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
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
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
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
Enhancing the firefighting protective clothing with exceptional thermal barrier and temperature sensing functions to ensure high fire safety for firefighters has long been anticipated,but it remains a major challenge....Enhancing the firefighting protective clothing with exceptional thermal barrier and temperature sensing functions to ensure high fire safety for firefighters has long been anticipated,but it remains a major challenge.Herein,inspired by the human muscle,an anisotropic fire safety aerogel(ACMCA)with precise self-actuated temperature monitoring performance is developed by combining aramid nanofibers with eicosane/MXene to form an anisotropically oriented conductive network.By combining the two synergies of the negative temperaturedependent thermal conductive eicosane,which induces a high-temperature differential,and directionally ordered MXene that establishes a conductive network along the directional freezing direction.The resultant ACMCA exhibited remarkable thermoelectric properties,with S values reaching 46.78μV K^(−1)andκvalues as low as 0.048 W m^(−1)K^(−1)at room temperature.Moreover,the prepared anisotropic aerogel ACMCA exhibited electrical responsiveness to temperature variations,facilitating its application in intelligent temperature monitoring systems.The designed anisotropic aerogel ACMCA could be incorporated into the firefighting clothing as a thermal barrier layer,demonstrating a wide temperature sensing range(50-400℃)and a rapid response time for early high-temperature alerts(~1.43 s).This work provides novel insights into the design and application of temperature-sensitive anisotropic aramid nanofibers aerogel in firefighting clothing.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Background N^(6)-methyladenosine(m^(6)A)methylation is a key epigenetic modification that can modulate gene expression and strongly affect mammalian developmental processes.However,the genome-wide methylation of long ...Background N^(6)-methyladenosine(m^(6)A)methylation is a key epigenetic modification that can modulate gene expression and strongly affect mammalian developmental processes.However,the genome-wide methylation of long non-coding RNAs(lncRNAs)and its implications for the development of skeletal muscle remain poorly understood.Bovine skeletal muscle samples from five developmental stages were analyzed in this study to establish lncRNA methylome and transcriptomic maps.Results Globally,59.67%of lncRNAs in skeletal muscle with m^(6)A modifications,and this percentage decreased progressively during development.lncRNA expression levels were positively associated with the number of m^(6)A peaks,with lncRNAs possessing 3 or more peaks showing significantly higher expression levels than those with 1 or 2 peaks.Specific lncRNAs involved in skeletal muscle development were identified through two analytical approaches.The first approach employed weighted gene co-expression network analysis(WGCNA)of transcriptomic data to identify correlations between annotated lncRNAs and growth-related traits,resulting in 21 candidate hub lncRNAs.The intersection of these 21 hub lncRNAs with 151 differentially methylated lncRNAs(DM-lncRNAs)identified 10 shared candidate lncRNAs.The second approach integrated MeRIP-seq and RNA-seq data to identify 36 lncRNAs that were both differentially m^(6)A modified and differentially expressed(dme-lncRNAs).GO and KEGG enrichment analyses of cis-target genes associated with these dme-lncRNAs identified eight candidate lncRNAs.Combining the results from the two approaches identified 16 key m^(6)A-modified lncRNAs likely involved in skeletal muscle development.Conclusions These findings highlight the regulatory and functional significance of dynamic lncRNA methylation in skeletal muscle development.展开更多
Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.S...Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.展开更多
Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of cor...BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of core muscle activation and a person's ability to stabilize the lumbopelvic complex.Preparatory cues and images can be used to increase the activation of these muscles.To attain optimal movement patterns,it will be necessary to determine what cueing will give the most effective results for core stability.AIM To investigate the effects of external and internal cues on core muscle activation during the Sahrmann five-level core stability test.METHODS Total 68 participants(21.83±3.47 years)were randomly allocated to an external(n=35)or internal cue group(n=33).Participants performed the Sahrmann fivelevel core stability test without a cue as baseline and the five-level stability exercises with an internal or external cue.External cue group received a pressure biofeedback unit(PBU),and the internal cue group received an audio cue.A Delsys Trigno^(TM)surface electromyography unit was used for muscle activation from the rectus abdominis,external oblique,and transverse abdominis/internal oblique muscles.RESULTS Linear mixed effects model analysis showed that cueing had a significant effect on core muscle activation(P=0.001);however,there was no significant difference between cue types(internal or external)(P=0.130).CONCLUSION Both external and internal cueing have significant effects on core muscle activation during the Sahrmann five-level core stability test and the PBU does not create higher muscle activation than internal cueing.展开更多
The“longevity protein”SIRT5 could hold the key to delaying age-related muscle decline.A study led by researchers from the Institute of Zoology(IOZ)of the Chinese Academy of Sciences and Capital Medical University in...The“longevity protein”SIRT5 could hold the key to delaying age-related muscle decline.A study led by researchers from the Institute of Zoology(IOZ)of the Chinese Academy of Sciences and Capital Medical University in Beijing reveals that SIRT5 mitigates skeletal muscle aging by blocking pro-inflammatory pathways.Published in Nature Metabolism on March 14,2025,the work identifies SIRT5’s interaction with protein kinase TBK1 as critical to preserving muscle mass and function.展开更多
Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through mic...Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through microbiome modulation,their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated.Employing dextran sulfate sodium(DSS)-induced gut dysfunction model and wide-spectrum antibiotics(ABX)-treated mice model,our study revealed that gut dysfunction instigates muscle and bone loss,accompanied by microbial imbalances.Importantly,Bifidobacterium animalis subsp.lactis A6(B.lactis A6)administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria.This intervention effectively restored depleted butyrate levels in serum,muscle,and bone tissues caused by gut dysfunction.Furthermore,butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria.Importantly,butyrate inhibited the NF-κB pathway activation,and reduced the secretion of corresponding inflammatory factors in T cells.Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B.lactis A6.These discoveries offer new microbiome directions for translational and clinical research,providing promising strategies for preventing and managing musculoskeletal diseases.展开更多
Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This ...Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control(n=40)and intervention(n=40)groups.The control group received conventional orthopedic treatment,whereas the intervention group received TEAS and conventional treatment.The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks.The primary out-comes were muscle thickness(MT)and cross-sectional area(CSA)of the rectus femoris and gastroc-nemius muscles,whereas the secondary outcome measure was echo intensity(EI).Data were collected before the fixation operations(baseline assessment)and 4 and 8 weeks after intervention.Results:Compared with baseline,the MT and CSA were reduced in both groups by the end of treatment,whereas EI increased in both groups.At week 4,the reduction in the rectus femoris CSA in the inter-vention group was significantly lower than that in the control group(P=0.02);however,the between-group differences in the MT and EI(all P>0.05)were not significant.No serious adverse events were observed in either group.Conclusion:Our study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA.Because this was only a pilot trial,subsequent studies will need longer follow-ups and larger sample sizes.展开更多
1.Background When searching for the term“muscle power”on Google Scholar,about 3.7 million hits come up in 60 ms,and for the past 3 years,there were approximately 225 yearly peer-reviewed publications dealing with mu...1.Background When searching for the term“muscle power”on Google Scholar,about 3.7 million hits come up in 60 ms,and for the past 3 years,there were approximately 225 yearly peer-reviewed publications dealing with muscle power.Muscle power has been used to assess and predict athletic performance,to determine muscle rehabilitation following injury or disease,to measure functional decline as occurs in aging,and many other topics.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 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.
基金funding support from Guiding Project of Scientific Research Plan of Education Department of Hubei Province and Wuhan Textile University School Fund(B)(k24016).
文摘Enhancing the firefighting protective clothing with exceptional thermal barrier and temperature sensing functions to ensure high fire safety for firefighters has long been anticipated,but it remains a major challenge.Herein,inspired by the human muscle,an anisotropic fire safety aerogel(ACMCA)with precise self-actuated temperature monitoring performance is developed by combining aramid nanofibers with eicosane/MXene to form an anisotropically oriented conductive network.By combining the two synergies of the negative temperaturedependent thermal conductive eicosane,which induces a high-temperature differential,and directionally ordered MXene that establishes a conductive network along the directional freezing direction.The resultant ACMCA exhibited remarkable thermoelectric properties,with S values reaching 46.78μV K^(−1)andκvalues as low as 0.048 W m^(−1)K^(−1)at room temperature.Moreover,the prepared anisotropic aerogel ACMCA exhibited electrical responsiveness to temperature variations,facilitating its application in intelligent temperature monitoring systems.The designed anisotropic aerogel ACMCA could be incorporated into the firefighting clothing as a thermal barrier layer,demonstrating a wide temperature sensing range(50-400℃)and a rapid response time for early high-temperature alerts(~1.43 s).This work provides novel insights into the design and application of temperature-sensitive anisotropic aramid nanofibers aerogel in firefighting clothing.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
基金supported by the National Key R&D Program of China(2023YFD1300103)the Science and Technology Plan Project of Yantai City(2023ZDCX024)+5 种基金the National Natural Science Foundation of China(32372852)the Science Fund for Distinguished Young Scholars of Shaanxi Province(2024JC-JCQN-30)Shaanxi Provincial Innovation Leadership Program in Sciences and Technologies for Young and Middle-aged Scientists(2023SR205)the China Agriculture Research System-beef(CARS-37)the Innovation Team of Cattle Industry in Technological System of Shandong Modern Agriculture Industry(SDAIT-09-03)the Key Research and Development Project in Shandong Province(Competitive Innovation Platform)(2022CXPT010).
文摘Background N^(6)-methyladenosine(m^(6)A)methylation is a key epigenetic modification that can modulate gene expression and strongly affect mammalian developmental processes.However,the genome-wide methylation of long non-coding RNAs(lncRNAs)and its implications for the development of skeletal muscle remain poorly understood.Bovine skeletal muscle samples from five developmental stages were analyzed in this study to establish lncRNA methylome and transcriptomic maps.Results Globally,59.67%of lncRNAs in skeletal muscle with m^(6)A modifications,and this percentage decreased progressively during development.lncRNA expression levels were positively associated with the number of m^(6)A peaks,with lncRNAs possessing 3 or more peaks showing significantly higher expression levels than those with 1 or 2 peaks.Specific lncRNAs involved in skeletal muscle development were identified through two analytical approaches.The first approach employed weighted gene co-expression network analysis(WGCNA)of transcriptomic data to identify correlations between annotated lncRNAs and growth-related traits,resulting in 21 candidate hub lncRNAs.The intersection of these 21 hub lncRNAs with 151 differentially methylated lncRNAs(DM-lncRNAs)identified 10 shared candidate lncRNAs.The second approach integrated MeRIP-seq and RNA-seq data to identify 36 lncRNAs that were both differentially m^(6)A modified and differentially expressed(dme-lncRNAs).GO and KEGG enrichment analyses of cis-target genes associated with these dme-lncRNAs identified eight candidate lncRNAs.Combining the results from the two approaches identified 16 key m^(6)A-modified lncRNAs likely involved in skeletal muscle development.Conclusions These findings highlight the regulatory and functional significance of dynamic lncRNA methylation in skeletal muscle development.
基金supported by the NSFC Distinguished Young Scholars Fund(82325010)the National Natural Science Foundation of China(82370874)+4 种基金the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212700)the Major Natural Science Project of the Scientific Research and Innovation Plan of Shanghai Municipal Commission of Education(2023ZKZD17)the Shanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)the Shanghai Key Discipline of Public Health Grants Award(GWVI-11.1-20)the Basic Scientific Research Project(General Cultivation Program)of Shanghai Sixth People’s Hospital(ynms202203).
文摘Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
文摘BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of core muscle activation and a person's ability to stabilize the lumbopelvic complex.Preparatory cues and images can be used to increase the activation of these muscles.To attain optimal movement patterns,it will be necessary to determine what cueing will give the most effective results for core stability.AIM To investigate the effects of external and internal cues on core muscle activation during the Sahrmann five-level core stability test.METHODS Total 68 participants(21.83±3.47 years)were randomly allocated to an external(n=35)or internal cue group(n=33).Participants performed the Sahrmann fivelevel core stability test without a cue as baseline and the five-level stability exercises with an internal or external cue.External cue group received a pressure biofeedback unit(PBU),and the internal cue group received an audio cue.A Delsys Trigno^(TM)surface electromyography unit was used for muscle activation from the rectus abdominis,external oblique,and transverse abdominis/internal oblique muscles.RESULTS Linear mixed effects model analysis showed that cueing had a significant effect on core muscle activation(P=0.001);however,there was no significant difference between cue types(internal or external)(P=0.130).CONCLUSION Both external and internal cueing have significant effects on core muscle activation during the Sahrmann five-level core stability test and the PBU does not create higher muscle activation than internal cueing.
文摘The“longevity protein”SIRT5 could hold the key to delaying age-related muscle decline.A study led by researchers from the Institute of Zoology(IOZ)of the Chinese Academy of Sciences and Capital Medical University in Beijing reveals that SIRT5 mitigates skeletal muscle aging by blocking pro-inflammatory pathways.Published in Nature Metabolism on March 14,2025,the work identifies SIRT5’s interaction with protein kinase TBK1 as critical to preserving muscle mass and function.
基金supported by funding from the National Natural Science Foundation of China(82272478,82002330,82202728)the National Key R&D Program of China(No.2022YFF1100100)the Natural Science Foundation of Beijing(L222086).
文摘Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through microbiome modulation,their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated.Employing dextran sulfate sodium(DSS)-induced gut dysfunction model and wide-spectrum antibiotics(ABX)-treated mice model,our study revealed that gut dysfunction instigates muscle and bone loss,accompanied by microbial imbalances.Importantly,Bifidobacterium animalis subsp.lactis A6(B.lactis A6)administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria.This intervention effectively restored depleted butyrate levels in serum,muscle,and bone tissues caused by gut dysfunction.Furthermore,butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria.Importantly,butyrate inhibited the NF-κB pathway activation,and reduced the secretion of corresponding inflammatory factors in T cells.Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B.lactis A6.These discoveries offer new microbiome directions for translational and clinical research,providing promising strategies for preventing and managing musculoskeletal diseases.
基金supported by the funded project(HYZHX M05005)in the field of space medical experiments of manned spaceflight engineering.
文摘Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control(n=40)and intervention(n=40)groups.The control group received conventional orthopedic treatment,whereas the intervention group received TEAS and conventional treatment.The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks.The primary out-comes were muscle thickness(MT)and cross-sectional area(CSA)of the rectus femoris and gastroc-nemius muscles,whereas the secondary outcome measure was echo intensity(EI).Data were collected before the fixation operations(baseline assessment)and 4 and 8 weeks after intervention.Results:Compared with baseline,the MT and CSA were reduced in both groups by the end of treatment,whereas EI increased in both groups.At week 4,the reduction in the rectus femoris CSA in the inter-vention group was significantly lower than that in the control group(P=0.02);however,the between-group differences in the MT and EI(all P>0.05)were not significant.No serious adverse events were observed in either group.Conclusion:Our study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA.Because this was only a pilot trial,subsequent studies will need longer follow-ups and larger sample sizes.
文摘1.Background When searching for the term“muscle power”on Google Scholar,about 3.7 million hits come up in 60 ms,and for the past 3 years,there were approximately 225 yearly peer-reviewed publications dealing with muscle power.Muscle power has been used to assess and predict athletic performance,to determine muscle rehabilitation following injury or disease,to measure functional decline as occurs in aging,and many other topics.
