Associations between cardiorespiratory fitness and lifestyle-related factors with DNA methylation-based ageing clocks in older men: WASEDA'S Health Study.

DNA methylation-based age estimators (DNAm ageing clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between cardiorespiratory fitness (CRF), measured directly by expiratory gas analysis, and DNAm ageing clocks are largely unknown. We investigated the relationships between CRF and the age-adjusted value from the residuals of the regression of DNAm ageing clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of CRF to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65-72 years were used to appraise first- (i.e., DNAmHorvath and DNAmHannum) and second- (i.e., DNAmPhenoAge, DNAmGrimAge, and DNAmFitAge) generation DNAm ageing clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrient intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. Both oxygen uptake at ventilatory threshold (VO2 /kg at VT) and peak oxygen uptake (VO2 /kg at Peak) showed a significant negative correlation with GrimAgeAccel, even after adjustments for chronological age and smoking and drinking status. Notably, VO2 /kg at VT and VO2 /kg at Peak above the reference value were also associated with delayed GrimAgeAccel. Multiple regression analysis showed that calf circumference, serum triglyceride, carbohydrate intake, and smoking status, rather than CRF, contributed more to GrimAgeAccel and FitAgeAccel. In conclusion, although the contribution of CRF to GrimAgeAccel and FitAgeAccel is relatively low compared to lifestyle-related factors such as smoking, the results suggest that the maintenance of CRF is associated with delayed biological ageing in older men.

Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines. Methods: The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-ß), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method. Findings: Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-ß in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05). Conclusion: Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22.

microRNAs slow translating ribosomes to prevent protein misfolding in eukaryotes.

Slower translation rates reduce protein misfolding. Such reductions in speed can be mediated by the presence of non-optimal codons, which allow time for proper folding to occur. Although this phenomenon is conserved from bacteria to humans, it is not known whether there are additional eukaryote-specific mechanisms which act in the same way. MicroRNAs (miRNAs), not present in prokaryotes, target both coding sequences (CDS) and 3' untranslated regions (UTR). Given their low suppressive efficiency, it has been unclear why miRNAs are equally likely to bind to a CDS. Here, we show that miRNAs transiently stall translating ribosomes, preventing protein misfolding with little negative effect on protein abundance. We first analyzed ribosome profiles and miRNA binding sites to examine whether miRNAs stall ribosomes. Furthermore, either global or specific miRNA deficiency accelerated ribosomes and induced aggregation of a misfolding-prone polypeptide reporter. These defects were rescued by slowing ribosomes using non-cleaving shRNAs as miRNA mimics. We finally show that proinsulin misfolding, associated with type II diabetes, was resolved by non-cleaving shRNAs. Our findings provide a eukaryote-specific mechanism of co-translational protein folding and a previously unknown mechanism of action to target protein misfolding diseases.

Collagen-Derived Dipeptides and Amino Acids Have Immunomodulatory Effects in M1-Differentiated RAW264.7 Cells and PBMC.

A number of food components, such as polyphenols and phytonutrients, have immunomodulatory effects. Collagen has various bioactivities, such as antioxidative effects, the promotion of wound healing, and relieving symptoms of bone/joint disease. Collagen is digested into dipeptides and amino acids in the gastrointestinal tract and subsequently absorbed. However, the difference in immunomodulatory effects between collagen-derived dipeptides and amino acids is unknown. To investigate such differences, we incubated M1 macrophages or peripheral blood mononuclear cells (PBMC) with collagen-derived dipeptides (hydroxyproline-glycine (Hyp-Gly) and proline-hydroxyproline (Pro-Hyp)) and amino acids (proline (Pro), hydroxyproline (Hyp), and glycine (Gly)). We first investigated the dose dependency of Hyp-Gly on cytokine secretion. Hyp-Gly modulates cytokine secretion from M1 macrophages at 100 µM, but not at 10 µM and 1 µM. We then compared immunomodulatory effects between dipeptides and mixtures of amino acids on M1 macrophages and PBMC. There was, however, no difference in cytokine secretion between dipeptides and their respective amino acids. We conclude that collagen-derived dipeptides and amino acids have immunomodulatory effects on M1-differentiated RAW264.7 cells and PBMC and that there is no difference in the immunomodulatory effects between dipeptides and amino acids.

Effects of 4'-Demethylnobiletin and 4'-Demethyltangeretin on Osteoclast Differentiation In Vitro and in a Mouse Model of Estrogen-Deficient Bone Resorption.

Citrus nobiletin (NOB) and tangeretin (TAN) show protective effects against disease-related bone destruction. We achieved demethylation of NOB and TAN into 4'-demethylnobiletin (4'-DN) and 4'-demethyltangeretin (4'-DT) using enzyme-manufacturing methods. In this study, we examined the effects of 4'-DN and 4'-DT on in vitro osteoclast differentiation, and on in vivo osteoporotic bone loss in ovariectomized (OVX) mice. 4'-DN and 4'-DT clearly suppressed the osteoclast differentiation induced by interleukin IL-1 or RANKL treatment. 4'-DN and 4'-DT treatments resulted in higher inhibitory activity in osteoclasts in comparison to NOB or TAN treatments. RANKL induced the increased expression of its marker genes and the degradation of IκBα in osteoclasts, while these were perfectly attenuated by the treatment with 4'-MIX: a mixture of 4'-DN and 4'-DT. In an in silico docking analysis, 4'-DN and 4'-DT directly bound to the ATP-binding pocket of IKKß for functional inhibition. Finally, the intraperitoneal administration of 4'-MIX significantly protected against bone loss in OVX mice. In conclusion, 4'-DN, 4'-DT and 4'-MIX inhibited the differentiation and function of bone-resorbing osteoclasts via suppression of the NF-κB pathway. Novel 4'-DN, 4'-DT and 4'-MIX are candidates for maintaining bone health, which may be applied in the prevention of metabolic bone diseases, such as osteoporosis.

Neutrophil Depletion Attenuates Acute Liver Stress after Exhaustive Exercise in Mice.

PURPOSE: Exhaustive exercise induces acute liver stress; however, the precise mechanisms remain unclear. METHODS: We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody ( n = 20), sedentary with antineutrophil antibody ( n = 20), exhaustive exercise with control antibody ( n = 20), and exhaustive exercise with antineutrophil antibody ( n = 20). Antineutrophil antibodies (1A8) or control antibodies were administered intraperitoneally before running on a treadmill. Immediately and at 24 h after running to exhaustion on a treadmill at a 7% gradient and a speed of 24 m·min -1 , blood neutrophil counts were measured by flow cytometry. Plasma activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. Hematoxylin-eosin staining was performed to calculate the liver stress score, and hepatic tumor necrosis factor-α was measured using enzyme-linked immunosorbent assay. RESULTS: Exercise increased blood neutrophil and neutrophil infiltration into the liver. Plasma AST and ALT activities were significantly higher immediately after exhaustive exercise than after sedentary control (AST, sedentary with control antibody: 52.2 ± 0.4, exhaustive exercise with control antibody: 210.0 ± 19.8; ALT, sedentary with control antibody: 29.8 ± 2.2, exhaustive exercise with control antibody: 87.2 ± 15.8). However, AST and ALT activities were significantly decreased with the 1A8 antibody (AST, 102.2 ± 12.9; ALT, 39.2 ± 4.0). In addition, the liver stress score increased after exercise but was significantly reduced by prior 1A8 antibody administration. The 1A8 antibody treatment also decreased hepatic tumor necrosis factor-α levels after exhaustive exercise. CONCLUSIONS: These results suggested that neutrophils play a critical role in increasing liver stress by regulating inflammation.

Evaluating the Magnolol Anticancer Potential in MKN-45 Gastric Cancer Cells.

Background and Objectives: Combination therapy improves the effect of chemotherapy on tumor cells. Magnolol, used in treating gastrointestinal disorders, has been shown to have anti-cancer properties. We investigated the synergistic effect of cisplatin and magnolol on the viability and maintenance of MKN-45 gastric cancer cells. Materials and Methods: The toxicity of magnolol and/or cisplatin was determined using the MTT technique. The trypan blue method was used to test magnolol and/or cisplatin's effect on MKN-45 cell growth. Crystal violet staining was used to assess the treated cells' tendency for colony formation. The expression of genes linked to apoptosis, cell cycle arrest, and cell migration was examined using the qPCR method. Results: According to MTT data, using magnolol and/or cisplatin significantly reduced cell viability. The ability of the treated cells to proliferate and form colonies was also reduced considerably. Magnolol and/or cisplatin treatment resulted in a considerable elevation in Bax expression. However, the level of Bcl2 expression was dramatically reduced. p21 and p53 expression levels were significantly increased in the treated cells, while MMP-9 expression was significantly reduced. Conclusions: These findings show that magnolol has a remarkable anti-tumor effect on MKN-45 cells. In combination with cisplatin, magnolol may be utilized to overcome cisplatin resistance in gastric cancer cells.

Proteomic profiling of intestinal epithelial-like cell-derived exosomes regulated by epigallocatechin gallate.

Exosomes are extracellular vesicles primarily responsible for intercellular communication, and they contain nucleic acids and proteins. Exosome secretion has been observed in the intestines, suggesting their physiological effects on the receptor cells of target tissues. It is possible that intestinal epithelial cells recognize food components as ligands, resulting in exosome secretion. However, research on intestine-derived exosomes regulated by food ingredients is limited. In this study, Caco-2 cells were utilized as an intestinal epithelial model for proteomic profiling. NanoLC-MS/MS analysis revealed the alteration of exosome properties by epigallocatechin gallate (EGCG) in differentiated Caco-2 cells. This natural polyphenol reduced both the number and size of secreted exosomes and altered the expression of exosomal proteins. The enriched proteins in exosomes were involved in immune response and cell proliferation. In contrast, those in the EGCG-treated group had distinctive functions in the maintenance of skin homeostasis. We also found variable expression of galectin-3-binding protein and fibronectin as molecular signatures in exosomes derived from EGCG-treated cells. These results could help elucidate the expression and mechanism of exosomal proteins related to food components.

Effect of 8 Weeks Aerobic Training and Saffron Supplementation on Inflammation and Metabolism in Middle-Aged Obese Women with Type 2 Diabetes Mellitus.

Background: This study aimed to investigate the effects of 8-week aerobic training (AT) and saffron supplementation on inflammation and metabolism in middle-aged obese women with type 2 diabetes mellitus (T2DM). Methods: Thirty-two obese women with T2DM were randomly divided into four groups (n = 8 in all groups): saffron + training (ST), placebo + training (PT), saffron supplementation (SS), and placebo (P). The ST and PT groups performed eight weeks of aerobic training (AT) (three sessions/week at 60−75% HRmax). A daily dose of 400 mg saffron powder was consumed by the ST and SS groups for 8 weeks. Blood samples were taken after 12 h of fasting, 48 h before the first AT session, 48 h and two weeks after the last AT session. Results: AT, saffron supplementation, and their combination affected body mass index (BMI), homeostatic model assessment for insulin resistance (HOMA-IR), and serum levels of insulin, adiponectin, interleukin-6 (IL-6), high-density lipoprotein cholesterol (HDL-C), cholesterol, and triglyceride (TG) (p < 0.05). However, body weight, body fat percentage, and serum levels of glucose, resistin, tumor necrosis factor-alpha (TNF-α), irisin, and low-density lipoprotein cholesterol (LDL-C) showed significant changes in the ST group only (p < 0.05). In addition, a significant difference was seen between all factors in post-training and follow-up in the ST group (p < 0.05). Conclusions: Saffron supplementation at a dose of 400 mg/day, when combined with AT, could improve inflammation, metabolism, glycemic status, and lipid profile in T2DM patients, and these changes are sustainable at up to 2 weeks of detraining.

Cystine/Glutamine Mixture Supplementation Attenuated Fatigue during Endurance Exercise in Healthy Young Men by Enhancing Fatty Acid Utilization.

Exercise-induced fatigue is a multi-origin physical and mental phenomenon. Efforts to diminish the above predisposition may contribute to endurance, along with athletic well-being, while development of nutritional strategies to optimize condition and exercise performance are essential issues for athletes and trainers. Dietary amino acids are being discussed for their specific health-promoting properties beyond their role as building blocks of proteins. Glutamine, along with cysteine, are two kinds of amino acids that are reported extensively for their anti-oxidation, anti-inflammation, and immune-regulation properties, and are promising in sport applications. In the present study, we designed a randomized, placebo-controlled, crossover trial to examine effects of 7-day supplementation of cystine/glutamine mixture (Cys2/Gln) on self-reporting fatigue index (ratings of perceived exertion, RPE), energy metabolism, and inflammation. We also employed a C2C12 myotube model to examine the capacity of cystine for fatty acid utilization. Cys2/Gln supplementation alleviated fatigue by decreasing RPE and enhanced fatty acid oxidation during a 60 min endurance exercise in human trials, while cystine increased fatty acid utilization in C2C12 myotubes by enhancing mitochondrial respiration. In summary, Cys2/Gln supplementation exerts positive effects on ameliorating exercise-induced fatigue, mechanisms of which can be attributed to enhancement of fatty acid utilization.

Fat-Free Mass Index as a Surrogate Marker of Appendicular Skeletal Muscle Mass Index for Low Muscle Mass Screening in Sarcopenia.

OBJECTIVES: We aimed to examine the relationship between the fat-free mass index (FFMI; FFM/height2) and appendicular skeletal muscle mass index (ASMI; ASM/height2), measured using both bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), and investigate the effects of age and obesity. We also evaluated the suitability of BIA-measured FFMI as a simple surrogate marker of the ASMI and calculated the optimal FFMI cutoff value for low muscle mass screening to diagnose sarcopenia. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: This study included 1313 adults (women, 33.6%) aged 40-87 years (mean age, 55 ± 10 years) from the WASEDA'S Health Study. METHODS: Body composition was measured using multifrequency BIA and DXA. Low muscle mass was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. RESULTS: BIA-measured FFMI showed strong positive correlations with both BIA- (r = 0.96) and DXA-measured (r = 0.95) ASMIs. Similarly, in the subgroup analysis according to age and obesity, the FFMI was correlated with the ASMI. The areas under the receiver operating characteristic curve for screening low muscle mass defined by DXA-measured ASMI using BIA-measured FFMI values were 0.95 (95% CI 0.93-0.97) for men and 0.91 (95% CI 0.87-0.94) for women. The optimal BIA-measured FFMI cutoff values for screening low muscle mass defined by DXA-measured ASMI were 17.5 kg/m2 (sensitivity 89%, specificity 88%) for men and 14.6 kg/m2 (sensitivity 80%, specificity 86%) for women. CONCLUSIONS AND IMPLICATIONS: The FFMI showed a strong positive correlation with BIA- and DXA-measured ASMIs, regardless of age and obesity. The FFMI could be a useful simple surrogate marker of the ASMI for low muscle mass screening in sarcopenia in community settings. The suggested FFMI cutoff values for predicting low muscle mass are <18 kg/m2 in men and <15 kg/m2 in women.

Athletes' Mesenchymal Stem Cells Could Be the Best Choice for Cell Therapy in Omicron-Infected Patients.

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.

Macrophage Depletion Attenuates Acute Renal Damage after Exhaustive Exercise in Mice.

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-1ß, 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.

High-intensity intermittent exercise induces a potential anti-inflammatory response in healthy women across the menstrual cycle.

AIM: This observational study aimed to examine cytokine responses to high-intensity intermittent exercise (HIIE) in the follicular and luteal phases of the menstrual cycle. METHODS: Fourteen healthy women (24 ± 2 years; body mass index [BMI]: 22.8 ± 1.9 kg⋅m2; maximal oxygen consumption [V̇O2max]: 41.5 ± 4.1 mL⋅kg-1⋅min-1) with regular menstrual cycles were randomly assigned to 4 experimental sessions, 2 during the follicular and 2 during the luteal phase. V̇O2max and maximum aerobic velocity (MAV) were determined prior to the experimental sessions through a graded exercise test during both follicular and luteal phases. Seventy-two hours after having completed the graded exercise test, all participants performed a HIIE session (10 x 1-min sprints with 1 min of rest) at 90% of their MAV. Serum concentrations of TNF-α, IL-6, IL-10 and IL-17 were measured before (Pre), immediately after (Post) and 1 h after (1 h Post) the HIIE sessions. RESULTS: Pre-exercise concentrations of TNF-α and IL-10 were significantly higher in the luteal phase compared to the follicular phase (P < 0.01), with no differences seen on IL-6 and IL-17, demonstrating an altered inflammatory status in the luteal phase. There was a significant interaction for IL-10 concentration (P < 0.01) with reductions in both luteal (Pre vs Post, 95 %CI: 1.086 to 6.156; and Pre vs 1 h Post, 95 %CI: 1.720 to 9.013, P < 0.01) and follicular phase (Pre vs 1 h Post, 95 %CI: 0.502 to 7.842, P < 0.05). Despite no significant phase × time interaction for TNF-α concentration, its concentration at 1 h Post was significantly lower compared to Pre in the luteal phase analysis (Pre vs 1 h Post, 95 %CI: 0.71 to 14.06; P < 0.05). These results are in agreement with IL-10 responses, highlighting a reduction on the inflammatory status after exercise. CONCLUSION: Mostly during the luteal phase, high-intensity intermittent exercise modulates cytokine responses, thus impacting exercise recovery. In this scenario, high-intensity intermittent exercise emerges as a non-pharmacology strategy to regulate inflammatory responses on healthy women who were affected by an inflammatory state given their menstrual cycle.

The combination of cardiorespiratory fitness and muscular fitness, and prevalence of diabetes mellitus in middle-aged and older men: WASEDA'S Health Study.

BACKGROUND: Although the negative relationship between cardiorespiratory fitness (CRF) or muscular fitness and diabetes mellitus were respectively observed in many previous studies, there is still a lack of studies that include CRF and muscular fitness simultaneously. Therefore, this study aimed to investigate the relationship between the combination of CRF and muscular fitness and diabetes through a cross-sectional study.  METHODS: This study was part of WASEDA'S Health Study, a cohort study launched in 2014. We used a part of the baseline data collected for this study. Maximal exercise test using a cycle ergometer and leg extension power (LEP) test were respectively used to evaluate CRF and muscular fitness. Since LEP is affected by body weight, relative LEP (rLEP) which is LEP per body weight, was used as an index of muscular fitness. 796 men (56.5 ± 10.4 years old) who completed a medical examination and fitness tests, were divided into two groups based on CRF and rLEP, respectively. The prevalence of diabetes was collected based on a self-reported questionnaire or blood test. Odds ratios and 95% confidence intervals (CIs) for the prevalence of diabetes were obtained using logistic regression models while adjusting for age, body mass index, exercise habits, family history of diabetes, smoking habits, and drinking habits. RESULTS: 55 (7%) participants had diabetes. Compared to participants with lower CRF or rLEP, the odds ratio (95% CIs) of diabetes in those with higher CRF or rLEP was 0.46 (0.21-0.98) or 0.34 (0.16-0.74), respectively. Furthermore, using the lower CRF and lower rLEP group as the reference, the odds ratio (95% CIs) for the lower CRF and higher rLEP group was 0.32 (0.12-0.88), and higher CRF and higher rLEP group was 0.21 (0.07-0.63), after adjusting for potential confounding factors. CONCLUSIONS: CRF and rLEP have independent and joint inverse associations with diabetes prevalence. In addition, participants with high CRF and high rLEP had a lower prevalence of diabetes compared to those with only high CRF or only high rLEP.

Combined Effects of Exercise Training and Nutritional Supplementation in Cancer Patients in the Context of the COVID-19: A Perspective Study.

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.

Effects of oral cystine and glutamine on exercise-induced changes in gastrointestinal permeability and damage markers in young men.

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.

Thermal dysregulation in patients with multiple sclerosis during SARS-CoV-2 infection. The potential therapeutic role of exercise.

Thermoregulation is a homeostatic mechanism that is disrupted in some neurological diseases. Patients with multiple sclerosis (MS) are susceptible to increases in body temperature, especially with more severe neurological signs. This condition can become intolerable when these patients suffer febrile infections such as coronavirus disease-2019 (COVID-19). We review the mechanisms of hyperthermia in patients with MS, and they may encounter when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Finally, the thermoregulatory role and relevant adaptation to regular physical exercise are summarized.

An Overview of Physical Exercise and Antioxidant Supplementation Influences on Skeletal Muscle Oxidative Stress.

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.

Cardiac Oxidative Stress and the Therapeutic Approaches to the Intake of Antioxidant Supplements and Physical Activity.

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.