Spatial distribution and influencing factors analysis of national key rural tourism villages in the Yangtze River Delta region based on geographically weighted regression.

National key rural tourism villages (NKRTVs) can lead to the high-quality development of rural tourism, and their spatial distribution is influenced by a variety of factors. However, existing studies have neglected the fact that influencing factors can have different directions and effects in different geographic spaces. This study investigates 156 NKRTVs in the Yangtze River Delta region of China as the research object and employs ArcGIS spatial analysis technology to examine their spatial distribution characteristics. Additionally, two new indicators of land and culture are introduced to enhance the index system of influencing factors. A geographically weighted regression model is utilized to identify the spatial heterogeneity of various factors that affect the spatial distribution of NKRTVs. The results of this study indicate the following: (1) The spatial distribution of NKRTVs in the Yangtze River Delta region is characterized by "small clustering and large dispersion." The spatial distribution exhibits strong spatial correlation, with Shanghai serving as the primary spatial clustering core and Huangshan city forming a secondary spatial clustering subcore. The distribution of NKRTVs is relatively scattered in other areas, with obvious differences in the spatial distribution of cold and hot spots. (2) The results of the geographically weighted regression model show that with the change in spatial location, the influence effect of each influencing factor on the spatial distribution of NKRTVs has obvious spatial differences. Based on the spatial heterogeneity of the influencing factors, this study proposes targeted suggestions for the development of rural tourism in different regions.

Efficacy and safety of Tongdutiaoshen acupuncture on insomnia in maintenance hemodialysis patients: A randomized clinical trial protocol.

Background: Patients undergoing maintenance hemodialysis (MHD) experience insomnia frequently. Poor sleep quality impairs the quality of life and adversely affects long-term outcomes. Currently, the treatment of insomnia in patients undergoing MHD is mainly based on medication, although it has severe side effects and poor compliance in patients. Therefore, developing complementary and alternative therapies with higher efficacies is important. This study explores the clinical efficacy and safety of Tongdutiaoshen acupuncture in treating insomnia in patients with MHD. Methods: This randomized controlled trial (RCT) will be performed at Beijing Luhe Hospital, affiliated with Capital Medical University in China. We will strictly adhere to the Standards for Reporting Interventions in Clinical Trials of Acupuncture (2010). A total of 110 MHD patients with insomnia will be randomly allocated in a 1:1 ratio to the drug control (DC) or Tongdutiaoshen acupuncture (TA) group. Patients in the control group will be administered estazolam tablets (1 mg/day) for four weeks, followed by a 4-week follow-up period. Based on the background therapy provided for the DC group, the TA group will be administered the interventional cohort three times a week for four weeks in a row, followed by a 4-week follow-up period. The primary endpoints will include the Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAM-A), TCM Insomnia Syndrome Score, and clinical response rate, which will be evaluated on days 0, 14, 28, and 56. Secondary endpoints will include sleep data monitoring and related laboratory indices, which will be evaluated on days 0, 28, and 56, respectively. Discussion: This study is designed based on a rigorous methodology to evaluate the efficacy and safety of Tongdutiaoshen acupuncture for insomnia in patients undergoing hemodialysis. The findings of this trial will be published in peer-reviewed journals as reliable evidence. Trial registration: Chinese Clinical Trial Registry ChiCTR2200061967. Registered on July 07, 2022.

Effects of high-flux hemodialysis and hemodiafiltration on the mortality of patients with end-stage kidney disease: a meta-analysis.

BACKGROUND: High-flux hemodialysis (HFHD) is widely used in hemodialysis centers and is the mode of hemodialysis actively recommended by the guidelines. Additionally, hemodiafiltration (HDF) is widely used in clinical practice. However, there are some inconsistencies in the results of studies on the effects of HDF and HFHD, which has caused controversy regarding which of these two dialysis modalities to select. OBJECTIVE: To explore the effect of HFHD and HDF on the survival of patients with end-stage kidney disease (ESKD). METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and VIP databases was conducted, focusing on cohort studies and randomized controlled trials on hemodialysis in patients with ESKD using HFHD or HDF. A meta-analysis of all-cause mortality and cardiovascular mortality was conducted using Review Manager 5.3 software, and fixed and random effect models were applied according to the heterogeneity results. RESULTS: A total of 13 studies, including six cohort studies and seven randomized controlled trials, were included in the final analysis. The results revealed that HFHD had no statistically significant effect on the all-cause mortality (odds ratio (OR): 1.16, 95% confidence interval (CI): 0.86, 1.57) or cardiovascular mortality (OR: 0.86, 95% CI: 0.64, 1.15) of patients with ESKD. However, compared with HDF, HFHD reduced the infection mortality rate (OR: 0.50, 95% CI: 0.33, 0.77). CONCLUSIONS: Compared with HDF, HFHD has no obvious benefits for all-cause mortality or cardiovascular mortality in patients with ESKD, but reduced risk of infection-related death.

Effects of Heat-Moisture-Treated High-Amylose Rice Flour on Body Weight, Lipid Metabolism, and Gut Microbiome Composition in Obese Rats.

The rising prevalence of lifestyle diseases, such as type 2 diabetes, cardiovascular diseases, and metabolic syndrome, has increased the need for effective dietary interventions. This study aimed to evaluate the effects of heat-moisture-treated high-amylose rice (HA-HMT) on body weight, lipid metabolism, and gut microbiome composition in a rat model of obesity. Starch digestibility-specifically, resistant starch-has been shown to provide various health benefits, including improved metabolic health and gut microbiome composition. We employed a sequential approach: firstly, utilizing diet-induced obesity rat models fed with HMT-processed and HMT-non-processed low- or high-amylose rice to investigate the potential of amylose content or HMT to alter phenotypic characteristics and lipid metabolism; and secondly, using the optimal rice flour identified in the previous step to explore the underlying mechanisms. Our findings indicate that heat-moisture treatment, rather than the level of the amylose content of the rice, contributes to the observed anti-obesity and cholesterol-lowering effects. We identified candidate genes contributing to the cholesterol-regulating potential and demonstrated that HMT rice flour could influence the gut microbiome, particularly the Ruminococcus taxa. This study provides valuable insights into the health benefits of HA-HMT rice and supports its potential as a functional food ingredient in the management of obesity and cholesterol-related disorders.

Postnatal nutrition environment reprograms renal DNA methylation patterns in offspring of maternal protein-restricted stroke-prone spontaneously hypertensive rats.

Maternal malnutrition hampers the offspring health by manipulating the epigenome. Recent studies indicate that the changes in DNA methylation could be reversed by afterbirth nutrition supplementation. In this study, we used DNA methylation arrays to comprehensively investigate the DNA methylation status of the renal promoter regions and the effects of postnatal protein intake on DNA methylation. We fed stroke-prone spontaneously hypertensive (SHRSP) rat dams a normal diet or a low-protein diet during pregnancy, and their 4-week-old male offspring were fed a normal diet or a high-/low-protein diet for 2 weeks. We found that the methylation status of 2,395 differentially methylated DNA regions was reprogrammed, and 34 genes were reset by different levels of postnatal protein intake in the offspring. Among these genes, Adora2b, Trpc5, Ar, Xrcc2, and Atp1b1 are involved in renal disease and blood pressure regulation. Our findings indicate that postnatal nutritional interventions can potentially reprogram epigenetic changes, providing novel therapeutic and preventive epigenetic targets for salt-sensitive hypertension.

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.

Linking chromatin acylation mark-defined proteome and genome in living cells.

A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and ß-hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr's gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the "metabolites-modification-regulation" axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.

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.

Transcriptome and Methylome Profiling in Rat Skeletal Muscle: Impact of Post-Weaning Protein Restriction.

Skeletal muscle is programmable, and early-life nutritional stimuli may form epigenetic memory in the skeletal muscle, thus impacting adult muscle function, aging, and longevity. In the present study, we designed a one-month protein restriction model using post-weaning rats, followed by a two-month rebound feeding, to investigate how early-life protein restriction affects overall body growth and muscle development and whether these influences could be corrected by rebound feeding. We observed comprehensive alterations immediately after protein restriction, including retarded growth, altered biochemical indices, and disturbed hormone secretion. Transcriptome profiling of the gastrocnemius muscle followed by gene ontology analyses revealed that "myogenic differentiation functions" were upregulated, while "protein catabolism" was downregulated as a compensatory mechanism, with enhanced endoplasmic reticulum stress and undesired apoptosis. Furthermore, methylome profiling of the gastrocnemius muscle showed that protein restriction altered the methylation of apoptotic and hormone secretion-related genes. Although most of the alterations were reversed after rebound feeding, 17 genes, most of which play roles during muscle development, remained altered at the transcriptional level. In summary, early-life protein restriction may undermine muscle function in the long term and affect skeletal muscle development at the both transcriptional and methylation levels, which may hazard future muscle health.

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.

Black Ginger (Kaempferia parviflora) Extract Enhances Endurance Capacity by Improving Energy Metabolism and Substrate Utilization in Mice.

Black ginger (Kaempferia parviflora) extract (KPE), extracted from KP, a member of the ginger family that grows in Thailand, has a good promotion effect on cellular energy metabolism and therefore has been used to enhance exercise performance and treatment of obesity in previous studies. However, the effect of single-dose administration of KPE on endurance capacity has not been thoroughly studied, and whether the positive effect of KPE on cellular energy metabolism can have a positive effect on exercise capacity in a single dose is unknown. In the present study, we used a mouse model to study the effects of acute KPE administration 1 h before exercise on endurance capacity and the underlying mechanisms. The purpose of our study was to determine whether a single administration of KPE could affect endurance performance in mice and whether the effect was produced through a pro-cellular energy metabolic pathway. We found that a single administration of KPE (62.5 mg/kg·bodyweight) can significantly prolong the exercise time to exhaustion. By measuring the mRNA expression of Hk2, Slc2a4 (Glut4), Mct1, Ldh, Cd36, Cpt1ß, Cpt2, Lpl, Pnpla2 (Atgl), Aco, Acadm (Mcad), Hadh, Acacb (Acc2), Mlycd (Mcd), Pparg, Ppargc1a (Pgc-1α), Tfam, Gp, Gs, Pfkm, Pck1 (Pepck), G6pc (G6pase), Cs, and Pfkl in skeletal muscle and liver, we found that acute high-concentration KPE administration significantly changed the soleus muscle gene expression levels (p < 0.05) related to lipid, lactate, and glycogen metabolism and mitochondrial function. In gastrocnemius muscle and liver, glycogen metabolism-related gene expression is significantly changed by a single-dose administration of KPE. These results suggest that KPE has the potential to improve endurance capacity by enhancing energy metabolism and substrate utilization in muscles and liver.

Activating transcription factor 4-dependent hsa-miR-663a transcription mediates mTORC1/p70S6K1 signaling underleucine deprivation.

The mechanistic target of rapamycin complex 1 (mTORC1) is involved in nutrient-induced signaling and is a master regulator of cell growth and metabolism. Amino acid-deficient conditions affect mTORC1 activity; however, its upstream regulators warrant further investigation. MicroRNAs are key regulators of nutrient-related responses; therefore, the present study aimed to assess the leucine starvation-induced microRNA profile and its impact on mTORC1 activity. Transcriptome analysis of human hepatocellular carcinoma cells (HepG2) under leucine deprivation revealed that hsa-miR-663a and hsa-miR-1469 were altered in a transcription factor 4-dependent manner. Overexpression of these microRNAs induced phosphorylation of the ribosomal protein S6 kinase beta-1, a mTORC1 downstream target. Furthermore, hsa-miR-663a downregulated proline-rich Akt1 substrate of 40 kDa (PRAS40), one of the mTORC1 components. In summary, this study provides new insights into the regulatory role of microRNAs in amino acid metabolism and demonstrates alterations in microRNA profile under leucine deprivation in human hepatocytes.

Effect of Genistein Supplementation on Exercise-Induced Inflammation and Oxidative Stress in Mice Liver and Skeletal Muscle.

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-1ß, 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.

Determinants of Resting Oxidative Stress in Middle-Aged and Elderly Men and Women: WASEDA'S Health Study.

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 (ß = -0.11, P = 0.002), leg extension power (ß = -0.12, P = 0.008), BMI (ß = 0.12, P = 0.004), and HDL-C (ß = 0.08, P = 0.040) were included in the regression model (adjusted R 2 = 0.018). In the F2-IsoP, smoking status (ß = 0.07, P = 0.060), BMI (ß = 0.07, P = 0.054), and HbA1c (ß = -0.06, P = 0.089) were included in the regression model (adjusted R 2 = 0.006). In TBARS, glucose (ß = 0.18, P < 0.001), CRF (ß = 0.16, P < 0.001), age (ß = 0.15, P < 0.001), TG (ß = 0.11, P = 0.001), antioxidant supplementation (ß = 0.10, P = 0.002), and HbA1c (ß = -0.13, P = 0.004) were included in the regression model (adjusted R 2 = 0.071). 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.

The Effects of Beverage Intake after Exhaustive Exercise on Organ Damage, Inflammation and Oxidative Stress in Healthy Males.

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 > 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.

A Low-Protein High-Fat Diet Leads to Loss of Body Weight and White Adipose Tissue Weight via Enhancing Energy Expenditure in Mice.

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.

A Low-Carbohydrate Ketogenic Diet and Treadmill Training Enhanced Fatty Acid Oxidation Capacity but Did Not Enhance Maximal Exercise Capacity in Mice.

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.

Changes in Urinary Biomarkers of Organ Damage, Inflammation, Oxidative Stress, and Bone Turnover Following a 3000-m Time Trial.

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-ß-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 < 0.05). However, a muscle damage marker, titin N-terminal fragments, did not change (p > 0.05). Inflammation-related factors (IRFs), such as interleukin (IL)-1ß, 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 < 0.05). IRFs such as tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-12p40, and interferon (IFN)-γ did not change (p > 0.05). Oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and nitrotyrosine, did not change following exercise (p > 0.05) whereas 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased (p < 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 > 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.

Organosulfur Compounds: A Review of Their Anti-inflammatory Effects in Human Health.

Phytonutrients are widely recognized for providing protective human health benefits. Among the phytonutrients, epidemiological and experimental studies show that dietary organosulfur compounds (OSC) play a significant role in preventing various human pathological progressions, including chronic inflammation, by decreasing inflammatory mediators such as nitric oxide (NO), prostaglandin (PG)E2, interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-17, which are all typical hallmarks of inflammation. Evidence supports OSC in reducing the expression of these markers, thereby attenuating chronic inflammatory processes. Nuclear factor-kappa B (NF-κB) is a key regulating factor during inflammation, and novel evidence shows that OSC downregulates this transcriptional factor, thus contributing to the anti-inflammatory response. In vitro and in vivo studies show that inflammation is mechanistically linked with acute and chronic pathological conditions including cancer, diabetes, obesity, neural dysfunction, etc. Furthermore, a considerable number of experiments have demonstrated that the anti-inflammatory properties of OSC occur in a dose-dependent manner. These experiments also highlight indirect mechanisms as well as potent co-functions for protective roles as antioxidants, and in providing chemoprotection and neuroprotection. In this brief review, we provided an overview of the anti-inflammatory effects of OSC and elucidated probable mechanisms that are associated with inflammation and chronic disorders.

Characterization and Modulation of Systemic Inflammatory Response to Exhaustive Exercise in Relation to Oxidative Stress.

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.