functional changes in the muscles. The dKO mice also showed normal adaptation to voluntary wheel running for 4 weeks, including the glycolytic-to-oxidative fiber type switch, and increases in mitochondrial markers, succinate dehydrogenase activity, and angiogenesis. In conclusion, our data demonstrate that the miR-23-27-24 clusters have subtle effects on skeletal muscle development and endurance-exercise-induced muscle adaptation.

The aim of this study was to examine the influence of peptide hormone use on oxidative stress and antioxidant responses to a single session of resistance exercise in male bodybuilders. Forty-five male bodybuilders were divided into three groups: bodybuilders using growth hormone for at least 1 year (i.e., 3 to 4 times in the year) (GH-user, n = 15), bodybuilders using insulin-like growth factor-1 for at least 1 year (i.e., 3 to 4 times in the year) (IGF-1-user, n = 15), and peptide hormone-free bodybuilders (Non-user, n = 15). The heavy resistance exercise protocol consisted of five sets with 80% of one repetition maximum for six exercises. Blood samples were obtained pre and post heavy resistance exercise (HRE) in order to evaluate changes in oxidative stress (8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and nitric oxide (NO)) and antioxidant biomarkers (glutathione peroxidase (GPx), catalase (CAT) and glutamate (GLU)) level. All the experimental groups showed increases in MDA (p = 0.038), NO (p = 0.028), GPx (p = 0.012), and GLU (p = 0.003) concentrations after resistance exercise. For 8-OHdG, the Non-user and IGF-1-user groups indicated increases at post-exercise (p = 0.001), without any significant changes in the GH-user group (p = 0.87). In addition, the changes in serum GPx and GLU levels were greater for the GH-user group than the Non-user and IGF-1-user groups (p = 0.001). In conclusion, HRE induced significant increases in 8-OHdG (except to GH-user group), MDA, NO, GPx, and GLU levels with greater changes in GPx and GLU for the GH-user group.

Inflammation is an essential part for the general or innate immune defenses to defend against tissue damage and accelerate the curing process by providing protection against pathogens. Sulforaphane (SFN) is a natural isothiocyanate that has potential properties against inflammation, along with other protective functions. The purpose of this study was to examine the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation in Raw 264.7 macrophages. Here, we compared LPS-challenged macrophages with or without SFN pretreatment. Macrophages were pre-incubated for 6 h with a wide range of concentrations of SFN (0 to 50 µM), and then treated with LPS for 24 h. Nitric oxide (NO) concentration and gene expression of different inflammatory mediators, i.e., interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, were measured. SFN neither directly reacted with cytokines, nor with NO. To understand the mechanisms, we performed analyses of the expression of regulatory enzyme inducible nitic oxide synthase (iNOS), the transcription factor NF-E2-related factor 2 (Nrf2), and its enzyme heme-oxygenase (HO)-1. Our results revealed that LPS increased significantly the expression of inflammatory cytokines and concentration of NO in non-treated cells. SFN was able to prevent the expression of NO and cytokines through regulating inflammatory enzyme iNOS and activation of Nrf2/HO-1 signal transduction pathway.

Chemokines are critical mediators of angiogenesis in several physiological and pathological conditions; however, a potential role for muscle-derived chemokines in exercise-stimulated angiogenesis in skeletal muscle remains poorly understood. Here, we postulated that the chemokine stromal cell-derived factor-1 (SDF-1α/C-X-C motif chemokine ligand 12: CXCL12), shown to promote neovascularization in several organs, contributes to angiogenesis in skeletal muscle. We found that CXCL12 is abundantly expressed in capillary-rich oxidative soleus and exercise-trained plantaris muscles. CXCL12 mRNA and protein were also abundantly expressed in muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α transgenic mice, which have a high proportion of oxidative muscle fibers and capillaries when compared with wild-type littermates. We then generated CXCL12 muscle-specific knockout mice but observed normal baseline capillary density and normal angiogenesis in these mice when they were exercise trained. To get further insight into a potential CXCL12 role in a myofiber-endothelial cell crosstalk, we first mechanically stretched C2C12 myotubes, a model known to induce stretch-related chemokine release, and observed increased CXCL12 mRNA and protein. Human umbilical vein endothelial cells (HUVECs) exposed to conditioned medium from cyclically stretched C2C12 myotubes displayed increased proliferation, which was dependent on CXCL12-mediated signaling through the CXCR4 receptor. However, HUVEC migration and tube formation were unaltered under these conditions. Collectively, our findings indicate that increased muscle contractile activity enhances CXCL12 production and release from muscle, potentially contributing to endothelial cell proliferation. However, redundant signals from other angiogenic factors are likely sufficient to sustain normal endothelial cell migration and tube formation activity, thereby preserving baseline capillary density and exercise training-mediated angiogenesis in muscles lacking CXCL12.

Waterpipe tobacco (WPT) smoking is a public health problem with similar or even stronger effects than cigarette smoking. Although it appears to be associated with extensive oxidative stress, there is a limited number of studies on the oxidative effects of WPT smoking in stressful conditions. We, therefore, compared the responses of salivary flow rate (SFR), uric acid (UA) concentration, and peroxidase (POX) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) activities between WPT smokers and non-smokers following a bout of exhaustive aerobic exercise (AE). Twenty-three sedentary young women (age: 22.95 ± 2.83 years) participated in this study, including 11 smokers (7.00 ± 1.41 uses/week) and 12 non-smokers. All participants were required to perform the Bruce protocol treadmill test at an initial gradient of 10% at 1.7 mph, with increases of these parameters every 3 min until exhaustion. Unstimulated saliva samples were collected before, immediately after, and 1 hour after AE. WPT smokers showed lower SFR compared with non-smokers at all time points (p &lt; 0.05). In comparison to WPT smokers, a larger increase in POX activity (approximately 23% vs 14%; p = 0.009) and a smaller decline in DPPH activity (approximately −8% vs −15%; p = 0.004) were found in non-smokers compared with WPT smokers. While these changes were slowly compensated within 1 hour after exhaustion, the activity of both markers was different from the pre-exercise values (p &lt; 0.001). There was also a trend for UA concentration in non-smokers to be higher during the recovery period, with no significant difference between the groups (p &gt; 0.05). It seems that WPT smoking is associated with negative effects on important human antioxidants and a diminished antioxidative response following acute exercise.

Background and objectives: Aroma therapy is a complementary therapy using essential oils diluted with carrier oils. Jojoba oils have been widely used as carrier oils. However, limited information is available regarding their effects on blood biochemical parameters. This study aimed to investigate the effect of transdermal administration of jojoba oil on blood biochemical parameters in mice. Materials and Methods: Eight-week-old male hairless mice were randomly divided into naïve control and treatment groups. In the treatment group, mice were topically administered 4 μL of jojoba oil, per gram of body weight, on the dorsa 30 min before euthanasia. Thereafter, serum biochemical parameters were assayed, and gene expression was analyzed in various tissues via a real-time polymerase chain reaction. Results: Serum non-esterified fatty acid (NEFA) levels increased significantly 30 min after topical application of jojoba oil (p &lt; 0.05). Atgl was significantly upregulated in the liver (p &lt; 0.05), and Atgl upregulation in the liver was positively correlated with serum NEFA levels (r = 0.592, p &lt; 0.05). Furthermore, a trend of decreasing fatty acid trafficking-related gene (FABPpm, FATP-1, FATP-3, and FATP-4) expression in the skin after topical application of jojoba oil (p = 0.067, 0.074, 0.076, and 0.082, respectively) was observed. Conclusions: Serum NEFA levels were elevated 30 min after transdermal administration of jojoba oil. The mechanisms of elevated serum NEFA levels might be related to both enhanced lipolysis in the liver and reduced fatty acid trafficking in the skin.

Studies have shown that diet and nutrition play significant roles in the prevention of depression and its clinical treatment. The present review aims to provide a clear understanding of the associations between diet patterns, specific foods, nutrients such as antioxidants, and depression. As a result, balanced dietary patterns such as the Mediterranean diet and certain foods such as fish, fresh vegetables, and fruits have been associated with a lower risk of depression or depressive symptoms, while high-fat Western diets and sugar-sweetened beverages have been associated with higher risk of depression or depressive symptoms. Dietary antioxidants such as green tea polyphenols or isoflavonoid intake have been negatively associated with depression or depressive symptoms. It is concluded that diet patterns, specific foods, and antioxidants play important roles in the prevention and clinical treatment of depression.

Background: Carbohydrate (CHO) supplementation during exercise attenuates exercise-induced increases in plasma Interleukin (IL)-6 concentration. However, the effects of CHO supplementation on muscle IL-6 production during endurance exercise is controversial. The purpose of this study was to investigate the effects of CHO supplementation on muscle IL-6 production during endurance exercise with a special focus on the IL-6 producing cells. Methods: C57BL/6J mice were divided into three groups—sedentary with water ingestion group as the control (Con; n = 10), exercise with water ingestion group (Ex; n = 10), and exercise with 6% glucose ingestion group (Ex + glucose; n = 10). The Ex and Ex + glucose groups completed 3 h of treadmill running (24 m/min, 7% incline) and were sacrificed immediately after exercise. Results: The exercise-induced increases of plasma IL-6 concentration and gastrocnemius IL-6 gene expression were attenuated by glucose ingestion. However, the increases of soleus IL-6 gene expression and gastrocnemius and soleus IL-6 protein expression were not attenuated by glucose ingestion. Furthermore, we observed that macrophages that infiltrated muscle produce IL-6 and glucose ingestion attenuated the infiltration of IL-6-producing macrophages. Conclusion: This study revealed that infiltrating macrophages may be one type of IL-6-producing cells during endurance exercise, and the infiltration of these cells in muscle was attenuated by glucose ingestion. However, the effects of glucose ingestion on muscle IL-6 production were limited.

Reduced levels of physical activity in people’s daily lives cause the development of metabolic syndromes or age-related disorders. Chronic inflammation is now understood to be an underlying pathological condition in which inflammatory cells such as neutrophils and monocyte/macrophages infiltrate into fat and other tissues and accumulate when people become obese due to overeating and/or physical inactivity. Pro-inflammatory mediators such as cytokines that are secreted in excess from inflammatory cells will not only lead to the development of arteriosclerosis when they chronically affect blood vessels but also bring tissue degeneration and/or dysfunction to various organs. Chronic inflammation is also involved in sarcopenia that brings hypofunction in the elderly, dementia, osteoporosis, or cancer and negatively affects many chronic diseases and people’s healthy life expectancy. In this paper, outlines of such studies are introduced in terms of homeostatic inflammation, which occurs chronically due to the innate immune system and its abnormalities, while focusing on the efficacy of exercise from aspects of immunology and oxidative stress. The preventative effects of functional food ingredients in combination with exercise are also introduced and described. The challenges and future directions in understanding the role of exercise in the control of chronic inflammation are discussed.

Exercise and inflammation induce multi-faceted physiological responses in their own right, let alone when considered together [...]

Background and Objectives: Although the effects of physical exercise on brain functions are well studied, the influence of mental activity is unknown. The aim of this study was to assess the influence of a session of mental activity on brain neurobiological factors in chess players. Materials and Methods: Ten elite and novice chess players were recruited to participate in this study as volunteers. The subjects performed a session of standard chess matches as a mental activity. Before and after each chess match, blood samples were drawn to analyze changes in serum brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Results: After each chess match, both the elite and novice groups showed significant increases in serum BDNF and IGF-1 concentrations. The elite group also showed significantly greater changes in BDNF and IGF-1 levels (p ≤ 0.05) than the novice group. Conclusions: Our findings indicate that a session of standard chess matches as a mental activity is effective for elevating BDNF and IGF-1 levels, and that their elevation in elite players seems to be more pronounced than those in novice players.

[Purpose] Little is known about the effectiveness of daily physical activity on depression biomarkers in older adults. This study aimed to investigate the effects of increased daily physical activity for 8 weeks on depression biomarkers in postmenopausal women. [Participants and Methods] Thirty-eight postmenopausal females were randomly assigned into a control or an active group and were asked to wear a uniaxial accelerometer for 8 weeks. Blood samples were obtained at baseline and at the end of the intervention. During the intervention, the active group was asked to increase their physical activity level above their usual lifestyle whereas those in the control group maintained their daily lifestyle. [Results] After the 8-week intervention, the step counts of the participants in the active group increased. The serum concentration of the brain-derived neurotrophic factor and serotonin increased significantly in the active group, but not in the control group, as compared with baseline values. The serum concentration of derivatives of reactive oxygen metabolites and biological antioxidant potential did not change after the intervention in either group. [Conclusion] These findings may suggest that promotion of daily physical activity in postmenopausal women has a positive impact on depression without any change in oxidative stress.

A ketogenic diet (KD) could induce nutritional ketosis. Over time, the body will acclimate to use ketone bodies as a primary fuel to achieve keto-adaptation. Keto-adaptation may provide a consistent and fast energy supply, thus improving exercise performance and capacity. With its anti-inflammatory and anti-oxidative properties, a KD may contribute to muscle health, thus preventing exercise-induced fatigue and damage. Given the solid basis of its potential to improve exercise capacity, numerous investigations into KD and exercise have been carried out in recent years. This narrative review aims to summarize recent research about the potential of a KD as a nutritional approach during endurance exercise, focusing on endurance capacity, recovery from fatigue, and the prevention of exhaustive exercise-induced muscle and organ damage.

Beta-cryptoxanthin (β-cry) is a typical carotenoid found abundantly in fruit and vegetables such as the Japanese mandarin orange, persimmon, papaya, paprika, and carrot, and exerts various biological activities (e.g., antioxidant effects). We previously reported that β-cry suppressed lipopolysaccharide (LPS)-induced osteoclast differentiation via the inhibition of prostaglandin (PG) E2 production in gingival fibroblasts and restored the alveolar bone loss in a mouse model for periodontitis in vivo. In this study, we investigated the molecular mechanism underlying the inhibitory effects of β-cry on osteoclast differentiation. In mouse calvarial organ cultures, LPS-induced bone resorption was suppressed by β-cry. In osteoblasts, β-cry inhibited PGE2 production via the downregulation of the LPS-induced mRNA expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1, which are PGE synthesis-related enzymes, leading to the suppression of receptor activator of NF-κB ligand (RANKL) mRNA transcriptional activation. In an in vitro assay, β-cry directly suppressed the activity of the inhibitor of NF-κB kinase (IKK) β, and adding ATP canceled this IKKβ inhibition. Molecular docking simulation further suggested that β-cry binds to the ATP-binding pocket of IKKβ. In Raw264.7 cells, β-cry suppressed RANKL-mediated osteoclastogenesis. The molecular mechanism underlying the involvement of β-cry in LPS-induced bone resorption may involve the ATP-competing inhibition of IKK activity, resulting in the suppression of NF-κB signaling.

OBJECTIVE: The aim of this study was to investigate the associations between dietary patterns and abdominal obesity among middle-aged and elderly Japanese people, using both waist circumference (WC) and visceral fat (VF) as indices. METHODS: A cross-sectional study was conducted with 829 adults (534 men and 295 women), 40 to 79 y of age, who participated in the Waseda Alumni's Sports, Exercise, Daily Activity, Sedentariness and Health Study (WASEDA'S Health Study). Dietary patterns were derived from principal component analysis. VF was measured using magnetic resonance imaging. To examine the associations of each dietary pattern with WC and VF, we calculated multivariate-adjusted means and 95% confidence intervals (CIs) of WC and VF for the tertile of each dietary pattern score. RESULTS: Two main dietary patterns were identified: "healthy Japanese" and "seafood and alcohol." The healthy Japanese dietary pattern score was inversely associated with WC and VF in men only. WC measurements were 84.9 cm (95% CI, 83.7-86.1), 83.9 cm (95% CI, 82.7-85.1), and 82.4 cm (95% CI, 81.2-83.6); Ptrend = 0.006, and VF measurements were 94.0 cm2 (95% CI, 85.6-102.4), 89.4 cm2 (95% CI, 81.1-97.7), and 80.4 cm2 (95% CI, 72.5-88.4); Ptrend = 0.027 for the lowest through the highest tertile of healthy Japanese dietary pattern scores in men. The seafood and alcohol dietary pattern was not associated with WC and VF. CONCLUSION: The healthy Japanese dietary pattern was negatively associated with WC and VF in middle-aged and elderly Japanese men.

【目的】運動開始30〜45分前の糖質摂取は、運動開始直後に急激な血糖値の低下を生じさせる。一方、糖質摂取後に安静状態を保った場合に比べ、血糖値がどの程度低下するのかは明らかでない。本研究では、運動誘発性の血糖値の低下が、糖質摂取後に安静状態を保った場合に比べてどの程度であるのか、実際のスポーツ現場に近い状況である朝食摂取条件下にて検討した。【方法】男子大学生15名に対し、実験開始3時間前に朝食を摂取させた状態で、運動試行、安静試行の2試行を行わせた。運動試行では、150gの糖質を摂取してから30分間安静状態を保った後、最大酸素摂取量の75%の強度で60分間自転車運動を行った。安静試行では、糖質摂取後に90分間安静状態を維持した。それぞれの試行において採血を行い、血糖値を測定した。【結果】運動試行では、運動開始15分後に急激に血糖値が低下し、安静試行に比べて28±29mg/dl低い値を示した。また、安静試行から運動試行への血糖低下量が大きい被験者は、血糖低下量が小さい被験者に比べて、最大酸素摂取量が有意に高い値を示した。【結論】朝食摂取条件下においても、糖質摂取後に運動を行うことで、同量の糖質を摂取して安静状態を保った場合に比べて、約30mg/dl程度の血糖値の低下が生じることが明らかとなった。また、血糖低下量が大きい被験者では、最大酸素摂取量が高い傾向が認められた。(著者抄録)

Exercise training is considered an effective way to prevent age-related skeletal muscle loss. However, the molecular mechanism has not been clarified. Growth and differentiation factor 11 (GDF11) has been controversially considered a regulator of skeletal muscle aging. In this study, we examined whether GDF11 is associated with skeletal muscle aging and the effects of exercise training on age-related skeletal muscle loss. First, we observed that Gdf11 mRNA and protein expression levels in young (5-month-old, n = 6) and aged (22-to 26-month-old, n = 5) mice were not significantly different. Aged mice were then divided into sedentary (n = 5) and exercise (n = 6) groups. The exercise group performed moderate-intensity treadmill running for 6 weeks. Treadmill exercise training increased Gdf11 mRNA expression in the soleus muscle, but its protein expression was not altered. In contrast, the GDF11 level in the plantaris muscle was not changed at either the mRNA or protein level. Collectively, our data demonstrate that GDF11 levels do not change during aging, and that treadmill exercise training increased Gdf11 mRNA expression in a predominantly slow-twitch muscle.

Atherosclerosis is a progressive pathological remodeling of the arteries and one of its hallmarks is the presence of chronic inflammation. Notably, there is an increased proportion and activation state of specific monocyte subsets in systemic blood circulation. Monocyte subsets have distinct contributions to the formation, progression, and destabilization of the atherosclerotic plaque. Strong clinical and epidemiological studies show that regular aerobic exercise mitigates the progression of cardiovascular disease. In fact, aerobic fitness is a powerful predictor of cardiovascular mortality in adults, independent of traditional risk factors such as hypertension and hyperlipidemia. Acute bouts and chronic exercise training modulate monocyte behavior, ranging from their recruitment from the bone marrow or marginal pool, to tissue margination and functional changes in cytokine and chemokine production. Such modulation could reflect a potential mechanism for the cardio-protective effect of exercise on atherosclerosis. This review summarizes the current knowledge of monocyte subsets and highlights what is known about their responses to exercise.

Adjusting dietary fat intake is reported to affect mitochondrial biogenesis and fatty acid oxidation (FAO), and thus may enhance exercise capacity. However, a high-fat diet where carbohydrate intake is not limited enough also makes it difficult for athletes to maintain weight, and may fail to force the body to utilize fat. As such, a low-carbohydrate, high-fat, ketogenic diet (KD) may be viable. We have previously reported that an eight-week KD enhances exercise capacity, and suggested the mechanism to be enhanced lipolysis and ketolysis. In the present study, we investigated how an eight-week KD alters mRNA expression during fatty acid mobilization, FAO and ketolysis. We found that an eight-week KD may remodel the lipid metabolism profile, thus contributing to influence exercise capacity. We also found that ketolysis, lipolysis and FAO adaptations may contribute to enhanced exhaustive exercise performance. Along with enhanced FAO capacity during exhaustive exercise, a KD may also alter IL-6 synthesis and secretion profile, thus contribute to fatty acid mobilization, ketolysis, lipolysis and preventing muscle damage. Both the lipid metabolism response and IL-6 secretion appeared to be muscle fiber specific. Taken together, the previous and present results reveal that an eight-week KD may enhance exercise performance by up-regulating ketolysis and FAO ability. Therefore, a KD may have the potential to prevent muscle damage by altering IL-6 secretion profile, indicating that a KD may be a promising dietary approach in endurance athletes, sports, and for injury prevention.

β-hydroxy β-methylbutyrate (HMB) is a bioactive metabolite formed from the breakdown of the branched-chain amino acid, leucine. Given the popularity of HMB supplements among different athletes, specifically, those who participate in regular resistance training, this review was performed to summarize current literature on some aspects of HMB supplementation that have received less attention. Because of the small number of published studies, it has not been possible to conclude the exact effects of HMB on cardiovascular parameters, oxidative stress, and inflammatory markers. Thus, the interpretation of outcomes should be taken cautiously. However, the data presented here suggest that acute HMB supplementation may attenuate the pro-inflammatory response following an intense bout of resistance exercise in athletes. Also, the available findings collectively indicate that chronic HMB consumption with resistance training does not improve cardiovascular risk factors and oxidative stress markers greater than resistance training alone. Taken together, there is clearly a need for further well-designed, long-term studies to support these findings and determine whether HMB supplementation affects the adaptations induced by resistance training associated with the body’s inflammatory condition, antioxidative defense system, and cardiovascular risk factors in humans.

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ. The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro. Together with the LCC-induced movement of intramuscular interstitial fluid detected by µCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

Endurance capacity is important for maintenance of quality of life as well as performance of endurance athletes. In order to improve endurance, intake of nutritional supplements as well as exercise training is also important. Indeed, polyphenolic extracts from plants are known to improve endurance capacity via increase of fatty acid utilization, mitochondrial biogenesis or inhibition of oxidative stress. Taheebo, the extract obtained from inner bark of Tabebuia avellanedae has been reported to have beneficial effects for treatment of inflammation, oxidative stress and obesity. Here, we investigated the effects and mechanisms of polyphenol fraction of taheebo (taheebo polyphenol; TP) on endurance capacity of mice. Single dose administration of TP significantly increased running time until exhaustion. Acute TP administration increased blood glucose and muscle glycogen levels (p < 0.05) through alteration on expression level of genes involved with glycogen metabolism and gluconeogenesis. Furthermore, TP administration decreased exercise-induced increase of protein carbonyls in skeletal muscle. These results suggest that TP administration improve endurance capacity via up-regulation of skeletal muscle glycogen levels and maintenance of blood glucose by acceleration of gluconeogenesis as well as inhibition of exercise-induced oxidative stress. Single administration of TP also increased phosphorylation of AMP-activated protein kinase (AMPK) and gene expression level of sirtuin 1 (SIRT1) but did not change the marker of mitochondrial biogenesis.

A low-carbohydrate, high-fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. In our previous study, we found that an eight-week ketogenic high-fat, low-carbohydrate diet increased the capacity of endurance exercise in mice without aggravated muscle injury, despite the decrease of absolute muscle volume. The potential mechanism is most possibly to be enhanced capacity to mobilize and utilize fat. In the present study, we investigated whether a ketogenic diet influences post-exercise recovery by measuring blood biomarkers, muscle and liver oxidative state as well as fatigue recovery 24 h post exercise by employing an open-field locomotion test. Several biochemistry markers indicating exercise-induced injury after exhaustive exercise were improved by KD, followed by a 24-h rest with free feed access, including lactate. No aggravated hepatic oxidative damage was observed, whereas muscular oxidative stress was increased by KD. Accelerated recovery induced by exhaustive exercise was also observed from blood biomarkers of injury. For fatigue recovery, lactate concentration, a marker often employed as exhaustion index was lowered by KD, whereas an open field test showed that KD application contributed to increased locomotion after exhaustive exercise, followed by a 24-h rest. These results suggest that KD has the potential to be used as a fatigue-preventing and/or recovery-promoting diet approach in endurance athletes.

The purpose of this study was to investigate the involvement of neutrophil dynamics and function in exercise-induced muscle damage (EIMD) and delayed-onset muscle soreness (DOMS), and the effect of molecular hydrogen (H₂) intake on these parameters. Nine healthy and active young men performed H₂ and placebo bath trial in a crossover design. They carried out downhill running (-8% slope) for 30 min at a speed corresponding to 75~85% of peak oxygen uptake (VO₂peak). Subsequently, they repeated bathing for 20 min per day for one week. Degree of muscle soreness (visual analogue scale: VAS), peripheral leukocyte counts, neutrophil dynamics and function, muscle damage, and inflammation markers were measured. Plasma interleukin (IL)-6 concentration was significantly correlated with peripheral neutrophil count, VAS, and serum creatine kinase activity, respectively, after downhill running. Peripheral neutrophil count and serum myoglobin concentration were also significantly correlated. Conversely, there were no effects of H₂ bath. These results suggest that IL-6 may be involved in the mobilization of neutrophils into the peripheral blood and subsequent EIMD and DOMS after downhill running; however, it is not likely that H₂ bath is effective for the inflammatory process that was centered on neutrophils after downhill running.

BACKGROUND: Aging is known to be associated with increased risk of lipid disorders related to the development of type 2 diabetes. Recent evidence revealed that change of lipid molecule species in blood is associated with the risk of type 2 diabetes. However, changes in lipid molecular species induced by aging are still unknown. We assessed the effects of age on the serum levels of lipid molecular species as determined by lipidomics analysis. METHODS: Serum samples were collected from ten elderly men (71.7 ± 0.5 years old) and women (70.2 ± 1.0 years old), ten young men (23.9 ± 0.4 years old), and women (23.9 ± 0.7 years old). Serum levels of lipid molecular species were determined by liquid chromatography mass spectrometry-based lipidomics analysis. RESULTS: Our mass spectrometry analysis revealed increases in the levels of multiple triacylglycerol molecular species in the serum of elderly men and women. Moreover, serum levels of total ester-linked phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were increased by aging. In contrast, serum levels of specific ether-linked PC and PE molecular species were lower in elderly individuals than in young individuals. CONCLUSIONS: Our finding indicates that specific lipid molecular species, such as ether- and ester- linked phospholipids, may be selectively altered by aging.

PURPOSE: It remains unclear whether rehydration restores retinal blood flow reduced by exhaustive exercise. We investigated the effect of fluid intake on retinal blood flow after exhaustive exercise. METHODS: Blood flow in the inferior (ITRA) and superior temporal retinal arterioles (STRA) was measured before and after incremental cycling exercise until exhaustion in 13 healthy males. After the exercise, the subjects rested without drinking (control condition: CON) or with drinking an electrolyte containing water (rehydrate condition: REH) and were followed up for a period of 120 min. To assess the hydration state, the body mass was measured, and venous blood samples were collected and plasma volume (PV) was calculated. RESULTS: Body mass decreased in CON after the trial [- 1.1 ± 0.1% (mean ± SE), p < 0.05]. PV was lower in CON than in REH during recovery. The ITRA and STRA blood flows decreased immediately after exercise from the resting baseline (ITRA; - 23 ± 4% in REH and - 30 ± 4% in CON, p < 0.05). The ITRA blood flow recovered baseline level at 15 min of recovery in REH (- 9 ± 3%, p = 0.5), but it remained reduced in CON (-14 ± 3%, p < 0.05). The STRA blood flow was higher in REH than in CON at 15 min (2 ± 3 vs. - 5 ± 3%, p < 0.05). CONCLUSIONS: The results of this study suggest that the reduction in retinal blood flow induced by exhaustive exercise can be recovered early by rehydration.

The inflammatory response of macrophages is involved in pathogenesis of lifestyle-related diseases. Green tea consumption reduces the incidence of lifestyle-related diseases. This study investigated the anti-inflammatory effect of polyphenols of green tea including gallic acid, (+)-catechin, (-)-catechin, (-)-epicatechin and (-) epigallocatechin-3-gallate (EGCG) in vitro. The macrophage cell line RAW264 cells were pre-treated with different concentrations of polyphenols (gallic acid, (+)-catechin, (-)-catechin, (-)-epicatechin and EGCG) for 4 h, and were stimulated with LPS for 45 min, 2 h and 24 h. After 24 h LPS challenge, cell lysates and supernatants were harvested. The protein concentration of whole cell lysate was used for determination of cell growth/viability by the BCA assay. The production of TNF-? and IL-6 was measured by ELISA. The total expression and phosphorylation of p38 MAPK was detected by Western blotting. Our results showed that the total protein content of cells was decreased after LPS challenge, while this effect was attenuated when cells were pre-treated with 10 ?M gallic acid and EGCG. Pre-treatment with 1 and 10 ?M EGCG and (-)-catechin significantly decreased the production of TNF-? and IL-6. Furthermore, pre-treatment with 10 ?M gallic acid significantly reduced the production of TNF-? and IL-6. Pre-treatment with 10 ?M (+)-catechin, (-)-catechin, (-) epicatechin, and EGCG enhanced the expression and phosphorylation of p38 MAPK after stimulation with LPS for 45 min and 2 h. By contrast, pre-treatment with gallic acid did not affect the production and phosphorylation of p38 MAPK. These results demonstrated that polyphenols with pyrogallol-type structures in green tea attenuate the activation of macrophages.

We aimed to examine the effects of ingestion of different amounts of carbohydrate (CHO) after endurance exercise on neutrophil count, circulating cytokine levels, and the markers of neutrophil activation and muscle damage. Nine participants completed three separate experimental trials consisting of 1 h of cycling exercise at 70% V · O₂ max, followed by ingestion of 1.2 g CHO·kg body mass-1·h-1 (HCHO trial), 0.2 g CHO·kg body mass-1·h-1 (LCHO trial), or placebo (PLA trial) during the 2 h recovery phase in random order. Circulating glucose, insulin, and cytokine levels, blood cell counts, and the markers of neutrophil activation and muscle damage were measured. The concentrations of plasma glucose and serum insulin at 1 h after exercise were higher in the HCHO trial than in the LCHO and PLA trials. Although there were significant main effects of time on several variables, including neutrophil count, cytokine levels, and the markers of neutrophil activation and muscle damage, significant time × trial interactions were not observed for any variables. These results suggest that CHO ingestion after endurance exercise does not enhance exercise-induced increase in circulating neutrophil and cytokine levels and markers of neutrophil activation and muscle damage, regardless of the amount of CHO ingested.

Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia) and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidative stress, and tissue damage are described not only in overloaded skeletal muscle, but also in other internal organs. Furthermore, we introduce preventive countermeasures against the exhaustive exercise-induced pathogenesis together with the possibility of antioxidant interventions.

[This corrects the article on p. 63 in vol. 4, PMID: 29312947.].

Aim of study: Taheebo polyphenols (TP) are water extracts of Tabebuia spp. (Bignoniaceae), taken from the inner bark of the Tabebuia avellanedae tree, used extensively as folk medicine in Central and South America. Some anti-inflammatory drugs act by inhibiting both cyclooxygenase-2 (COX-2) and COX-1 enzymes. COX-2 syntheses prostaglandin (PG) E2, which is a species of endogenous pain-producing substance, whereas COX-1 acts as a house-keeping enzyme. Inhibiting both COX-1 and -2 simultaneously can have side effects such as gastrointestinal bleeding and renal dysfunction. Some polyphenols have been reported for its selective inhibiting activity toward COX-2 expression. Our study aimed to demonstrate the potential and mechanisms of TP as an anti-inflammation action without the side effects of COX-1 inhibition. Materials and methods: Free fatty acid-stimulated macrophage cell lines were employed to mimic macrophage behaviors during lifestyle-related diseases such as atherosclerosis and non-alcoholic steatohepatitis. Real-time polymerase chain reaction was used to detect expression of inflammatory cytokine mRNA. Griess assay was used to measure the production of nitric oxide (NO). ELISA was used to measure PG E2 production. Molecular docking was adopted to analyze the interactions between compounds from T. avellanedae and COX-2. Results: TP significantly suppressed the production of NO production, blocked the mRNA expression of iNOS, and COX-2 in both cell lines, blocked the mRNA expression of TNF-α, IL-1β, IL-6, and PGE2 in the murine cell line. However, there was no inhibitory effect on COX-1. Molecular docking result indicated that the inhibitory effects of TP on COX-2 and PGE2 could be attributed to acteoside, which is the main compound of TP that could bind to the catalytic zone of COX-2. After the interaction, catalytic ability of COX-2 is possibly inhibited, followed by which PGE2 production is attenuated. COX inhibitor screening assay showed TP as a selective inhibitor of COX-2 enzyme. Conclusion: The anti-inflammatory effects of TP can possibly regulate macrophages due to the targeted inhibition of COX-2 activity, without affecting COX-1 activity with other anti-inflammatory effects including suppression of iNOS and inflammatory cytokines. As such, TP is potentially useful in prevention and treatment of lifestyle-related disease by attenuating inflammation caused by macrophages infiltration.

Background: -Hydroxy--methylbutyrate-free acid (HMB-FA) has been ingested prior to exercise to reduce muscle damage, however the effects of HMB-FA supplementation on hormonal, strength and power adaptation are unclear. Methods: Sixteen healthy men were matched and randomized into two groups and performed six-week resistance training while supplementing with either HMB-FA or placebo (3 g per day). The subjects were evaluated for 1 repetition maximum (1RM) bench press and leg press and vertical jump (VJ) prior to and after training intervention. In addition, blood samples were obtained before and after resistance training to evaluate resting growth hormone (GH), insulin like growth factor 1 (IGF-1), testosterone (TEST), cortisol (CORT), and adrenocorticotropic hormone (ACTH) responses. The HMB-FA supplementation group showed greater gains compared with the placebo group in peak power (effect size ES = 0.26 vs. 0.01) and 1RM leg press (ES = 1.52 vs. 0.96). In addition, the HMB-FA supplementation group indicated greater decrements in ACTH and CORT responses to training in comparison to the placebo group (p &lt; 0.05). Likewise, in GH (ES = 1.41 vs. 0.12) and IGF-1 (ES = 0.83 vs. 0.41), the HMB-FA indicated greater training effects when compared with the placebo group. Conclusions: These findings provide further support for the potential anabolic benefits associated with HMB-FA supplementation.

Many studies have attempted to determine the associations between blood biomarkers and exercise-induced muscle damage. However, poor correlations between the changes in biomarker levels and the magnitude of muscle symptoms have been reported. Recent advances in proteomic tools offer a strategy for the comprehensive analysis of protein expression, which can be used to identify biomarkers. Here, we used a proteomic analysis to identify urinary proteins that appear in response to a calf-raise exercise, including repetitive eccentric muscle contractions, and found that a titin (also known as connectin) N-terminal fragment molecule appears in the urine after eccentric exercise. We measured the titin fragment in urine samples from nine individuals before and after eccentric exercise using a newly-established enzyme-linked immunosorbent assay and found that the titin fragment excretion rate increased 96 h after the exercise (5.1 to 77.6 pg/min, p &lt; 0.01). The changes in the titin fragment excretion rate were correlated strongly with blood markers of muscle damage and with muscle symptoms. These findings suggest that the urinary titin fragment is potentially a noninvasive biomarker of muscle damage.

Corylin is a main compound isolated from Psoralea corylifolia L. (Fabaceae). A variety of pharmacological effects such as antioxidant, anti-proliferation, and anti-inflammatory properties of corylin have been reported. Nevertheless, the effect of corylin in microbial infection and sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of corylin. Our experimental results demonstrated that corylin inhibited the production of TNF-α, IL-6 and NO by both LPS-activated RAW 264.7 cells and LPS-activated murine peritoneal macrophages. Moreover, corylin suppressed the expression levels of iNOS and COX-2, reduced the production of PGE2 and HMGB1, blocked the translocation of HMGB1 from the nucleus to cytosol, and decreased the phosphorylation of MAPKs in LPS-activated RAW 264.7 cells as well as suppressed the activity of NF-κB in LPS-activated J-Blue cells. In addition, the administration of corylin reduced the production of NO and TNF-α, decreased LPS-induced liver damage markers (AST and ALT) and kidney damage markers (BUN and CRE), attenuated infiltration of inflammatory cells and tissue damage of lung, liver and kidney, and enhanced the survival rate of LPS-challenged mice. Taken together, these results show the anti-inflammatory properties of corylin on LPS-induced inflammation and sepsis. Corylin could potentially be a novel anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.

Cold water immersion and active recovery are common post-exercise recovery treatments. However, little is known about whether these treatments influence inflammation and cellular stress in human skeletal muscle after exercise. We compared the effects of cold water immersion versus active recovery on inflammatory cells, pro-inflammatory cytokines, neurotrophins and heat shock proteins (HSPs) in skeletal muscle after intense resistance exercise. Nine active men performed unilateral lower-body resistance exercise on separate days, at least 1 week apart. On one day, they immersed their lower body in cold water (10 degrees C) for 10 min after exercise. On the other day, they cycled at a low intensity for 10 min after exercise. Muscle biopsies were collected from the exercised leg before, 2, 24 and 48 h after exercise in both trials. Exercise increased intramuscular neutrophil and macrophage counts, MAC1 and CD163 mRNA expression (P &lt; 0.05). Exercise also increased IL1 beta, TNF, IL6, CCL2, CCL4, CXCL2, IL8 and LIF mRNA expression (P &lt; 0.05). As evidence of hyperalgesia, the expression of NGF and GDNF mRNA increased after exercise (P &lt; 0.05). The cytosolic protein content of alpha B-crystallin and HSP70 decreased after exercise (P &lt; 0.05). This response was accompanied by increases in the cytoskeletal protein content of alpha B-crystallin and the percentage of type II fibres stained for alpha B-crystallin. Changes in inflammatory cells, cytokines, neurotrophins and HSPs did not differ significantly between the recovery treatments. These findings indicate that cold water immersion is no more effective than active recovery for reducing inflammation or cellular stress in muscle after a bout of resistance exercise.

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

Sleep disorder is a risk factor for several systemic inflammation-related diseases and there are extensive data showing that schizophrenia is associated with chronic low-grade systemic inflammation. This study investigated the associations between sleep quality and inflammatory markers in patients with schizophrenia, which has not been examined before. Sleep quality (total sleep time, sleep efficiency, sleep onset latency, total activity counts, wake after sleep onset, number of awakening, and average length of awakening) was measured using actigraphy in 199 schizophrenia inpatients. The state of inflammation was measured using blood concentration of white blood cells (WBC) and neutrophils, together with neutrophil lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR). The results showed that total sleep time was negatively associated with NLR and PLR, and sleep efficiency was negatively associated with neutrophil counts and NLR. Sleep onset latency, total activity counts, wake after sleep onset, and number of awakening were positively associated with WBC and neutrophil counts. The average length of awakening was positively associated with NLR and PLR. This is the first report to suggest that improving sleep quality may modulate the state of inflammation in patients with schizophrenia.

Purpose The infiltration of macrophages in skeletal muscle during exhaustive exercise promotes inflammation, myofiber lesion, and muscle injury. Although neutrophils upregulate macrophage infiltration in skeletal muscles during exercise, the role of neutrophils in promoting muscle injury after exhaustive exercise remains unclear. In this study, we investigated the effects of preexercise neutrophil depletion with antineutrophil antibody treatment on muscle injury, inflammation, and macrophage infiltration after exhaustive exercise.
Methods Male C57BL/6J mice were randomly assigned to four groups, namely, sedentary with control antibody (n = 10), sedentary with antineutrophil antibody (n = 10), exhaustive exercise with control antibody (n = 10), and exhaustive exercise with antineutrophil antibody (n = 10). The mice were given intraperitoneal injection of the antineutrophil antibody (anti-Ly-6G, clone 1A8) or the control antibody (anti-Ly-6G, clone 2A3), and remained inactive or performed exhaustive exercise on a treadmill 48 h after the injection. Twenty-four hours after the exhaustive exercise, the gastrocnemius muscles were removed for histological and polymerase chain reaction (PCR) analyses. Infiltration of neutrophils and macrophages was evaluated with Ly-6G and F4/80 immunohistochemistry staining procedures. Muscle fiber injury was detected based on the number of IgG staining fiber. The mRNA expression levels of proinflammatory cytokines and chemokines were evaluated with real-time reverse transcription PCR.
Results Exhaustive exercise increased neutrophil infiltration into the gastrocnemius muscle substantially by 3.1-fold and caused muscle injury, but these effects were markedly suppressed by preexercise treatment with antineutrophil antibody (neutrophil infiltration, 0.42-fold, and muscle injury, 0.18-fold). Treatment with antineutrophil antibody also decreased macrophage infiltration (0.44-fold) and mRNA expression of tumor necrosis factor- (0.55-fold) and interleukin-6 (0.51-fold) in the skeletal muscle after exhaustive exercise.
Conclusion These results suggest that neutrophils contribute to exacerbating muscle injury by regulating inflammation through the induction of macrophage infiltration.

Introduction: Disuse-induced skeletal muscle atrophy is a serious concern; however, there is not an effective mouse model to elucidate the molecular mechanisms. We developed a noninvasive atrophy model in mice. Methods: After the ankle joints of mice were bandaged into a bilateral plantar flexed position, either bilateral or unilateral hindlimbs were immobilized by wrapping in bonsai steel wire. Results: After 3, 5, or 10 days of immobilization of the hip, knee, and ankle, the weight of the soleus and plantaris muscles decreased significantly in both bilateral and unilateral immobilization. MAFbx/atrogin-1 and MuRF1 mRNA was found to have significantly increased in both muscles, consistent with disuse-induced atrophy. Notably, the procedure did not result in either edema or necrosis in the fixed hindlimbs. Conclusions: This method allows repeated, direct access to the immobilized muscle, making it a useful procedure for concurrent application and assessment of various therapeutic interventions.

Purpose The infiltration of macrophages in skeletal muscle during exhaustive exercise promotes inflammation, myofiber lesion, and muscle injury. Although neutrophils upregulate macrophage infiltration in skeletal muscles during exercise, the role of neutrophils in promoting muscle injury after exhaustive exercise remains unclear. In this study, we investigated the effects of preexercise neutrophil depletion with antineutrophil antibody treatment on muscle injury, inflammation, and macrophage infiltration after exhaustive exercise.
Methods Male C57BL/6J mice were randomly assigned to four groups, namely, sedentary with control antibody (n = 10), sedentary with antineutrophil antibody (n = 10), exhaustive exercise with control antibody (n = 10), and exhaustive exercise with antineutrophil antibody (n = 10). The mice were given intraperitoneal injection of the antineutrophil antibody (anti-Ly-6G, clone 1A8) or the control antibody (anti-Ly-6G, clone 2A3), and remained inactive or performed exhaustive exercise on a treadmill 48 h after the injection. Twenty-four hours after the exhaustive exercise, the gastrocnemius muscles were removed for histological and polymerase chain reaction (PCR) analyses. Infiltration of neutrophils and macrophages was evaluated with Ly-6G and F4/80 immunohistochemistry staining procedures. Muscle fiber injury was detected based on the number of IgG staining fiber. The mRNA expression levels of proinflammatory cytokines and chemokines were evaluated with real-time reverse transcription PCR.
Results Exhaustive exercise increased neutrophil infiltration into the gastrocnemius muscle substantially by 3.1-fold and caused muscle injury, but these effects were markedly suppressed by preexercise treatment with antineutrophil antibody (neutrophil infiltration, 0.42-fold, and muscle injury, 0.18-fold). Treatment with antineutrophil antibody also decreased macrophage infiltration (0.44-fold) and mRNA expression of tumor necrosis factor- (0.55-fold) and interleukin-6 (0.51-fold) in the skeletal muscle after exhaustive exercise.
Conclusion These results suggest that neutrophils contribute to exacerbating muscle injury by regulating inflammation through the induction of macrophage infiltration.

Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity-dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-alpha, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS-mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox-associated adaptation. (C) 2016 Elsevier Inc. All rights reserved.

BACKGROUND: Reproductive hormones are likely to be involved in thermoregulation through body fluid dynamics. In the present study, we aimed to investigate the effect of the menstrual cycle and water consumption on physiological responses to prolonged exercise at moderate intensity in hot conditions.
METHODS: Eight healthy young women with regular menstrual cycles performed cycling exercise for 90 minutes at 50% VO2peak intensity during the low progesterone (LP) level phase and high progesterone (HP) level phase, with or without water consumption, under hot conditions (30 degrees C, 50% relative humidity). For the water consumption trials, subjects ingested water equivalent to the loss in body weight that occurred in the earlier non-consumption trial. For all four trials, rectal temperature, cardiorespiratory responses, and ratings of perceived exertion (RPE) were measured.
RESULTS: Throughout the 90-minute exercise period, rectal temperatures during HP were higher than during LP by an average of 0.4 degrees C in the non-consumption trial (P&lt; 0.01) and 0.2 degrees C in the water consumption trial (P&lt; 0.05). During exercise, water consumption affected the changes in rectal temperature and heat rate (HR) during HP, but it did not exert these effects during LP. Furthermore, we found a negative correlation between estradiol levels and rectal temperature during LP.
CONCLUSIONS: During prolonged exercise at moderate intensity under hot conditions, water consumption is likely to be useful for suppressing the associated increase in body temperature and HR, particularly during HP, whereas estradiol appears to be useful for suppressing the increase in rectal temperature during LP.

Exhaustive exercise promotes muscle injury, including myofiber lesions; however, its exact mechanism has not yet been elucidated. In this study, we tested the hypothesis that macrophage depletion by pretreatment with clodronate liposomes alters muscle injury and inflammation following exhaustive exercise. Male C57BL/6J mice were divided into four groups: rest plus control liposome (n=8), rest plus clodronate liposome (n=8), exhaustive exercise plus control liposome (n=8), and exhaustive exercise plus clodronate liposome (n=8). Mice were treated with clodronate liposome or control liposome for 48 h before undergoing exhaustive exercise on a treadmill. Twenty-four hours after exhaustive exercise, the gastrocnemius muscles were removed for histological and PCR analyses. Exhaustive exercise increased the number of macrophages in the muscle; however, clodronate liposome treatment reduced this infiltration. Although exhaustive exercise resulted in an increase in injured myofibers, clodronate liposome treatment following exhaustive exercise reduced the injured myofibers. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the skeletal muscle after exhaustive exercise. These results suggest that macrophages play a critical role in increasing muscle injury by regulating inflammation.

Exercise dynamically changes skeletal muscle protein synthesis to respond and adapt to the external and internal stimuli. Many studies have focused on overall protein synthesis to understand how exercise regulates the muscular adaptation. However, despite the probability that each gene transcript may have its own unique translational characteristics and would be differentially regulated at translational level, little attention has been paid to how exercise affects translational regulation of individual genes at a genome-wide scale. Here, we conducted a genome-wide translational analysis using ribosome profiling to investigate the effect of a single bout of treadmill running (20 m/min for 60 min) on mouse gastrocnemius. Global translational profiles largely differed from those in transcription even at a basal resting condition as well as immediately after exercise. As for individual gene, Slc25a25 (Solute carrier family 25, member 25), localized in mitochondrial inner membrane and maintaining ATP homeostasis and endurance performance, showed significant up-regulation at translational level. However, multiple regression analysis suggests that Slc25a25 protein degradation may also have a role in mediating Slc25a25 protein abundance in the basal and early stages after acute endurance exercise.

Several studies have reported that molecular hydrogen (H2) acts as a therapeutic medical gas owing to scavenging reactive oxygen species (ROS). However, little is known about effects of H2 on exercise-induced oxidative stress. The purpose of this study was to investigate the effects of weekly hydrogen bathing on exercise-induced oxidative stress and delayed-onset muscle soreness (DOMS). Nine healthy and active young men participated in this study, and each subject performed hydrogen bathing trial and placebo bathing trial in a crossover design. The subjects performed downhill running (8 % decline) at 75 % peak oxygen uptake (VO2peak) for 30 min, and each subjects conducted hydrogen or placebo bathing for 20 min, respectively, 1-6 days after downhill running. Before and after exercise, we measured visual analogue scale (VAS) and collected blood samples (Pre-and 5 min, 60 min after the end of bathing, 1day, 2days, 3days, 7days after downhill running). Blood sample analyses include creatine kinase (CK), myoglobin (Mb), malondialdehyde (MDA), reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-17a (IL-17a) and lactate concentrations. Weekly hydrogen bathing had no effects of exercise-induced oxidative stress and muscle damage. On the other hand, hydrogen bathing significantly reduced DOMS (VAS) 1 and 2days after downhill running (p=0.033). These findings suggest that hydrogen bath after downhill exercise can be effective for reduction of DOMS.

Green tea (Camellia sinensis) has anti-oxidative and anti-inflammatory effects, which may be beneficial to athletes performing high-intensity exercise. This study investigated the effects of carbohydrate and green tea coingestion on sprint cycling performance and associated oxidative stress and immunoendocrine responses to exercise. In a crossover design, 9 well-trained male cyclists completed 3 sets of 8 repetitions of 100-m uphill sprint cycling while ingesting green tea and carbohydrate (TEA) (22 mg/kg body mass catechins, 6 mg/kg body mass caffeine, 230 mg/kg glucose, and 110 mg/kg fructose) or carbohydrate only (CHO) (230 mg/kg body mass glucose and 110 mg/kg body mass fructose) during each 10-min recovery period between sets. Blood samples were collected before exercise, 10 min after exercise, and 14 h after exercise. There was no effect of acute TEA ingestion on cycling sprint performance (p = 0.29), although TEA maintained postexercise testosterone and lymphocyte concentrations, which decreased significantly in the CHO group (p &lt; 0.001). While there was a trend for lower postexercise neutrophil count with TEA (p = 0.05), there were no significant differences between TEA and CHO for circulating cytokines (p &gt; 0.20), markers of oxidative stress and antioxidant capacity (p &gt; 0.17), adiponectin concentration (p = 0.60), or muscle damage markers (p &gt; 0.64). While acute green tea ingestion prevents the postexercise decrease in testosterone and lymphocytes, it does not appear to benefit cycling sprint performance or reduce markers of oxidation and inflammation when compared with carbohydrate alone.

The purpose of this study was to determine the effects of vitamin C supplementation on low-intensity prolonged exercise training-induced changes of metabolic and antioxidant enzyme activities in rat skeletal muscle. Male Sprague-Dawley rats were assigned to one of four groups: a control group, exercise training group, vitamin C supplemented group, and vitamin C supplemented exercise training group. Rats in the vitamin C supplemented groups were given vitamin C (500 mg/kg/day). The vitamin C supplemented animals were given vitamin C in their drinking water during a 2-week pretraining period. The rats in the vitamin C supplemented groups were administered vitamin C with a feeding needle 1h before each training session in the training period. Rats in the exercise training groups swam without a load for 6 h in two 3 h bouts, separated by 45 min of rest. The rats performed the training once a day for 10 days. Vitamin C supplementation attenuated oxidative stress and increased glutathione level and catalase activity. Exercise training increased citrate synthase and hexokinase activities. However, vitamin C did not change these enzyme activities. These results suggest that vitamin C does not prevent the training-induced activation of metabolic enzymes, but attenuates oxidative stress via induction of antioxidants in skeletal muscle.

The innate immune system is associated with the development of local inflammation. Neutrophils play an essential role in the development of the adipose tissue (AT) inflammation associated with obesity by producing elastase, which can promote the activation and infiltration of macrophages. Exercise training attenuates AT inflammation via suppression of macrophage infiltration. However, the mechanisms driving this phenomenon remains to be elucidated. Here, we evaluated the effects of exercise training on the infiltration of neutrophils and elastase expression in an obese mouse model. Four-week-old male C57BL/6J mice were randomly assigned to one of three groups that either received a normal diet (ND) plus sedentary activity (n = 15), a high-fat diet (HFD) plus sedentary activity (n = 15), or a HFD plus exercise training (n = 15). Mice were fed the ND or HFD from the age of 4 weeks until 20 weeks. Mice in the exercise group ran on a treadmill for 60 min/day, 5 days/week over the same experimental period. Mice fed with the HFD had increased content of macrophages in the AT and increased inflammatory cytokine mRNA levels, which were reduced by exercise training. Similarly, AT from the HFD sedentary mice contained more neutrophils than AT from the ND mice, and the amount of neutrophils in this tissue in HFD-fed mice was lowered by exercise training. The mRNA levels of neutrophil elastase in AT were lower in the HFD exercise-trained mice than those in the HFD sedentary mice. These results suggest that exercise training plays a critical role in reducing macrophage infiltration and AT inflammation by regulating the infiltration of neutrophils.

Purpose
To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men.
Methods
Fourteen healthy male participants aged 24.3 +/- 0.8 years (mean +/- standard error) performed endurance exercise in the morning (0900-1000 h) on one day and then in the evening (1700-1800 h) on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake ((V) over dotO(2max)) on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise.
Results
Plasma interleukin (IL)-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P &lt; 0.01, both). Serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at 2 h after exercise (P &lt; 0.05). Furthermore, a significant correlation was observed between the levels of IL-6 immediately post-exercise and free fatty acids 2 h post-exercise in the evening (r = 0.68, P &lt; 0.01).
Conclusions
These findings suggest that the effect of acute endurance exercise in the evening enhances the plasma IL-6 and adrenaline concentrations compared to that in the morning. In addition, IL-6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning.

Purpose: To assess the effect of exercise-induced muscle damage on muscle hardness and evaluate the relationship between muscle hardness and muscle damage indicators.
Methods: Seven men (mean 25.3 years; 172.7 cm; 66.8 kg) performed the single-leg ankle plantar flexion exercise involving both concentric and eccentric contractions (10 sets of 40 repetitions). The hardness of the medial gastrocnemius (MG) was evaluated using ultrasound real-time tissue elastography before, from day 1 to 4, and day 7 after exercise. The strain ratio between the MG and a reference material was calculated. Simultaneously, we evaluated the magnetic resonance T2 value (an index of edema) of the triceps surae, the ankle dorsiflexion range of motion (ROM), and calf muscle soreness. Serum creatine kinase activity was assessed before, 2 and 4 h, and from day 1 to 4 after exercise.
Results: The MG showed lower strain ratio, indicating increased muscle hardness, on day 4 post-exercise (P &lt; 0.01) and higher T2 values on days 1-7 post-exercise (P &lt; 0.01) relative to each pre-exercise value. The ankle dorsiflexion ROM was lower on days 2-4 post-exercise (P &lt; 0.01). The serum creatine kinase markedly increased on days 3 and 4 post-exercise (not significant). The degree of muscle soreness among the post-exercise time points was similar. The decreased strain ratio did not correlate with the increased T2, the decreased joint ROM or muscle soreness.
Conclusion: Muscle hardness increased after strenuous resistance exercise, but the change was not related with muscle edema, decreased joint ROM, or muscle soreness resulting from muscle damage.

Background: Sedentary behavior, which includes sitting and TV viewing, has been identified as an independent risk factor for type 2 diabetes and cardiovascular disease. Breaking sedentary behavior improves metabolic health such as postprandial glycaemia and insulinemia. However, the mechanisms underlying this effect are unclear. Objectives: Here, we examined whether breaking sitting by standing and acute exercise reduces postprandial oxidative stress. Patient and Methods: Fifteen participants performed 3 trials (sitting, standing, and exercise), each lasting 2 days, in a randomised order. On day one of sitting trial, participants sat in a chair. For the standing trial, the participants stood 6 times, for a 45-minute period each time. For the exercise trial, the participants walked or ran at approximately 60% of age-predicted maximum heart rate for 30 minutes. On day two of each trial, participants rested and consumed the standardised breakfast and lunch. Blood samples were collected in the morning and afternoon on day one, and fasting and at 2, 4, and 6 hours postprandially on day two. Results: The concentrations of serum derivatives of reactive oxygen metabolites (d-ROMs) measured at 4 hours (P = 0.064) and 6 hours (P = 0.071) tended to be higher than that in the fasting state in the sitting trial, but not standing and exercise trial (two-factor analysis of variance (ANOVA), trial × time interaction, P = 0.006). Conclusions: Our results indicate the importance of reducing sitting time for improving postprandial oxidative stress status.

Thioredoxin (TRX) is a 12 kDa protein that is induced by oxidative stress, scavenges reactive oxygen species (ROS) and modulates chemotaxis. Furthermore it is thought to play a protective role in renal ischemia/reperfusion injury Complement 5a (C5a) is a chemotactic factor of neutrophils and is produced after ischemia/reperfusion injury in the kidney. Both TRX and C5a increase after endurance exercise. Therefore, it may be possible that TRX has an association with C5a in renal disorders and/or renal protection caused by endurance exercise. Accordingly, the aim of this study was to investigate relationships among the changes of urine levels of TRX, C5a and acute kidney injury (AKI) caused by ischemia/repetfusion, inflammatory responses, and oxidative stress following intensive endurance exercise. Also, we applied a newly-developed measurement system of neutrophil migratory activity and ROS-production by use of ex vivo hydrogel methodology with an extracellular matrix to investigate the mechanisms of muscle damage. Fourteen male triathletes participated in a duathlon race consisting of 5 km of running, 40 km of cycling and 5 km of running were recruited to the study Venous blood and urine samples were collected before. immediately following, 1.5 It and 3 It after the race. Plasma, serum and urine were analyzed using enzyme-linked immunosorbent assays, a free radical analytical system, and the ex vivo neutrophil functional measurement system. These data were analyzed by assigning participants to damaged and minor-damage groups by the presence and absence of renal tubular epithelial cells in the urinary sediments. We found strong associations among urinary TRX C5a. interleukin (IL)-2, IL-4, IL-8. IL-10, interferon (IFN)-gamma and monocyte chemotactic protein (MCP)-1. From the data it might be inferred that urinary TRX, MCP-1 and beta-N-acetyl-D-glucosaminidase (NAG) were associated with renal tubular injury. Furthermore. TRX may be influenced by levels of IL-10, regulate chemotactic activity of C5a and IL-8, and control inflammatory progress by C5a and In the longer duration group (minor-damage group), circulating neutrophil count, plasma concentration of myeloperoxidase (MPO) and serum concentration of myoglobin were markedly increased. In the higher intensity group (damaged group), neutrophil activation and degranulation of MPO might be inhibited, because not only was ROS production observed to be higher. hut also antioxidant capacity and an inflammatory cytokines were increased. Critically, the newly-developed ex vivo methodology corroborated the neutrophil activation levels in the two groups of participants.

Cytokines are important mediators of various aspects of health and disease, including appetite, glucose and lipid metabolism, insulin sensitivity skeletal muscle hypertrophy and atrophy Over the past decade or so, considerable attention has focused on the potentiallar regular exercise to counteract a range of disease states by modulating cylokine production. Exercise stimulates moderate to large increases in the circulating concentrations of interleukin IL-8, IL-10, IL-1 receptor antagonist. granulocyte-colony stimulating factor, and smaller increases in tumor necrosis factor-alpha, monocyte chentotactic protein-I, IL-1 beta, brain-derived neurotrophic factor; IL-12p35/p40 and IL-15. Although many of these cytokines are also expressed in skeletal muscle, not all are released from skeletal muscle into the circulation during exercise. Conversely some cytokines that are present in the circulation are not expressed in skeletal muscle after exercise. The reasons for these discrepant cytokine responses to exercise are unclear In this review, we address these uncertainties by summarizing the capacity of skeletal muscle cells to produce cytokines, analyzing other potential cellular sources of circulating cytokines during exercise. and discussing the soluble factors and intracellular signaling pathways that regulate cytokine synthesis (e.g., RNA-binding proteins, micaoRNAs, suppressor of cytokine signaling proteins, soluble receptors).

Elevated postprandial hyperglycaemia and oxidative stress increase the risks of type 2 diabetes and CVD. Green tea catechin possesses antidiabetic properties and antioxidant capacity. In the present study, we examined the acute and continuous effects of ingestion of catechin-rich green tea on postprandial hyperglycaemia and oxidative stress in healthy postmenopausal women. Participants were randomly assigned into the placebo (P, n 11) or green tea (GT, n 11) group. The GT group consumed a catechin-rich green tea (catechins 615 mg/350 ml) beverage per d for 4 weeks. The P group consumed a placebo (catechins 92 mg/350 ml) beverage per d for 4 weeks. At baseline and after 4 weeks, participants of each group consumed their designated beverages with breakfast and consumed lunch 3 h after breakfast. Venous blood samples were collected in the fasted state (0 h) and at 2, 4 and 6 h after breakfast. Postprandial glucose concentrations were 3% lower in the GT group than in the P group (three-factor ANOVA, group x time interaction, P&lt;0.05). Serum concentrations of the derivatives of reactive oxygen metabolites increased after meals (P&lt;0.05), but no effect of catechin-rich green tea intake was observed. Conversely, serum postprandial thioredoxin concentrations were 5% higher in the GT group than in the P group (three-factor ANOVA, group x time interaction, P&lt;0.05). These findings indicate that an acute ingestion of catechin-rich green tea has beneficial effects on postprandial glucose and redox homeostasis in postmenopausal women.

Although numerous sources of evidence show that regular physical activity is beneficial to health, most individuals do not engage in a sufficient amount of physical activity to meet the guidelines set out by expert panels. In addition, the minimum amount of physical activity associated with reduced cardiovascular disease risk markers is not clear in older adults. The purpose of this study was to determine the effects of a 12-week walking program involving an exercise volume below the current minimum physical activity recommendation on cardiovascular disease risk markers in older adults. The participants were recruited from the following two groups separately: a walking group (n = 14) and a control group (n = 14). In the walking group, participants walked 30 to 60 minutes per session on 2 days per week for 12 weeks (average walking time, 49.4 +/- 8.8 min/session). Plasma oxidised low-density lipoprotein concentrations tended to be lower than baseline values in the walking group after 12 weeks (paired t-test, p = 0.127). The ratio of oxidised low-density lipoprotein to high-density lipoprotein cholesterol was significantly lower than the baseline ratio in the walking group after 12 weeks (paired t-test, p = 0.035). Resting systolic blood pressure and diastolic blood pressure were significantly lower than baseline values in the walking group after 12 weeks (paired t-tests, p = 0.002, p < 0.0005, respectively). Our findings demonstrate that a 12-week walking program comprising a low volume of physical activity confers a benefit to cardiovascular-related health in older adults.

Background: Sex hormones are known to regulate some responses during exercise. Evaluation of the differences in exercise response with regard to menstrual cycle will help understand the menstrual cycle phase specific adaptations to exercise and athletic performance.Methods: We investigated the effects of menstrual cycle phase and carbohydrate (CHO) ingestion on immune response during endurance exercise at 30 degrees C. Six healthy women completed 4 trials comprising 90 min of cycling at 50% peak aerobic power ((V) over dotO(2peak)) and a high intensity time trial performance test (POST). They ingested a placebo- or CHO-containing beverage during the trials, which were performed during both the follicular and luteal phases of the menstrual cycle. In all trials, thermoregulatory, cardiorespiratory, and immune responses were measured during exercise and after POST.Results: Although the thermoregulatory responses differed between the menstrual cycle phases, the cardiorespiratory responses were not different. After placebo ingestion, leukocyte concentration (cells/mu L) at POST (15.9 x 10(3)) in the luteal phase was significantly higher than that in the follicular phase (12.9 x 10(3)). The rise in leukocyte concentration was attenuated upon CHO ingestion, and the difference between menstrual cycle phases disappeared. A significant positive correlation was found between leukocyte concentration and serum free fatty acid concentrations. Interleukin-6, calprotectin, and myeloperoxidase concentrations significantly increased at POST in all trials, but no significant differences were observed between menstrual cycle phase or beverage type. Concentrations of other cytokines did not change during exercise in any of the 4 trials. Menstrual cycle phase and beverage type had no significant effect on the POST outcome. Thus, differences in leukocyte mobilization between menstrual cycle phases could result from the effect of sex hormones on substrate utilization.Conclusions: The menstrual cycle affected circulating leukocyte concentrations during endurance exercise with POST when a placebo was ingested. Therefore, we recommend ingesting CHO beverages to attenuate immune disturbances, especially in the luteal phase, even though they are unlikely to enhance test performance.

The purpose of this study was to investigate the effects of curcumin supplementation on exercise-induced oxidative stress in humans. 10 male participants, ages 26.8 +/- 2.0 years (mean +/- SE), completed 3 trials in a random order: (1) placebo (control), (2) single (only before exercise) and (3) double (before and immediately after exercise) curcumin supplementation trials. Each participant received oral administration of 90 mg of curcumin or the placebo 2 h before exercise and immediately after exercise. Each participant walked or ran at 65 % of (V) over dotO(2max) on a treadmill for 60 min. Blood samples were collected pre-exercise, immediately after exercise and 2 h after exercise. The concentrations of serum derivatives of reactive oxygen metabolites measured immediately after exercise were significantly higher than pre-exercise values in the placebo trial (308.8 +/- 12.9 U. CARR, P &lt; 0.05), but not in the single (259.9 +/- 17.1 U. CARR) or double (273.6 +/- 19.7 U. CARR) curcumin supplementation trials. Serum biological antioxidant potential concentrations measured immediately after exercise were significantly elevated in the single and double curcumin supplementation trials compared with pre-exercise values (P &lt; 0.05). These findings indicate that curcumin supplementation can attenuate exercise-induced oxidative stress by increasing blood antioxidant capacity.

Chronic stress is an important risk factor for atherosclerosis, which is a chief process in the development of cardiovascular disease. Increased circulating levels of corticosterone have been documented in several animal models of chronic stress. However, it remains to be established whether corticosterone is sufficient to exacerbate atherosclerosis. To test this hypothesis, apolipoprotein E (ApoE)-deficient mice were fed a high-fat diet for 13 weeks with exposure to either corticosterone or vehicle in the drinking water (CORT and Con). Corticosterone treatment significantly increased atherosclerotic plaque area at the aortic root. Such exacerbation of atherosclerosis was accompanied by significantly lower levels of circulating white blood cells and serum interleukin-1 beta (IL-1 beta), and significantly elevated serum concentrations of total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and small dense low-density lipoprotein (sd-LDL) in CORT mice when compared to Con mice. These findings demonstrate that corticosterone is sufficient to exacerbate atherosclerosis in vivo despite its anti-inflammatory properties and that this marked pro-atherogenic phenotype is primarily associated with increased dyslipidaemia. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

We investigated physiological responses and changes in circulating immune cells following exercise in cold and thermoneutral conditions. Participants were short track skaters (n=9) who were acclimatized to cold conditions, and inline skaters (n=10) who were not acclimatized. All skaters were young, and skating at a recreational level three days per week for at least one year. Using a cross-over design, study variables were measured during 60 min of submaximal cycling (65% VO(2)max) in cold (ambient temperature: 5 +/- 1 degrees C, relative humidity: 41 +/- 9%) and thermoneutral conditions (ambient temperature: 21 +/- 1 degrees C, relative humidity: 35 +/- 5%). Heart rate, blood lactate and tympanic temperature were measured at rest, during exercise and recovery. Plasma cortisol, calprotectin and circulating blood cell numbers were measured before and after 60 min of cold or thermoneutral conditions, and during recovery from exercise. Heart rate was lower in both groups during exercise in cold versus thermoneutral conditions (P&lt;0.05). The increase in total leukocytes during recovery was primarily due to an increase in neutrophils in both groups. The cold-acclimatized group activated neutrophils after exercise in cold exposure, whereas the non-acclimatized group activated lymphocyte and cortisol after exercise in cold exposure. Lymphocyte subsets significantly changed in both groups over time during recovery as compared to rest. Immediately after exercise in both groups, CD16+ and CD69+ cells were elevated compared to rest or before exercise in both conditions. Acclimatization to exercise in the cold does not appear to influence exercise-induced immune changes in cold conditions, with the possible exception of neutrophils, lymphocytes and cortisol concentration.

The aim of this study was to investigate the short-term effects of green tea consumption on selected salivary defense proteins, antibacterial capacity and anti-oxidation activity in taekwondo (TKD) athletes, following intensive training. Twenty-two TKD athletes performed a 2-hr TKD training session. After training, participants ingested green tea (T, caffeine 6 mg/kg and catechins 22 mg/kg) or an equal volume of water (W). Saliva samples were collected at three time points: before training (BT-T; BT-W), immediately after training (AT-T; AT-W), and 30 min after drinking green tea or water (Rec-T; Rec-W). Salivary total protein, immunoglobulin A (SIgA), lactoferrin, a-amylase activity, free radical scavenger activity (FRSA) and antibacterial capacity were measured. Salivary total protein, lactoferrin, SIgA concentrations and a-amylase activity increased significantly immediately after intensive TKD training. After tea drinking and 30 min rest, a-amylase activity and the ratio of a-amylase to total protein were significantly higher than before and after training. In addition, salivary antibacterial capacity was not affected by intense training, but green tea consumption after training enhanced salivary antibacterial capacity. Additionally, we observed that salivary FRSA was markedly suppressed immediately after training and quickly returned to pre-exercise values, regardless of which fluid was consumed. Our results show that green tea consumption significantly enhances the activity of a-amylase and salivary antibacterial capacity.

It is widely recognized that exercise has an important role in inflammation regulation. To understand inflammatory mechanisms, extensive studies on the transcriptome and proteome have been conducted. However, interpreting these results is difficult, partly due to technical difficulties that impose some restriction on the accuracy and comprehensiveness of measurements. Here we first mention some limitations of studies involving large scale proteomics and high-throughput transcriptomics and further introduce a newly developed genome-wide translational analysis which may overcome some of the limitations and discover novel cellular dynamics. We then show preliminary results obtained by conducting a genome-wide translational analysis of the early inflammatory response of macrophages in response to lipopolysaccharide (LPS), and discuss the potential to identin) novel factors by employing a genome-wide translational analysis.

This investigation determined whether existing muscle damage markers and organ damage markers respond to an acute eccentric exercise protocol and are associated with affected muscle symptoms. Nine healthy-young men completed one-leg calf-raise exercise with their right leg on a force plate. They performed 10 sets of 40 repetitions of exercise at 0.5 Hz with a load corresponding to half of their body weight, with 3 mm rest between sets. The tenderness of medial gastrocnemius, lateral gastrocnemius and soleus, and the ankle active range of motion (ROM) were assessed before, immediately after, 24 h and 48 h, 72 h, 96 h and 168 h after exercise. Blood and urine were collected pre-exercise and 2 h, 4 h, 24 h, 48 h, 72 h and 96 h post-exercise. Serum was analyzed for creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and aldolase (ALD) activities. We also determined hearttype fatty acid-binding protein (H-FABP), intestinal-type fatty acid-binding protein (I-FABP) and liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-17A, IL-23, nerve growth factor (NGF), soluble-Endothelial (sE)-selectin, s-Leukocyte (L)-selectin, 5Platelets (P)-selectin, and 8-isoprostane in plasma and urine. The tenderness of proximal and middle gastrocnemius increased significantly 72 h (p&lt;0.05, p&lt;0.01) after exercise. Ankle active ROM in dorsal flexion decreased significantly 48 h (p&lt; 0.05) and 72 h (p&lt;0.01) after exercise. CK and ALD activities significantly increased at 72 h (p&lt;0.05) and remained elevated at 96 h (p&lt; 0.01) postexercise compared to pre-exercise values. Also, ALD which showed relatively lower interindividual variability was significantly correlated with tenderness of middle gastrocnemius at 72 h. LDH activity significantly increased 96 h postexercise (p&lt; 0.01), whereas the increase in AST and ALT activities 96 h post-exercise was not significantly different from pre-exercise values. There were no significant changes in FABPs, NGAL, IL-17A, IL-23, NGF, selectins and 8-isoprostanes in plasma and urine. In conclusion, calf-raise exercise induced severe local muscle damage symptoms which were accompanied by increases in both serum CK and ALD activities, but we could not detect any changes in examined markers of organ damage, inflammation and oxidative stress. Further research is needed to determine other more sensitive biomarkers and the underlying mechanisms of exercise-induced muscle damage.

Downhill running causes muscle damage, and induces oxidative stress and inflammatory reaction. Recently, it is shown that curcumin possesses anti-oxidant and anti-inflammatory potentials. Interestingly, curcumin reduces inflammatory cytokine concentrations in skeletal muscle after downhill running of mice. However, it is not known whether curcumin affects oxidative stress after downhill running-induced muscle damage. Therefore, the purpose of this study was to investigate the effects of curcumin on oxidative stress following downhill running induced-muscle damage. We also investigated whether curcumin affects macrophage infiltration via chemokines such as MCP-1 and CXCL14. Male C57BL/6 mice were divided into four groups; rest, rest plus curcumin, downhill running, or downhill running plus curcumin. Downhill running mice ran at 22 m/min, -15% grade on the treadmill for 150 min. Curcumin (3 mg) was administered in oral administration immediately after downhill running. Hydrogen peroxide concentration and NADPH-oxidase mRNA expression in the downhill running mice were significantly higher than those in the rest mice, but these variables were significantly attenuated by curcumin administration in downhill running mice. In addition, mRNA expression levels of MCP-1, CXCL14 and F4/80 reflecting presence of macrophages in the downhill running mice were significantly higher than those in the rest mice. However, MCP-1 and F4/80 mRNA expression levels were significantly attenuated by curcumin administration in downhill running mice. Curcumin may attenuate oxidative stress following downhill running-induced muscle damage. (C) 2013 Elsevier Inc. All rights reserved.

Tissue fibrosis, such as that which occurs in obesity, is associated with chronic inflammatory diseases. Although regular exercise reduces adipose tissue inflammation, the mechanisms regulating the effects of exercise on adipose tissue fibrosis are unclear. This study aimed to clarify whether exercise training attenuates adipose tissue fibrosis with consequent reduction of extracellular matrix including collagens. Male C57BL/6J (4-week old) mice were randomly assigned to four groups that received a normal diet (ND) plus sedentary (n = 8), an ND plus exercise training (n = 8), a high-fat diet (HFD) plus sedentary (n = 12), and an HFD plus exercise training (n = 12). Mice were fed the ND or HFD from 4 to 20 weeks of age. The exercise groups were trained on a motorized treadmill for 60 min/day, 5 times/week over the same period. Histological hepatic fibrosis detected by Sirius red and alpha-smooth muscle actin staining were attenuated in HFD exercise mice compared with HFD sedentary mice. mRNA levels of transforming growth factor-beta and tissue inhibitors of metalloproteinase-1, major regulators of tissue fibrosis, were increased in HFD sedentary mice but were attenuated in HFD exercise mice. Similarly, adipose tissue from the HFD sedentary mice contained higher macrophages than adipose tissue from the ND mice, and this was also lowered by exercise training. These findings suggest that exercise training may be effective for attenuating adipose tissue inflammation in obesity. (C) 2013 Elsevier Inc. All rights reserved.

Aim. The aim of this pilot investigation was to examine the influence of bovine colostrum protein concentrate (CPC) supplementation on salivary hormones, salivary IgA and heart rate variability over consecutive days of competitive cycling. Methods. Ten highly-trained male road cyclists (mean±SEM
age=22.2±4.7 yr
mass=70.5±4.5 kg
VO2max=72. 9±3.8 mL.kg-1.min-1) were randomly assigned to a control (N.=6, 10g whey protein concentrate/day) or bovine CPC group (N.=4, 10 g bovine CPC/day). Cyclists provided a baseline saliva sample before commencing eight weeks of supplementation, and competing in a five day cycle race. Cyclists provided saliva samples and measured heart rate variability (HRV) each day of the race. Saliva samples were analysed for cortisol, testosterone and IgA concentrations. Results. Bovine CPC supplementation was associated with increased morning cortisol concentration on the first day of racing when compared to the control group (P=0.004) and significantly prevented a decrease in testosterone concentration over the race period (P≤0.05). Across the race period parasympathetic indices of HRV were elevated in the bovine CPC group and reduced in the control group (P≤0.05), while there were no significant differences in salivary IgA between groups. Conclusion. Bovine CPC supplementation maintained salivary testosterone concentration and modulated autonomic activity over consecutive days of competitive cycling. This pilot study provides justification to explore the effects of bovine CPC on recovery in endurance athletes further.

Oxidative stress increases with advancing age and is a mediator of several diseases including cancer, cardiovascular disease, and diabetes. Moreover, postmenopausal women have a lower estrogen concentration, which is associated with elevated oxidative stress. However, there is no definitive evidence regarding the relationship between daily physical activity and oxidative stress status in older adults, including postmenopausal women. Twenty- nine adults (age, 70.1 ± 1.0 years, mean ± SE; 12 women and 17 men) were examined in this cross-sectional study. Prior to blood collection, the participants were asked to wear a uniaxial accelerometer for 4 consecutive weeks to determine their level of physical activity. After a 48-h period of physical activity avoidance and a 10-h overnight fast, venous blood samples were obtained from each participant. Fasting plasma derivatives of reactive oxygen metabolites (d-ROMs) and malondialdehyde (MDA) concentrations of oxidative stress markers were negatively correlated with the amount of physical activity in women (d-ROMs; r = -0.708, p = 0.002) (MDA; r = -0.549, p = 0.028), but not in men. Fasting plasma biological antioxidant potential of antioxidant capacity marker was positively correlated with the amount of physical activity in women (BAP; r = 0.657, p = 0.006) (GSH; r = 0.549, p = 0.028), but not in men. Moreover, superoxide dismutase activity of antioxidant capacity marker was positively correlated with the amount of physical activity in men (r = 0.627, p = 0.039), but not in women. There were no associations between physical activity and other oxidative stress markers (reduced and oxidized glutathione, glutathione peroxidise, thioredoxin). These findings suggest that regular physical activity may have a protective effect against oxidative stress by increasing total antioxidant capacity, especially in postmenopausal women. © Journal of Sports Science and Medicine.

We investigated the effects of two carbohydrate-based sports drinks on fluid intake and immunoendocrine responses to cycling. Six well-trained male cyclists completed trials on three separate days that involved cycling at 60% V(O) over dot(2peak) for 90 min in hot conditions (28.1 +/- 1.5 degrees C and 52.6 +/- 3.1% relative humidity). During each trial, the subjects consumed ad libitum (1) an isotonic sports drink (osmolality 317 mOsm/kg), (2) a hypotonic sports drink (osmolality 193 mOsm/kg) or (3) plain water. The cyclists consumed significantly (p&lt;0.05) more of the isotonic drink (1.23 +/- 0.35 L) and hypotonic drink (1.44 +/- 0.55 L) compared with water (0.73 +/- 0.26 L). Compared with water ( 0.96 +/- 0.26 kg), body mass decreased significantly less after consuming the hypotonic drink (-0.50 +/- 0.38 kg) but not the isotonic drink (-0.51 +/- 0.41 kg). Blood glucose concentration was significantly higher at the end of the isotonic and hypotonic drink trials compared with the water trial. Neutrophil count and the plasma concentrations of catecholamines, interleukin 6 (IL-6), myeloperoxidase, calprotectin and myoglobin increased significantly during all three trials. IL-6 and calprotectin were significantly lower following the hypotonic drink trial compared with the water trial. In conclusion, hypotonic sports drinks are appealing for athletes to drink during exercise, and may help to offset fluid losses and attenuate some inflammatory responses to exercise.

Background: Both exercise and vitamin E supplementation have been shown to reduce oxidative stress and cardiovascular disease risk in older adults, and when combined there is evidence suggesting that they act synergistically. The currently recommended amount of exercise for older adults is 150 min/week of moderate-intensity exercise; however, the minimum amount of exercise necessary to achieve health benefits is not known. The purpose of this study was to investigate the effects of 12 weeks of participation in a low-volume walking exercise programme (i.e. 90 min/week) combined with daily vitamin E supplementation on thiobarbituric acid reactive substances (TBARS) and oxidised low-density lipoprotein (LDL) concentrations in older adults. Methods. The participants were recruited from the following four groups separately: 1) control (CG, n = 14), 2) vitamin E supplementation (SG, n = 10), 3) walking (WG, n = 7), or 4) walking + supplementation (WSG, n = 7). In the CG, participants were advised to maintain their normal lifestyle during the study. Participants in both the SG and WSG received 450 IU (300 mg) /day of α-tocopherol for 12 weeks. The exercise programme for the WG and WSG consisted of two 30-60 minute sessions weekly for 12 weeks (average walking time was 44.5 ± 1.6 min/session). Blood samples were collected at baseline and at 12 weeks. Results: Delta plasma oxidised LDL concentrations did not differ among four groups (One-factor ANOVA, P = 0.116). However, negative delta plasma TBARS, a marker of oxidative damage, concentrations were observed in the WG, WSG and SG relative to the CG at the end of the study period (One-factor ANOVA, P = 0.001; post hoc tests; CG compared with WG, WSG and SG, P = 0.005; P = 0.021; P = 0.024, respectively). Conclusion: These findings suggest that a low-volume of physical activity and/or vitamin E supplementation may be an effective intervention strategy for reducing TBARS concentrations of older adults. Trial registration. UMIN000008304. © 2013 Park et al.; licensee BioMed Central Ltd.

The purpose of this study was to investigate the effects of low-volume exercise training (100 min/week) on oxidative stress and neutrophils activation markers in older adults. Twenty-eight older adults (age range 65-78 years) were assigned into control (n = 14) or exercise (n = 14) groups. The exercise program consisted of walking 30-60 min/session, 2 days each week for 12 weeks. Blood samples were taken before starting the sessions (baseline) and when they ended. Fasting plasma and serum oxidative stress and inflammatory markers were measured using commercial kits. Cell surface expression of adhesion molecules on circulating leukocytes (CD66b and CD62L) was determined using flow cytometry. The concentrations of derivatives of reactive oxygen metabolites tended to be lower than the baseline values only in the exercise group (P = 0.05). The biological antioxidant potential, thioredoxin concentrations, and glutathione peroxidase activities significantly increased only in the exercise group (P < 0.05 for all). While CD66b expression tended to decrease only in the exercise group, CD62L expression significantly increased (P < 0.05). Our findings indicate that exercise training below the current recommended level of at least 150 min/week attenuates basal oxidative stress and neutrophil activation in older adults. Thus, our findings may encourage more people to incorporate a small amount of physical activity into their lives. © 2012 Springer-Verlag Berlin Heidelberg.

We examined the effects of polyphenols on migratory activity of neutrophils into the hydrogel and their production of reactive oxygen species (ROS). Origonol and lychee polyphenol were diluted to medium in wide-range concentrations. Each solution was added on hydrogel, and the mixture of blood and luminol was layered on it in each tube. The ROS production was measured by luminol-dependent chemiluminescence, whereas the cell count in the hydrogel was quantified as migratory activity of neutrophils. The migratory activity of neutrophils was not affected, whereas ROS production of neutrophils was significantly decreased above 100 μg/ml, but increased below the concentration.<br>

It has been well known that protein level is estimated by the expression level of its mRNA. However, it is also argued that correlation between mRNA abundance and protein levels is weaker than previously thought. Recently a newly developed technique called ribosome profiling has drawn attention as a drastic countermeasure to improve the weak correlation. Here it is discussed that weak association of protein and mRNA levels seen in genome-wide analysis of gene expression such as microarray is attributable to post-transcriptional regulation including translational inhibition. This review further discusses how these issues are resolved by ribosome profiling and also addresses a possibility of biomarker discovery derived from this technique.<br>

:The purpose of this study was to investigate the effects of low-volume exercise training (90 min/wk) and vitamin E supplementation on oxidative stress markers in postmenopausal women. The participants were non-randomly assigned the following four groups: control (C, n=8), vitamin E (S, n=8), exercise (Ex, n=6), or vitamin E and exercise (S+Ex, n=7). The S and S+Ex groups were instructed to take vitamin E (α-tocopherol, 300 mg/d) capsules for 12 wk. The exercise program of Ex and S+Ex groups consisted of walking for a 30-60 min/session 2 d per week for 12 wk. The serum derivatives of reactive oxygen metabolites concentrations were significantly decreased in the Ex, and S+Ex groups after 12 wk compared with the baseline values (three-factor ANOVA, an interaction between exercise and time, p&lt;0.05). Conversely, serum biological antioxidant potential concentrations in the S and Ex groups were significantly higher at 12 wk than at the baseline, but not in the S+Ex group (three-factor ANOVA, an interaction between supplementation, exercise and time, p&lt;0.05). Plasma thioredoxin concentrations in the S, Ex, and S+Ex groups were significantly higher at 12 wk than at the baseline values (th

The purpose of this study was to investigate the effects of low-volume exercise training (90 min/wk) and vitamin E supplementation on oxidative stress markers in postmenopausal women. The participants were non-randomly assigned the following four groups: control (C, n=8), vitamin E (S, n=8), exercise (Ex, n=6), or vitamin E and exercise (S+Ex, n=7). The S and S+Ex groups were instructed to take vitamin E (α-tocopherol, 300 mg/d) capsules for 12 wk. The exercise program of Ex and S+Ex groups consisted of walking for a 30-60 min/session 2 d per week for 12 wk. The serum derivatives of reactive oxygen metabolites concentrations were significantly decreased in the Ex, and S+Ex groups after 12 wk compared with the baseline values (three-factor ANOVA, an interaction between exercise and time, p<0.05). Conversely, serum biological antioxidant potential concentrations in the S and Ex groups were significantly higher at 12 wk than at the baseline, but not in the S+Ex group (three-factor ANOVA, an interaction between supplementation, exercise and time, p<0.05). Plasma thioredoxin concentrations in the S, Ex, and S+Ex groups were significantly higher at 12 wk than at the baseline values (three-factor ANOVA, interactions between exercise and time, and between supplementation, exercise and time, p<0.05). Our findings suggest that low-volume physical activity may improve resting oxidative stress status in postmenopausal women.

The aim of this study was to investigate the effects of one night of sleep deprivation on maximal fat oxidation during a graded exercise test. Ten healthy young males underwent two 2-day control and sleep deprivation trials. Participants were allowed normal sleep from 2300 to 0700 for the control trial, whereas they were required to stay awake for 34 h during the sleep deprivation trial. At 1700 on day 2, participants performed a graded exercise test to exhaustion on a treadmill; this allowed us to determine maximal oxygen uptake and maximal fat oxidation. Before and immediately after the graded exercise test, blood samples were collected in order to measure glucose, insulin, free fatty acid, and triglyceride concentrations. Plasma glucose concentrations were significantly higher in the sleep deprivation trial than in the control trial before the graded exercise test. Serum insulin and free fatty acid concentrations were not significantly different between the two trials. Serum triglyceride concentrations were significantly lower in the sleep deprivation trial than in the control trial. The maximal fat oxidation rate, oxygen uptake, and heart rate at maximal fat oxidation intensity, during the graded exercise test, were not significantly different between the two trials. These findings suggest that maximal fat oxidation during graded exercise is unaffected by one night of sleep deprivation.

Obesity is associated with the pathogenesis of chronic inflammatory diseases, such as type II diabetes and nonalcoholic steatohepatitis, which in turn have been attributed to the chronic inflammation in visceral adipose tissue and liver. The innate immune system via macrophages, neutrophils and lymphocytes is related to development of chronic inflammation. Exercise has anti-inflammatory effects and may prevent the development of chronic inflammatory diseases. To elucidate mechanisms of chronic inflammation improvement and/or prevention in the local tissue due to exercise is important to ensure development of effective exercise therapy. This review provides information to elucidate the molecular mechanisms from the perspective of immune regulation on the improvement of chronic inflammation due to exercise.

The purpose of this study was to determine the relationships among delayed-onset muscle soreness (DOMS), muscle damage and inflammatory responses to eccentric exercise and investigate the underlying mechanisms. Nine healthy males performed one-leg calf-raise exercise with their right leg on a force plate. They performed 10 sets of 40 repetitions of exercise at 0.5 Hz by the load corresponding to the half of their body weight, with a rest for 3 min between sets. DOMS was evaluated by a visual analogue scale (VAS). Blood and urine samples were collected before and 2, 4, 24, 48, 72 and 96 h post-exercise. Blood samples were analyzed for leucocyte differential counts and neutrophil functions (migratory activity and oxidative burst activity). We also determined a serum marker of muscle damage, myoglobin (Mb), and plasma and urinary prostaglandin E2 as an algesic substance. As for the inflammatory mediators, plasma and urine were analyzed for cytokines (interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, tumour necrosis factor-alpha, interferon-gamma, monocyte chemotactic protein-1, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and granulocyte macrophage colony-stimulating factor), leucocyte activation markers (calprotectin and myeloperoxidase), and neutrophil chemotactic factor complement 5a. All subjects reported muscle soreness on subsequent days and VAS peaked at 72 h after exercise. Serum Mb concentration significantly increased (p < 0.05) at 72 h after exercise as compared with the pre-exercise values which was correlated with the increases in VAS at 72 h (r = 0.73, p < 0.05). Circulating neutrophil count and migratory activity increased significantly (p < 0.01, and p < 0.05, respectively) at 4 h after exercise, whereas there were no significant changes in the other plasma and urinary inflammatory mediators. These results suggest that neutrophils can be mobilized into the circulation and migrate to the muscle tissue several hours after the eccentric exercise. There were also positive correlations between the exercise-induced increases in neutrophil migratory activity at 4 h and the increases in Mb at 48 h (r = 0.67, p < 0.05). These findings suggest that neutrophil mobilization and migration after exercise may be involved in the muscle damage and inflammatory processes.

It has been consistently shown that circulating levels of interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1ra) and IL-10 increase remarkably following endurance exercise longer than 2 h such as marathon and triathlon races. However, no studies have compared changes in the plasma and urinary levels of these cytokines after endurance exercise, including the recovery period. In the present study, we investigated kinetic changes in the urinary excretion of cytokines following endurance exercise up to 3 h after exercise to evaluate the magnitude of change in comparison to the plasma levels and to explore the possible biological significance and the mechanisms of cytokine dynamics following exercise. Fourteen male athletes participated in a duathlon race consisting of 5 km of running, 40 km of cycling, and 5 km of running. Venous blood and urine samples were collected before, immediately after, 1.5 h and 3 h after the race. Plasma and urine were analyzed using enzyme-linked immunosorbent assays (ELISA). Plasma concentrations of IL-1 beta, IL-1ra, IL-6, IL-8, IL-10 and monocyte chemotactic protein (MCP)-1 increased significantly after the race, whereas tumour necrosis factor (TNF)-alpha, IL-2, IL-4, IL-12 and interferon (IFN)-gamma did not change significantly. Urinary concentrations of IL-1 beta, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-gamma and MCP-1 increased significantly after the race. When the urine concentrations were adjusted by creatinine concentration, urine volume and sampling time, the increases of IL-2, IL-4, IL-8, IL-10, IFN-gamma and MCP-1 were evident and these were notably present in urine of the stressed athletes suffering from renal tubular epithelial damage. The present study provides new evidence that the kinetics and magnitude of changes in urinary cytokine concentrations differ from plasma cytokine concentrations following endurance exercise, especially, in the recovery period several hours after exercise, and that the damaged kidney might be responsible at least in part for the kinetics of some cytokines. Urinary cytokines may be sensitive biomarkers of the impact of exhaustive exercise workload on renal damage and inflammation in the recovery period after endurance exercise.

The discovery of microRNAs (miRNAs) and following studies reporting that miRNAs are stably present in the circulation, paved the way for possible use of miRNAs as biomarkers. Identification of circulating miRNAs that are functional upon delivery to the recipient cells, suggests miRNAs play roles in cell-to-cell communication as well as hormones and cytokines. This review provides a basic understanding of miRNAs and the current understanding of circulating miRNA as biomarkers and focuses on their putative roles and regulation under stressed conditions including physical exercise.<br>

Objective: The overproduction of reactive oxygen species leads to oxidative stress, which is related to lifestyle-related disease and cancer. Although antioxidants are considered as one of the countermeasures to oxidative stress, it is necessary to develop the assessment methodology for the antioxidant capacity which is closer to the inner body conditions. In this study, we examined antioxidant actions of plant extracts by using newly-developed neutrophil activity measurement system.<br> Method: Lemon verbena, Green tea, Camellia japonica and Antiallerge^® were used as plant extracts, and were diluted to medium in wide-range concentrations. Each solution was added on modified Mebiol Gel^® (hydrogel), and the mixture of blood and luminol were set onto the hydrogel in each tube. The amount of reactive oxygen species were measured by luminol-dependent chemiluminescence, whereas the cell count in the hydrogel was quantified as migratory activity of neutrophils.<br> Result: Lemon verbena and Green tea significantly inhibited reactive oxygen species in a concentration-dependent manner, whereas Camellia japonica and Antiallerge^® did not. The migratory activity of neutrophils was not affected by those plant extracts. Also, damaged cells were not detected.<br> Conclusion: It was suggested that Lemon verbena and Green tea scavenged reactive oxygen species without causing cell death of neutrophils. This new method for measuring neutrophil activities can be applied not only for assessing the status of inflammation and oxidative stress but also as the screening system for predicting the effectiveness of antioxidant and anti-inflammatory substances.<br>

BACKGROUND/AIM: Oxidative stress in cancer patients has been demonstrated to be partly mediated by neutrophils. Although it is reported that natural antioxidants, such as green tea extract, reduce oxidative stress, there is limited evidence of their effects in cancer patients. This study aimed to determine the effect of green tea extract on reactive oxygen species produced by neutrophils from cancer patients. MATERIALS AND METHODS: Peripheral blood samples were obtained from eighteen patients with advanced cancer. Green tea extract was added to the blood samples with luminol on Mebiol gel, and luminol-dependent chemiluminescence was measured to monitor the production of reactive oxygen species from migrated neutrophils into the gel, at 37°C. RESULTS: Luminol-dependent chemiluminescence was significantly down-regulated in the presence of green tea extract in a concentration-dependent manner. CONCLUSION: These results indicate the antioxidant effect of green tea extract on reactive oxygen species produced by neutrophils, which may be effective in reducing oxidative stress in cancer patients.

Background: Although the systemic inflammatory condition can be confirmed in cancer patients, the pathophysiological importance of reactive oxygen species (ROS) produced by neutrophils has not yet been defined. Patients and Methods: Twenty-one patients with inoperable, chemoresistant and radioresistant cancer were enrolled in this Study. At least 4 weeks prior to sampling, the patients were free from antitumor treatments. Control samples were also obtained from a healthy donor (39-year-old male). Peripheral blood samples were set 150 mu l each on the 2 ml tube with 50 mu l Mebiol Gel, and the production of ROS from neutrophils was detected by luminol-dependent chemiluminescence (LmCL) in a kinetic mode at 30-minute intervals for 2.5 hours with a luminometer at 37 degrees C. Results: Each point, peak value and sum of values of LmCL in the patient group was statistically higher than those in the healthy donor. There were no differences in LmCL according to performance status (PS), type of cancer, age, or gender in cancer patients. Conclusion: Our findings suggested that ROS produced by neutrophils universally reflects the systemic inflammatory condition in cancer patients.

The purpose of this study was to investigate the effects of three different intensities of exercise on oxidative stress and antioxidant capacity. Eight healthy male subjects performed three different intensities of exercise for 20 minutes: (1) 70% anaerobic threshold (AT) (light intensity, LI), (2) 100% AT (moderate intensity, MI), and (3) 130% AT (high intensity, HI) on a cycle ergometer. A control (C) trial was conducted under resting conditions. Blood samples were taken pre-exercise, immediately and 30 min after exercise. In the HI trial only, the concentrations of plasma derivatives of reactive oxygen metabolites (d-ROMs) were significantly higher immediately (P<0.01) and 30 min after exercise (P<0.05) than at pre-exercise. Furthermore, plasma trolox equivalent antioxidant capacity was significantly higher immediately after exercise in the HI trial (P<0.01). And, plasma glutathione peroxidase (GPX) activity was significantly higher immediately after exercise than at pre-exercise in the MI (P<0.05) and HI trials (P<0.01). These data suggest that 20 min of pedaling exercise above the AT level may increase ROS production, while endogenous enzyme activity (especially GPX activity) or non-enzymatic antioxidants may modulate exercise-induced ROS generation. Thus, exercise under the AT level induces very little oxidative stress damage in young people.

The synergistic stimulating effect of combined intake of carbohydrate and protein on plasma insulin concentration has been reported previously. However, it remains unclear whether the amount of protein ingested after exercise affects the concentrations of plasma insulin and amino acids. This study of trained men compared the effects of post-exercise co-ingestion of carbohydrate plus different amounts of whey protein hydrolysates (WPHs) with carbohydrate alone on (1) blood biochemical parameters of carbohydrate metabolism during the post-exercise phase, and (2) endurance performance. Eight trained men exercised continuously for 70 min. Immediately after exercise and 30, 60, 90, and 120 min later, the participants received supplements containing: (1) 17.5 g carbohydrate, (2) 3.0 g WPHs and 17.5 g carbohydrate (L-WPH), or (3) 8.0 g WPHs and 17.5 g carbohydrate (H-WPH). After a 2-h recovery period, the participants performed an endurance performance test. The concentrations of blood glucose were lower and plasma insulin significantly higher in the H-WPH trial compared with the carbohydrate trial. The concentrations of plasma amino acids were increased in a dose-dependent manner following ingestion of different amounts of WPHs with carbohydrate. Endurance performance was not significantly different between the three trials. Co-ingestion of carbohydrate and H-WPH was more effective than ingestion of carbohydrate alone for stimulating insulin secretion and increasing the availability of plasma amino acids. These results suggest that plasma concentrations of amino acids during the recovery period are determined by the amount of dietary protein ingested, and that it is necessary to increase the concentration of plasma amino acids above a certain level to stimulate insulin secretion.

Muscle atrophy is caused by accelerated protein degradation and occurs in many pathological states. Two muscle-specific ubiquitin ligases, MAFbx/atrogin-1 and muscle RING-finger 1 (MuRF1), are prominently induced during muscle atrophy and mediate atrophy-associated protein degradation. Blocking the expression of these two ubiquitin ligases provides protection against muscle atrophy. Here we report that miR-23a suppresses the translation of both MAFbx/atrogin-1 and MuRF1 in a 3'-UTR-dependent manner. Ectopic expression of miR-23a is sufficient to protect muscles from atrophy in vitro and in vivo. Furthermore, miR-23a transgenic mice showed resistance against glucocorticoid-induced skeletal muscle atrophy. These data suggest that suppression of multiple regulators by a single miRNA can have significant consequences in adult tissues.

Epidemiological studies suggest that highly trained athletes are more susceptible to upper respiratory tract infections (URTI) compared with the general population. Upper respiratory symptoms (URS) often appear as either primary invasion of pathogenic organisms and/or reactivation of latent viruses such as Epstein-Barr virus (EBV). The purpose of this study was to examine the relationship between EBV reactivation and the appearance of URS during intensive training in collegiate rugby football players. We evaluated EBV-DNA expression in saliva and examined the relationship between onset of URS and daily changes in EBV-DNA as well as secretory immunoglobulin A (SIgA) levels among 32 male collegiate rugby football players during a 1-month training camp. The EBV-DNA expression tended to be higher in subjects who exhibited sore throat (p = 0.07) and cough (p = 0.18) than that of those who had no symptoms, although their differences were not significant. The SIgA level was significantly lower 1 day before the EBV-DNA expression (p &lt; 0.05). The number of URS increased along with the EBV-DNA expression and decrease of SIgA levels. These results suggest that the appearance of URS is associated with reactivation of EBV and reduction of SIgA during training.

AIM:Oxidised low-density lipoprotein (LDL) is considered a risk marker for cardiovascular disease. However, it remains unclear whether oxidised LDL concentrations differ with the physical activity status in older adults. The purpose of this study was to examine the relationship between the amount of physical activity and oxidised LDL in older adults.;METHODS:Twenty-seven older adults (aged 69.9 ± 4.3 years, mean ± SD.; 16 female and 11 male) were analysed in the cross-sectional design. Prior to blood collection, participants were asked to wear an uniaxial accelerometer for 4 consecutive weeks to determine the physical activity status. After a 48-h period of physical activity avoidance and a 10-h overnight fast, fasting venous blood samples were obtained from each participant.;RESULTS:Fasting plasma oxidised LDL concentrations and plasma monocyte chemoattractant pro-tein-1 concentrations were negatively correlated with the amount of physical activity (r=-0.409, p=0.034; r=-0.385, p=0.047, respectively).;CONCLUSIONS:This study demonstrates that regular physical activity may play a protective role in the oxidation of LDL in older adults.

The purpose of this study was to examine effects of moderate-intensity endurance exercise on reactive oxygen species production and leukocyte activation markers in young and middle-aged persons. Blood samples were collected before and after the jogging of 10 km. Although cytokines recruiting and priming neutrophils and monocytes were released into the circulation and functional after the jogging of 10 km, reactive oxygen metabolites-derived compounds (d-ROMs) were not significantly increased. It was indicated that chemokines and leukocyte activation markers at rest were increased with aging, and that might be accompanied by the higher level of d-ROMs in the elderly.<br>

We analyzed the relation between subjective fatigue by hard exercise and stress hormone and cytokine data. The subjects are eight healthy men who had exercise experience. In this experiment, hard exercise was carried out in the first place. After two-hour rest, a performance test was carried out. The blood test was conducted 4 times (before exercise, after exercise, rest, and a performance test). Subjective fatigue was indicated using visual analogue scale (VAS). After the hard exercise and performance test, VAS increased and showed the significant difference. Lactic acid, adrenaline, noradrenaline, growth hormone, IL-6, and IL-8 increased after each exercise and showed the significant difference. Subjective fatigue and the value of lactic acid, and IL-6 showed significant positive correlations. These results suggest that lactic acid, and IL-6 may become an index of fatigue in this exertion model.<br>

Completion of an Ironman triathlon results in muscle damage, indicated by reductions in muscle function and muscle soreness. However, the time course of recovery from this damage has received little attention. The purpose of this case study was to examine the time course of changes in blood markers of muscle damage and inflammation, muscle function, muscle soreness, and economy of motion following an Ironman event. An experienced well-trained male triathlete aged 35 years completed the Western Australian Ironman triathlon in 11 h 38 min 41 s (winner's time: 8 h 3 min 56 s). Before and on several occasions in the 15 days after the event, the participant performed an incremental cycling test to exhaustion, running economy test at 12 km center dot h-1 (2% incline), maximal isometric knee flexion and extension at 90 degrees knee flexion, and maximal squat and countermovement jumps. Venous blood samples and muscle soreness were also assessed. Maximal oxygen consumption, efficiency of motion, maximal muscle strength, and jump performance were all markedly reduced (4.5-54%) following the event, but returned to baseline within 15, 8, 2, and 8 days following the event, respectively. Muscle soreness and blood markers peaked 2-24 h after the race but returned to baseline within 8 days. In conclusion, although the Ironman triathlon induces marked muscle damage, a trained triathlete recovered almost completely within approximately one week, without the use of any therapeutic interventions after the event.

Purpose: Recent studies suggest that exchange of macrophage phenotype (M1/M2) in adipose tissue is associated with chronic low-grade inflammation in obesity. M1 macrophages enhance a chronic inflammatory state in adipose tissues, whereas M2 macrophages inhibit it. Although exercise training might inhibit pro-inflammatory cytokine gene expression in adipose tissue, it remains unclear whether exercise training affects the phenotypic switch of macrophage polarization in adipose tissue. Therefore, we investigated the effect of exercise training on the macrophage phenotypic switch in adipose tissue in high-fat-induced obese mice. Methods: Male C57BL/6 mice were divided into four groups; normal diet (ND) control (n=7), ND exercise (n=7), high-fat-diet (HFD) control (n=12), and HFD exercise (n=12) groups. All exercised mice ran on a treadmill at 12-20 m/min for 60 min/day for 16 weeks. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, F4/80, monocyte chemotactic protein (MCP)-1, CXCL14, inter-cellular adhesion molecule (ICAM)-1, vascular-cellular adhesion molecule (VCAM)- I, CD11c, CD163 and toll-like receptor (TLR)4 mRNA expressions in adipose tissue were evaluated by real time-RT-PCR. Results: In HFD mice, exercise training did not induce loss of body or adipose tissue mass, exercise training nevertheless markedly inhibited TNF-alpha and F4/80 mRNA expression in adipose tissue. The exercise training attenuated HFD-induced increase in ICAM-I mRNA expression, but not MCP-1, CXCL14 and VCAM-1 mRNA expressions. In addition, increased CD11c mRNA expression, which is a M1 macrophage specific marker, with HFD treatment was attenuated by exercise training. In contrast, although the mRNA expression of CD163, a M2 macrophage specific marker, in adipose tissue was significantly decreased by HFD, the exercise training significantly increased its expression. Also, the higher mRNA expression of TLR4, which induces pro-inflammatory cytokine production after fatty acid recognition, was strongly inhibited by the exercise training in HFD mice. Conclusion: Exercise training might induce the phenotypic switching from M1 macrophage to M2 macrophage in obese adipose tissue besides inhibiting M1 macrophage infiltration into adipose tissue. Therefore, chronic exercise might contribute to inhibit inflammation in adipose tissue via down regulation of TLR4.

This study examined the effects of maintaining euhydration by ingesting fluids with or without carbohydrate on subjective responses of untrained men during prolonged exercise in a hot environment. Six healthy untrained subjects completed 90 min of cycling exercises at 55% maximal oxygen consumption (V(O2max)) in a hot environment (temperature: 28 degrees C. humidity: 50%) under three different experimental conditions. During the first trial. subjects did not ingest fluids during exercise (dehydration (DH) trial). In the second and third trials, subjects received mineral water (MW) and hypotonic fluid containing carbohydrate (HF), respectively, in amounts equaling their weight loss in the DH trial. At the end of exercise, the overall rating of perceived exertion (RPE-O) was lower in the MW and HF trials than in the DH trial (14.3+/-1.0 and 13.7+/-0.6 vs 17.7+/-1.0. p&lt;0.05. respectively). RPE-cardiovascular and RPE-legs were lower at the end of exercise in the HF trial compared with the DH trial. V(O2), heart rate (HR), and rectal temperature increased during exercise in the three trials. At the end of exercise, the drift in V(O2) was lower in the MW and HF trials than in the DH trial (304+/-41 and 339+/-40 vs 458+/-33 mL, p&lt;0.05. respectively). HR at the end of exercise in the HF trial was lower than in the DH. trial (158+/-5 vs 173+/-7 bpm. p&lt;0.05). These results suggest that maintaining euhydration during prolonged exercise in untrained men could attenuate RPE-O and that hypotonic electrolyte-carbohydrate solution could attenuate RPE-legs during exercise.

Aim. The authors hypothesized that inconsistent SIgA response to exercise is caused by the different adaptative status of subjects to a cold environment. The purposes of the study were to examine whether moderate-intense exercise in a cold environment decreases SIgA and whether adaptation to a cold environment has any effect on SIgA.
Methods. Young male skaters, short track (N=9) and inline (N=10), participated in this study. All subjects cycled for 60 min at 65% (V) over dot(2max) in cold (ambient temperature: 5+/-1 degrees C, relative humidity 41+/-9%) and thermoneutral (ambient temperature: 21+/-1 degrees C, relative humidity 35+/-5%) conditions. Saliva samples were collected as follows: before and after 1 hour of environmental exposure; immediately, 30-min, 60-min and 120-min after the exercise.
Results and conclusion. Salivary SIgA and saliva flow rate decreased after the exercise in both groups only in thermoneutral conditions. The SIgA secretion rate did not decrease after moderate-high intensity exercise in a cold environment, and the SIgA response to exercise was not affected by the different adaptative status of subjects to the cold environment.

The aim of this cross-sectional study was to compare body composition and risk factors of lifestyle-related diseases between young and older male rowers and sedentary controls. Healthy males aged 19-73 years participated in the study, and were divided into four groups: 26 young rowers, 24 senior rowers, 23 young sedentary controls, and 22 senior sedentary controls. Total and regional lean soft tissue, fat mass, and bone mineral density were measured using dual-energy X-ray absorptiometry. The HDL-cholesterol of senior rowers (67.4 +/- 13.4 mg . dl(-1)) was significantly (P < 0.05) higher than that of senior sedentary controls (59.2 +/- 11.9 mg . dl(-1)), while HDL-cholesterol was similar in senior rowers and young rowers (66.1 +/- 10.8 mg . dl(-1)). Arm, leg, and trunk lean soft tissue mass were significantly higher in senior rowers (5.6 +/- 0.6 kg, 18.2 +/- 1.8 kg, and 27.3 +/- 3.2 kg respectively) than in senior sedentary controls (5.1 +/- 0.4 kg, 16.3 +/- 1.4 kg, and 24.6 +/- 1.7 kg respectively; P < 0.05). Bone mineral density was also significantly higher in senior rowers than in senior sedentary controls (ribs, lumbar spine, and pelvic segments; P < 0.05). We conclude that age-related increases in the risk of lifestyle-related diseases, such as osteoporosis and sarcopenia, are attenuated in male rowers. These results suggest that regular rowing exercise may have a positive influence in the prevention of lifestyle-related diseases in older Japanese people.

The effects of increased training (IT) load on plasma concentrations of lipopolysaccharides (LPS), proinflammatory cytokines, and anti-LPS antibodies during exercise in the heat were investigated in 18 male runners, who performed 14 days of normal training (NT) or 14 days of 20% IT load in 2 equal groups. Before (trial 1) and after (trial 2) the training intervention, all subjects ran at 70% maximum oxygen uptake on a treadmill under hot (35 degrees C) and humid (similar to 40%) conditions, until core temperature reached 39.5 degrees C or volitional exhaustion. Venous blood samples were drawn before, after, and 1.5 h after exercise. Plasma LPS concentration after exercise increased by 71% (trial 1, p &lt; 0.05) and 21% (trial 2) in the NT group and by 92% (trial 1, p &lt; 0.01) and 199% (trial 2, p &lt; 0.01) in the IT group. Postintervention plasma LPS concentration was 35% lower before exercise (p &lt; 0.05) and 47% lower during recovery (p &lt; 0.01) in the IT than in the NT group. Anti-LPS IgM concentration during recovery was 35% lower in the IT than in the NT group (p &lt; 0.05). Plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha concentrations after exercise (IL-6, 3-7 times, p &lt; 0.01, and TNF-alpha, 33%, p &lt; 0.01) and during recovery (IL-6, 2-4 times, p &lt; 0.05, and TNF-alpha, 30%, p &lt; 0.01) were higher than at rest within each group. These data suggest that a short-term tolerable increase in training load may protect against developing endotoxemia during exercise in the heat.

Objective.-Considering the adverse effects of exercise-induced cortisol secretion on health in athletes, it is important to determine the environmental and individual factors that contribute to the variations in exercise-induced cortisol secretion. In this study, the effects of cold environment exposure and cold acclimatization on exercise-induced salivary cortisol responses were investigated. Methods.-Short track skaters (n = 11), who usually practice under cold conditions, and inline skaters (n = 11), who usually practice under room temperature conditions, participated in a randomized crossover study. All participants cycled for 60 minutes at 65% V̇o2 max under cold (ambient temperature: 5 ± 1°C, relative humidity 41% ± 9%) and room temperature (ambient temperature: 21 ± 1°C, relative humidity 35% ± 5%) conditions. The participants had a 120-minute bed rest recovery phase at room temperature after both exercise bouts. Cortisol levels were measured in saliva samples collected pre-exercise and postexercise at 1 minute, 30 minutes, 60 minutes, and 120 minutes. Results.-Both short track and inline skaters exhibited clear cortisol responses to exercise under cold and room temperature conditions. The magnitude of the cortisol response, however, was different between skaters and conditions. The inline skaters exhibited significantly higher cortisol values under cold conditions than under room temperature conditions (7.6 nmol/L and 4.2 nmol/L, respectively). However, the short track skaters exhibited significantly higher cortisol values under cold conditions compared to room temperature conditions (8.7 nmol/L and 5.4 nmol/L, respectively). Conclusions.-The effects of cold environment exposure on exercise-induced cortisol response were different between skaters who usually practice under cold or room temperature conditions. These results can be interpreted as acclimatization to either cold or room temperature conditions attenuating the cortisol response, suggesting that acclimatization may be beneficial in reducing the exercise-induced cortisol response. © 2009 Wilderness Medical Society.

We investigated dehydroepiandrosterone (DHEA) secretion in response to acute psychosocial stress and the relations of DHEA secretion to cortisol secretion, cardiovascular activity, and negative mood changes. Thirty-three male students (mean age 22.6 years) were subjected to the psychosocial stress test "Trier Social Stress Test" (TSST), in which the participants were asked to deliver a speech and perform a mental arithmetic task in front of two audiences. Collections of saliva, measurements of blood pressure and heart rate, and assessments of negative mood by visual analog scales were conducted before, during, and after TSST. Acute psychosocial stress significantly increased salivary DHEA level by an average of 60% immediately after TSST. The peak of DHEA concentration preceded that of cortisol concentration by about 10 min. DHEA response was moderately correlated to cortisol response (r = .34, rs = .49) but not to cardiovascular response. Lower DHEA level and elevated cortisol/DHEA ratio during TSST were significantly and moderately correlated with increased negative mood during and after TSST. These results indicated that an acute increase in DHEA concentration under stressful situations might be partly mediated by the activity of hypothalamus-pituitary-adrenal axis and could have some significance in the improvement of negative mood. © 2008 Elsevier B.V. All rights reserved.

CC-chemokine receptor 2 (CCR2) and its ligand, monocyte chemotactic protein-1 (MCP-1, also known as CCL2), are crucial for the recruitment of monocytes/macrophages to sites of inflammation. We conducted a series of experiments to investigate the relationship between stress, monocyte CCR2 expression and migration activity. First, we collected peripheral blood mononuclear cells (PBMC) from untrained subjects (n = 8) and measured CCR2 expression on CD14(+) monocytes cultured with cortisol, epinephrine and norepinephrine. Second, we collected PBMC from the subjects before and after they cycled for 60 min at 70% peak O-2 uptake (V-O2peak), and measured alterations in CCR2 expression on monocytes following exercise. Third, we cultured PBMC with serum obtained before and after exercise and the glucocorticoid antagonist RU-486 to determine the effect of cortisol on CCR2 expression in vitro. Last, we measured the ability of PBMC treated with serum or cortisol to migrate through membrane filters in response to CCL2. Cortisol (but not epinephrine or norepinephrine) increased CCR2 expression on monocytes in a dose- and time-dependent manner. Exercise did not influence CCR2 expression on PBMC, whereas incubation of PBMC with post-exercise serum significantly increased CCR2 expression. Both cortisol and post-exercise serum increased the migration of PBMC toward CCL2. The increase in CCR2 expression on PBMC following stimulation with cortisol and serum was blocked by the glucocorticoid receptor antagonist RU-486. In conclusion, cortisol released during exercise increased monocyte CCR2 expression and migration activity in vitro. These alterations may influence inflammation and regeneration of damaged tissue after acute stress. (C) 2008 Elsevier Inc. All rights reserved.

The aim of the present study was to determine the effect of carbohydrate (CHO; sucrose) ingestion and environmental heat on the development of fatigue and the distribution of power output during a 16.1-km cycling time trial. Ten male cyclists ((V) over dot O-2max = 61.7 +/- 5.0 ml.kg(-1).min(-1), mean +/- SD) performed four 90-min constant-pace cycling trials at 80% of second ventilatory threshold (220 +/- 12 W). Trials were conducted in temperate (18.1 +/- 0.4 degrees C) or hot (32.2 +/- 0.7 degrees C) conditions during which subjects ingested either CHO (0.96 g.kg(-1).h(-1)) or placebo (PLA) gels. All trials were followed by a 16.1-km time trial. Before and immediately after exercise, percent muscle activation was determined using superimposed electrical stimulation. Power output, integrated electromyography (iEMG) of vastus lateralis, rectal temperature, and skin temperature were recorded throughout the trial. Percent muscle activation significantly declined during the CHO and PLA trials in hot (6.0 and 6.9%, respectively) but not temperate conditions (1.9 and 2.2%, respectively). The decline in power output during the first 6 km was significantly greater during exercise in the heat. iEMG correlated significantly with power output during the CHO trials in hot and temperate conditions (r = 0.93 and 0.73; P &lt; 0.05) but not during either PLA trial. In conclusion, cyclists tended to self-select an aggressive pacing strategy (initial high intensity) in the heat.

We investigated the influence of rectal temperature on the immune system during and after exercise. Ten well-trained male cyclists completed exercise trials (90 min cycling at 60% (V) over dotO(max) + 16.1 - km time trial) on three separate occasions: once in 18 degrees C and twice in 32 degrees C. Twenty minutes after the trials in 32 degrees C, the cyclists sat for - 20 min in cold water (14 degrees C) on one occasion, whereas on another occasion they sat at room temperature. Rectal temperature increased significantly during cycling in both conditions, and was significantly higher after cycling in 32 degrees C than in 18 degrees C (P &lt; 0.05). Leukocyte counts increased significantly during cycling but did not differ between the conditions. The concentrations of serum interleukin (IL)-6, IL-8 and IL-10, plasma catecholamines, granulocyte-colony stimulating factor, myeloperoxidase and calprotectin increased significantly following cycling in both conditions. The concentrations of serum IL-8 (25%), IL-10 (120%), IL-1 receptor antagonist (70%), tumour necrosis factor-alpha (17%), plasma myeloperoxidase (26%) and norepinephrine (130%) were significantly higher after cycling in 32 degrees C than in 18 degrees C. During recovery from exercise in 32 degrees C, rectal temperature was significantly lower in response to sitting in cold water than at room temperature. However, immune changes during 90 min of recovery did not differ significantly between sitting in cold water and at room temperature. The greater rise in rectal temperature during exercise in 32 degrees C increased the concentrations of serum IL-8, IL-10, IL-1ra, TNF-alpha and plasma myeloperoxidase, whereas the greater decline in rectal temperature during cold water immersion after exercise did not affect immune responses.

To test the effect of a cold condition on metabolic substrate and possible development of muscle injuries, short track skaters (n=9) and inline skaters (n=10) took rest and submaximal cycled (65% VO^^・_2max) in cold (ambient temperature: 5±1℃, relative humidity: 41±8%) and warm conditions (ambient temperature: 21±1℃, relative humidity: 35±5%), for 60min, each. Blood glucose (BG), triglyceride (TG), free fatty acid (FFA), and total cholesterol (TC) were determined to investigate the effect on energy metabolism. To estimate possible muscle injury in the cold condition, creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb) were also measured. TG and FFA levels were increased during exercise in the cold condition, but were unaffected by the difference of skaters. Of the myocellular enzymes, CK was significantly higher during the transition from submaximal exercise to recovery phase in a short track skater compared with inline skater group, indicating a higher physical strain. Additionally, the level of Mb in the inline skater group significantly elevated during recovery phase in the cold compared with in the warm condition. It is concluded that exercise caused stress that was dependent on the ambient temperature. Therefore, exercise in the cold condition altered the circulating level of energy substrate and increased muscle injuries.

We investigated whether cold acclimation leads to increased activity of the antioxidant defense enzymes and muscle injury. Comparisons were between short track skaters (n=6) and inline skaters (n=6) during rest and at submaximal cycling (65% VO_2max) in cold (ambient temperature: 5±1℃, relative humidity: 41±8%) and warm conditions (ambient temperature: 21±1℃, relative humidity: 35±5%), during 60min, respectively, and during the recovery phase. Erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHpx), reduced glutathione (GSH), thiobarbituric substance acid (TBARS), serum creatine kinase (CK), lactate dehydrogenase (LDH), plasma myoglobin (Mb) and cortisol were determined. Activities of CAT and GSHpx and the level of GSH and TBARS in erythrocyte and the level of LDH in serum were elevated in cold acclimated subjects. We suggested that the compensatory increase in antioxidative defense enzymes resulting from long-term cold exposure may reflect the elevated reactive oxygen species (ROS) production and muscle injury at this environment acclimation.

Objective: The purpose of this study was to compare the performance of the salivary cortisol immunoassay kits that were manufactured by DRG International, Inc., Salimetrics, LLC., and IBL Hamburg, which were widely used in neuroendocrine research. Correlations between plasma and salivary cortisol concentrations and between enzyme-linked immunosorbent assay (ELISA) and luminescence immunoassay (LIA) were investigated.<br> Methods: Saliva and plasma samples were collected in eight participants who took part in the study of the exercise stress testing. In total, forty salivary cortisol samples were assayed by means of the three salivary cortisol immunoassay kits. Plasma cortisol concentrations were determined by ELISA kit (IBL).<br> Results: Salivary cortisol concentrations measured by the three immunoassay kits were significantly and highly correlated with plasma cortisol concentrations (r ≥ .863). Scattergrams also indicated that exponential curve well explained the relationship between salivary and plasma cortisol concentrations (r ≥ .925). Salivary cortisol concentrations measured by LIA (IBL) was correlated with salivary cortisol concentrations measured by ELISA (DRG and Salimetrics: r=.943 and .985, respectively). Values of cortisol concentration measured by ELISA (DRG) were higher than those by ELISA (Salimetrics) and LIA (IBL).<br> Conclusion: Salivary cortisol concentrations that were measured by the three immunoassay kits reflected the variations of plasma cortisol concentration. Differences in immunoassay methods (ELISA and LIA) did not influence the values of cortisol concentration. These findings indicated that it is possible to assess stress by measuring salivary cortisol without the need for blood sampling.<br>

An objective assessment of stress is needed to manage stress and prevent the development of stress-related diseases such as depression and coronary heart disease. In this paper, we discussed the possibility of applying saliva to an assessment of stress. We illustrated the procedures for collecting and analyzing saliva, and reviewed the relationships of acute, chronic, psychological, or physical stress to seven salivary substances: Cortisol, Dehydroepiandrosterone, Testosterone, Chromogranin A, 3-Methoxy-4-hydroxyphenyglycol, α-Amylase, and Secretory Immunoglobulin A. Considering unique characteristics of each salivary substance and purposes of the study or the non-invasive assessment, salivary substances should be selected for the assessment of stress.<br>

Interest in the relationship between inflammation and oxidative stress has increased dramatically in recent years, not only within the clinical setting but also in the fields of exercise biochemistry and immunology. Inflammation and oxidative stress share a common role in the etiology of a variety Of Chronic diseases. During exercise, inflammation and oxidative stress are linked via muscle metabolism and muscle damage. Because oxidative stress and inflammation have traditionally been associated with fatigue and impaired recovery from exercise, research has focused on nutritional strategies aimed at reducing these effects. In this review, we have evaluated the findings of studies involving antioxidant supplementation on alterations in markers of inflammation (e.g., cytokines, C-reactive protein and cortisol). This review focuses predominantly on the role of reactive oxygen and nitrogen species generated from muscle metabolism and muscle damage during exercise and on the modulatory effects of antioxidant supplements. Furthermore, we have analyzed the influence of factors such as the dose, timing, supplementation period and bioavailability of antioxidant nutrients. (C) 2007 Elsevier Inc. All rights reserved.

Granulysin is a cytolytic granule protein released by natural killer cells and activated cytotoxic T lymphocytes. The influence of exercise training on circulating granulysin concentration is unknown, as is the relationship between granulysin concentration, natural killer cell number and natural killer cell cytotoxicity. We examined changes in plasma granulysin concentration, natural killer cell number and cytotoxicity following acute exercise and different training loads. Fifteen highly trained male cyclists completed a baseline 40-km cycle time trial (TT(40)1) followed by five weeks of normal training and a repeat time trial (TT(40)2). The cyclists then completed four days of high intensity training followed by another time trial (TT(40)3) on day five. Following one final week of normal training cyclists completed another time trial (TT(40)4). Fasting venous blood was collected before and after each time trial to determine granulysin concentration, natural killer cell number and natural killer cell cytotoxicity. Granulysin concentration increased significantly after each time trial (P&lt;0.001). Pre-exercise granulysin concentration for TT(40)3 was significantly lower than pre-exercise concentration for TT(40)1 (-20.3 +/- 7.5%, P&lt;0.026), TT(40)2 (-16.7 +/- 4.3%, P&lt;0.003) and TT(40)4 (-21 +/- 4.2%, P&lt;0.001). Circulating natural killer cell numbers also increased significantly post-exercise for each time trial (P&lt;0.001), however there was no significant difference across TT40 (P&gt;0.05). Exercise did not significantly alter natural killer cell cytotoxicity on a per cell basis, and there were no significant differences between the four time trials. In conclusion, plasma granulysin concentration increases following moderate duration, strenuous exercise and is decreased in response to a short-term period of intensified training.

We investigated the effects of an Ironman triathlon race on markers of muscle damage, inflammation and heat shock protein 70 (HSP70). Nine well-trained male triathletes (mean +/- SD age 34 +/- 5 years; VO2peak 66.4 ml kg(-1) min(-1)) participated in the 2004 Western Australia Ironman triathlon race (3.8 km swim, 180 km cycle, 42.2 km run). We assessed jump height, muscle strength and soreness, and collected venous blood samples 2 days before the race, within 30 min and 14-20 h after the race. Plasma samples were analysed for muscle proteins, acute phase proteins, cytokines, heat shock protein 70 (HSP70), and clinical biochemical variables related to dehydration, haemolysis, liver and renal functions. Muscular strength and jump height decreased significantly (P &lt; 0.05) after the race, whereas muscle soreness and the plasma concentrations of muscle proteins increased. The cytokines interleukin (IL)-1 receptor antagonist, IL-6 and IL-10, and HSP70 increased markedly after the race, while IL-12p40 and granulocyte colony-stimulating factor (G-CSF) were also elevated. IL-4, IL-1 beta and tumour necrosis factor-alpha did not change significantly, despite elevated C-reactive protein and serum amyloid protein A on the day after the race. Plasma creatinine, uric acid and total bilirubin concentrations and gamma-glutamyl transferase activity also changed after the race. In conclusion, despite evidence of muscle damage and an acute phase response after the race, the pro-inflammatory cytokine response was minimal and anti-inflammatory cytokines were induced. HSP70 is released into the circulation as a function of exercise duration.

The purpose of this study was to compare the effects of exercise intensity and exercise-induced muscle damage on changes in anti-inflammatory cytokines and other inflammatory mediators. Nine well-trained male runners completed three different exercise trials on separate occasions: ( 1) level treadmill running at 60% VO2max (moderate-intensity trial) for 60 min; (2) level treadmill running at 85% VO2max (high-intensity trial) for 60 min; (3) downhill treadmill running ( - 10% gradient) at 60% VO2 max (downhill running trial) for 45 min. Blood was sampled before, immediately after and 1 h after exercise. Plasma was analyzed for interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-5, IL-10, IL-12p40, IL-13, monocyte chemotactic protein-1 (MCP-1), prostaglandin E-2, leukotriene B-4 and heat shock protein 70 (HSP70). The plasma concentrations of IL-1ra, IL-12p40, MCP-1 and HSP70 increased significantly (P&lt; 0.05) after all three trials. Plasma prostaglandin E-2 concentration increased significantly after the downhill running and high-intensity trials, while plasma IL-10 concentration increased significantly only after the high-intensity trial. IL-4 and leukotriene B4 did not increase significantly after exercise. Plasma IL-1ra and IL-10 concentrations were significantly higher ( P&lt; 0.05) after the high-intensity trial than after both the moderate-intensity and downhill running trials. Therefore, following exercise up to 1 h duration, exercise intensity appears to have a greater effect on anti-inflammatory cytokine production than exercise-induced muscle damage.

Introduction: Unaccustomed eccentric exercise often results in muscle damage and neutrophil activation. We examined changes in plasma cytokines stress hormones, creatine kinase activity and myoglobin concentration, neutrophil surface receptor expression, degranulation. and the capacity of neutrophils to generate reactive oxygen species in response to in vitro stimulation after downhill running. Methods: Ten well-trained male runners ran downhill on a treadmill at a gradient of - 10% for 45 min at 60% VO2max.. Blood was sampled immediately before (PRE) and after (POST), 1 h (1 h POST), and 24 h (24 h POST) after exercise. Results: At POST, there were significant increases (P &LT; 0.01) in neutrophil count (32%), plasma interleukin (IL)-6 concentration (460%), myoglobin (Mb) concentration (1100%), and creatine kinase (CK) activity (40%). At 1 h POST, there were further increases above preexercise values for neutrophil count (85%), plasma Mb levels (1800%), and CK activity (56%), and plasma IL-6 concentration remained above preexercise values (410%) (P &LT; 0.01). At 24 h POST, neutrophil counts and plasma IL-6 levels had returned to baseline, whereas plasma Mb concentration (100%) and CK activity (420%) were elevated above preexercise values (P &LT; 0.01). There were no significant changes in neutrophil receptor expression, degranulation and respiratory burst activity, and plasma IL-8 and granulocyte-colony stimulating factor concentrations at any time after exercise. Neutrophil count correlated with plasma Mb concentration at POST (r = 0.64, P &LT; 0.05), and with plasma CK activity at POST (r = 0.83, P &LT; 0.01) and I h POST (r = 0.78, P &LT; 0.01). Conclusion: Neutrophil activation remains unchanged after downhill running in well-trained runners, despite increases in plasma markers of muscle damage.

Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscle proteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.

Intense exercise stimulates the systemic release of a variety of factors that alter neutrophil surface receptor expression and functional activity. These alterations may influence resistance to infection after intense exercise. The aim of this study was to examine the influence of exercise intensity on neutrophil receptor expression, degranulation (measured by plasma and intracellular myeloperoxidase concentrations), and respiratory burst activity. Ten well-trained male runners ran on a treadmill for 60 min at 60% [moderate-intensity exercise (MI)] and 85% maximal oxygen consumption [high-intensity exercise (HI)]. Blood was drawn immediately before and after exercise and at 1 h postexercise. Immediately after HI, the expression of the neutrophil receptor CD 16 was significantly below preexercise values (P &lt; 0.01), whereas MI significantly reduced CD35 expression below preexercise values (P &lt; 0.05). One hour after exercise at both intensities, there was a significant decline in CD llb expression (P &lt; 0.05) and a further decrease in CD16 expression compared with preexercise values (P &lt; 0.01). CD16 expression was lower 1 h after HI than I h after MI (P &lt; 0.01). Immediately after HI, intracellular myeloperoxidase concentration was less than preexercise values (P &lt; 0.01), whereas plasma myeloperoxidase concentration was greater (P &lt; 0.01), indicating that HI stimulated neutrophil degranulation. Plasma myeloperoxidase concentration was higher immediately after HI than after MI (P &lt; 0.01). Neutrophil respiratory burst activity increased after HI (P &lt; 0.01). In summary, both MI and HI reduced neutrophil surface receptor expression. Although CD16 expression was reduced to a greater extent after III, this reduction did not impair neutrophil degranulation and respiratory burst activity.

It is generally accepted that moderate physical activity can improve immune functions and potentially reduce the risk of developing infectious diseases and cancer. There is accumulating evidence to show that moderate physical activity can enhance the activities of T cells, natural killer cells and macrophages, cytokine productivity and serum immunoglobulin (Ig) G and salivary IgA levels. In contrast, however, exhaustive exercise causes the systemic release of immunosuppressive stress hormones and anti-inflammatory cytokines, and temporarily causes a decrease in circulating lymphocyte counts and the reduction in activities of T cells and natural killer cells and salivary IgA levels. Consequently, these negative alterations in immune function and cytokine imbalance may enhance host susceptibility to infections and promote allergic disposition. Although exercise-induced mobilization and activation of phagocytic cells such as neutrophils and monocytes can result in muscular, vascular and systemic inflammation and oxidative stress due to the production of reactive oxygen species, these deleterious responses may be attenuated by the appropriate use of antioxidants and nutritional supplements. This review presents the findings from recent studies in the field of exercise immunology, and offers some insight into how these findings may be applied in the broad realm of preventive, complementary and alternative medicine.<br>

Neutrophils produce free radicals known as reactive oxygen species (ROS), which assist in the clearance of damaged host tissue. Tissue damage may occur during exercise due to muscle damage, thermal stress and ischaemia/reperfusion. When produced in excess, neutrophil-derived ROS may overwhelm the body's endogenous antioxidant defence mechanisms, and this can lead to oxidative stress. There is increasing evidence for links between oxidative.stress and a variety of pathological disorders such as cardiovascular diseases, cancer, chronic inflammatory diseases and post-ischaemic organ injury. A small number of studies have investigated whether there is a link between neutrophil activation and oxidative stress during exercise. In this review, we have summarised the findings of these studies. Exercise promotes the release of neutrophils into the circulation, and some evidence suggests that neutrophils mobilised after exercise have an enhanced capacity to generate some forms of ROS when stimulated in vitro. Neutrophil activation during exercise may challenge endogenous antioxidant defence mechanisms, but does not appear to increase lipid markers of oxidative stress to any significant degree, at least in the circulation. Antioxidant supplements such as N-acetylcysteine are effective at attenuating increases in the capacity of neutrophils to generate ROS when stimulated in vitro, whereas vitamin E reduces tissue infiltration of neutrophils during exercise. Free radicals generated during intense exercise may lead to DNA damage in leukocytes, but it is unknown if this damage is the result of neutrophil activation. Exercise enhances the expression of inducible haem (heme)-oxygenase (HO-1) in neutrophils after exercise, however, it is uncertain whether oxidative stress is the stimulus for this response.

Purpose: To investigate whether cytokines and neutrophils mediate exercise-related pathogenesis, we examined their responses and possible association after exhaustive exercise. Methods: Plasma and urine samples were obtained from 10 male runners before and after a 42.195-km marathon race. Major cytokines and neutrophil activation markers [myeloperoxidase (MPO) and lactoferrin (LTF)] were measured by enzyme-linked immunosorbent assays. Functional modulation of standard neutrophils and monocytes by plasma was determined in vitro on their luminol-dependent chemiluminescence responses. Results: The race induced peripheral neutrophilia accompanied by an increase in band neutrophils and monocytosis. Plasma MPO and LTF concentrations increased significantly by 1.8 and 1.4 times after the race. There was a greater increase in urine concentrations of MPO and LTF, 12.3 and 3.5 times after exercise, respectively, suggesting that neutrophil activation occurred and that renal clearance exceeded the increase in plasma concentrations. Plasma interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), and monocyte chemotactic protein 1 (MCP-1) increased significantly after the race, and urine IL-beta, IL-6, G-CSF, M-CSF, and MCP-1 increased significantly. The plasma IL-6 responses correlated with the increases of band neutrophil count (r = 0.860, P &lt; 0.01), suggesting IL-6-mediated bone marrow release of neutrophils. Furthermore, the increases in urine MPO concentration were correlated with increases in urine IL-6 (r = 0.868, P &lt; 0.01) and G-CSF (r = 0.875, P &lt; 0.01), suggesting that these cytokines promoted neutrophil activation in vivo. However, in vitro preincubation of neutrophils and monocytes with postexercise plasma could not cause priming responses, possibly because of the exercise-induced enhancement of plasma antioxidant activity. Conclusion: Although many cytokines recruiting and priming neutrophils and monocytes were secreted and functional after exhaustive exercise, overwhelming antioxidant and anti inflammatory defenses were induced, preventing exercise-induced oxidative stress.

It is known that interleukin (IL)-12 p70 promotes the differentiation of type-1 helper T (Th1) cells, which produce type-1 cytokines such as IL-2 and interferon (IFN), thereby supporting cellular immunity, whereas IL-12 p40 acts as an antagonist of IL-12 p70. In contrast, IL-4 and IL-6 promote the differentiation of Th2 cells, which produce type-2 cytokines IL-4, IL-6 and IL-10, induce humoral immunity and are involved in allergic reactions. Exhaustive exercise causes the suppression of T lymphocyte activity while asthmatic and allergic diseases are subclinically more prevalent in athletes. One of the mechanisms behind these observations might be a lower type-1 and higher type-2 cytokine balance, which we previously demonstrated to occur after exhaustive exercise. In the present study, we investigated the type-1/type-2 cytokine balance by measuring plasma concentrations of IL-2, IL-4, IL-5, IL-10, tumor necrosis factor (TNF)-alpha and IFN-gamma with microparticle-based flow cytometric technology. IL-5, IL-6 and IL-13 were measured by enzyme-linked immunosorbent assay (ELISA). IL-12 p40 and p70 were measured separately, also by ELISA. Plasma IL-12 p40 concentration rose significantly after maximal exercise and to an even greater extent after a marathon race. Conversely, plasma IL-12 p70 could not be detected even using two different assays. The marathon race caused a marked increase in the plasma concentrations of IL-6 and IL-10. Their responses were correlated (r=0.78, p&lt;0.01), indicating that IL-6 is an inducer of IL-10, and may partly induce the type-1 &lt; type-2 cytokine balance. With the exception of one study involving maximal exercise, other studies have failed to show any change in circulating IL-12 concentration with exercise. The present study demonstrated that IL-12 p40 was present in excess of p70 especially after exercise. This may be one of the mechanisms behind several phenomena including cellular immunosuppression, an increase in the relative proportion of type-2 cytokines following exhaustive exercise, and the higher incidence of infections and allergic disorders in regularly exercising endurance athletes.

We investigated whether there is a break point of creatine kinase (CK) release after daily endurance exercise and whether CK response depends on individual physical characteristics. Fifteen healthy young men performed 90 min of bicycle exercise for 3 consecutive days. Body composition, properties of the quadriceps femoris muscle (QFM), and aerobic and anaerobic capacities were estimated before the test. Blood samples were obtained 22 times during the experimental period. Endurance exercise significantly elevated serum CK from 3 h after the first exercise session (P &lt; 0.05) and gradually increased thereafter. Subjects were classified into two groups according to their peak CK values: high responders (HR; &gt;500 IU/l of CK) and low responders (LR; &lt;300 IU/l of CK). Peak CK values during the experimental period correlated (P &lt; 0.01) with workload/cross-sectional area of the QFM (r = 0.658), workload/volume of the QFM (r = 0.648), and knee extensor strength/body mass (r = -0.634); however, the HR and LR groups were separated in each variable. Thus the break point of CK release after endurance exercise under these conditions is 300-500 IU/l, two or three times higher than in the resting condition, and is associated with properties of the QFM.

We examined the hypothesis that the short, intensive exercise-induced increase in circulating neutrophil counts is affected by the interaction between the endocrine and immune systems. Twelve male winter-sports athletes underwent a maximal exercise test on a treadmill. Blood samples were collected before, immediately after (Post), and 1 h (Post 1 h) and 2 h (Post 2 h) after the exercise. The neutrophil counts increased significantly at Post 1 h (P &lt; 0.05) and remained significantly high even at Post 2 h (P &lt; 0.05), showing a leftward shift. Plasma granulocyte colony-stimulating factor (G-CSF) increased at Post (P &lt; 0.05), and interleukin-6 (IL-6) increased at Post 1 h (P &lt; 0.05). Plasma G-CSF at Post significantly correlated with the numbers of both neutrophils and stab cells at Post 1 h (P &lt; 0.05). Plasma IL-6 at Post 1 h levels also correlated significantly with the number of neutrophils at Post 2 h (P &lt; 0.05). The increase in the levels of plasma G-CSF and IL-6 after intensive exercise may play a role in the mobilization of neutrophils into the circulatory system.

We studied changes in serum opsonic activity (SOA) in male judoists who were engaged in active weight reduction. Serum immunoglobulins, complements and SOA, measured by neutrophil-associated chemiluminescence responses. were investigated 20 days, 7 days and I day before a competition and 5 days after the competition, In addition, muscle strength and anaerobic work capacity, as well as body composition, were also determined. A dietary survey was conducted daily during the observation period, Body weight decreased by 4.2 kg over 19 days. SOA significantly decreased 5 days alter the competition. as well as the concentrations of serum immunoglobulins. complements and total proteins. These trends were noted in the marked weight reduction group (i.e. reduction weight of body fat/body fat weight before weight reduction greater than or equal to25%() more than the slight reduction group (&lt;25%). Depressed SOA was closely correlated with the decreased concentrations of intmunoglobulins and complements. These results suggest that the decrease in immunoglobulins and complements following weight reduction is associated with reduced SOA, which might cause susceptibility to infections. This study demonstrated that such immunosuppression appeared in the recovery period after the competition rather than immediately before the competition. Copyright (C) 2002 John Wiley Sons. Ltd.

It has been documented that strenuous exercise not only induces pyrogenesis but also elicits mobilization and functional augmentation of neutrophils and monocytes whereas it suppresses cellular immunity leading to increased susceptibility to infections. As mediators Of these phenomena, cytokines released into the circulation have been a recent focus of attention. Indeed, there are as many as one hundred original reports concerning exercise and cytokines, and half of them have been published in rapid succession from 2000, resulting in a tremendous accumulation of new knowledge within such a short term.
The first aim of this review is to comprehensively summarize previous studies on systemic cytokine kinetics following exercise, with a special focus on reproducibility and quantitative comparison in human studies using specific immunoassays. Although tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta have traditionally been understood to be the main inducer cytokines of acute phase reactions, the majority of studies have shown that the circulating concentration of these cytokines is either unchanged following exercise, or exhibits relatively small, delayed increments. Plasma interferon (IFN)-alpha and IFN-gamma do not appear to change following exercise, whereas IL-2 decreases after endurance exercise. The small changes of these proinflammatory and immunomodulatory cytokines could well be mediated by anti-inflammatory cytokines such as IL-1 receptor antagonist (IL-1ra), IL-6 and IL-10 and cytokine inhibitors (cortisol, prostaglandin E-2 and soluble receptors against TNF and IL-2), which are known to increase markedly in the circulation following endurance exercise. Moreover it has been recently demonstrated that endurance exercise induces systemic release of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), IL-8 and monocyte chemotactic protein 1 (MCP-1).
Although the majority of available data have been obtained following prolonged exercise, it remains to be elucidated whether short-duration intensive exercise also causes rapid systemic cytokine release. In addition, there have been few studies that have simultaneously compared the extent of each cytokine response to exercise from a wider perspective. The second aim of this study was to examine possible changes of not only plasma but also urine concentrations of a broad spectrum of cytokines (16 kinds) following maximal exercise, including the time course of recovery. Although plasma TNF-alpha could not be detected throughout, it was present in urine 2 It after exercise. Plasma IL-1 beta rose significantly 2 h after exercise, but plasma IL-1ra increased more rapidly and markedly than IL-1 beta, thus IL-1 bioactivity should be blocked at least in the circulation. Although there was only a trend toward increased plasma IL-6 concentrations after exercise, urine IL-6 rose significantly I h after exercise, indicating that IL-6 was released systemically but eliminated rapidly into the urine. Furthermore, it is shown for the first time that plasma and urine IL-4 concentrations were significantly elevated 2 h after exercise. Therefore, it is possible that anti-inflammatory cytokines might be released into the circulation as a regulatory mode of the cytokine network for adaptation against systemic inflammatory stress. Additionally, we have demonstrated that plasma concentrations of G-CSF granulocyte-macrophage CSF (GM-CSF), M-CSF IL-8 and MCP-1 increased immediately after short-duration exercise and that the urine concentrations of these cytokines were much more pronounced than the changes observed in plasma.
In conclusion, cytokines that are considered to induce systemic bioactivity following exercise are not only anti-inflammatory cytokines but also colony-stimulating factors and chemokines, which were secreted in an earlier phase of exercise without the kinetic involvement of traditional proinflammatory cytokines. Although the wider physiological and pathological implications are still not clearly understood, these cytokine kinetics may partly explain suppressed cell-mediated immunity and increased allergic reactions derived from a lower type-1 to type-2 cytokine ratio, along with mobilization and functional augmentation of neutrophils and monocytes. The sources and stimuli of cytokine production are not fully elucidated at present, but several hypotheses based on recent experimental evidence are discussed in this review herein.

To investigate the effects of zinc on non-specific immune functions, we used the chemiluminescence method to examine the capacity of human neutrophils to produce reactive oxygen species and accompanying serum opsonic activity. When neutrophils were stimulated with both opsonized zymosan and phorbol myristate acetate in the presence of 1-10(-3) mmol/L zinc lucigenin-dependent CL responses were stable or declined, whereas luminol-dependent CL responses were significantly enhanced. The results suggest that zinc activates protein kinase C and promotes MPO degranulation and ROS metabolism, especially in hypochlorous acid production, which have the direct action of causing microbial death. Further, the lucigen-dependent CL response stimulated with OZ was strongly enhanced by anti-MPO antibodies, whereas the enhancement was less in the presence of zinc, suggesting that zinc may suppress the receptor-mediated signal transduction process. Both responses were inhibited at 10 mmol/L. Serum opsonic activity was enhanced by zinc at 10(-4) and 10(-3) mmol/L but reduced at 10 mmol/L. These data indicate that addition of zinc around and above normal physiological concentrations facilitates neutrophil functional activity and serum opsonic activity, whereas these are inhibited by a lack of zinc or an excessive amount, suggesting that zinc is essential for optimal functioning of nonspecific immunity. Copyright (C) 2000 John Wiley & Sons, Ltd.

Decaglycerol monooleate (DGMO), a type of polyglycerol esters of fatty acids (PGEF), was evaluated for its in vitro effect on phagocytosis and respiratory burst activity of isolated human neutrophils using flow cytometric assay. Opsonized zymosan particles labelled with FITC (FITC-OZ) were employed as an indicator of phagocytosis. Fluorescence of FITC-OZ attached on to the surface of neutrophils was quenched by addition of trypan blue solution. After 10 minutes of incubation with DGMO up to a concentration of 10 mg/ml, neutrophil phagocytosis was not affected markedly. At the same time, the DGMO emulsion left little influence on complement receptor type three (CR3) that is associated with phagocytosis. On the other hand, oxidation of hydroethidine, which was used as an indicator of intracellular generation of reactive oxygen species (mainly for superoxide anion), was significantly inhibited by DGMO over 1 mg/ml. However, this phenomenon was not seen in DGMO-treated neutrophils when DGMO was removed after incubation. The present data suggest that DGMO does not affect phagocytosis of human neutrophils but down-regulates respiratory burst activity. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.

To investigate the mechanisms of exercise-induced immune perturbations, we measured promising immunomodulatory hormones and cytokines in plasma of 16 male marathon runners before and after a competitive 42.195-km race. Interleukin 1-beta (IL-1 beta) and interferon gamma (IFN-gamma) concentrations remained unchanged after the marathon. The cytokines IL-12, IFN-alpha and tumour necrosis factor alpha (TNF-alpha) could not be detected even using highly sensitive specific immunoassays, indicating at least that overshooting responses of these cytokines had not occurred after exercise. As mechanisms for the small changes in these cytokines, we demonstrated for the first time a significant rise in concentrations of inhibitory cytokine IL-10 in addition to the immunosuppressive hormone cortisol, although concentrations of IL-4 and transforming growth factor-beta (TGF-beta) were unaffected by the race. Furthermore, concentrations of IL-1 receptor antagonist (IL-1ra) and IL-6, which are negative-feedback inhibitors of cytokine production, increased by more than 100 times. As for humoral mediators of neutrophil mobilization, concentrations of growth hormone (GH), cortisol and granulocyte colony-stimulating factor (G-CSF) increased significantly. In addition, concentrations of neutrophil-priming substances (IL-6, IL-8, G-CSF, GH and prolactin) also increased significantly and the induction of IL-8 and G-CSF with exercise was demonstrated for the first time in the present study. In contrast, IL-2 concentration decreased, by 32%, and this was correlated with the induction of nitric oxide (NO) production. Muscle damage, monitored using changes in concentrations of creatine kinase and myoglobin, was also observed. These results suggested that exercise-induced pathogenesis including previously reported immunosuppression and neutrophil hyper-reactivity might be attributed, at least partly, to the systemic dynamics of the above bioactive substances.

Much attention has been focused on the biological activity of geometrical isomers of beta -carotene. In the present study, the in vitro antioxidant activities of a natural 9-cis beta -carotene purified from Dunaliella bardawil and synthetic all-trans beta -carotene were studied using enhanced human neutrophil chemiluminescence upon stimulation with opsonized zymosan. Lucigenin-dependent chemiluminescence was used for largely measuring superoxide anion (O-2(-)) production, luminol-dependent chemiluminescence with sodium azide (NaN3) and horseradish peroxidase (HRP) was used for measuring hydrogen peroxide (H2O2) production, and luminol-dependent chemiluminescence without oxidant metabolism modulator was used for determination of myeloperoxidase (MPO)-mediated production. With beta -carotene concentration of 1.4 mu M, neutrophils showed a decrease:in lucigenin-dependent chemiluminescence to 75% and 78% of controls (p&lt;0.05) by natural 9-cis carotene and synthetic all-trans beta -carotene, respectively. With beta -carotene concentration of 1.86 mu M, neutrophils also showed a decrease in luminol-dependent chemiluminescence in the presence of NaN3 and HRP to 86% and 81% of controls (p&lt;0.05) by natural 9-cis beta -carotene and synthetic all-trans beta -carotene, respectively. On the other hand, neutrophils did not show a statistically significant difference in any chemiluminescence assay by the same concentration of natural 9-cis beta -carotene and synthetic all-trans beta -carotene. These results suggest that, up to the concentration of 1.86 mu M, natural 9-cis beta -carotene and-synthetic all-trans beta -carotene exert equal antioxidant activities assessed by enhanced human neutrophil chemiluminescence. (C) 1999 Elsevier Science Inc.

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in "delayed onset" and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day I, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

Carbon monoxide (CO) derived from heme oxygenase has recently been shown to play a role in controlling hepatobiliary function, but intrahepatic distribution of the enzyme is unknown. We examined distribution of two kinds of the heme oxygenase isoforms (HO-1 and HO-2) in rat liver immunohistochemically suing monoclonal antibodies. The results showed that distribution of the two isoforms had distinct topographic patterns: HO-1, an inducible isoform, was observed only in Kupffer cells, while HO-2, a constitutive form, distributed to parenchymal cells, but not to Kupffer cells. Both isoforms were undetectable in hepatic stellate cells and sinusoidal endothelial cells. Of the two isoforms, HO-2 in the parenchymal cell rather than HO-1 in the Kupffer cell, appears to play a major role in regulation of microvascular tone. In the perfused liver, administration of HbO(2), a CO-trapping reagent that can diffuse across the fenestrated endothelium into the space of Disse, elicited a marked sinusoidal constriction, while administration of a liposome-encapsulated Hb that cannot enter the space had no effect on the microvascular tone. These results suggest that CO evolved by HO-2 in the parenchymal cells, and released to the extrasinusoidal space, served as the physiological relaxant for hepatic sinusoids.

The chemiluminescence (CL) assay has been used to measure the reactive oxygen species (ROS)-generating capacity of phagocytes. To achieve more optimal measurement conditions for a multi-channel microplate photon-counting CL analyzer with the cooled charge-coupled device (CCD) camera which offers enhanced sensitivity, we investigated factors affecting the variability in lucigenin-dependent CL (LgCL) measurement of human neutrophil; stimulated with either opsonized zymosan (OZ) or phorbol myristate acetate (PMA). We obtained sensitive LgCL responses with good reproducibility and rapid data-acquisition using 50 mu l neutrophils (3 x 10(6) cells/ml) and 50 mu l of 0.5 mM lucigenin per well, in addition to either 100 mu l of OZ (5 mg/ml) when zymosan was opsonized with 10-20% serum or; 100 mu l of PMA solution (1 x 10(-6) M) with automatic regular intervals of mixing and detection during the continuous measurement at 37 degrees C. Furthermore, we studied the contribution of various ROS to LgCL and luminol-dependent CL (LmCL) using modulators of ROS metabolism including superoxide dismutase (SOD), catalase, deferoxamine and sodium azide (NaN3). LgCL was inhibited by SOD but not by the other agents, whereas LmCL was inhibited by NaN, and deferoxamine, Thus, it was demonstrated that LgCL detects the superoxide anion with high selectivity whereas the LmCL assay measures myeloperoxidase (MPO)-mediated formation of hypochlorous acid, Such microplate-based multiple measurements facilitate the accurate assessment of phagocytic function. (C) 1997 Elsevier Science B.V.

To investigate the cause of disagreement within the large body of literature concerning the effect of exercise on the capacity of circulating neutrophils to produce reactive oxygen species (ROS), 10 male endurance-trained athletes underwent maximal exercise. The generation of superoxide radical (O-2(-).) by neutrophils was first detected on a cell-by-cell basis by using histochemical nitro blue tetrazolium tests performed directly on fresh unseparated blood, which showed that responsive neutrophils under several stimulatory conditions relatively decreased after exercise. Similarly, O--(2). detected with bis-N-methylacridinium nitrate (lucigenin)-dependent chemiluminescence (CL) of a fixed number of purified neutrophils on stimulation with opsonized zymosan was decreased slightly after exercise. In contrast, the 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)dependent CL response of the neutrophils indicative of the myeloperoxidase (MPO)-mediated formation of highly reactive oxidants was significantly enhanced after exercise. It therefore suggests that the pathway of neutrophil ROS metabolism might be forwarded from the precursor O-2(-). production to the stages of more reactive oxidant formation due to the facilitation of MPO degranulation. In addition, these phenomena were closely associated with the exercise-induced mobilization of neutrophils from the marginated pool into the circulation, which was mediated by the overshooting of catecholamines during exercise. These findings indicate that the use of different techniques for detecting ROS or the different stages of neutrophil ROS metabolism could explain some of the disparate findings of the previous studies.

Whereas endurance exercise is known to induce marked neutrophilia, it remains to be fully understood as to whether the cell functions are altered as well as whether the adaptability of the responses to training occurs. To address both of these issues, we undertook the present longitudinal investigation in ten healthy untrained men (20-24 years, VO(2)max 39.1 +/- 4.2 ml/kg/min). The exercise protocol was 7 consecutive sessions of the same workload performed each day for 1.5 h at an intensity of 70 % of VO(2)max. Peripheral blood samples were obtained before, immediately after, and 1 h after exercise on Days 1, 4, and 7, and served for determination of total and differential leukocyte counts, chemotaxis and chemiluminescence of neutrophils. Acute endurance exercise caused marked peripheral neutrophilia with significant increase in both absolute number and relative proportion of band neutrophils (p &lt; 0.01, respectively), indicating partial recruitment of bone marrow neutrophils. While chemotaxis remained unaltered following exercise, reactive oxygen species generation of neutrophils, measured by luminol-dependent chemiluminescence upon stimulation with opsonized zymosan, was not only significantly enhanced following exercise (p &lt; 0.01), but also associated with the proportional increase in band neutrophils (r = 0.727, p &lt; 0.05), suggesting that neutrophils mobilized from the bone marrow following endurance exercise may possess higher responsiveness. On the other hand, the magnitude of the exercise-induced changes was reduced gradually by daily repeated exposure to endurance exercise, but none of the trends were significant except the decline in resting segmented neutrophil counts (p &lt; 0.05) at least during a 1-wk period of repeated exercise sessions.

To evaluate the chronic effects of voluntary exercise at lower levels on primary cardiovascular risk factors, inactive strain male Fischer rats were housed either with or without free access to activity wheels under controlled environmental conditions. The average amount of exercise for the 35-week duration was 722 (SD 362) m . day(-1). rat(-1), which was among the lowest found in the existing reports. Nonetheless, the body mass gains of the exercising rats were markedly inhibited, being 13% less (P &lt; 0.001) than those of the sedentary controls, despite a 22% increase in food consumption (P &lt; 0.0001), suggesting a remarkable prevention of adiposity. A noticeable improvement of serum lipid profiles was also found; a 53% reduction in triglyceride concentrations (P &lt; 0.01) and a 13% increase in high density lipoprotein cholesterol concentrations (P &lt; 0.05). In addition, resting systolic blood pressure was lowered by 7% (P &lt; 0.01). These results would suggest that even lower-level physical activity, if continued regularly, will attenuate the age-related development of cardiovascular risk factors associated with a sedentary lifestyle.

運動トレーニングは皮下脂肪組織の熱産生機能を向上させる効果を有することが報告されているが、この現象の分子メカニズムについては不明である。本研究では、運動トレーニングによる脂肪組織の熱産生機能の向上に対する免疫担当細胞の役割を検討することを目的とした。C57/BL6J雄マウス18匹を通常食餌+安静群、高脂肪食餌+安静群、高脂肪食餌+運動トレーニング群に群分けした。運動トレーニングは走行運動を1日60分間、週5回の頻度で8週間実施した。本研究の結果、高脂肪食餌負荷により減少する皮下脂肪組織のUCP-1およびベージュ細胞マーカーのmRNA発現は運動トレーニングにより増加が認められた。マクロファージマーカーと炎症性サイトカインの発現は高脂肪食餌負荷により増加が認められるが、これらの発現は運動トレーニングにより減少が認められた。以上のことから、運動トレーニングによるUCP1発現の増強には、マクロファージの浸潤抑制を介した慢性炎症の減弱が関与している可能性がある。(著者抄録)

本研究課題では、不動性筋萎縮モデルとして尾部懸垂を用い、筋萎縮におけるプロスタノイドの産生動態をLC-MS 質量分析による定量、質量分析顕微鏡を用いた質量分析イメージングにより観察し、プロスタノイドが筋萎縮の主因となるか否かを検討した。これまでに、プロスタノイドの検出から、その産生阻害剤の効果検証を段階的に進め、演繹的な実験計画により分子標的の同定を試みてきた。今年度は、その効果検証として、尾部懸垂マウスにおけるプロスタノイド阻害剤の投与効果の検討を行った。前年度までに得られた筋萎縮におけるプロスタノイド産生の結果をもとに、プロスタノイドの産生阻害剤をマウスに投与し、筋萎縮の抑制効果を判定した。これら実験の結果、プロスタノイド産生阻害剤の投与マウスでは筋萎縮の改善効果が認められた。さらに、筋組織におけるプロスタノイドの発現解析により、尾部懸垂により萎縮する筋組織におけるプロスタノイド産生細胞の動態解析を行った。既存法であるIn vivo 発光イメージャー、３次元マイクロCT 解析を併せて行った結果、筋萎縮におけるプロスタノイド産生細胞に関わる候補細胞を解析した。これらは炎症性疾患に関わるいくつかの免疫細胞などで構成されていることが明らかとなった。さらに、産生細胞を調べたところ、血球系細胞であるマクロファージ系の細胞によるプロスタノイド産生が筋萎縮に関与することが示唆された。細胞培養実験を併せて行った結果、マクロファージではプロスタノイド合成酵素の産生が亢進していた。本研究成果は、将来の廃用性筋萎縮やサルコペニア、広くはロコモティブシンドロームの治療につながる分子標的としてのプロスタノイド産生阻害剤の開発のみならず、SiRNA 導入、受容体拮抗阻害薬、天然由来機能性因子を活用し、不動性筋萎縮の新規な治療薬や治療因子の開発につなげてゆきたい。令和元年度が最終年度であるため、記入しない。令和元年度が最終年度であるため、記入しない

Using aging-model mice and young mice together with acute exercise model mice and endurance exercise model mice, grobal mRNA sequence and ribosome profiling were performed using next-generation sequencer. Changed variables and factors based on the analyses were further confirmed by real-time PCR and western blotting, and messages and proteins were quantified. In addition, gene network analyses were performed to capture changes at the system level of skeletal muscle, and found interesting genes and their potentially new functions

Not only the dynamic changes in transcription, but also those in translation in relation with mechanisms of action have great impacts on biological systems. In addition, recently, technological advancement due to ribosome profiling using the next-generation sequencer ennables us to analyze translational dynamics globally and with a high degree of accuracy for one nucreotide unit. Using this technology, we investigated the effect of exercise on translational dynamics with a genome-wide, and revealed new mechanisms of action together with nobel cis-elements in response to acute pro- and anti-inflammatory responses

In order to explore new biomarkers which respond to exercise and stress, we performed proteomics using blood and urine samples before and after exhaustive exercise and identified the molecules using mass spectrometric analyses. Among the molecules which exhibited remarkable increases, we developed measurement system using ELISA. Also, we identified several microRNAs in the blood circulation in response to acute resistant exercise using microarray, and quantified expression levels using real-time PCR. Furthermore, we set up global analyses of translation dynamics using ribosome profiling for biomarker discovery

Although exercise induces muscle damage, the underlying mechanisms are not fully understand. The present study examined the involvement of neutrophils and macrophages in the exhaustive exercise-induced acute muscle damage in mice by application of the inhibitory neutrophil migration model and macrophage depletion model. The administlation of anti-neutrophil antibody inhibited the infiltration of Ly-6G positive cells (neutrophils) in the gastrocnemius, and the administration of clodronate liposome reduced the infiltration of F4/80 positive cells (macrophages) and related inflammatory reactions. Therefore, it was demonstrated that neutrophils and macrophages are involved in the exercise-induced muscle damage

This study examined that the Gas6 expression and regulation of macrophages functions by Gas6 in injured-skeletal muscle. In the results, it observed that injured-skeletal muscle by Cardiotoxin-induction was increased Gas6 expression compared with control muscle. In addition, it observed that Gas6 stimulation regulate macrophages phenotype

Little information is available regarding the relationships among human obesity-related genes, cardiorespiratory fitness and metabolic syndrome (MS) or predisposition to MS (MP). The purpose of this study was to investigate the contribution of obese-related genes and cardiorespiratory fitness to the MS in middle-aged and old men and women. Seven hundred fifty eight healthy men and women participated in this study. We measured maximal oxygen uptake (VO2max) during an incremental cycle ergometer exercise test. Serum BDL-cholesterol, triglyceride and plasma glucose levels were measured in all subjects. Total and regional lean soft tissue and fat mass were also measured by dual-energy X-ray absorptiometry (DXA). We analysed the genotype of b3-adrenergic receptor (ADRB3 64 T>A), peroxisome proliferator-activated receptor gamma (PPARG 1431 C>. Pro12Ala), uncoupling protein 1(UCP1 3826 A>G), and fatty acid-binding protein 2(FABP2 54 A>T) using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Significant associations were observed between VO2max less than 32 nil/kg/min in men and 30 ml/kg/min in women and increases in the number of risk factors of MS (P<0.05). Poor VO2max was associated with the prevalence of MS in men and women independently of the 1431 C>T polymorphism in PPAR_Y. It is important to maintain high cardiorespiratory fitness regardless of the obesity gene variance for the prevention of metabolic syndrome.

This study was designed to observe physiological response during one bout of high-intensity intermittent short time rowing exercise and to evaluate the effect of repeated bouts of the exercise on rowing performance for college oarsmen.
The high-intensity, intermittent exercise consisted of either five or eight bouts of 20-sec rowing with the maximal effort of the subjects, and each bout was separated by 10-sec rest. In the first experiment, subjects reached to the maximal level of VO_2 and heart rate at the fourth set during both 5- and 8- sets of high-intensity, intermittent exercises. However, blood lactate concentration after high-intensity, intermittent exercise was significantly lower in the 5-set protocol than in the 8-set protocol (9.0±1.2vs. 11.3±1.6mM, p<0.05), suggesting that the 8-set protocol is much vigorous and better than the 5-set protocol as high-intensity, intermittent rowing exercise for rowers. In the 6-week rowing training, low frequency group (LF: 2 times/week) markedly improved their rowing performance (Δ3.2±1.9sec/1000m, Δ8.4±5.5sec/2000m time trials), whereas high frequency group (HF: 5 times/week) improved only in 1000m trial (Δ4.5±2.3sec).
Bowers performed 5-week training regimens by single scull boat on water which consisted of high-intensity rowing exercise(8 sets/bout, 2 times/week). Their rowing performance in the 2000m-time trial on ergometer was significantly improved.
These results suggest that high-intensity, intermittent rowing exercise on both ergometer and on water, which consists of 20-sec maximal exertion with 10-sec interval, 8 sets/bout, 2 times/week, more than 6 weeks, could be recommended to the collegiate rowers in order to improve their rowing performance.

運動やストレスに伴う免疫学的パラメータの変化は多数報告されているものの、その意義は未だ明らかにならず、実用的な研究が少ない。そこで2003年7月国際運動免疫学会コペンハーゲン大会の将来構想委員会において、今後スポーツ選手など運動に伴う免疫学的な問題に焦点を当てることを提案した。その結果、2005年モナコでの学術集会、2007年10月日本での学術集会では実用的な研究に焦点を当てることになり、本研究の代表者永富は国際運動免疫学会副会長に選出され、同時に2005年学術集会のプログラム委員長を務めることになった。この決定に伴い、これまでほとんど行われてこなかったスポーツの現場での免疫系が関連する問題点の調査を実施した。様々なレベルのスポーツ種目指導者に面接の上、質問紙を作成し、平成15年12月〜2月にかけて、大学生、プロスポーツ選手、実業団スポーツ選手、目本代表候補選手などを対象に無記名のアンケート調査を実施し1409名から回答を得た。有効街回答1367件を分析した結果、およそ20%にあたる274名が免疫に関連する疾患がスポーツ活動の障害になっていることを申告した。原因疾患として48.9%が急性上気道感染症を、25.2%がインフルエンザを、22.3%が花粉症を挙げた。インフルエンザ以外は軽症疾患といえどもスポーツ実施者にとっては無視できない問題であることがあらためて浮き彫りにされた。詳細な分析結果は現在報告書にまとめつつあり、各競技団体に配布する予定である。また本研究代表者が代表を務める日本運動免疫学研究会では2005年、2007年の学会に向けて今回明らかになった現場での問題点に関連する研究を奨励していく予定である

First, in order to advance the various researches in laboratory animals, we examined fundamental measurement conditions for detecting reactive oxygen species of rat peripheral neutrophils by use of flow cytometry. For measuring phagocytic activity with flow cytometry, Staphylococcus aureus was labeled with fluoresce in isothiocynate (FITC) and used as phagocytic particles. We decided the optimal concentrations of FITC in regard to the fluorescent intensity. As for the measurement of reactive oxygen-producing activity, hydroethidine (HE) which reacts with superoxide was used and the suitable concentration was determined by dependency of the fluorescent intensity. Furthermore, simultaneous measurement of both of these activities was made possible by detecting FITC and HE at the different wave length. In addition, nitroblue tetrazolium (NBT) reduction method was also performed using the same samples. As a result, strong correlations were confirmed between both measurement methods.Next, we investigated the fundamental measurement conditions in case of human peripheral blood. It was found that hemolysis procedure after the cellular reaction could affect flow cytometry distribution of neutrophils, lymphocytes and monocytes, and we improved the operation methods. On the other hand, isolated neutrophils lose activity soon, and there was a necessity to measure reactive oxygen production soon after the separation from the whole blood. Then we tried to examine the high sensitivity detection probe by comparing HE with Dihydrorhodamine (DHR) -123, Dichrolo Fluorescein Diacetate (DCFH-DA). DHR-123 was superior in sensitivity, by coexisting NaN3 which is the inhibitor of myeloperoxidase, compared with DCFH-DA. Concerning the phagocytic particles, FITC-labeled Staphylococcus aureus and zymosan were used, but the culture of pathogens is dangerous and not easy to handle to label with FITC. In addition, zymosan caused aggregation of neutrophils and was not suitable for the measurement of flow cytometry method. For those reasons, Carboxylate Microspheres of the diameter 1 μ m with fluorescence dye was used, and it became possible to measure phagocytic activity without such difficulties. We could set up the detection wave length of Carboxylate Microspheres without interference of those of HE and DHR-123, and simultaneous analyses of phagocytosis and reactive oxygen production became possible.Furthermore, by applying the principle of flow cytometry that can measure several indices simultaneously by changing detection wave length, the simultaneous measurement of various molecules using human plasma samples became possible. Conventional enzyme-linked immunosorbent assay (ELISA) takes larger sample volume and takes time for the measurement. On the other hand, this method have greater range of measurement, but the sensitivity was poorer than ELISA method. Taken together, flow cytometry method is enable us to measure multi-channel parameters that we could not do until recently

前年度に引き続き、免疫能、炎症、老化に関する機序の解析と運動・栄養による予防医学的介入研究を進めた。前年度は極端な激運動について検討を行ったが、本年度は運動処方を念頭に置いた健康増進運動についても検討を進めた。健常若年者を対象とした歩行運動の介入研究(1日30分、週6日、3週間)では、トレーニングによって白血球・リンパ球サブセット、NK細胞活性、Tリンパ球幼弱化反応に有意な変化は認められなかったが、血漿インターロイキン12p40濃度に有意な減少が認められ、細胞性免疫が活性化されやすい状態になる可能性が示唆された。高齢者を対象とした12週間の低強度筋力トレーニングでは、CRP、SSA、HSP70に有意な低下が認められ、筋肥厚とCRP、TNF-αの変化率に逆相関が認められたことから炎症の軽減が筋肥大にも関わる可能性が示唆された。前立腺癌がん患者を対象とした筋力トレーニングの介入研究では、インスリン濃度が低下した以外にはホルモン、サイトカインに顕著な影響は認められなかったものの、筋力改善によるADLの改善効果が示され、運動トレーニングががん患者においても有用であることを示した。なお、運動・トレーニングの影響を評価するためのバイオマーカーの検索も試みたが、現状では実用化に値するような研究結果を得ることはできなかっだ。今後も引き続き研究を行う予定である

遅発性筋肉痛は、伸張性筋収縮などの運動後数時間から1日程度経過後より発現し、2、3日後にピークとなり1週間程度で消失するが、その機序は明らかではない。運動により白血球(好中球)の活性酸素産生能と抗酸化システムのバランスが崩れると、生体に傷害を与え、サイトカイン産生や筋組織に好中球の侵入が起きるため、筋肉痛の原因として損傷・炎症説や活性酸素による傷害説が提唱されている。そこで、健康な男性8人に片足カーフレイズ運動を負荷し、運動負荷前、直後、1日後、2日後、3日後、4日後に筋肉痛の評価と下腿周径囲を測定し、採血を行った。全血より好中球が選択的に侵入する熱可逆ハイドロゲルを用いて遊走能を測定し、ルミノール依存性化学発光により活性酸素産生能を測定した。さらに血液中の筋損傷マーカーと炎症関連物質の測定を行い、筋肉痛との関連性を検討した。その結果、運動負荷1日後から筋肉痛が発現し2、3日後がピークとなり、4日後には痛みが減少した。好中球の活性酸素産生能は運動直後に上昇し、4日後には運動前と比較して有意に低下した。筋損傷マーカーのGOTは有意に上昇し、CK、ミオグロビンは上昇傾向を示した。サイトカインは抗炎症性サイトカインのIL-10のみ運動直後に有意に上昇し、GOT、CKとの間に有意な負の相関が認められた。激運動や持久性運動では好中球数が増加し活性酸素産生能が亢進する一方、生体には運動により発生する活性酸素を消去する抗酸化システムが存在する。先行研究では運動後に得られた血漿に活性酸素消去能の亢進が示されたが、本研究でもそのために好中球活性酸素産生能の抑制が生じたか、IL-10が好中球機能を抑制した可能性が考えられた

This study investigated the relationships between the degree of muscle fatigue and changes in the delayed onset muscle soreness(DOMS), biochemical markers of muscle damage and joint performance, induced by calf-raise exercises at two different frequencies. The results suggest that 1) muscle fatigue is less by the faster exercise, 2) the degree of DOMS and the amount of muscle damage markers are related with the degree of muscle fatigue and muscle-specific, but joint performance rapidly recovers after fatigue regardless of soreness or retained biochemical changes, and that 3) fascicle and tendon behavior during exercise is altered in relation to the observed changes

　本研究では好中球機能検査法のなかでも、温度官能性ハイドロゲルを用いた血中好中球の接着・遊走能と活性酸素産生能の測定、および酵素免疫測定法による血漿のミエロペルオキシダーゼ（myeloperoxidase: MPO）とカルプロテクチン（calprotectin）の濃度測定を評価系として設定し、各種の酸化ストレスや炎症の条件化で検討を行った。好中球接着・遊走能については、従来の顕微鏡下での血球計算盤を用いた計測に加え、蛍光をによる核染色を用いた定量法も採用し、測定系の一部自動化にも取り組んだ。　好中球数の臨床検査としての応用については、炎症性腸疾患患者の白血球除去療法の治療経過のモニターとして検討したが、有意な影響は認められなかった。また高齢者では好中球機能が亢進し慢性炎症の状態となるが、身体活動量の高い者と低い者との間に有意差は認められなかった。一方、運動負荷の前後の検討では、伸張性筋活動の後にやや好中球機能が上昇する傾向がみられたが、数日後の遅発性筋肉痛の発症時には変化が認められなかった。一方、持久性運動負荷の後には血漿のミエロペルオキシダーゼとカルプロテクチン濃度の上昇が若年者でも中高年者でも認められた。よって、好中球機能は持久性運動によって亢進することが確かめられた。がん患者では健常者より好中球活性酸素産生能の亢進がみられ、抗酸化物質の使用により酸化ストレスの軽減効果が示唆された。そこで、各種植物抽出成分のin vitroでの機能性評価に応用したところ、ビタミンC、カテキン、ポリフェノールなど抗酸化作用が報告されている物質群では濃度依存性の有意な抑制効果が観察されたが、とくにそのような効果が報告されていない物質群では影響は認められず、このハイドロゲルを用いた好中球機能測定系が抗酸化作用、抗炎症作用のスクリーニング系として有用である可能性が示された。　そこで今後は、運動負荷による炎症反応や酸化ストレス、がん患者や高齢者の軽度の慢性炎症（chronic low-grade inflammation）への抗酸化物質の介入研究による評価に応用していくことになった。

　まずハイドロゲルを用いたシングルチューブによる標準型測定系について、従来は細胞数計測の部分を血球計算盤を用いて顕微鏡下に目視で行ってきたが、手作業で手間がかかる上に主観も入るため、客観的に短時間で定量的な評価を行うために自動分析装置を導入し、測定系の充実をはかり、細胞数と蛍光強度がほぼ比例関係にあることを確認した。　次に、好中球機能がストレスの評価指標となりうるかどうかを検討した。持久性運動負荷や手術侵襲では生体負担を反映して好中球活性酸素産生能が上昇し、他の酸化ストレスの生体指標よりも鋭敏に生体反応を捉えられることが示唆された。しかし、筋損傷を起こす伸張性運動負荷では、遅発性筋肉痛をはじめとする炎症症状やクレアチンキナーゼ等の筋損傷マーカーの上昇は顕在化するにもかかわらず、好中球活性酸素産生能の上昇は認められず、エネルギー枯渇やストレスホルモンの分泌が生じるストレス状態においてのみ測定値の上昇が生じる可能性が考えられた。　臨床検査への応用としては、重症肺炎や原因不明で難病指定となっている炎症性腸疾患（潰瘍性大腸炎、クローン病）の患者での治療前後の検討を30症例ほど検討し、診断や治療モニタリングの指標としてよく炎症状態を反映する可能性が示された。さらに各種抗炎症薬や抗酸化物質を用いたin vitroの作用解析を行い、この測定系が各種薬剤や健康食品成分の評価に応用できる研究成果を示し、日本補完代替医療学会にて発表した。

　メビオール株式会社との共同研究にて開発した白血球の遊走能と活性酸素産生能の測定系について、まず基礎的検討を進めた。好中球の遊走因子であるインターロイキン８については、200pg/ml以上の高濃度では遊走細胞数の増加を認めたものの、高価な試薬であるため臨床検査に用いるには難しいと判断された。一方、単球を遊走させるためにmonocyte chemotactic protein 1（MCP-1）を用いたが、基材との関係で遊走活性や活性酸素生成を検出することはできなかった。また活性酸素産生能を呈色反応として検出するためにnitroblue tetrazolium（NBT）を用いたが、化学発光とくらべ定量性、再現性に問題があり、NBTを臨床検査に用いるのは困難と考えられた。　次に、従来法を用いて各種物質、薬剤の好中球機能に及ぼす影響を検討した。ビタミンCは活性酸素生成を濃度依存的に抑制したが、遊走細胞数には影響を及ぼさず、本検査法は抗酸化物質の活性評価や酸化ストレスの評価に有用と考えられた。次にストレスホルモンの代表としてエプネフリンの作用を検討したが、濃度・作用時間の影響は認められなかった。一方、ハイドロコルチゾンは濃度依存的に遊走細胞数を減少させ、抗炎症作用・免疫抑制作用の評価に有用と考えられた。このように生理活性物質や薬物の作用解析・薬剤感受性の評価に好中球機能検査法が応用できる可能性を示した。　健康診断・臨床検査への応用に関しては、国立国際医療センターで臨床検査としての倫理申請が認められたので、今後臨床検体での検討を進め、妥当性の検証を進めることとなった。

　白血球活性酸素産生能の測定系として、全血を温度官能性ゲルと接触させると白血球が浸潤することをメビオール社との共同研究にて検討し、その素材を利用してさらに遊走した白血球が産生する活性酸素をluminol依存性化学発光法やdihydrorhodamine 123, hydroethidine（蛍光）にて測定できるよう条件設定を進めた。　この測定系を運動負荷研究に応用したところ、白血球のゲルへの浸潤（遊走能）が高まる傾向を示した。ストレスホルモンやケモカインの変動とケモカイン受容体CCR2の発現との関連を調べたところ、CCR2はエピネフリン、ノルエピネフリンの影響を受けなかったが、コルチゾールの濃度に依存して増強した。さらにCCR2の発現の増強により、白血球の移動能力も増加した。この結果はストレスによって分泌されるストレスホルモンがCCR2の発現を増強させた可能性を示している。　

　サイトカインは、免疫系や炎症の制御分子として注目されている生理活性物質である。著者らは、マラソンのような激しい持久性運動によってサイトカインの血中濃度が変動することを明らかにしてきた。しかし、従来、運動負荷に伴う血中サイトカイン濃度の変動は、運動の強度に依存するものか、あるいは運動による骨格筋の損傷に伴うものであるのか明らかではなかった。そこで本研究では、最大酸素摂取量の60％強度と85％強度でそれぞれ60分間の水平トレッドミル走、最大酸素摂取量の60％強度で-10％の傾斜のあるダウンヒルのトレッドミル走（筋損傷が顕在化しやすい典型的運動負荷）の３条件を設定し、同一の被験者９名に３種類の運動を負荷して、運動条件間の比較検討を行った。運動強度の指標としては、コルチゾール、カテコールアミンなどのストレスホルモンの血中濃度を測定し、筋損傷の指標としては血中ミオグロビン濃度、クレアチンキナーゼ活性を測定したが、３条件はそれぞれの指標に特徴的に顕著な影響を及ぼし、実験条件の設定は良好であった。本研究では、９種類のサイトカインの測定を行ったが、IL-6、IL-1ra、IL-10、IL-12p40、MCP-1、HSP70は運動強度依存的に有意な上昇を示し、これに比し、筋損傷とは関連は認められなかった。これらのサイトカインは、細胞性免疫を抑制する作用があり、炎症の全身性波及を抑制する適応機構として働く反面、感染に対する抵抗能力を低下させる可能性が考えられる。またこれらのサイトカインの変動は、コルチゾール、カテコールアミンなどのストレスホルモンとの間に強い相関が認められ、神経内分泌因子と免疫系の連動が密接であることを証明できた。さらにこのような全身的なストレス要因を排除して筋損傷の影響を検討するために、局所的な肘進展モデルを用いた遅発性筋炎に伴う血中サイトカイン濃度の変動も検討したが、筋損傷マーカーの劇的な変動にも関わらずサイトカインの変動は軽微であり、血中サイトカイン濃度の変動は運動強度（ストレス）依存性であることが確認できた。これらの成果は、米国生理学会にて報告し、また５月のアジアスポーツ医学会で報告する予定であり、既に掲載された論文と現在米国スポーツ医学会誌に投稿中の論文が成果として出つつある。

「意外に知られていない運動と免疫の関係 “適度”な運動で免疫力を高めよう」に関する記事作成で取材を受けた。
http://wol.nikkeibp.co.jp/article/trend/20120727/130901/?P=2

「過激な運動に注意 免疫力低下、感染しやすく」に関する記事作成で取材を受けた。
http://mainichi.jp/feature/news/20120726ddm010100023000c.html

「五輪選手ほど風邪を引きやすい！？運動と免疫の意外な関係」で取材を受けた。
http://www.sponichi.co.jp/society/yomimono/mimiyori/kiji/K20120718003704590.html

「過激な運動に注意 免疫力低下、感染しやすく」に関する記事作成で取材を受けた。
http://mainichi.jp/feature/news/20120726ddm010100023000c.html

運動と免疫に関する記事作成で取材を受けた。
http://newspaperwords.seesaa.net/article/190135001.html

第166回 「決定版！スタミナの真実」にて取材を受け、全身持久力の観点から医学的知識を解説した。
http://kakaku.com/tv/channel=6/programID=5253/episodeID=255659/

「予防医学の普及で生活習慣病を減らすことが課題—体の免疫力を高めるための栄養・運動とは—」の内容で研究活動が紹介された（54〜63ページ）