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.

Variation in the relationship between odd isotopes of tin in mass-independent fractionation induced by the magnetic isotope effect.

Experimental results are presented showing the variation in the relationship between odd isotopes of tin (Sn) in mass-independent fractionation caused by the magnetic isotope effect (MIE), which has previously only been observed for mercury. These results are consistent with the trend predicted from the difference between the magnitudes of nuclear magnetic moments of odd isotopes with a nuclear spin. However, the correlation between odd isotopes in fractionation induced by the MIE for the reaction system used in this study (solvent extraction using a crown ether) was different from that reported for the photochemical reaction of methyltin. This difference between the two reaction systems is consistent with a theoretical prediction that the correlation between odd isotopes in fractionation induced by the MIE is controlled by the relationship between the spin conversion time and radical lifetime. The characteristic changes in the correlation between odd isotopes in fractionation induced by the MIE observed for Sn in this study provide a guideline for quantitatively determining fractionation patterns caused by the MIE for elements that have multiple isotopes with a nuclear spin. These results improve our understanding of the potential impact of the MIE on mass-independent fractionation observed in natural samples, such as meteorites, and analytical artifacts of high-precision isotope analysis for heavy elements.

Neutrophil depletion attenuates acute renal injury after exhaustive exercise in mice.

Prolonged intense exercise induces acute renal injury; however, the precise mechanism remains unclear. 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; sedentary with antineutrophil antibody; exhaustive exercise with control antibody; and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered i.p. to the mice before they ran on a treadmill. Plasma levels of creatinine and blood urea nitrogen (BUN) were measured. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using an enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using qRT-PCR. Furthermore, NADPH oxidase activity and the hydrogen peroxide concentration in the kidney were measured. Immediately after exhaustive exercise, plasma BUN was significantly increased, but creatinine was not. The increase in BUN after exercise was suppressed by 1A8 treatment. The pathological changes manifested as congested and swollen glomeruli and nuclear infiltration after exhaustive exercise. These changes were suppressed by treatment with the 1A8 antibodies. The KIM-1 concentration increased after exhaustive exercise but was reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and oxidative stress.

The Immunomodulatory Effects of Sulforaphane in Exercise-Induced Inflammation and Oxidative Stress: A Prospective Nutraceutical.

Sulforaphane (SFN) is a promising molecule for developing phytopharmaceuticals due to its potential antioxidative and anti-inflammatory effects. A plethora of research conducted in vivo and in vitro reported the beneficial effects of SFN intervention and the underlying cellular mechanisms. Since SFN is a newly identified nutraceutical in sports nutrition, only some human studies have been conducted to reflect the effects of SFN intervention in exercise-induced inflammation and oxidative stress. In this review, we briefly discussed the effects of SFN on exercise-induced inflammation and oxidative stress. We discussed human and animal studies that are related to exercise intervention and mentioned the underlying cellular signaling mechanisms. Since SFN could be used as a potential therapeutic agent, we mentioned briefly its synergistic attributes with other potential nutraceuticals that are associated with acute and chronic inflammatory conditions. Given its health-promoting effects, SFN could be a prospective nutraceutical at the forefront of sports nutrition.

Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Enhancing Grip Strength and Inhibiting Protein Catabolism Induced by Exhaustive Exercise.

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of HMPA on muscle function remains unknown. This study investigated the effects of HMPA on muscle strength and exercise endurance capacity. Mice were orally administered low and high doses of HMPA for 14 days and subjected to grip force and treadmill exhaustion tests to evaluate muscle function. Our results showed that HMPA-administered groups significantly enhanced absolute grip strength (p = 0.0256) and relative grip strength (p = 0.0209), and low-dose HMPA decreased the plasma level of blood urea nitrogen after exercise (p = 0.0183), but HMPA did not affect endurance performance. Low-dose HMPA administration increased Myf5 expression in sedentary mice (p = 0.0106), suggesting that low-dose HMPA may promote muscle development. Additionally, HMPA improved hepatic glucose and lipid metabolism, and inhibited muscular lipid metabolism and protein catabolism, as indicated by changes in mRNA expression levels of related genes. These findings suggest that HMPA may be a promising dietary supplement for muscle health and performance.

Direct Quantification of Attogram Levels of Strontium-90 in Microscale Biosamples Using Isotope Dilution-Thermal Ionization Mass Spectrometry Assisted by Quadrupole Energy Filtering.

Although thermal ionization mass spectrometry (TIMS) has been employed for the high-precision analysis of isotope ratios, direct quantification of artificial mono-nuclide in the environment is difficult by even using isotope dilution (ID) due to the coexistence of the great magnitude of natural stable nuclides or isobars. In traditional TIMS and ID-TIMS, a sufficient amount of stable Sr doped on a filament is required to realize a stable and adequate ion-beam intensity (i.e., thermally ionized beams). However, the background noise (BGN) at m/z 90, detected by an electron multiplier, disturbs 90Sr analysis at low concentration levels due to peak tailing of a significant 88Sr ion beam dependent on the 88Sr-doping amount. Here, TIMS assisted by quadruple energy filtering was successfully employed for the direct quantification of attogram levels of an artificial monoisotopic radionuclide strontium-90 (90Sr) in microscale biosamples. Direct quantification was achieved by integrating the ID quantification of natural Sr and simultaneous 90Sr/86Sr isotope ratio analysis. Additionally, the measurement amount calculated by the combination of the ID and intercalibration was corrected for the net result amount of 90Sr by subtracting dark noise and the detected amount derived from the survived 88Sr, which are equivalent with the BGN intensity at m/z 90. Background correction revealed that the detection limits were in the range of 6.15 × 10-2-3.90 × 10-1 ag (0.31-1.95 µBq), depending on the concentration of natural Sr in a 1 µL sample, and the quantification of 0.98 ag (5.0 µBq) of 90Sr in 0-300 mg/L of natural Sr was successful. This method could analyze small sample quantities (1 µL), and the quantitative results were verified against authorized radiometric analysis techniques. Furthermore, the amount of 90Sr in actual teeth was successfully quantified. This method will be a powerful tool for measuring 90Sr in the measurement of micro-samples, which are required to assess and understand the degree of internal radiation exposure.

Electrical pulse stimulation-induced muscle contraction alters the microRNA and mRNA profiles of circulating extracellular vesicles in mice.

Extracellular vesicles, such as exosomes, are secreted by skeletal muscle tissues and may play a role in physiological adaptations induced by exercise. Endurance exercise changes the microRNA (miRNA) profile of circulating extracellular vesicles; however, the effects of resistance exercise are unknown. In this study, we examined the effect of resistance exercise as electrical pulse stimulation (EPS)-induced muscle contraction on the miRNA and mRNA profiles of circulating extracellular vesicles in mice using a comprehensive RNA sequencing-based approach. EPS-induced muscle contraction resulted in changes in the miRNA profile of circulating extracellular vesicles. In particular, 90 min after EPS-induced muscle contraction, a considerable increase in expression of muscle-specific microRNAs, such as miR-1, miR-133, and miR-206, was observed. Furthermore, we found that the expression of 208 mRNAs was considerably altered immediately after EPS-induced muscle contraction and that of 267 mRNAs changed considerably after 90 min. Gene ontology enrichment analysis showed that mRNA expression changes in circulating extracellular vesicles after EPS-induced muscle contraction promoted angiogenesis and regulated the immune response. Changes in the properties of circulating extracellular vesicles owing to muscle contraction may play an important role in resistance exercise-induced physiological adaptations.

No strong association among epigenetic modifications by DNA methylation, telomere length, and physical fitness in biological aging.

Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging are strongly influenced by environmental and lifestyle factors, whether DNA methylation (DNAm) is affected by exercise training, remains unclear. In the present study, we investigated the relationships between physiological functions, maximal oxygen uptake (VO2max), vertical jump, working memory, telomere length (TL) assessed by RT-PCR, DNA methylation-based estimation of TL (DNAmTL), and DNA methylation-based biomarkers of aging of master rowers (N = 146) and sedentary subjects (N = 95), aged between 37 and 85 years. It was found that the TL inversely correlated with chronological age. We could not detect an association between telomere length and VO2max, vertical jump, and working memory by RT-PCR method, while these physiological test results showed a correlation with DNAmTL. DNAmGrimAge and DNAmPhenoAge acceleration were inversely associated with telomere length assessed by both methods. It appears that there are no strong beneficial effects of exercise or physiological fitness on telomere shortening, however, the degree of DNA methylation is associated with telomere length.

Coffee consumption and skeletal muscle mass: WASEDA'S Health Study.

Few studies have examined the association between coffee consumption and muscle mass; their results are conflicting. Therefore, we examined the association between coffee consumption and low muscle mass prevalence. We also performed an exploratory investigation of the potential effect modification by demographic, health status-related and physical activity-related covariates. This cross-sectional study included 2085 adults aged 40-87 years. The frequency of coffee consumption was assessed using a self-administered questionnaire. Muscle mass was assessed as appendicular skeletal muscle mass/height2 using a multifrequency bioelectrical impedance analyser. We defined low muscle mass using cut-offs recommended by the Asian Working Group for Sarcopenia. Multivariable-adjusted OR for low muscle mass prevalence were estimated using a logistic regression model. The prevalence of low muscle mass was 5·4 % (n 113). Compared with the lowest coffee consumption group (< 1 cup/week), the multivariable-adjusted OR (95 % CI) of low muscle mass prevalence were 0·62 (0·30, 1·29) for 1-3 cups/week, 0·53 (0·29, 0·96) for 4-6 cups/week or 1 cup/d and 0·28 (0·15, 0·53) for ≥ 2 cups/d (P for trend < 0·001). There were no significant interactions among the various covariates after Bonferroni correction. In conclusion, coffee consumption may be inversely associated with low muscle mass prevalence.

The effects of guar gum supplementation on lipid profile in adults: a GRADE-assessed systematic review, meta-regression and dose-response meta-analysis of randomised placebo-controlled trials.

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), LDL, TAG and 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 % CI were estimated via a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. Pooled analysis of nineteen randomised controlled trials (RCT) 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 TAG and HDL among adults in comparison with control group. Our outcomes suggest that guar gum supplementation lowers TC and LDL in adults. Future large RCT on various populations are needed to show further beneficial effects of guar gum supplementation on lipid profile and establish guidelines for clinical practice.

Sulforaphane Attenuates Neutrophil ROS Production, MPO Degranulation and Phagocytosis, but Does Not Affect NET Formation Ex Vivo and In Vitro.

Sulforaphane has several effects on the human body, including anti-inflammation, antioxidation, antimicrobial and anti-obesity effects. In this study, we examined the effect of sulforaphane on several neutrophil functions: reactive oxygen species (ROS) production, degranulation, phagocytosis, and neutrophil extracellular trap (NET) formation. We also examined the direct antioxidant effect of sulforaphane. First, we measured neutrophil ROS production induced by zymosan in whole blood in the presence of 0 to 560 µM sulforaphane. Second, we examined the direct antioxidant activity of sulforaphane using a HOCl removal test. In addition, inflammation-related proteins, including an azurophilic granule component, were measured by collecting supernatants following ROS measurements. Finally, neutrophils were isolated from blood, and phagocytosis and NET formation were measured. Sulforaphane reduced neutrophil ROS production in a concentration-dependent manner. The ability of sulforaphane to remove HOCl is stronger than that of ascorbic acid. Sulforaphane at 280 µM significantly reduced the release of myeloperoxidase from azurophilic granules, as well as that of the inflammatory cytokines TNF-α and IL-6. Sulforaphane also suppressed phagocytosis but did not affect NET formation. These results suggest that sulforaphane attenuates neutrophil ROS production, degranulation, and phagocytosis, but does not affect NET formation. Moreover, sulforaphane directly removes ROS, including HOCl.

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.

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.

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.

Regular exercise stimulates endothelium autophagy via IL-1 signaling in ApoE deficient mice.

Regular exercise maintains arterial endothelial cell homeostasis and protects the arteries from vascular disease, such as peripheral artery disease and atherosclerosis. Autophagy, which is a cellular process that degrades misfolded or aggregate proteins and damaged organelles, plays an important role in maintaining organ and cellular homeostasis. However, it is unknown whether regular exercise stimulates autophagy in aorta endothelial cells of mice prone to atherosclerosis independently of their circulating lipid profile. Here, we observed that 16 weeks of voluntary exercise reduced high-fat diet-induced atherosclerotic plaque formation in the aortic root of ApoE deficient mice, and that this protection occurred without changes in circulating triglycerides, total cholesterol, and lipoproteins. Immunofluorescence analysis indicated that voluntary exercise increased levels of the autophagy protein LC3 in aortic endothelial cells. Interestingly, human umbilical vein endothelial cells (HUVECs) exposed to serum from voluntarily exercised mice displayed significantly increased LC3-I and LC3-II protein levels. Analysis of circulating cytokines demonstrated that voluntary exercise caused changes directly relevant to IL-1 signaling (ie, decreased interleukin-1 receptor antagonist [IL-1ra] while also increasing IL-1α). HUVECs exposed to IL-1α and IL-1ß recombinant protein significantly increased LC3 mRNA expression, LC3-I and LC3-II protein levels, and autophagy flux. Collectively, these results suggest that regular exercise protects arteries from ApoE deficient mice against atherosclerosis at least in part by stimulating endothelial cell autophagy via enhanced IL-1 signaling.

The effects of different temperatures of post-exercise protein-containing drink on gastric motility and energy intake in healthy young men.

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.

Association between alcohol dietary pattern and prevalence of dyslipidaemia: WASEDA'S Health Study.

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 2171 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 LDL-cholesterol levels. The fully adjusted OR (95 % CI) of high LDL-cholesterol 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 TAG 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.

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.

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.

The Association of Inflammatory Markers, IL-1α and TGF-ß, with Dietary Insulin Load and Dietary Insulin Index in Overweight and Obese Women with Healthy and Unhealthy Metabolic Phenotypes: A Cross-Sectional Study.

Context Research has shown IL-1α might play a role in the associations between the MH group and DII and DIL. Objective. We evaluated the association of inflammatory markers, IL-1α and TGF-ß, with dietary insulin load and index in women with healthy and unhealthy obesity phenotypes. Materials and Methods. 228 obese/overweight women aged 18-48 years were included in this study. Biochemical factors were obtained from blood samples. Body composition, anthropometric measures, and physical activity assessments were performed. Dietary intakes, DII, and DIL were assessed. Results. Significant associations were observed between the MH group and the DII group (OR = 2.142, 95% CI = 1.421, 2.850, and p = 0.040), in which IL-1α may play a role. Discussion and Conclusion. Significant associations were observed between the MH group and DII. IL-1α might play a role in these associations.