BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic...BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.展开更多
Background: Post-workout supplementation has been used in athletes and recreational exercisers;however, responses between normal and overweight individuals on exercise performance and muscle recovery are less known.Me...Background: Post-workout supplementation has been used in athletes and recreational exercisers;however, responses between normal and overweight individuals on exercise performance and muscle recovery are less known.Methods: Normal and overweight young adult males(21 subjects/group) participated in resistance and fatiguing exercises before receiving post-workout supplements: placebo, coenzyme Q10(CoQ10), or sports drink in a crossover design. Resistance exercises included upper body exercise(bench press, upright row, and standing shoulder press) and lower body exercise(dead lift, back squat, and front squat) at 75% of one-repetition maximum(1 RM). Fatiguing exercise was performed on a cycle ergometer with 3 min of all-out effort at 3.5% of body mass. Participants consumed post-workout supplements within 10 min of exercise completion and repeated-bout exercise was performed 1 h later, followed by cardiovascular responses, urinary biomarkers, and delayed onset muscle soreness(DOMS) assessments.Results: There were effects of overweight on resistance exercise volume, critical power, fatigue index, and postexercise diastolic blood pressure(DBP). However, no differences in urinary biomarkers of muscle damage(potassium and creatinine) or DOMS between normal and overweight individuals. After supplementation, CoQ10 and sports drink increased resistance exercise volume regardless of body mass and increased critical power in the normal group. Additionally, CoQ10 supplementation was associated with a reduction in urinary biomarkers and DOMS in both groups.Conclusion: These findings are beneficial for sport scientists, nutritionists, and exercise physiologists in guiding post-workout supplementation with CoQ10 and sports drink to improve exercise performance and muscle recovery in normal and overweight individuals.展开更多
Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in thi...Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in this process.Methods: 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E-5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area(CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1(Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism.Results: Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically,Prmt1 regulated the p38 mitogen-activated protein kinase(p38)/activating transcription factor 2(ATF2)pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2(AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α(PGC-1α) signaling pathway.Conclusions: Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway.展开更多
Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be el...Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.展开更多
Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on ...Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factorα,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.展开更多
To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles ar...To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles are different,and the importance of these potential differences.In the present study,we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles.We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways.In terms of spatial distribution patterns,sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons.In addition,the neuronal innervation of limb muscles exhibited four different characteristics:sympathetic neuron-rich muscle,sensory neuron-rich muscle,neuron-sparse muscle,and motor neuron-rich muscle.Sensory neuron density was mainly associated with muscle contractile structure and cell pH,whereas sympathetic neuron density was associated with protein kinase activity,muscle vasculature,muscle calcium-dependent protein kinase activity,lipid transport,and vesicle release.Motor neuron density was mainly associated with protein kinase activity,cell adhesion,oxidoreductase activity,and exocytosis.These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions,thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.展开更多
Purpose:ATLAS is a cross-sectional study aiming to investigate environmental and genetic determinants of athletic performance in healthy Greek competitive athletes(CA).This article presents the study design,investigat...Purpose:ATLAS is a cross-sectional study aiming to investigate environmental and genetic determinants of athletic performance in healthy Greek competitive athletes(CA).This article presents the study design,investigates the muscle strength performance(MSP)of 289 adult and teenage CA,exercisers,and physically inactive individuals(PI),and proposes predictive models of MSP for adults.Methods:Muscle maximal,speed,and explosive strength(MMS/MSS/MES)at unilateral maximal concentric flexion and extension contraction(FC/EC)were evaluated using Biodex System 3 PRO^(TM)at 60°/s,180°/s,and 300°/s,while additional performance markers were assessed through field ergometric testing.Participants were interviewed about their lifestyle,dietary habits,physical activity,injury,and medical history.Body composition was assessed via bioelectrical impedance.gDNA was extracted from biochemical samples and then genotyped.Statistical analysis was conducted using IBM SPSS Statistics v21.0 and R.Results:Age,fitness,and sex impacted correlations of MSP with body composition and anthropometric measurements(p<0.05).Among CA,females outperformed males in accuracy(p<0.001)while,males outperformed females in anaerobic power,MSP,speed,and endurance(p<0.001).Adult CA outperformed exercisers and PI in MMS,MSS,and MES(p<0.05).Multiple linear regression models,with predictors age,FFM,body extremity,training load explained the majority of variation in MMS(R^(2)_(adj):71.4%–88.9%),MSS(R^(2)_(adj):64.8%–78.4%),and MES(R^(2)_(adj):52.7%–68.4%)at EC,FC,and their mean(p<0.001).Conclusions:Muscle-strengthening strategies should be customized according to individual fitness levels,body composition,and anthropometric measurements.The innovative sex-specific regression models assessing MMS,MSS,and MES at EC and FC provide a framework for personalizing rehabilitation and skill-specific training strategies.展开更多
Objectives:Postmenopausal women with stress urinary incontinence(SUI)exhibit low androgen expression.This study aimed to evaluate the efficacy and safety of vaginal androgen combined with pelvic floor muscle training(...Objectives:Postmenopausal women with stress urinary incontinence(SUI)exhibit low androgen expression.This study aimed to evaluate the efficacy and safety of vaginal androgen combined with pelvic floor muscle training(PFMT)in the treatment of SUI in postmenopausal women.Methods:Postmenopausal women with SUI were recruited from Hainan West Central Hospital between January 2024 and March 2025.Participants were randomly assigned in a double-blind manner to receive either vaginal androgen cream combined with PFMT(treatment group)or a visually identical placebo cream(without androgens)combined with PFMT(control group).The vaginal cream was applied to the vaginal wall at a dose of 0.5 g per application,twice weekly for a total of 10 applications,while PFMT was conducted for 8 weeks.The clinical efficacy and safety were compared between the two groups.Results:A total of 61 patients were finally enrolled,with 31 in the treatment group and 30 in the control group.At both 3-month and 6-month follow-ups,the treatment group demonstrated significantly lower values in daily pad usage(p<0.05),24-h pad test scores(p<0.05),and ICIQ-UI SF scores(p<0.05)compared to the control group.The improvement rate of urinary incontinence was significantly higher in the treatment group(p<0.05).Compared to baseline,the treatment group showed statistically significant reductions in all three outcome measures(all p<0.05).No severe adverse events were reported in either group during the treatment period.Conclusions:Androgen therapy combined with PFMT significantly improved the urinary incontinence remission rate in postmenopausal women with SUI,with no severe adverse effects observed.These findings suggest that androgen therapy may represent a novel therapeutic approach for SUI management in postmenopausal women.展开更多
Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,d...Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,disrupting proteostasis and increasing vulnerability to sarcopenia.High-intensity training(HIT)can counteract these declines by activating protective pathways such as the HSP response.HSPs are highly responsive to stress,examining their regulation during aging is important,as altered HSP activity is linked to the progressive loss of muscle mass.Methods This study investigated the abundance and phosphorylation of HSPs in skeletal muscle from healthy,active young and older adults(n=7 per group),assessed at baseline and again in the older group following 12 weeks of HIT.Using calibrated Western blotting on both whole-muscle homogenates and pooled single muscle fibres,we quantified HSP content and phosphorylation to determine how aging and exercise influence stress–responsive protein regulation at both the tissue and cellular levels.Results In whole muscle homogenates,HSPs(HSP72,HSP27,andαB-crystallin)did not differ between young and older adults,while higher phosphorylation of small HSPs(sHSPs):phospho-HSP27 at Serine15(pHSP27 Ser15)and phospho-αB-crystallin at Serine59(pαB-crystallin Ser59)(∼1.8-fold and∼2.9-fold,respectively)were found in muscle from older adults,indicating higher cellular stress associated with aging.A 12-week HIT intervention in older adults reduced homogenate pHSP27 Ser15 and pαB-crystallin Ser59 abundances to similar levels found in young adults.Total HSPs typically displayed a distinct fiber-type profile in both age groups,with more in type I compared to type II fibers,distinguished by the presence of myosin heavy chain I(MHCI)or MHCII.Phosphorylation at pHSP27 Ser15 and pαB-crystallin Ser59 was not different between type I and type II fibers.The HIT in older adults decreased total and phosphorylated sHSPs in both type I and type II fibers but increased HSP72 in type I fibers.Conclusion HIT has the potential to mitigate age-related cellular stress and modulate protein expression patterns in aging skeletal muscle and,perhaps,has the potential to delay age-related muscle decline,thereby improving muscle health in older adults.展开更多
Skeletal muscle accounts for approximately 40%of body mass and 50%–75%of whole-body protein,playing a central role in meat production and quality.Efficient protein synthesis in skeletal muscle relies on an adequate s...Skeletal muscle accounts for approximately 40%of body mass and 50%–75%of whole-body protein,playing a central role in meat production and quality.Efficient protein synthesis in skeletal muscle relies on an adequate supply of nutrient substrates and a balanced amino acid profile.Branched-chain amino acids(BCAA),including leucine(Leu),isoleucine(Ile),and valine(Val),are the most abundant essential amino acids in skeletal muscle and contribute to both protein synthesis and oxidative energy production.Additionally,BCAA function as signaling molecules that regulate gene expression and protein phosphorylation cascades,which significantly influence physiological processes,such as protein synthesis and degradation,glucose and lipid metabolism,and cell apoptosis and autophagy.These processes are primarily mediated through the PI3K/AKT/AMPK/mTOR signaling pathways.This review summarizes BCAA transporters and catabolic metabolism,their role as signaling molecules in regulating protein metabolism and glucose and lipid equilibrium,and applications in animal production.These findings offer both theoretical insights and practical guidelines for the precise regulation of feed efficiency and production performance through tailored dietary BCAA supplementations.展开更多
The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensi...The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes.The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages.Hi-C was used to build chromatin architectures during four representative stages.Ch IP-seq was conducted to identify enhancers and promoters in these four stages,which are occupied by histone H3K27ac and H3K4me3 peaks.Results show that large-scale genome architecture changes are mostly unidirectional,and coupled by complex on/off dynamic patterns of gene expression.Specifically,we observed 258.30 Mb of the genome undergoing A/B compartment switching.Notable alterations(316.57 Mb)of interaction frequencies within TADs were observed.Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development.Some muscle-related gene promoters that interacted with active enhancers during development,and some myopathy/aging-associated genes that were activated in aging muscle were founded.These results provide key insights into skeletal muscle development in vivo,and offer a valuable resource that allows in-depth functional characterization of candidate genes.展开更多
Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reti...Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.展开更多
Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-in...Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.展开更多
Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to su...Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to sustain BCAAs releasing rate may facilitate muscle protein synthesis.To examine this hypothesis,we conducted a series of protein supplements including modified slow-digesting whey(SDW),whey,hydrolyzed whey and casein,orally to mice undergoing endurance running.Our results showed that the SDW gavage constant supplied BCAAs in the serum of mice within 6 h and significantly enhanced(P<0.01)endurance exercise capacity,compared to other groups.In addition,the SDW supplementation increased the crosssectional area of mice gastrocnemius fibers,as well as their muscle and liver glycogen content.It also increased the testosterone/cortisol ratio in serum and interleukin-6(IL-6)levels in muscle,while it decreased the tumor necrosis factor-alpha(TNF-α)levels and oxidative stress in muscle.Moreover,it may activate mechanistic target of rapamycin signaling by upregulating mRNA(bcat-1 and pgc-1α)expression.Thus,our findings illustrate that prolonged BCAAs supply duration promotes mice endurance running capacity and skeletal muscle growth,contributing to the advancement of sports nutrition practices.展开更多
Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)indu...Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.展开更多
Legged robots have considerable potential for traversing unstructured situations;nonetheless,their inflexible frameworks often constrain adaptability and obstacle negotiation.The study article presents a revolutionary...Legged robots have considerable potential for traversing unstructured situations;nonetheless,their inflexible frameworks often constrain adaptability and obstacle negotiation.The study article presents a revolutionary Soft Tri-Legged Robot(STLR)that improves movement and obstacle-avoidance skills by using a bio-inspired pneumatic artificial muscle(Bubble Artificial Muscles)and a bio-inspired tactile sensor(TacTip).The STLR is activated by BAMs,which are flexible,pneu-matic-driven actuators that provide fine control over forward,backward,and steering movements.Obstacle identification and avoidance are facilitated by the TacTip sensor,which delivers tactile input for traversing unstructured terrains.We delineate the mechanical features of the BAMs,assess the functionality of the robot's legs,and elaborate on the incorpora-tion of the tactile sensing system.Experimental results demonstrate that the STLR can effectively achieve multi-directional flexible movement and obstacle avoidance through a cross-modal perception-actuation mechanism.This study highlights the promise of soft robotics for search and rescue,medical aid,and autonomous exploration,while delineating difficulties and opportunities for future improvements in functionality and efficiency.展开更多
Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopeni...Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopenia is common in patients with MASLD,with a prevalence ranging from 20%to 40%depending on the population and diagnostic criteria used.In advanced stages,such as metabolic dysfunction-associated steatohepatitis and fibrosis,its prevalence is even higher.Sarcopenia exacerbates insulin resistance,systemic inflammation,and oxidative stress,all of which worsen MASLD.It is an independent risk factor for fibrosis progression and poor outcomes including mortality.Myosteatosis refers to the abnormal accumulation of fat within muscle tissue,leading to decreased muscle quality.Myosteatosis is prevalent(>30%)in patients with MASLD,especially those with obesity or type 2 diabetes,although this can vary with the imaging techniques used.It reduces muscle strength and metabolic efficiency,further contributing to insulin resistance and is usually associated with advanced liver disease,cardiovascular complications,and lower levels of physical activity.Altered muscle metabolism,which includes mitochondrial dysfunction and impaired amino acid metabolism,has been reported in metabolic syndromes,including MASLD,although its actual prevalence is unknown.Altered muscle metabolism limits glucose uptake and oxidation,worsening hyperglycemia and lipotoxicity.Reduced muscle perfusion and oxygenation due to endothelial dysfunction and systemic metabolic alterations are common in MASLD associated with comorbidities,such as obesity,hypertension,and atherosclerosis.It decrea-ses the muscle capacity for aerobic metabolism,leading to fatigue and reduced physical activity in patients with MASLD,aggravating metabolic dysfunction.Various SMA in MASLD worsen insulin resistance and hepatic fat accumulation,may accelerate progression to fibrosis and cirrhosis,and increase the risk of cardiovascular disease and mortality.Management strategies for SMA include resistance training,aerobic exercise,and nutritional support(e.g.,high-protein diets,vitamin D,and omega-3 fatty acids),which are essential for mitigating skeletal muscle loss and improving outcomes.However,pharmacological agents that target the muscle and liver(such as glucagon-like peptide-1 receptor agonists)show promise but have not yet been approved for the treatment of MASLD.展开更多
The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secr...The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secreting myogenic cytokines,thereby regulating metabolism throughout the entire body.Maintaining muscle function requires iron homeostasis.Recent studies suggest that disruptions in iron metabolism and ferroptosis,a form of iron-dependent cell death,are essential contributors to the progression of a wide range of muscle diseases and disorders,including sarcopenia,cardiomyopathy,and amyotrophic lateral sclerosis.Thus,a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention.This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury,as well as associated muscle diseases and disorders.Moreover,we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders.Finally,we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.展开更多
Vein graft(VG)failure(VGF)is associated with VG intimal hyperplasia,which is characterized by abnormal accumulation of vascular smooth muscle cells(VSMCs).Most neointimal VSMCs are derived from pre-existing VSMCs via ...Vein graft(VG)failure(VGF)is associated with VG intimal hyperplasia,which is characterized by abnormal accumulation of vascular smooth muscle cells(VSMCs).Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition,also known as dedifferentiation.There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation,exerting vasoprotective functions;however,the precise mechanisms have not been fully characterized.Therefore,we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation.Ginger significantly inhibited neointimal hyperplasia and promoted lumen(L)opening in a 3-month VG,which was primarily achieved by reducing ferroptotic stress.Ferroptotic stress is a pro-ferroptotic state.Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type,forming neointima(NI)after vein transplantation.Ginger and its two main vasoprotective ingredients(6-gingerol and 6-shogaol)inhibit VSMC dedifferentiation by reducing ferroptotic stress.Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53,while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase(Alox5),both promoting ferroptosis.Furthermore,both ingredients co-target peroxisome proliferator-activated receptor gamma(PPARγ),decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 1(Nox1)expression.Nox1 promotes intracellular reactive oxygen species(ROS)production and directly induces VSMC dedifferentiation.In addition,Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production,indirectly leading to VSMC dedifferentiation.Ginger,a natural multi-targeted ferroptotic stress inhibitor,finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.展开更多
文摘BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.
基金supported by the MUSC-TU Scholarship for Human Resource Development in Science & Technology in the Remembrance of Late King Rama Ⅸ of ThailandPartial Funding for Graduate Student Thesis for the Year 2021 by the Faculty of Graduate Studies and Graduate Studies of Mahidol University Alumni Association。
文摘Background: Post-workout supplementation has been used in athletes and recreational exercisers;however, responses between normal and overweight individuals on exercise performance and muscle recovery are less known.Methods: Normal and overweight young adult males(21 subjects/group) participated in resistance and fatiguing exercises before receiving post-workout supplements: placebo, coenzyme Q10(CoQ10), or sports drink in a crossover design. Resistance exercises included upper body exercise(bench press, upright row, and standing shoulder press) and lower body exercise(dead lift, back squat, and front squat) at 75% of one-repetition maximum(1 RM). Fatiguing exercise was performed on a cycle ergometer with 3 min of all-out effort at 3.5% of body mass. Participants consumed post-workout supplements within 10 min of exercise completion and repeated-bout exercise was performed 1 h later, followed by cardiovascular responses, urinary biomarkers, and delayed onset muscle soreness(DOMS) assessments.Results: There were effects of overweight on resistance exercise volume, critical power, fatigue index, and postexercise diastolic blood pressure(DBP). However, no differences in urinary biomarkers of muscle damage(potassium and creatinine) or DOMS between normal and overweight individuals. After supplementation, CoQ10 and sports drink increased resistance exercise volume regardless of body mass and increased critical power in the normal group. Additionally, CoQ10 supplementation was associated with a reduction in urinary biomarkers and DOMS in both groups.Conclusion: These findings are beneficial for sport scientists, nutritionists, and exercise physiologists in guiding post-workout supplementation with CoQ10 and sports drink to improve exercise performance and muscle recovery in normal and overweight individuals.
基金funded by research grants from the National Natural Science Foundation of China (32171135 and 32371168)。
文摘Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in this process.Methods: 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E-5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area(CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1(Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism.Results: Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically,Prmt1 regulated the p38 mitogen-activated protein kinase(p38)/activating transcription factor 2(ATF2)pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2(AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α(PGC-1α) signaling pathway.Conclusions: Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway.
基金funded by research grant from National Natural Science Foundation of China(32171135).
文摘Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
基金funded by the Project of National Key Research and Development Program of China(2022YFD2101001)the Project of National Natural Science Foundation of China(32172226)+4 种基金China Agriculture Research System(CARS-40-K25CARS-40-S11)the Special Fund for Anhui Agriculture Research System(AHCYJSTX-NCPJG)-15the Project of Key Laboratory for Animal Food Green Manufacturing and Resource Ming of Anhui Province(PA2023GDSK0125)the Cooperative Project of Hefei University of Technology-Anhui Rongda Food Co.,Ltd.(W2020JSKF0489).
文摘Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factorα,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.
基金supported by the National Natural Science Foundation of China,No.82072162(to XY).
文摘To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles are different,and the importance of these potential differences.In the present study,we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles.We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways.In terms of spatial distribution patterns,sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons.In addition,the neuronal innervation of limb muscles exhibited four different characteristics:sympathetic neuron-rich muscle,sensory neuron-rich muscle,neuron-sparse muscle,and motor neuron-rich muscle.Sensory neuron density was mainly associated with muscle contractile structure and cell pH,whereas sympathetic neuron density was associated with protein kinase activity,muscle vasculature,muscle calcium-dependent protein kinase activity,lipid transport,and vesicle release.Motor neuron density was mainly associated with protein kinase activity,cell adhesion,oxidoreductase activity,and exocytosis.These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions,thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.
文摘Purpose:ATLAS is a cross-sectional study aiming to investigate environmental and genetic determinants of athletic performance in healthy Greek competitive athletes(CA).This article presents the study design,investigates the muscle strength performance(MSP)of 289 adult and teenage CA,exercisers,and physically inactive individuals(PI),and proposes predictive models of MSP for adults.Methods:Muscle maximal,speed,and explosive strength(MMS/MSS/MES)at unilateral maximal concentric flexion and extension contraction(FC/EC)were evaluated using Biodex System 3 PRO^(TM)at 60°/s,180°/s,and 300°/s,while additional performance markers were assessed through field ergometric testing.Participants were interviewed about their lifestyle,dietary habits,physical activity,injury,and medical history.Body composition was assessed via bioelectrical impedance.gDNA was extracted from biochemical samples and then genotyped.Statistical analysis was conducted using IBM SPSS Statistics v21.0 and R.Results:Age,fitness,and sex impacted correlations of MSP with body composition and anthropometric measurements(p<0.05).Among CA,females outperformed males in accuracy(p<0.001)while,males outperformed females in anaerobic power,MSP,speed,and endurance(p<0.001).Adult CA outperformed exercisers and PI in MMS,MSS,and MES(p<0.05).Multiple linear regression models,with predictors age,FFM,body extremity,training load explained the majority of variation in MMS(R^(2)_(adj):71.4%–88.9%),MSS(R^(2)_(adj):64.8%–78.4%),and MES(R^(2)_(adj):52.7%–68.4%)at EC,FC,and their mean(p<0.001).Conclusions:Muscle-strengthening strategies should be customized according to individual fitness levels,body composition,and anthropometric measurements.The innovative sex-specific regression models assessing MMS,MSS,and MES at EC and FC provide a framework for personalizing rehabilitation and skill-specific training strategies.
基金supported by Joint Program on Health Science&Technology Innovation of Hainan Province(WSJK2024QN093)Discipline Leader Development Program for Outstanding Talents of Hainan West Central Hospital.
文摘Objectives:Postmenopausal women with stress urinary incontinence(SUI)exhibit low androgen expression.This study aimed to evaluate the efficacy and safety of vaginal androgen combined with pelvic floor muscle training(PFMT)in the treatment of SUI in postmenopausal women.Methods:Postmenopausal women with SUI were recruited from Hainan West Central Hospital between January 2024 and March 2025.Participants were randomly assigned in a double-blind manner to receive either vaginal androgen cream combined with PFMT(treatment group)or a visually identical placebo cream(without androgens)combined with PFMT(control group).The vaginal cream was applied to the vaginal wall at a dose of 0.5 g per application,twice weekly for a total of 10 applications,while PFMT was conducted for 8 weeks.The clinical efficacy and safety were compared between the two groups.Results:A total of 61 patients were finally enrolled,with 31 in the treatment group and 30 in the control group.At both 3-month and 6-month follow-ups,the treatment group demonstrated significantly lower values in daily pad usage(p<0.05),24-h pad test scores(p<0.05),and ICIQ-UI SF scores(p<0.05)compared to the control group.The improvement rate of urinary incontinence was significantly higher in the treatment group(p<0.05).Compared to baseline,the treatment group showed statistically significant reductions in all three outcome measures(all p<0.05).No severe adverse events were reported in either group during the treatment period.Conclusions:Androgen therapy combined with PFMT significantly improved the urinary incontinence remission rate in postmenopausal women with SUI,with no severe adverse effects observed.These findings suggest that androgen therapy may represent a novel therapeutic approach for SUI management in postmenopausal women.
文摘Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,disrupting proteostasis and increasing vulnerability to sarcopenia.High-intensity training(HIT)can counteract these declines by activating protective pathways such as the HSP response.HSPs are highly responsive to stress,examining their regulation during aging is important,as altered HSP activity is linked to the progressive loss of muscle mass.Methods This study investigated the abundance and phosphorylation of HSPs in skeletal muscle from healthy,active young and older adults(n=7 per group),assessed at baseline and again in the older group following 12 weeks of HIT.Using calibrated Western blotting on both whole-muscle homogenates and pooled single muscle fibres,we quantified HSP content and phosphorylation to determine how aging and exercise influence stress–responsive protein regulation at both the tissue and cellular levels.Results In whole muscle homogenates,HSPs(HSP72,HSP27,andαB-crystallin)did not differ between young and older adults,while higher phosphorylation of small HSPs(sHSPs):phospho-HSP27 at Serine15(pHSP27 Ser15)and phospho-αB-crystallin at Serine59(pαB-crystallin Ser59)(∼1.8-fold and∼2.9-fold,respectively)were found in muscle from older adults,indicating higher cellular stress associated with aging.A 12-week HIT intervention in older adults reduced homogenate pHSP27 Ser15 and pαB-crystallin Ser59 abundances to similar levels found in young adults.Total HSPs typically displayed a distinct fiber-type profile in both age groups,with more in type I compared to type II fibers,distinguished by the presence of myosin heavy chain I(MHCI)or MHCII.Phosphorylation at pHSP27 Ser15 and pαB-crystallin Ser59 was not different between type I and type II fibers.The HIT in older adults decreased total and phosphorylated sHSPs in both type I and type II fibers but increased HSP72 in type I fibers.Conclusion HIT has the potential to mitigate age-related cellular stress and modulate protein expression patterns in aging skeletal muscle and,perhaps,has the potential to delay age-related muscle decline,thereby improving muscle health in older adults.
基金partly funded by National Key R&D Program of China(2023YFD1301405)the 2115 Talent Development Program of China Agricultural University。
文摘Skeletal muscle accounts for approximately 40%of body mass and 50%–75%of whole-body protein,playing a central role in meat production and quality.Efficient protein synthesis in skeletal muscle relies on an adequate supply of nutrient substrates and a balanced amino acid profile.Branched-chain amino acids(BCAA),including leucine(Leu),isoleucine(Ile),and valine(Val),are the most abundant essential amino acids in skeletal muscle and contribute to both protein synthesis and oxidative energy production.Additionally,BCAA function as signaling molecules that regulate gene expression and protein phosphorylation cascades,which significantly influence physiological processes,such as protein synthesis and degradation,glucose and lipid metabolism,and cell apoptosis and autophagy.These processes are primarily mediated through the PI3K/AKT/AMPK/mTOR signaling pathways.This review summarizes BCAA transporters and catabolic metabolism,their role as signaling molecules in regulating protein metabolism and glucose and lipid equilibrium,and applications in animal production.These findings offer both theoretical insights and practical guidelines for the precise regulation of feed efficiency and production performance through tailored dietary BCAA supplementations.
基金supported by the National Key R&D Program of China(2023YFD1300040 and 2022YFF1000100)the Sichuan Science and Technology Program,China(2022NSFSC0132,2021YFYZ0009 and 2022JDJQ0054)the National Natural Science Foundation of China(32225046)。
文摘The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes.The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages.Hi-C was used to build chromatin architectures during four representative stages.Ch IP-seq was conducted to identify enhancers and promoters in these four stages,which are occupied by histone H3K27ac and H3K4me3 peaks.Results show that large-scale genome architecture changes are mostly unidirectional,and coupled by complex on/off dynamic patterns of gene expression.Specifically,we observed 258.30 Mb of the genome undergoing A/B compartment switching.Notable alterations(316.57 Mb)of interaction frequencies within TADs were observed.Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development.Some muscle-related gene promoters that interacted with active enhancers during development,and some myopathy/aging-associated genes that were activated in aging muscle were founded.These results provide key insights into skeletal muscle development in vivo,and offer a valuable resource that allows in-depth functional characterization of candidate genes.
文摘Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.
基金supported by grants from the Knut and Alice Wallenberg foundation(P-OB,JRZ,and AK)the Swedish Research Council(JRZ and AK),Centrum för idrottsforskning(AK and JRZ)+7 种基金the NovoNordisk Foundation Metabolic Stress Associated Molecules(MSAM)consortium NNF15SA0018346 and Metabolite-related Inflammation and Disease(MeRIAD)consortium Grant number 0064142(AK)the Swedish Diabetes Foundation(AK and JRZ)the European Foundation for the Study of Diabetes(JRZ and AK)the Region Stockholm(ALF project)(JRZ and KC)the Strategic Research Program in Diabetes at Karolinska Institutet(JRZ and AK)supported by the Strategic Research Programme in Diabetes(SRP Diabetes)for use of the Seahorse flux analyzer.Human islets were made possible through the Juvenile Diabetes Research Foundation(JDRF)award 31-2008-416(European Coordinating Infrastructure for Islet Transplantation(ECIT),Islet for Basic Research program)AK holds a Distinguished Investigator Grant within Endocrinology and Metabolism from the Novo Nordisk Foundation(NNF24OC0088739)JRZ received the 2024 European Association for the Study of Diabetes(ESAD)-Novo Nordisk Foundation Diabetes Prize for Excellence(NNF24SA0092609).
文摘Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.
基金financially supported by the Fundamental Research Funds for the Central Universities(JUSRP622014)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University(2022-3-2)National Key Research and Development Program of China(2022YFF1100300).
文摘Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to sustain BCAAs releasing rate may facilitate muscle protein synthesis.To examine this hypothesis,we conducted a series of protein supplements including modified slow-digesting whey(SDW),whey,hydrolyzed whey and casein,orally to mice undergoing endurance running.Our results showed that the SDW gavage constant supplied BCAAs in the serum of mice within 6 h and significantly enhanced(P<0.01)endurance exercise capacity,compared to other groups.In addition,the SDW supplementation increased the crosssectional area of mice gastrocnemius fibers,as well as their muscle and liver glycogen content.It also increased the testosterone/cortisol ratio in serum and interleukin-6(IL-6)levels in muscle,while it decreased the tumor necrosis factor-alpha(TNF-α)levels and oxidative stress in muscle.Moreover,it may activate mechanistic target of rapamycin signaling by upregulating mRNA(bcat-1 and pgc-1α)expression.Thus,our findings illustrate that prolonged BCAAs supply duration promotes mice endurance running capacity and skeletal muscle growth,contributing to the advancement of sports nutrition practices.
基金funded by Yunnan Youth Top-notch Talent Support Program(YNWR-QNBJ2018-173)Agricultural Joint project of Yunnan Provincial S&T Programs(202301BD070001-195)+2 种基金S&T project of Yunnan provincial finance(K212020001-01)supported by Yunnan Province Education Department’s Engineering Research Center of Eco-friendly Products from Yunnan Characteristic Edible FungiYunnan Province Yongsheng County Farmer Academician Technology service station.
文摘Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.
基金the Natural Science Foundation of China(Project for Young Scientists:Grant No.52105010,Regular Project:Grant No.62173096)Natural Science Foundationof Guangdong Province(Regular Project:Grant No.2025A1515012124,Grant No.2022A1515010327)Guangdong-Hong Kong-Macao Key Laboratory of Multi-scaleInformation Fusion and Collaborative Optimization Control Manufacturing Process.
文摘Legged robots have considerable potential for traversing unstructured situations;nonetheless,their inflexible frameworks often constrain adaptability and obstacle negotiation.The study article presents a revolutionary Soft Tri-Legged Robot(STLR)that improves movement and obstacle-avoidance skills by using a bio-inspired pneumatic artificial muscle(Bubble Artificial Muscles)and a bio-inspired tactile sensor(TacTip).The STLR is activated by BAMs,which are flexible,pneu-matic-driven actuators that provide fine control over forward,backward,and steering movements.Obstacle identification and avoidance are facilitated by the TacTip sensor,which delivers tactile input for traversing unstructured terrains.We delineate the mechanical features of the BAMs,assess the functionality of the robot's legs,and elaborate on the incorpora-tion of the tactile sensing system.Experimental results demonstrate that the STLR can effectively achieve multi-directional flexible movement and obstacle avoidance through a cross-modal perception-actuation mechanism.This study highlights the promise of soft robotics for search and rescue,medical aid,and autonomous exploration,while delineating difficulties and opportunities for future improvements in functionality and efficiency.
基金Supported by Russian Science Foundation,No.19-76-30014.
文摘Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopenia is common in patients with MASLD,with a prevalence ranging from 20%to 40%depending on the population and diagnostic criteria used.In advanced stages,such as metabolic dysfunction-associated steatohepatitis and fibrosis,its prevalence is even higher.Sarcopenia exacerbates insulin resistance,systemic inflammation,and oxidative stress,all of which worsen MASLD.It is an independent risk factor for fibrosis progression and poor outcomes including mortality.Myosteatosis refers to the abnormal accumulation of fat within muscle tissue,leading to decreased muscle quality.Myosteatosis is prevalent(>30%)in patients with MASLD,especially those with obesity or type 2 diabetes,although this can vary with the imaging techniques used.It reduces muscle strength and metabolic efficiency,further contributing to insulin resistance and is usually associated with advanced liver disease,cardiovascular complications,and lower levels of physical activity.Altered muscle metabolism,which includes mitochondrial dysfunction and impaired amino acid metabolism,has been reported in metabolic syndromes,including MASLD,although its actual prevalence is unknown.Altered muscle metabolism limits glucose uptake and oxidation,worsening hyperglycemia and lipotoxicity.Reduced muscle perfusion and oxygenation due to endothelial dysfunction and systemic metabolic alterations are common in MASLD associated with comorbidities,such as obesity,hypertension,and atherosclerosis.It decrea-ses the muscle capacity for aerobic metabolism,leading to fatigue and reduced physical activity in patients with MASLD,aggravating metabolic dysfunction.Various SMA in MASLD worsen insulin resistance and hepatic fat accumulation,may accelerate progression to fibrosis and cirrhosis,and increase the risk of cardiovascular disease and mortality.Management strategies for SMA include resistance training,aerobic exercise,and nutritional support(e.g.,high-protein diets,vitamin D,and omega-3 fatty acids),which are essential for mitigating skeletal muscle loss and improving outcomes.However,pharmacological agents that target the muscle and liver(such as glucagon-like peptide-1 receptor agonists)show promise but have not yet been approved for the treatment of MASLD.
基金the National Natural Science Foundation of China(82471593 to J.M.32330047 and 31930057 to F.W.+2 种基金and 82071970 to Y.W.and 82072506 to Y.L.)the Science Fund for Distinguished Young Scholars of Hubei Province(2023AFA109 to Y.W.)Hubei Provincial Natural Science Foundation of China(2024AFB963 to Q.R.).
文摘The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secreting myogenic cytokines,thereby regulating metabolism throughout the entire body.Maintaining muscle function requires iron homeostasis.Recent studies suggest that disruptions in iron metabolism and ferroptosis,a form of iron-dependent cell death,are essential contributors to the progression of a wide range of muscle diseases and disorders,including sarcopenia,cardiomyopathy,and amyotrophic lateral sclerosis.Thus,a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention.This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury,as well as associated muscle diseases and disorders.Moreover,we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders.Finally,we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.
基金supported by grants from the Natural Science Foundation of Shandong Province,China(Grant Nos.:ZR2019ZD28 and ZR2022QH008)the National Natural Science Foundation of China(Grant Nos.:82270301 and 82200465)+1 种基金China Postdoctoral Science Foundation(Grant No.:2023M731842)Shandong Postdoctoral Science Foundation,China(Grant No.:SDCX-ZG-202203013).
文摘Vein graft(VG)failure(VGF)is associated with VG intimal hyperplasia,which is characterized by abnormal accumulation of vascular smooth muscle cells(VSMCs).Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition,also known as dedifferentiation.There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation,exerting vasoprotective functions;however,the precise mechanisms have not been fully characterized.Therefore,we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation.Ginger significantly inhibited neointimal hyperplasia and promoted lumen(L)opening in a 3-month VG,which was primarily achieved by reducing ferroptotic stress.Ferroptotic stress is a pro-ferroptotic state.Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type,forming neointima(NI)after vein transplantation.Ginger and its two main vasoprotective ingredients(6-gingerol and 6-shogaol)inhibit VSMC dedifferentiation by reducing ferroptotic stress.Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53,while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase(Alox5),both promoting ferroptosis.Furthermore,both ingredients co-target peroxisome proliferator-activated receptor gamma(PPARγ),decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 1(Nox1)expression.Nox1 promotes intracellular reactive oxygen species(ROS)production and directly induces VSMC dedifferentiation.In addition,Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production,indirectly leading to VSMC dedifferentiation.Ginger,a natural multi-targeted ferroptotic stress inhibitor,finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.
