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: 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
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
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
Sarcomerogenesis,the addition of serial sarcomeres in skeletal muscle myofibrils and fibres,is a natural occurrence during growth and maturation of animals,including humans.However,the detailed mechanisms that allow f...Sarcomerogenesis,the addition of serial sarcomeres in skeletal muscle myofibrils and fibres,is a natural occurrence during growth and maturation of animals,including humans.However,the detailed mechanisms that allow for sarcomerogenesis are not fully understood.In some diseases,such as cerebral palsy in children,sarcomerogenesis appears to be inhibited or at least reduced,1,2 often causing severe restrictions in muscle and joint function.展开更多
BACKGROUND Improving our understanding of whether increased dietary intake ofω-3 polyunsaturated fatty acids(PUFAs)is beneficial for increasing skeletal muscle mass in patients with metabolic dysfunction-associated f...BACKGROUND Improving our understanding of whether increased dietary intake ofω-3 polyunsaturated fatty acids(PUFAs)is beneficial for increasing skeletal muscle mass in patients with metabolic dysfunction-associated fatty liver disease(MAFLD)could provide an important clinical evidence base for the development of relevant nutritional guidelines.AIM To investigate the effect of total dietaryω-3 PUFAs and their subtypes on skeletal muscle mass in MAFLD.METHODS This cross-sectional study involved 2316 participants from four National Health and Nutrition Examination Survey cycles between 2011 and 2018.Dietary intake ofω-3 PUFAs was collected through 24-hour dietary recall interviews.Appendicular skeletal muscle mass index(ASMI)was calculated by dividing ASM in kilograms by height squared.RESULTS The multiple linear regression model showed significant relationships for dietary intake of totalω-3 PUFAs with higher ASMI(β:0.06,95%CI:0.01-0.11)in MAFLD patients.Dietary a-linolenic acid(ALA)(β:0.06,95%CI:0.01-0.12),docosapentaenoic acid(β:1.28,95%CI:0.01-2.54),and docosahexaenoic acid(DHA)(β:0.19,95%CI:0.01-0.37)were significantly associated with higher ASMI,while intake of stearidonic acid and eicosapentaenoic acid did not improve ASMI.In patients with high probability of liver fibrosis,dietary intake of ALA was associated with higher ASMI(β:0.11,95%CI:0.03-0.18).Stratified analysis found that DHA was associated with higher ASMI in patients with obesity and higher metabolic risk.CONCLUSION Increasing dietary intake ofω-3 PUFAs improved skeletal muscle health in patients with MAFLD.Patient with obesity and higher metabolic risk were more likely to benefit from intake of DHA.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: Aging-induced cardiac hypertrophy and reduced skeletal muscle strength contribute to increased disease risk and life burden in the elderly. FNDC5 acts as a protective muscle factor in both cardiac and skel...Background: Aging-induced cardiac hypertrophy and reduced skeletal muscle strength contribute to increased disease risk and life burden in the elderly. FNDC5 acts as a protective muscle factor in both cardiac and skeletal muscle. This study aims to examine the relationship between cardiac FNDC5 and aging-related cardiac hypertrophy and decreased skeletal muscle strength. Methods: Male young C57BL/6 mice (5 months old, n = 6) and aged mice (21 months old, n = 6) were utilized in the study and housed in a specific pathogen-free (SPF) environment. Prior to the experiment, grip strength tests were performed on the mice, and heart tissues were collected for morphological analysis, including the assessment of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and fibronectin type III-containing structural domain 5 (FNDC5) protein levels. Furthermore, myosin heavy chain II (MyHC II), skeletal muscle-specific transcription factor (MyoD), muscle RING-finger protein-1 (MuRF1), and FNDC5 levels were evaluated in the quadriceps muscle. The correlations between heart weight and FNDC5 expression levels, as well as skeletal muscle indices in the mice, were subsequently analyzed. Result: Aging leads to cardiac hypertrophy and reduced expression of PGC-1α and FNDC5 proteins. Concurrently, there is a decline in the strength of skeletal muscle, along with decreased expression of MyHC II and increased expression of MURF1 and MyoD. Correlation analysis demonstrated strong positive associations between myocardial FNDC5 protein levels and limb grip strength, as well as MyHC II, and strong negative associations with MyoD and MuRF1. Conclusion: There may be a significant association between aging-induced cardiac hypertrophy and decreased skeletal muscle strength, with FNDC5 potentially playing a crucial role as a regulatory molecule facilitating communication between the heart and skeletal muscle.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
Skeletal muscle satellite cells are stem cells characterized by their multipotency and capacity for in vitro proliferation.However,primary skeletal muscle satellite cells demonstrate limited proliferative capacity in ...Skeletal muscle satellite cells are stem cells characterized by their multipotency and capacity for in vitro proliferation.However,primary skeletal muscle satellite cells demonstrate limited proliferative capacity in vitro,which impedes their investigation in poultry skeletal muscle research.Cell immortalization techniques have emerged as valuable tools to address this limitation and facilitate the study of skeletal muscle satellite cell functions.This study achieved the immortalization of chicken skeletal muscle satellite cells through the transduction of primary cells with TERT(telomerase reverse transcriptase)amplified from chicken(chTERT)using a lentiviral vector via telomerase activity reconstitution.While the cells successfully overcame replicative senescence,complete immortalization was not achieved.Initial functional characterization revealed that the proliferative properties and cell cycle characteristics of the immortalized chicken skeletal muscle satellite cell lines(ICMS)closely resembled those of chicken primary muscle satellite cells(CPMSCs).Serum dependency analysis and soft agar assays confirmed that ICMS did not undergo malignant transformation.Furthermore,induced differentiation experiments demonstrated preserved differentiation capacity in ICMS.The established cell lines provide a fundamental framework for developing immortalized poultry cell lines and offer a cellular model for investigating poultry skeletal muscle-related functional genes.展开更多
1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site o...1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site of insulin resistance,with impaired insulin signaling and reduced glucose transport activity contributing to metabolic dysfunction.展开更多
BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is...BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is even less common.CASE SUMMARY A 58-year-old male with known history of RCC presented with a recurrence that was diagnosed through imaging and biopsies.Mucosa abnormalities of small bowel noted during endoscopy were biopsied as well as lesion in the psoas muscle that was noted.CONCLUSION This case report emphasizes that RCC can not only recur but can do so even decades later and present as metastatic foci at atypical sites.展开更多
Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations,such as sarcopenia,myoste-atosis,and metabolic dysregulation,which play a key r...Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations,such as sarcopenia,myoste-atosis,and metabolic dysregulation,which play a key role in its pathogenesis and progression.Recent literature,including an article by Isakov,highlights the bidirectional interactions between muscle and liver,underscoring shared mechanisms such as insulin resistance,inflammation,and myokine imbalance.This letter reflects on key findings from the review,noting strengths such as its integration of mechanistic insights,discussion of emerging biomarkers,and emphasis on lifestyle and pharmacological interventions.It also identifies areas for further development,including standardization of diagnostic criteria and more rigorous evaluation of translational data.As muscle health gains promi-nence in metabolic dysfunction-associated steatotic liver disease research,multidisciplinary strategies that target both hepatic and muscular systems may offer more effective avenues for prevention and treatment.展开更多
BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and progno...BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.展开更多
Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still u...Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.展开更多
Objectives:Skeletal muscle ischemia/reperfusion injury(IRI)occurs as a result of a marked reduction in arterial perfusion to a limb and can lead to tissue death and threaten limb viability.This work assessed the effec...Objectives:Skeletal muscle ischemia/reperfusion injury(IRI)occurs as a result of a marked reduction in arterial perfusion to a limb and can lead to tissue death and threaten limb viability.This work assessed the effects of 20-hydroxyecdysone(20E)on hindlimb skeletal tissue following tourniquet-induced ischemia/reperfusion injury.Methods:Animals were divided into 4 groups—control group(Control),Control+20E(C+20E),mice with IRI(IRI),and mice with IRI+20E(IRI+20E).IRI was modeled by applying a tourniquet to the hind limb for 2 h with reperfusion for 1 h.5 mg/kg of 20E was administered intraperitoneally for 14 days.Afterward,the physical activity of mice,the histological structure of the quadriceps femoris,the expression of genes encoding proteins induced by hypoxia and involved in tissue adaptation to ischemia,and the functional parameters of skeletal muscle mitochondria were assessed.Results:It was shown that IRI of the limbs leads to functional disorders,depression of muscle function,accumulation of malondialdehyde(MDA)in mitochondria,and a decrease in their Ca2+buffering capacity,as well as an increase in the expression of HIF-1α,VGEF-A,PGC1αand PDGF-BB genes associated with adaptation to ischemia.20E reduced the intensity of degenerative processes in skeletal muscles,which was expressed in a decrease in the number of centrally nucleated fibers.Analysis of gene expression levels indicated a high degree of adaptation of animals to IRI.20E reduced the level of MDA in mitochondria,but did not affect the rate of respiration and calcium retention capacity of organelles both in normal conditions and during IRI.Conclusion:20E partially alleviates the skeletal muscle damage caused by IRI and can be used as part of combination therapy.展开更多
Soft biological tissues are challenging materials for both testing and modeling.Despite the development of many constitutive models,the processing of choosing the most suitable model remains heuristic,relying signific...Soft biological tissues are challenging materials for both testing and modeling.Despite the development of many constitutive models,the processing of choosing the most suitable model remains heuristic,relying significantly on personal experience and preference.Another issue is that the amount of collected experimental data is always finite.In this study,we trained a constitutive artificial neural network based on experimental data of cattle skeletal muscle tissue for the self-directed auto-discovery of constitutive models.The discovered models inherently satisfy thermodynamic consistency,material objectivity,polyconvexity,and necessary physical restrictions.Two constitutive models have been discovered by the trained neural network.Considering the constraints of finite experimental data,the generality and reliability of the auto-discovered con-stitutive models remain to be analyzed.Through experimental data of pig skeletal muscle tissue,we assess the goodness-of-fit and parameter identifiability of the automatically discovered constitutive models.At first glance,both auto-discovered models have excellent prediction accuracy.Further exploration from the perspective of information geometry suggests that one of the auto-discovered models is superior to the other in terms of parameter identifiability.The findings of the current work are expected to extend our understanding of auto-discovered constitutive models and offer a new perspective to advance machine learning-driven mechanics.展开更多
Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease(COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathw...Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease(COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy-and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.展开更多
BACKGROUND Fibro-adipogenic progenitors(FAPs)are a group of mesenchymal stem cells that cause fibro-fatty degeneration in skeletal muscle in various chronic disease mode-ls.FAPs also play a role in preventing muscle d...BACKGROUND Fibro-adipogenic progenitors(FAPs)are a group of mesenchymal stem cells that cause fibro-fatty degeneration in skeletal muscle in various chronic disease mode-ls.FAPs also play a role in preventing muscle degeneration at acute stages during disease progression.However,few studies have reported the changes in and function of FAPs in the acute phase after tendon rupture.AIM To clarify the changes in the number of FAPs and their impact on skeletal muscle soon after tendon rupture to facilitate future studies targeting FAPs to treat muscle degeneration.METHODS We utilized Pdgfra-H2B::eGFP mice to trace and quantify FAPs in a tibialis anterior tenotomy(TAT)model at 0 and 3 days,1 week,2 weeks,3 weeks,4 weeks,5 weeks,and 6 weeks post-injury,and the results were further validated using fluorescence-activated cell sorting analysis with C57BL/6 mice at the same post-injury timepoints.We subsequently used PdgfraCreERT::RosaDTA mice,and evaluated the severity of post-TAT skeletal muscle degeneration with or without FAP-depletion.RESULTS The number of FAPs peaked at 1 week post-TAT before gradually declining to a level comparable to that pre-TAT.The change in the number of FAPs was potentially temporally correlated with the progression of skeletal muscle degeneration after TAT.FAP-depletion led to more severe degeneration early after TAT,indicating that FAPs potentially alleviate muscle degeneration after tendon rupture in the early post-injury phase.CONCLUSION FAPs potentially alleviate the degeneration of skeletal muscle in the acute stage after tendon rupture.展开更多
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.
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.
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 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Sarcomerogenesis,the addition of serial sarcomeres in skeletal muscle myofibrils and fibres,is a natural occurrence during growth and maturation of animals,including humans.However,the detailed mechanisms that allow for sarcomerogenesis are not fully understood.In some diseases,such as cerebral palsy in children,sarcomerogenesis appears to be inhibited or at least reduced,1,2 often causing severe restrictions in muscle and joint function.
基金Supported by The National Natural Science Foundation of China,No.82103356.
文摘BACKGROUND Improving our understanding of whether increased dietary intake ofω-3 polyunsaturated fatty acids(PUFAs)is beneficial for increasing skeletal muscle mass in patients with metabolic dysfunction-associated fatty liver disease(MAFLD)could provide an important clinical evidence base for the development of relevant nutritional guidelines.AIM To investigate the effect of total dietaryω-3 PUFAs and their subtypes on skeletal muscle mass in MAFLD.METHODS This cross-sectional study involved 2316 participants from four National Health and Nutrition Examination Survey cycles between 2011 and 2018.Dietary intake ofω-3 PUFAs was collected through 24-hour dietary recall interviews.Appendicular skeletal muscle mass index(ASMI)was calculated by dividing ASM in kilograms by height squared.RESULTS The multiple linear regression model showed significant relationships for dietary intake of totalω-3 PUFAs with higher ASMI(β:0.06,95%CI:0.01-0.11)in MAFLD patients.Dietary a-linolenic acid(ALA)(β:0.06,95%CI:0.01-0.12),docosapentaenoic acid(β:1.28,95%CI:0.01-2.54),and docosahexaenoic acid(DHA)(β:0.19,95%CI:0.01-0.37)were significantly associated with higher ASMI,while intake of stearidonic acid and eicosapentaenoic acid did not improve ASMI.In patients with high probability of liver fibrosis,dietary intake of ALA was associated with higher ASMI(β:0.11,95%CI:0.03-0.18).Stratified analysis found that DHA was associated with higher ASMI in patients with obesity and higher metabolic risk.CONCLUSION Increasing dietary intake ofω-3 PUFAs improved skeletal muscle health in patients with MAFLD.Patient with obesity and higher metabolic risk were more likely to benefit from intake of DHA.
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.
文摘Background: Aging-induced cardiac hypertrophy and reduced skeletal muscle strength contribute to increased disease risk and life burden in the elderly. FNDC5 acts as a protective muscle factor in both cardiac and skeletal muscle. This study aims to examine the relationship between cardiac FNDC5 and aging-related cardiac hypertrophy and decreased skeletal muscle strength. Methods: Male young C57BL/6 mice (5 months old, n = 6) and aged mice (21 months old, n = 6) were utilized in the study and housed in a specific pathogen-free (SPF) environment. Prior to the experiment, grip strength tests were performed on the mice, and heart tissues were collected for morphological analysis, including the assessment of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and fibronectin type III-containing structural domain 5 (FNDC5) protein levels. Furthermore, myosin heavy chain II (MyHC II), skeletal muscle-specific transcription factor (MyoD), muscle RING-finger protein-1 (MuRF1), and FNDC5 levels were evaluated in the quadriceps muscle. The correlations between heart weight and FNDC5 expression levels, as well as skeletal muscle indices in the mice, were subsequently analyzed. Result: Aging leads to cardiac hypertrophy and reduced expression of PGC-1α and FNDC5 proteins. Concurrently, there is a decline in the strength of skeletal muscle, along with decreased expression of MyHC II and increased expression of MURF1 and MyoD. Correlation analysis demonstrated strong positive associations between myocardial FNDC5 protein levels and limb grip strength, as well as MyHC II, and strong negative associations with MyoD and MuRF1. Conclusion: There may be a significant association between aging-induced cardiac hypertrophy and decreased skeletal muscle strength, with FNDC5 potentially playing a crucial role as a regulatory molecule facilitating communication between the heart and skeletal muscle.
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.
基金supported by the grants from the National Natural Science Foundation of China(32372873,32441084 and 32172720)the Program for Science&Technology Innovation Talents in Universities of Henan Province,China(22HASTIT038)the Zhongyuan Youth Talent Support Program of China(ZYYCYU202012156).
文摘Skeletal muscle satellite cells are stem cells characterized by their multipotency and capacity for in vitro proliferation.However,primary skeletal muscle satellite cells demonstrate limited proliferative capacity in vitro,which impedes their investigation in poultry skeletal muscle research.Cell immortalization techniques have emerged as valuable tools to address this limitation and facilitate the study of skeletal muscle satellite cell functions.This study achieved the immortalization of chicken skeletal muscle satellite cells through the transduction of primary cells with TERT(telomerase reverse transcriptase)amplified from chicken(chTERT)using a lentiviral vector via telomerase activity reconstitution.While the cells successfully overcame replicative senescence,complete immortalization was not achieved.Initial functional characterization revealed that the proliferative properties and cell cycle characteristics of the immortalized chicken skeletal muscle satellite cell lines(ICMS)closely resembled those of chicken primary muscle satellite cells(CPMSCs).Serum dependency analysis and soft agar assays confirmed that ICMS did not undergo malignant transformation.Furthermore,induced differentiation experiments demonstrated preserved differentiation capacity in ICMS.The established cell lines provide a fundamental framework for developing immortalized poultry cell lines and offer a cellular model for investigating poultry skeletal muscle-related functional genes.
基金supported by the Swedish Research Council(201500165)a Wallenberg Scholars Award from the Knut and Alice Wallenberg Foundation(KAW 2023.0312)The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen,partially funded by an unrestricted donation from the Novo Nordisk Foundation(NNF23SA0084103).
文摘1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site of insulin resistance,with impaired insulin signaling and reduced glucose transport activity contributing to metabolic dysfunction.
文摘BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is even less common.CASE SUMMARY A 58-year-old male with known history of RCC presented with a recurrence that was diagnosed through imaging and biopsies.Mucosa abnormalities of small bowel noted during endoscopy were biopsied as well as lesion in the psoas muscle that was noted.CONCLUSION This case report emphasizes that RCC can not only recur but can do so even decades later and present as metastatic foci at atypical sites.
文摘Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations,such as sarcopenia,myoste-atosis,and metabolic dysregulation,which play a key role in its pathogenesis and progression.Recent literature,including an article by Isakov,highlights the bidirectional interactions between muscle and liver,underscoring shared mechanisms such as insulin resistance,inflammation,and myokine imbalance.This letter reflects on key findings from the review,noting strengths such as its integration of mechanistic insights,discussion of emerging biomarkers,and emphasis on lifestyle and pharmacological interventions.It also identifies areas for further development,including standardization of diagnostic criteria and more rigorous evaluation of translational data.As muscle health gains promi-nence in metabolic dysfunction-associated steatotic liver disease research,multidisciplinary strategies that target both hepatic and muscular systems may offer more effective avenues for prevention and treatment.
基金Supported by Chongqing Young and Middle-aged Medical High-end Talents,No.YXGD202405Chongqing District and County Head Goose Talents,Chongqing Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.2024ZYYB036Chongqing Banan District Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.BNWJ202300112.
文摘BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.
基金supported by the National Natural Science Foundation of China(82003447,32202023)the Natural Science Foundation of Shandong Province(ZR2021QC177)the Young Scholars Program of Shandong University(2018WLJH33,2018WLJH34)。
文摘Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.
基金supported by a grant from the Russian Science Foundation(23-75-01061)。
文摘Objectives:Skeletal muscle ischemia/reperfusion injury(IRI)occurs as a result of a marked reduction in arterial perfusion to a limb and can lead to tissue death and threaten limb viability.This work assessed the effects of 20-hydroxyecdysone(20E)on hindlimb skeletal tissue following tourniquet-induced ischemia/reperfusion injury.Methods:Animals were divided into 4 groups—control group(Control),Control+20E(C+20E),mice with IRI(IRI),and mice with IRI+20E(IRI+20E).IRI was modeled by applying a tourniquet to the hind limb for 2 h with reperfusion for 1 h.5 mg/kg of 20E was administered intraperitoneally for 14 days.Afterward,the physical activity of mice,the histological structure of the quadriceps femoris,the expression of genes encoding proteins induced by hypoxia and involved in tissue adaptation to ischemia,and the functional parameters of skeletal muscle mitochondria were assessed.Results:It was shown that IRI of the limbs leads to functional disorders,depression of muscle function,accumulation of malondialdehyde(MDA)in mitochondria,and a decrease in their Ca2+buffering capacity,as well as an increase in the expression of HIF-1α,VGEF-A,PGC1αand PDGF-BB genes associated with adaptation to ischemia.20E reduced the intensity of degenerative processes in skeletal muscles,which was expressed in a decrease in the number of centrally nucleated fibers.Analysis of gene expression levels indicated a high degree of adaptation of animals to IRI.20E reduced the level of MDA in mitochondria,but did not affect the rate of respiration and calcium retention capacity of organelles both in normal conditions and during IRI.Conclusion:20E partially alleviates the skeletal muscle damage caused by IRI and can be used as part of combination therapy.
基金supported by the National Natural Science Foundation of China(NNSFC)(Grant Nos.12272132 and 11922206).
文摘Soft biological tissues are challenging materials for both testing and modeling.Despite the development of many constitutive models,the processing of choosing the most suitable model remains heuristic,relying significantly on personal experience and preference.Another issue is that the amount of collected experimental data is always finite.In this study,we trained a constitutive artificial neural network based on experimental data of cattle skeletal muscle tissue for the self-directed auto-discovery of constitutive models.The discovered models inherently satisfy thermodynamic consistency,material objectivity,polyconvexity,and necessary physical restrictions.Two constitutive models have been discovered by the trained neural network.Considering the constraints of finite experimental data,the generality and reliability of the auto-discovered con-stitutive models remain to be analyzed.Through experimental data of pig skeletal muscle tissue,we assess the goodness-of-fit and parameter identifiability of the automatically discovered constitutive models.At first glance,both auto-discovered models have excellent prediction accuracy.Further exploration from the perspective of information geometry suggests that one of the auto-discovered models is superior to the other in terms of parameter identifiability.The findings of the current work are expected to extend our understanding of auto-discovered constitutive models and offer a new perspective to advance machine learning-driven mechanics.
基金supported by the National Natural Science Foundation of China(No.82172551)the Health Discipline Leader Project of Shanghai Municipal Health Commission(No.2022XD044),China.
文摘Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease(COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy-and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
基金Supported by National Natural Science Foundation of China,No.82172509.
文摘BACKGROUND Fibro-adipogenic progenitors(FAPs)are a group of mesenchymal stem cells that cause fibro-fatty degeneration in skeletal muscle in various chronic disease mode-ls.FAPs also play a role in preventing muscle degeneration at acute stages during disease progression.However,few studies have reported the changes in and function of FAPs in the acute phase after tendon rupture.AIM To clarify the changes in the number of FAPs and their impact on skeletal muscle soon after tendon rupture to facilitate future studies targeting FAPs to treat muscle degeneration.METHODS We utilized Pdgfra-H2B::eGFP mice to trace and quantify FAPs in a tibialis anterior tenotomy(TAT)model at 0 and 3 days,1 week,2 weeks,3 weeks,4 weeks,5 weeks,and 6 weeks post-injury,and the results were further validated using fluorescence-activated cell sorting analysis with C57BL/6 mice at the same post-injury timepoints.We subsequently used PdgfraCreERT::RosaDTA mice,and evaluated the severity of post-TAT skeletal muscle degeneration with or without FAP-depletion.RESULTS The number of FAPs peaked at 1 week post-TAT before gradually declining to a level comparable to that pre-TAT.The change in the number of FAPs was potentially temporally correlated with the progression of skeletal muscle degeneration after TAT.FAP-depletion led to more severe degeneration early after TAT,indicating that FAPs potentially alleviate muscle degeneration after tendon rupture in the early post-injury phase.CONCLUSION FAPs potentially alleviate the degeneration of skeletal muscle in the acute stage after tendon rupture.
