Search Results (198)

Background: Durative exercise-induced fatigue influences muscle structure and exercise performance. Dietary supplements combining bioavailable proteins with essential vitamins and minerals may help reduce fatigue. Compared with proteins, whey peptides, as easily absorbed energy sources, are regarded as better promoting the utilization of vitamins and minerals. This study investigated whether the combination of whey peptides and micronutrients could synergistically improve exercise-induced fatigue and exercise performance. Methods: Four-week-old male C57BL/6J mice were forced to exercise using a treadmill for four weeks to evaluate the supplemental effects of whey peptides and/or micronutrients on exercise performance. Results: Compared with mice receiving whey peptides or micronutrients alone, mice receiving a combination of whey peptides and micronutrients displayed increased muscle mass, muscle fiber cross-sectional area, muscle strength, and exercise performance, including running exhausting time and swimming exhausting time. Consistent results were obtained in detecting fatigue-associated serum metabolites and markers reflecting muscle injury. To elucidate the anti-fatigue mechanisms of whey peptides and micronutrients, RNA transcriptome in the muscle tissues were analyzed. Enrichment analysis results suggest that micronutrients and/or whey protein alleviate exercise-induced fatigue, not only via reducing oxidative stress but also repressing excessive immune activation in muscle tissue, thereby decreasing the tissue injury caused by strenuous exercise. Conclusions: Overall, the current study indicates that the combination of whey peptides and micronutrients produces a synergistic effect on promoting exercise performance. Our findings provide scientific evidence for the development of novel and efficient anti-fatigue functional foods using whey peptides and micronutrients. Full article

Exercise-induced fatigue involves oxidative stress and metabolic dysregulation. While the anti-aging protein α-Klotho regulates metabolism and oxidative stress, its role in exercise fatigue is unexplored. This study investigated whether α-Klotho supplementation mitigates cumulative exercise-induced fatigue and elucidated the underlying tissue-specific mechanisms. Male C57BL/6J mice were divided into three groups (n = 10 per group), the control group, fatigue treated with saline, or α-Klotho (0.2 mg/kg, i.p. daily) group. Fatigue was induced by a 6-day exhaustive swimming protocol (5% body weight load). Tissues were collected 24h post-final exercise. Assessments included daily exhaustion time, grip strength, serum creatine kinase (CK), urea nitrogen (BUN), oxidative stress markers (H₂O₂, MDA, SOD, GSH/GSSG), tissue glycogen, and pathway protein expression (Western blot). α-Klotho supplementation prevented exercise-induced weight loss and restored grip strength. While exhaustive exercise markedly increased serum CK and BUN levels, α-Klotho selectively normalized CK without effecting serum BUN. α-Klotho attenuated oxidative damage by reducing hydrogen peroxide levels while enhancing antioxidant capacity, accompanied by activation of the NRF2/HO-1 pathway and further upregulation of PGC-1α. Notably, α-Klotho induced striking hepatic glycogen supercompensation through activation of the AKT/GS signaling pathway and upregulation of GLUT4, whereas muscle glycogen levels remained unchanged. In conclusion, α-Klotho ameliorates cumulative exercise-induced fatigue through dual recovery-phase mechanisms: NRF2/HO-1-mediated antioxidant protection in skeletal muscle and AKT/GS-triggered hepatic glycogen supercompensation, thereby facilitating oxidative stress resolution and enhancing energy reserve restoration. Full article

Sea cucumber peptides have been shown to possess a number of functions, including antioxidant, anti-inflammatory, anti-tumor, and anti-fatigue effects, as well as immune regulation and promotion of collagen synthesis. Among these, high F-value oligopeptides are a promising natural active ingredient demonstrating excellent anti-fatigue effects. This study utilized fresh sea cucumbers as the primary raw material, employing membrane separation technology to investigate the simultaneous separation of sea cucumber polysaccharides and peptides. The process for removing aromatic amino acids during the preparation of high F-value oligopeptides from sea cucumbers was optimized, and the mechanism underlying their anti-fatigue effects was explored. A two-step enzymatic hydrolysis method using neutral protease and composite flavor protease was employed, followed by membrane separation using a 10,000 Da molecular weight ultrafiltration membrane, yielding a sea cucumber peptide yield of 45.00 ± 0.12% and a sea cucumber polysaccharide yield of 51.28 ± 0.63%. Following the removal of aromatic amino acids by means of activated carbon adsorption, the F-value of the high-F-value oligopeptides attained 23.82, with a yield of 24.56%. The experimental findings demonstrated that high-F-value oligopeptides exhibited a substantial increase in the swimming duration of mice and a notable enhancement in their grip strength. These observations signified their substantial anti-fatigue potential. Furthermore, studies have indicated that sea cucumber high-F-value oligopeptides reduce metabolites produced by exercise, enhance muscle protection, increase the activity of antioxidant enzymes in the body, and alleviate fatigue, thereby achieving an anti-fatigue effect. Full article

Major depressive disorder is increasingly recognized as a metabolic–immune disorder in which chronic inflammation diverts tryptophan (Trp) metabolism toward the kynurenine pathway (KP), reducing serotonin synthesis and producing neurotoxic metabolites such as quinolinic acid (QA). Elevated kynurenine (KYN)/Trp ratios and an altered QA/kynurenic acid (KYNA) balance have been consistently reported in depressed individuals, implicating the KP as a key therapeutic target. Exercise provides a unique, translationally relevant intervention: unlike pharmacological agents acting directly on neurotransmission, contracting skeletal muscle acts as a “kynurenine sink” by inducing kynurenine aminotransferases that convert circulating KYN into neuroprotective KYNA, thereby reducing brain KYN uptake and mitigating excitotoxicity. Clinical studies and meta-analyses confirm that aerobic, resistance, and high-intensity training produce antidepressant effects comparable to pharmacotherapy, while also improving cognition, fatigue tolerance, and cardiometabolic function. Beyond KP remodeling, exercise-induced myokines (irisin, IL-6, BDNF, apelin, FGF21) and adipokines (adiponectin, leptin modulators) coordinate systemic anti-inflammatory and neurotrophic adaptations that enhance resilience and brain plasticity. Furthermore, pharmacological “exercise mimetics” and metabolic modulators, such as PPAR agonists, AMPK activators, NAD⁺ boosters, meldonium, trimetazidine, and adiponectin receptor agonists, may be promising adjuncts for patients with low exercise capacity or metabolic comorbidities. This review provides a novel concept, positioning exercise as a systemic antidepressant that breaks the kynurenine lock of depression. Through proper interpretation of skeletal muscle as an endocrine organ of resilience, we integrate molecular, clinical, and translational findings to show how exercise remodels Trp–KYN metabolism and inflammatory signaling and how pharmacological mimetics may extend these benefits. This perspective consolidates scattered mechanistic and clinical data and outlines a forward-looking therapeutic framework that links exercise and lifestyle, metabolism, and drug discovery. We highlight that re-consideration of our understanding of depression, as a whole-body disorder, should provide new opportunities for precision interventions. Full article

Several antioxidants play an important role in improving athletic performance. Increased inflammation and oxidative stress during physical performance result in the production of free radicals, including reactive oxygen species (ROS), which leads to fatigue, muscle damage, and impaired performance. However, moderate and transient increases in ROS are physiologically essential, acting as signaling mediators that trigger adaptive cellular responses. Despite their harmful effects on athletic performance, ROS may also enhance physical protection by acting as signaling molecules against increased physical stress. Healthy dietary patterns such as the Mediterranean diet (MD) may contribute to decrease oxidative stress thanks to its content in fruits, vegetables, olive oil, legumes, and herbs/spices. Indeed, the beneficial effects of the MD can be attributed not only to its antioxidant properties but also to its well-documented anti-inflammatory effects, lipid-modulating actions, immune-supportive functions, and modulation of gut microbiota composition, which collectively influence metabolic and physiological resilience. The MD also plays a key role in competitive sport and training. In addition, several researchers have reported that the MD is essential for reducing risk of injury and illness, recovering and adapting between bouts of activity, and enhancing performance. In this context, following the key principles of an MD could also represent a useful framework for good dietary in competitive athletes. In this narrative review, we discuss the potential effects of antioxidants in sport and the impact of individual foods or compounds of the MD on oxidative stress and exercise performance in competitive athletes and physically active individuals. The potential modifications which could be made to the MD will be highlighted to maximize health and performance effects, in accordance with contemporary sports nutrition practices. Full article

Background/Objectives: Nutritional supplementation has been proposed as a potential adjunct strategy in myopia prevention and control through antioxidative, anti-inflammatory, and extracellular matrix-regulating mechanisms. This systematic review aimed to evaluate randomized controlled trial (RCT) evidence on the effects of carotenoids, anthocyanins, polyunsaturated fatty acids, and combined nutraceutical formulations on refractive outcomes, axial length, macular pigment optical density (MPOD), visual function, and symptoms of visual fatigue. Methods: The review was registered in PROSPERO (CRD420251149727) and conducted in accordance with PRISMA 2020 and AMSTAR-2 guidelines. PubMed, Web of Science, and Scopus were searched up to 5 August 2025. Eligible studies were RCTs involving individuals with myopia or at risk of myopia, comparing nutritional supplementation with placebo or active controls. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Results: Nine RCTs were included. Carotenoids such as crocetin, lutein, zeaxanthin, and astaxanthin produced modest benefits, including improved MPOD, reduced visual fatigue, and—in one pediatric trial—slightly less axial elongation. Anthocyanin-rich extracts improved mesopic contrast sensitivity and subjective asthenopia. A combined carotenoid–polyphenol formulation enhanced accommodative facility. However, no consistent clinically meaningful reduction in myopia progression was observed. Trials were generally small, heterogeneous, and short in duration. Conclusions: Nutritional supplementation may improve visual function and retinal antioxidant status but lacks strong evidence for slowing myopia progression. Larger, long-term RCTs are needed before recommending supplementation for routine myopia management. Full article

Uphill wheelchair propulsion requires considerable upper-limb effort and often leads to rapid fatigue, limiting user mobility and independence. Therefore, mechanical solutions that enhance propulsion safety and efficiency are essential. This study aimed to evaluate the effect of an anti-rollback module on upper-limb muscle activity and user load during uphill propulsion. Eight male participants propelled a manual wheelchair under three conditions: without the module (NAR), with a flexible roller (EAR), and with a stiff roller (SAR). Electromyographic (EMG) signals were recorded from four upper-limb muscles—anterior deltoid, triceps brachii, biceps brachii, and extensor carpi radialis—along with propulsion kinematics. The analyzed parameters included the number of push cycles, cycle duration, normalized muscle activity (EMG_norm), cumulative muscle load (CML), and its rate over time (CML/s). On average, participants performed 13.4 push cycles in NAR, 14.3 in EAR, and 14.4 in SAR, with corresponding cycle durations of 1.22 s, 1.59 s, and 1.39 s. The EAR configuration reduced fluctuations in EMG amplitude and CML/s compared to NAR, indicating smoother and more stable propulsion. No significant differences in mean EMG_norm or total CML were observed (p > 0.99). The flexible anti-rollback module improved propulsion stability and control without increasing muscle effort, suggesting its potential benefits for safer and more efficient manual wheelchair use on inclines. Full article

Hymenaea spp. (Fabaceae) are widely used in folk medicine to treat fatigue, inflammation, respiratory, and gastrointestinal disorders. However, comprehensive evidence-based evaluations of their pharmacological potential remain limited. This systematic review brought together the existing pharmacological and phytochemical evidence on the significant therapeutic potential of Hymenaea spp. A total of 17 studies were included; phytochemical analyses identified flavonoids, triterpenes, procyanidins, xyloglucans, and caryophyllene oxide among the major bioactive constituents. The reported biological activities were primarily anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, and antiproliferative. Mechanistic findings consistently substantiated anti-inflammatory evidence through COX/LOX inhibition, cytokines, and redox-related modulations. Despite these promising results, the molecular mechanisms and translational evidence remain poorly defined. In conclusion, Hymenaea spp. exhibit significant pharmacological potential. Future studies integrating metabolomics and preclinical and clinical validation are essential to translating traditional knowledge of this species into evidence-based therapeutics. Full article

Non-coeliac wheat sensitivity (NCWS) is characterised by gastrointestinal and extra-intestinal symptoms following gluten/wheat ingestion in individuals without coeliac disease or wheat allergy but remains controversial due to symptom overlap with irritable bowel syndrome (IBS). This narrative review aims to provide a comprehensive, critical analysis of NCWS as a clinical and biological entity, examining the evidence for its distinction from related disorders. While self-reported rates are high (often >10%) in the general population, rigorous double-blind, placebo-controlled challenge (DBPCC) studies confirm the diagnosis in only a minority of cases (typically <30%). The clinical presentation is heterogeneous, combining IBS-like symptoms with systemic complaints such as “brain fog,” headaches, and fatigue. The pathophysiology is distinct from coeliac disease, involving innate immune activation, altered intestinal barrier function, and gut dysbiosis. Non-gluten wheat components, particularly fructans and amylase-trypsin inhibitors, are implicated as potential triggers. Diagnosis is challenging, requiring the exclusion of other disorders and adherence to complex dietary challenge protocols such as the Salerno Experts’ Criteria, which are impractical for routine clinical use. The search for validated biomarkers is a key research area and investigated candidates include serological markers such as IgG anti-gliadin antibodies, inflammatory markers such as faecal calprotectin, and proteins related to intestinal permeability such as zonulin, but results have been conflicting and require further validation. Management primarily involves elimination of wheat and gluten from the diet, although a low-FODMAP diet has also proven effective as an adjunctive treatment. In conclusion, NCWS is a clinical entity whose study and management are critically hampered by the absence of validated diagnostic criteria and biomarkers. Progress requires methodologically rigorous DBPCC trials to elucidate its mechanisms and develop reliable diagnostic tools. Full article

This study investigated the anti-fatigue and anti-aging benefits of continuous intake of resveratrol (RES)-rich beverages. Locomotion and forelimb grip strength performance were significantly improved in medium- and high-dose RES groups. In terms of aging indices, the scores for the medium- and high-dose groups were significantly lower than those of the control group. In the PAT and active shuttle avoidance tests, the three RES groups performed better than the control group. A significant increase in SOD and catalase activity in the liver and a reduction in TBARS and 8-OHdG levels in the brain were observed in the medium- and high-dose groups. Thus, supplementation with RES-rich beverages for 13 weeks significantly improved fatigue, locomotor performance, learning and memory abilities, and liver antioxidant activity and reduced brain peroxide levels in SAMP8 mice. Full article

Background/Objectives: Functional p53 is critical for anti-tumor activity of mitomycin-C. In wild-type TP53 human papillomavirus (HPV)-positive squamous cell carcinoma (SCC) cell lines, mitomycin-C repressed E6 oncoprotein expression and induced p53, p21, and Bax, resulting in apoptosis. In mutant TP53 HPV-negative SCC cell lines, mitomycin-C was inactive. The primary aim of this trial was to determine the objective response rate (ORR) with mitomycin-C among patients with HPV-positive (cohort A) and HPV-negative (cohort B) platinum-refractory, recurrent or metastatic head and neck SCC (RM-HNSCC). Methods: Patients with platinum-refractory RM-HNSCC received mitomycin-C (10 mg/m² on day one every five weeks) until discontinuation criteria were met. Tumor response was assessed by RECIST1.1. We hypothesized an ORR of ≥30% (H₁) with mitomycin-C (vs. H₀ ORR of ≤10%). Using a two-stage Simon phase 2 design for each cohort, 2 or more responses among 12 evaluable patients were required to enroll 23 additional patients. H₁ was accepted if 6 or more responses occurred among 35 evaluable patients (power 0.90; one-sided α = 0.10). Results: Forty-seven patients were treated with mitomycin-C: 34 in cohort A and 13 in cohort B. Tumor response occurred in 3 of 33 evaluable patients in cohort A (ORR 9.1%, 95%CI: 0–19.4) and in 0 of 12 evaluable patients in cohort B. The duration of tumor responses in cohort A was 2.3, 2.5, and 4.5 months. The most common treatment-related AEs of any grade were anemia (96%), fatigue (62%), and thrombocytopenia (40%). No treatment-related deaths occurred. Conclusions: Mitomycin-C had limited activity in HPV-positive, and no activity in HPV-negative, platinum-refractory RM-HNSCC. Full article

Background: L-arginine is a conditionally essential amino acid that serves as a substrate for nitric oxide synthase and regulates energy metabolism. While its ergogenic effects have been proposed, the mechanisms underlying its anti-fatigue properties are not fully understood. Methods: Male ICR mice were orally administered L-arginine (300, 600, or 1200 mg/kg bw/day) for 28 days. Fatigue was chronically induced using twice-weekly forced swimming or treadmill running, and fatigue resistance was then assessed under these paradigms. Blood, skeletal muscle, and liver were analyzed for biomarkers including glucose, lactate, LDH, CPK, NEFA, ammonia, glycogen, nitric oxide, cortisol, and antioxidant enzymes. In parallel, C2C12 myoblasts were treated with L-arginine under proliferative and differentiated conditions to assess hexokinase (HK) activity, myogenin expression, and ROS generation. Results: In vivo, L-arginine decreased serum LDH, CPK, NEFA, ammonia, nitric oxide, and cortisol, while enhancing blood glucose and glycogen storage in both muscle and liver. Forced swimming reduced serum lactate, whereas treadmill exercise elevated intramuscular lactate, suggesting context-dependent lactate regulation. Importantly, L-arginine did not significantly improve forced-swimming immobility time, whereas treadmill time-to-exhaustion increased at the highest dose. Antioxidant responses were improved, as reflected by normalized hepatic catalase activity. In vitro, L-arginine increased HK activity, promoted myogenin expression, and reduced ROS levels, supporting improved glucose utilization, muscle differentiation, and oxidative stress resistance. Conclusions: These findings demonstrate that L-arginine supplementation under chronic fatigue-inducing paradigms improves endurance and alleviates fatigue by enhancing energy metabolism, preserving glycogen, reducing muscle injury, and attenuating oxidative stress. L-arginine shows potential as a functional ingredient for promoting exercise performance and recovery. Full article

MicroRNA-22 (miR-22) is a negative regulator of mitochondrial biogenesis, as well as lipid and glucose metabolism, in metabolically active tissues. Silencing miR-22 holds promise as a potential treatment of obesity and metabolic syndrome, as it restores metabolic capacity—enhancing oxidative metabolism—and reduces ectopic fat accumulation in chronic obesity, a driver of impaired metabolic flexibility and muscle mass loss. Intramuscular adipose accumulation and defective mitochondrial function are features associated with obese-mediated muscle atrophy and hallmarks of neuromuscular disorders such as Duchenne muscular dystrophy. Therefore, miR-22 could represent a compelling molecular target to improve muscle health across various muscle-wasting conditions. This study describes a pharmacological strategy for the inhibition of miR-22 in skeletal muscle by employing a mixmer antisense oligonucleotide (ASO, anti-miR-22). Administration of the ASO in a mouse model of obesity positively modulated myogenesis while protecting dystrophic mice from muscle function decline, enhancing fatigue resistance, and limiting pathological fibrotic remodeling. Mechanistically, we show that anti-miR-22 treatment promotes derepression of genes involved in mitochondrial homeostasis, favoring oxidative fiber content regardless of the disease model, thus promoting a more resilient phenotype. Furthermore, we suggest that miR-22 inhibition increases autophagy by transcriptional activation of multiple negative regulators of mammalian target of rapamycin (mTOR) signaling to decrease immune infiltration and fibrosis. These findings position miR-22 as a promising therapeutic target for muscle atrophy and support its potential to restore muscle health. Full article

As a key piece of equipment in badminton, the surface treatment technology of rackets has garnered significant attention in the fields of material science and sports engineering. This study is the first to systematically review research on racket coatings, integrating interdisciplinary knowledge on the classification of functional coatings, their performance-enhancing principles, and their relationship with competitive levels, thereby addressing a gap in theoretical research in this field. This study focuses on four major functional coating systems: superhydrophobic coatings (to improve environmental adaptability and reduce air resistance), anti-scratch coatings (to prolong the life of the equipment), vibration-damping coatings (to optimise vibration damping performance), and strength-enhancing coatings (to safeguard structural stability). In badminton, differences in player skill levels and usage scenarios lead to variations in racket materials, which, in turn, result in different preparation processes and performance effects. The use of vibration-damping materials alleviates the impact force on the wrist, effectively preventing sports injuries caused by prolonged training; leveraging the aerodynamic properties of superhydrophobic technology enhances racket swing speed, thereby improving hitting power and accuracy. From the perspective of performance optimization, coating technology improves athletic performance in three ways: nanocomposite coatings enhance the fatigue resistance of the racket frame; customized damping layers reduce muscle activation delays; and surface energy regulation technology improves grip stability. Challenges remain in the industrial application of environmentally friendly water-based coatings and the evaluation system for coating lifespan under multi-field coupling conditions. Future research should integrate intelligent algorithms to construct a tripartite optimization system of “racket-coating-user” and utilize digital sports platforms to analyze its mechanism of influence on professional athletes’ tactical choices, providing a theoretical paradigm and technical roadmap for the targeted development of next-generation smart badminton rackets. Full article

Rheumatoid arthritis (RA) is a widespread autoimmune disease that significantly impacts the lives of RA patients. It is often typified as swelling and deformation of small joints, as well as systemic inflammation. Rhodiola rosea has been utilized for millennia to treat various ailments and is known to contain numerous active compounds, including saponins, volatile oils, coumarins, and flavonoids. Recent studies have underscored the pivotal role of salidroside (SAL), a key constituent of Rhodiola rosea L. Modern research indicates that SAL has various pharmacological activities, such as its antioxidant, anti-inflammatory, anti-fatigue, and anti-cancer effects. Despite this, the pathogenesis of RA remains highly complex, and a notable lack exists in overview studies investigating the anti-RA mechanisms of SAL. Therefore, the purpose of this article is to review the present research efforts on the anti-RA mechanisms of SAL and to explore future research prospects for this compound. Full article