How the state of living muscles modulates the features of nonlinear elastic waves generated by external dynamic loads remains unclear because of the challenge of directly observing and modeling nonlinear elastic waves...How the state of living muscles modulates the features of nonlinear elastic waves generated by external dynamic loads remains unclear because of the challenge of directly observing and modeling nonlinear elastic waves in skeletal muscles in vivo,considering their active deformation behavior.Here,this important issue is addressed by combining experiments performed with an ultrafast ultrasound imaging system to track nonlinear shear waves(shear shock waves)in muscles in vivo and finite element analysis relying on a physically motivated constitutive model to study the effect of muscle activation level.Skeletal muscle was loaded with a deep muscle stimulator to generate shear shock waves(SSWs).The particle velocities,second and third harmonics,and group velocities of the SSWs in living muscles under both passive and active states were measured in vivo.Our experimental results reveal,for the first time,that muscle states have a pronounced effect on wave features;a low level of activation may facilitate the occurrence of both the second and third harmonics,whereas a high level of activation may inhibit the third harmonic.Finite element analysis was further carried out to quantitatively explore the effect of active muscle deformation behavior on the generation and propagation of SSWs.The simulation results at different muscle activation levels confirmed the experimental findings.The ability to reveal the effects of muscle state on the features of SSWs may be helpful in elucidating the unique dynamic deformation mechanism of living skeletal muscles,quantitatively characterizing diverse shock wave-based therapy instruments,and guiding the design of muscle-mimicking soft materials.展开更多
The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal g...The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
A synthetic isoflavone （ISO-S） or genistein was added in culture medium at different concentrations （0, 10, 20, 30, 40, and 80 p.mol L^-1） to investigate the effects of soybean isoflavones on antioxidative capacit...A synthetic isoflavone （ISO-S） or genistein was added in culture medium at different concentrations （0, 10, 20, 30, 40, and 80 p.mol L^-1） to investigate the effects of soybean isoflavones on antioxidative capacity of porcine skeletal muscle satellite cells. After 48 h incubation, the suspension was cryopreserved for the determination of superoxide dismutase （SOD）, catalase （CAT）, glutathione peroxidase （GSH-Px） activities, and malondialdehyde （MDA） content. The mRNA levels of SOD, CAT, and GSH-Px gene in cells were detected with Taqman fluorescent probe method. The results showed that the content of MDA and the activities and the mRNA levels of SOD of porcine skeletal muscle satellite cells were influenced by supplemented soybean isoflavone （P〈0.05） when adding 10-80 μmol L^-1 ISO-S or genistein in the medium. The MDA contents, SOD and CAT activities and their mRNA expression levels of porcine skeletal muscle cells responded quadratically （P〈 0.05） as the level of ISO-S or genistein increased. Pre-incubation of porcine skeletal muscle satellite cells with ISO-S or genistein at 10-40 pmol L-1 elevated the activities and the mRNA expression levels of SOD and CAT in cells concurrently and decreased the cellular content of MDA （P〈 0.05）. The results indicated that pre-incubation of ISO-S or genistein at 10- 40μmol L^-1 could improve the antioxidative capacity of porcine skeletal muscle satellite cells.展开更多
Objective: To study on relationship of inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) content in the injured local soft tissue with injured degrees of the soft tissue in the third lumbar vertebr...Objective: To study on relationship of inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) content in the injured local soft tissue with injured degrees of the soft tissue in the third lumbar vertebrae (L3) transverse process syndrome model rat and to observe the effect of needle-knife therapy. Methods: One hundred and sixty male SD rats were randomly divided into normal group, model group, aminoguanidine (AG) group, needle-knife group, 40 rats in each group. The L3 transverse process syndrome rat model was established, and after treatment of needle-knife and AG, iNOS activities and NO contents and histomorpholocal changes in the soft tissues around L3 transverse process on 1, 3, 7 and 14 days were observed in the groups. Results: Compared with the normal group, iNOS activity and NO content in the model group were significantly increased (P<0.01); Compared with the model group, iNOS activities and NO contents were significantly decreased in both the needle-knife group and the AG group (both P<0.01); And both iNOS activities and NO contents were identical with both local inflammation response and injured degrees of the injured tissue in the groups. Conclusion: Needle-knife therapy can significantly inhibit generation of NO, alleviate inflammatory response and injured degree of the injured soft tissue, improve microcirculation, prevent formation of pathological scar tissue, and promote repair of the chronic soft tissue injury.展开更多
Calcineurin（Cn or CaN） is implicated in the control of skeletal muscle fiber phenotype and hypertrophy. However, little information is available concerning the expression of Cn in chickens. In the present study, the...Calcineurin（Cn or CaN） is implicated in the control of skeletal muscle fiber phenotype and hypertrophy. However, little information is available concerning the expression of Cn in chickens. In the present study, the expression of two Cn subunit genes（Cn Aα and Cn B1） was quantified by q PCR in the lateral gastrocnemius（LG, mainly composing of red fast-twitch myofibers）, the soleus（mainly composing of red slow-twitch myofibers） and the extensor digitorum longus（EDL, mainly composing of white fast-twitch myofibers） from Qingyuan partridge chickens（QY, slow-growing chicken breed） and Recessive White chickens（RW, fast-growing chicken breed） on different days（1, 8, 22, 36, 50 and 64 days post-hatching）. Although Cn Aα and Cn B1 gene expressions were variable with different trends in different skeletal muscles in the two chicken breeds during postnatal growth, it is highly muscle phenotype and breed specific. In general, the levels of Cn Aα and Cn B1 gene expressions of the soleus were lower than those of EDL and LG in both chicken breeds at the same stages. Compared between the two chicken breeds, the levels of Cn Aα gene expression of the three skeletal muscles in QY chickens were higher than those in RW chickens on days 1 and 22. However, on day 64, the levels of both Cn Aα and Cn B1 gene expressions of the three skeletal muscles were lower in QY chickens than those in RW chickens. Correlation analysis of the levels of Cn Aα and Cn B1 gene expressions of the same skeletal muscle showed that there were positive correlations for all three skeletal muscle tissues in two chicken breeds. These results provide some valuable clues to understand the role of Cn in the development of chicken skeletal muscles, with a function that may be related to meat quality.展开更多
Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol...Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.展开更多
In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and nutrients.This study explored the complex interplay be...In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and nutrients.This study explored the complex interplay between skeletal muscle and endothelial cells in the vascularization ofmuscle tissue.By harnessing the capabilities of three-dimensional(3D)bioprinting and modeling,we developed a novel approach involving the co-construction of endothelial and muscle cells,followed by their subsequent differentiation.Our findings highlight the importance of the interaction dynamics between these two cell types.Notably,introducing endothelial cells during the advanced phases of muscle differentiation enhanced myotube assembly.Moreover,it stimulated the development of the vascular network,paving the way for the early stages of vascularized skeletal muscle development.The methodology proposed in this study indicates the potential for constructing large-scale,physiologically aligned skeletal muscle.Additionally,it highlights the need for exploring the delicate equilibrium and mutual interactions between muscle and endothelial cells.Based on the multicell-type interaction model,we can predict promising pathways for constructing even more intricate tissues or organs.展开更多
Objective:To explore the mechanism of the degradation of human hair keratin (HHK) scaffold material implanted in damaged skeletal muscle tissues. Methods: Six New Zealand rabbits with HHK scaffold material implants (c...Objective:To explore the mechanism of the degradation of human hair keratin (HHK) scaffold material implanted in damaged skeletal muscle tissues. Methods: Six New Zealand rabbits with HHK scaffold material implants (composed of 3 different types of HHK material with varied degradation speed) after musclectomy were divided into 3 groups (2 in each group) to observe the degradation of the material at 1, 3, 6weeks after operation. Another rabbit without operation was used as the control group. The degradation of HHK was observed with light microscopy, histochemistry of ubiquitin and electron microscopy. Results:Light microscopy showed that human hair cuticles fell off from the HHK material and emerged, and the macrophagocytes and multinucleate giant cells were attached onto the surface of the material, which became homogeneous at the first postoperative week. The HHK scaffold material was degraded into particles that was phagocytosed by macrophagocytes and multinucleate giant cells at the third week. Ubiquitin enzymatic histochemistry showed that the macrophagocytes and the multinucleate giant cells were positive at the first week. Under electron microscope, HHK scaffold material was degraded into particles, and at the sixth week,part of HHK scaffold material was further degraded. Conclusion: Large mass of the HHK scaffold material is degraded via ubiquitin system, and the resultant particles are phagocytosed and degraded with the cooperation of lysosome and ubiquitin.展开更多
Pneumatic artificial muscles(PAMs)can generate multimodal movements,e.g.,linear contraction/extension,spiral torsion,and bending motions.Among these motions,contraction and extension movements can be achieved using li...Pneumatic artificial muscles(PAMs)can generate multimodal movements,e.g.,linear contraction/extension,spiral torsion,and bending motions.Among these motions,contraction and extension movements can be achieved using linear PAMs(LPAMs)designed to mimic human skeletal muscle.LPAMs have considerable potential for wearable applications and can be integrated into soft wearable robotic systems.Due to their inherent compliance,excellent human-robot interaction,safety,and low cost,LPAMs are considered potential alternatives as actuator components in the construction of wearable robots.This review presents a comprehensive overview of the bio-inspired design of LPAMs and their wearable applications.The biomechanics of human skeletal muscle,including anatomy,morphology,and biomechanical characterization,is analyzed to provide design inspirations for LPAMs and determine the assistance requirements of LPAM-based wearable robots.Herein,LPAMs are classified into four categories based on their structural shapes,including cylindrical-shaped muscles,flat-shaped muscles,fold-shaped muscles,and muscles with other shapes.In addition,this review provides an overview of the diverse physical interfaces utilized in wearable robots and presents a comparative analysis of the actuation characteristics of LPAMs and the assistance performance of LPAM-based wearable robots.This analysis was conducted in consideration of several key metrics,including the contraction ratio,maximum force,specific force,response frequency,assistive torque/bodyweight,and net metabolic cost.Finally,this review summarizes the ongoing challenges and future research directions.展开更多
Heart failure(HF)is a complex clinical syndrome that promotes high morbidity and multi-systemic damage.Skeletal muscle can be directly affected by HF through a loss of physical capacity and various inflammatory,hormon...Heart failure(HF)is a complex clinical syndrome that promotes high morbidity and multi-systemic damage.Skeletal muscle can be directly affected by HF through a loss of physical capacity and various inflammatory,hormonal,and metabolic mechanisms observed in this cardiac condition,which collectively contribute to a high prevalence of sarcopenia in HF patients.Therefore,the aim of this review was to compile the main recent clinical and epidemiological data on muscle health in HF patients.Nine studies were selected from systematic reviews and clinical trials,which demonstrated a high prevalence of sarcopenia in patients with HF,particularly in males,hospitalized patients,the elderly,and those with HF with reduced ejection fraction.Oxidative stress markers and higher levels of natriuretic peptides were also observed in HF patients who exhibited damaged muscle parameters.Furthermore,the overall deterioration of prognosis in HF was associated with criteria defining sarcopenia,such as low muscle strength and lean mass loss.These findings reinforce the importance of evaluating skeletal muscle in HF patients,which can provide improvements in morbidity and functionality.展开更多
To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles ar...To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles are different,and the importance of these potential differences.In the present study,we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles.We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways.In terms of spatial distribution patterns,sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons.In addition,the neuronal innervation of limb muscles exhibited four different characteristics:sympathetic neuron-rich muscle,sensory neuron-rich muscle,neuron-sparse muscle,and motor neuron-rich muscle.Sensory neuron density was mainly associated with muscle contractile structure and cell pH,whereas sympathetic neuron density was associated with protein kinase activity,muscle vasculature,muscle calcium-dependent protein kinase activity,lipid transport,and vesicle release.Motor neuron density was mainly associated with protein kinase activity,cell adhesion,oxidoreductase activity,and exocytosis.These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions,thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.展开更多
Purpose: 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
Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelim...Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelimb grip strength,hanging performance,and locomotor activity were assessed.Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis,contractile-marker features,senescence-and DNA damage-associated markers,inflammatory signaling,and mitochondrial proteins.Oxidative status was assessed by determining antioxidant capacity,lipid peroxidation,and oxidative DNA damage.Transcriptomic profiling was also performed,and selected targets were validated by quantitative RT-PCR and immunostaining.In addition,differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract;senescence-associated β-galactosidase,DNA damage signaling,and cell viability were measured.Results:Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion.It also reduced collagen deposition,preserved contractile-marker immunoreactivity,attenuated senescence-and inflammation-associated signals,and increased mitochondrial protein immunoreactivity.Oxidative DNA damage was notably reduced by nacre extract.Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression,which were supported by tissue-level validation.In C2C12 myotubes,nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability.Conclusions:Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress,inflammation,mitochondrial features,and cellular senescence.展开更多
Genetic improvement of meat production traits has always been the primary goal of pig breeding.Geographical isolation,natural and artificial selection led to significant differences in the phenotypes of meat productio...Genetic improvement of meat production traits has always been the primary goal of pig breeding.Geographical isolation,natural and artificial selection led to significant differences in the phenotypes of meat production traits between Chinese local pigs and Western commercial pigs.Comparative genomics and transcriptomics analysis provided powerful tools to identify genetic variants and genes associated with skeletal muscle growth.However,the number of available genetic variants and genes are still limited.In this study,a comprehensive comparison of transcriptomes showed that ribosomal protein S27-like(RPS27L)gene was highly expressed in skeletal muscle and up-regulated in Chinese local pigs when compared with Western commercial pigs.Functional analysis revealed that overexpression of RPS27L promoted myoblast proliferation and repressed differentiation in pig skeletal muscle cells.Conversely,the knockdown of RPS27L led to the inhibition of myoblast proliferation and the promotion of differentiation.Notably,a 13-bp insertion-deletion(InDel)mutation was identified within the RPS27L promoter,inserted in Chinese local breeds and predominantly deleted in Western commercial breeds.Luciferase reporter assay suggested this InDel modulated RPS27L expression by influencing transcription factor 3(TCF3)and myogenic differentiation antigen(MYOD)binding to the promoter.Furthermore,a positive correlation was observed between RPS27L expression and backfat thickness.Association studies demonstrated this InDel was significantly associated with the body weight of pigs at the age of 240 d.Together,our results suggested that RPS27L was a regulator of skeletal muscle development and growth,and was a candidate marker for improving meat production traits in pigs.This study not only provided a biomarker for animal breeding,but also was helpful for understanding skeletal muscle development and muscular disease in humans.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
Mechanical tension is widely recognized as the primary stimulus underlying the molecular mechanisms that influence muscle hypertrophy induced by resistance training.Despite this,several outdated or overstated concepts...Mechanical tension is widely recognized as the primary stimulus underlying the molecular mechanisms that influence muscle hypertrophy induced by resistance training.Despite this,several outdated or overstated concepts continue to persist,both in the scientific literature and in the practical application of resistance training coaching and program design.Claims that acute hormonal responses,metabolic stress,cell swelling or“the pump”meaningfully contribute to hypertrophy are not supported by scientific evidence.Additionally,the concept of sarcoplasmic hypertrophy as a distinct and functionally meaningful contributor to hypertrophy lacks strong evidence.In this review,we critically evaluate several persistent misconceptions and contrast them with evidence-based mechanistic insights into load-induced hypertrophy.Specifically,we discuss the role(or lack thereof)of systemic hormones,metabolites,and cell swelling in promoting muscle hypertrophy.We also critically review the concept of sarcoplasmic hypertrophy and propose that it is not a meaningful contributor to muscle hypertrophy.Lastly,to translate knowledge for trainees and coaches,we discuss the upper limit of muscle hypertrophy and provide readers with evidence-based,reasonable expectations for muscle hypertrophy.We aimed,through this review,to use scientific evidence to enhance our understanding of what drives muscle hypertrophy and provide an evidence-based framework for resistance exercise training.展开更多
Objective： To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods： Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by earl...Objective： To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods： Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by early Tuina and routine Tuina. The number of satellite cells of skeletal muscles was observed. Results： The number of the satellite cells continued to grow in both groups, and it began to increase significantly 3-5 days after Tuina treatment. Early Tuina treatment produces larger number of satellite cells than routine Tuina treatment. Conclusion： Early Tuina treatment is helpful to the marked recovery of skeletal muscles by increasing the number of satellite cell.展开更多
The biological mechanism by which maternal undernutrition increases the metabolic disorder risk of skeletal muscles in offspring is not fully understood.We hypothesize that maternal intake restriction influences metab...The biological mechanism by which maternal undernutrition increases the metabolic disorder risk of skeletal muscles in offspring is not fully understood.We hypothesize that maternal intake restriction influences metabolic signals in the skeletal muscles of offspring via a glucagon-mediated pathway.Twentyfour pregnant goats were assigned to the control group(100%of the nutrients requirement,n=12)and restricted group(60%of the control feed allowance from pregnant days 45 to 100,n=12).Blood and Longissimus thoracis muscle were sampled from dams(100 d of gestation),fetuses(100 d of gestation),and kids(90 d after birth)in each group.The data were analyzed using the linear MIXED model,with the multiple comparison method of SIDAK applied.Intake restriction reduced(P<0.05)the total blood protein of dams and fetuses.Maternal restriction decreased(P<0.05)the cAMP-responsive element-binding protein 1(CREB1),CREB-binding protein(CREBBP),protein kinase A(PKA),aryl hydrocarbon receptor nuclear translocator-like protein 1(BMAL1),protein kinase B(AKT1),mammalian target of rapamycin(mTOR),and regulatory-associated protein of mTOR(RPTOR)mRNA expression in the fetuses,and reduced(P<0.05)the CREBBP,nuclear receptor subfamily 1 group H member 3(NR1 H3),D-box binding PAR bZIP transcription factor(DBP)and PKA mRNA levels in the kids,but increased(P<0.05)the peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC1 A)and tuberous sclerosis 2(TSC2)mRNA levels in the fetuses.The mRNA expression of clock circadian regulator(CLOCK)and TSC2 genes was increased(P<0.05)in the restricted kids.The protein expression of total PKA and phosphorylated PKA in the restricted fetuses and kids were downregulated(P<0.05),and the protein expression of total mTOR and phosphorylated mTOR were reduced(P<0.05)in the restricted fetuses and kids.Maternal intake restriction regulated fat oxidation,protein synthesis,and circadian clock expression in the muscles of the offspring probably via the glucagon-mediated PKA-CREB pathway,which reveals a noteworthy molecular pathway that maternal undernutrition leads to metabolic adaptation of skeletal muscle in offspring.展开更多
基金supported by the National Students Training Program for Innovation(Grant No.202210007029)。
文摘How the state of living muscles modulates the features of nonlinear elastic waves generated by external dynamic loads remains unclear because of the challenge of directly observing and modeling nonlinear elastic waves in skeletal muscles in vivo,considering their active deformation behavior.Here,this important issue is addressed by combining experiments performed with an ultrafast ultrasound imaging system to track nonlinear shear waves(shear shock waves)in muscles in vivo and finite element analysis relying on a physically motivated constitutive model to study the effect of muscle activation level.Skeletal muscle was loaded with a deep muscle stimulator to generate shear shock waves(SSWs).The particle velocities,second and third harmonics,and group velocities of the SSWs in living muscles under both passive and active states were measured in vivo.Our experimental results reveal,for the first time,that muscle states have a pronounced effect on wave features;a low level of activation may facilitate the occurrence of both the second and third harmonics,whereas a high level of activation may inhibit the third harmonic.Finite element analysis was further carried out to quantitatively explore the effect of active muscle deformation behavior on the generation and propagation of SSWs.The simulation results at different muscle activation levels confirmed the experimental findings.The ability to reveal the effects of muscle state on the features of SSWs may be helpful in elucidating the unique dynamic deformation mechanism of living skeletal muscles,quantitatively characterizing diverse shock wave-based therapy instruments,and guiding the design of muscle-mimicking soft materials.
基金This project was supported by the National Natural Science Foundation of China(No.81673757 and No.81603652).
文摘The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.
基金supports of the grants from the Ministry of Science and Technology of China and the Department of Science and Tech-nology of Guangdong Province, Chinasupported by the National Basic Research Program of China (973 Program, 2004CB117500)the Earmarked Fund for Modern Agro-Industry Technology Research System, China
文摘A synthetic isoflavone （ISO-S） or genistein was added in culture medium at different concentrations （0, 10, 20, 30, 40, and 80 p.mol L^-1） to investigate the effects of soybean isoflavones on antioxidative capacity of porcine skeletal muscle satellite cells. After 48 h incubation, the suspension was cryopreserved for the determination of superoxide dismutase （SOD）, catalase （CAT）, glutathione peroxidase （GSH-Px） activities, and malondialdehyde （MDA） content. The mRNA levels of SOD, CAT, and GSH-Px gene in cells were detected with Taqman fluorescent probe method. The results showed that the content of MDA and the activities and the mRNA levels of SOD of porcine skeletal muscle satellite cells were influenced by supplemented soybean isoflavone （P〈0.05） when adding 10-80 μmol L^-1 ISO-S or genistein in the medium. The MDA contents, SOD and CAT activities and their mRNA expression levels of porcine skeletal muscle cells responded quadratically （P〈 0.05） as the level of ISO-S or genistein increased. Pre-incubation of porcine skeletal muscle satellite cells with ISO-S or genistein at 10-40 pmol L-1 elevated the activities and the mRNA expression levels of SOD and CAT in cells concurrently and decreased the cellular content of MDA （P〈 0.05）. The results indicated that pre-incubation of ISO-S or genistein at 10- 40μmol L^-1 could improve the antioxidative capacity of porcine skeletal muscle satellite cells.
基金supported by a grant from National "973" Project (No: 2006CB504508)
文摘Objective: To study on relationship of inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) content in the injured local soft tissue with injured degrees of the soft tissue in the third lumbar vertebrae (L3) transverse process syndrome model rat and to observe the effect of needle-knife therapy. Methods: One hundred and sixty male SD rats were randomly divided into normal group, model group, aminoguanidine (AG) group, needle-knife group, 40 rats in each group. The L3 transverse process syndrome rat model was established, and after treatment of needle-knife and AG, iNOS activities and NO contents and histomorpholocal changes in the soft tissues around L3 transverse process on 1, 3, 7 and 14 days were observed in the groups. Results: Compared with the normal group, iNOS activity and NO content in the model group were significantly increased (P<0.01); Compared with the model group, iNOS activities and NO contents were significantly decreased in both the needle-knife group and the AG group (both P<0.01); And both iNOS activities and NO contents were identical with both local inflammation response and injured degrees of the injured tissue in the groups. Conclusion: Needle-knife therapy can significantly inhibit generation of NO, alleviate inflammatory response and injured degree of the injured soft tissue, improve microcirculation, prevent formation of pathological scar tissue, and promote repair of the chronic soft tissue injury.
基金The National Natural Science Foundation of China (31301967)the Key Technology Support Program of Jiangsu Province, China (BK2012268)the Earmarked Fund for Modern Agro-Industry Technology Research System, China (CARS-42-G03) supported this research
文摘Calcineurin（Cn or CaN） is implicated in the control of skeletal muscle fiber phenotype and hypertrophy. However, little information is available concerning the expression of Cn in chickens. In the present study, the expression of two Cn subunit genes（Cn Aα and Cn B1） was quantified by q PCR in the lateral gastrocnemius（LG, mainly composing of red fast-twitch myofibers）, the soleus（mainly composing of red slow-twitch myofibers） and the extensor digitorum longus（EDL, mainly composing of white fast-twitch myofibers） from Qingyuan partridge chickens（QY, slow-growing chicken breed） and Recessive White chickens（RW, fast-growing chicken breed） on different days（1, 8, 22, 36, 50 and 64 days post-hatching）. Although Cn Aα and Cn B1 gene expressions were variable with different trends in different skeletal muscles in the two chicken breeds during postnatal growth, it is highly muscle phenotype and breed specific. In general, the levels of Cn Aα and Cn B1 gene expressions of the soleus were lower than those of EDL and LG in both chicken breeds at the same stages. Compared between the two chicken breeds, the levels of Cn Aα gene expression of the three skeletal muscles in QY chickens were higher than those in RW chickens on days 1 and 22. However, on day 64, the levels of both Cn Aα and Cn B1 gene expressions of the three skeletal muscles were lower in QY chickens than those in RW chickens. Correlation analysis of the levels of Cn Aα and Cn B1 gene expressions of the same skeletal muscle showed that there were positive correlations for all three skeletal muscle tissues in two chicken breeds. These results provide some valuable clues to understand the role of Cn in the development of chicken skeletal muscles, with a function that may be related to meat quality.
基金supported by Korea Environment Industry&Technology Institute through Project to make multi-ministerial national biological research resources more advanced Project,funded by Korea Ministry of Environment(grant number RS-2023-00230403).
文摘Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.
基金support from the National Natural Science Foundation of China(Nos.T2222029,U21A20396,and 62127811)the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(No.XDA16020802)the CAS Project for Young Scientists in Basic Research(No.YSBR-012).
文摘In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and nutrients.This study explored the complex interplay between skeletal muscle and endothelial cells in the vascularization ofmuscle tissue.By harnessing the capabilities of three-dimensional(3D)bioprinting and modeling,we developed a novel approach involving the co-construction of endothelial and muscle cells,followed by their subsequent differentiation.Our findings highlight the importance of the interaction dynamics between these two cell types.Notably,introducing endothelial cells during the advanced phases of muscle differentiation enhanced myotube assembly.Moreover,it stimulated the development of the vascular network,paving the way for the early stages of vascularized skeletal muscle development.The methodology proposed in this study indicates the potential for constructing large-scale,physiologically aligned skeletal muscle.Additionally,it highlights the need for exploring the delicate equilibrium and mutual interactions between muscle and endothelial cells.Based on the multicell-type interaction model,we can predict promising pathways for constructing even more intricate tissues or organs.
文摘Objective:To explore the mechanism of the degradation of human hair keratin (HHK) scaffold material implanted in damaged skeletal muscle tissues. Methods: Six New Zealand rabbits with HHK scaffold material implants (composed of 3 different types of HHK material with varied degradation speed) after musclectomy were divided into 3 groups (2 in each group) to observe the degradation of the material at 1, 3, 6weeks after operation. Another rabbit without operation was used as the control group. The degradation of HHK was observed with light microscopy, histochemistry of ubiquitin and electron microscopy. Results:Light microscopy showed that human hair cuticles fell off from the HHK material and emerged, and the macrophagocytes and multinucleate giant cells were attached onto the surface of the material, which became homogeneous at the first postoperative week. The HHK scaffold material was degraded into particles that was phagocytosed by macrophagocytes and multinucleate giant cells at the third week. Ubiquitin enzymatic histochemistry showed that the macrophagocytes and the multinucleate giant cells were positive at the first week. Under electron microscope, HHK scaffold material was degraded into particles, and at the sixth week,part of HHK scaffold material was further degraded. Conclusion: Large mass of the HHK scaffold material is degraded via ubiquitin system, and the resultant particles are phagocytosed and degraded with the cooperation of lysosome and ubiquitin.
基金supported by the National Natural Science Foundation of China(No.52475067).
文摘Pneumatic artificial muscles(PAMs)can generate multimodal movements,e.g.,linear contraction/extension,spiral torsion,and bending motions.Among these motions,contraction and extension movements can be achieved using linear PAMs(LPAMs)designed to mimic human skeletal muscle.LPAMs have considerable potential for wearable applications and can be integrated into soft wearable robotic systems.Due to their inherent compliance,excellent human-robot interaction,safety,and low cost,LPAMs are considered potential alternatives as actuator components in the construction of wearable robots.This review presents a comprehensive overview of the bio-inspired design of LPAMs and their wearable applications.The biomechanics of human skeletal muscle,including anatomy,morphology,and biomechanical characterization,is analyzed to provide design inspirations for LPAMs and determine the assistance requirements of LPAM-based wearable robots.Herein,LPAMs are classified into four categories based on their structural shapes,including cylindrical-shaped muscles,flat-shaped muscles,fold-shaped muscles,and muscles with other shapes.In addition,this review provides an overview of the diverse physical interfaces utilized in wearable robots and presents a comparative analysis of the actuation characteristics of LPAMs and the assistance performance of LPAM-based wearable robots.This analysis was conducted in consideration of several key metrics,including the contraction ratio,maximum force,specific force,response frequency,assistive torque/bodyweight,and net metabolic cost.Finally,this review summarizes the ongoing challenges and future research directions.
文摘Heart failure(HF)is a complex clinical syndrome that promotes high morbidity and multi-systemic damage.Skeletal muscle can be directly affected by HF through a loss of physical capacity and various inflammatory,hormonal,and metabolic mechanisms observed in this cardiac condition,which collectively contribute to a high prevalence of sarcopenia in HF patients.Therefore,the aim of this review was to compile the main recent clinical and epidemiological data on muscle health in HF patients.Nine studies were selected from systematic reviews and clinical trials,which demonstrated a high prevalence of sarcopenia in patients with HF,particularly in males,hospitalized patients,the elderly,and those with HF with reduced ejection fraction.Oxidative stress markers and higher levels of natriuretic peptides were also observed in HF patients who exhibited damaged muscle parameters.Furthermore,the overall deterioration of prognosis in HF was associated with criteria defining sarcopenia,such as low muscle strength and lean mass loss.These findings reinforce the importance of evaluating skeletal muscle in HF patients,which can provide improvements in morbidity and functionality.
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Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelimb grip strength,hanging performance,and locomotor activity were assessed.Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis,contractile-marker features,senescence-and DNA damage-associated markers,inflammatory signaling,and mitochondrial proteins.Oxidative status was assessed by determining antioxidant capacity,lipid peroxidation,and oxidative DNA damage.Transcriptomic profiling was also performed,and selected targets were validated by quantitative RT-PCR and immunostaining.In addition,differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract;senescence-associated β-galactosidase,DNA damage signaling,and cell viability were measured.Results:Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion.It also reduced collagen deposition,preserved contractile-marker immunoreactivity,attenuated senescence-and inflammation-associated signals,and increased mitochondrial protein immunoreactivity.Oxidative DNA damage was notably reduced by nacre extract.Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression,which were supported by tissue-level validation.In C2C12 myotubes,nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability.Conclusions:Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress,inflammation,mitochondrial features,and cellular senescence.
基金supported by the Sustainable Development Special Project from Shenzhen,China(KCXFZ20201221173213037)the National Natural Science Foundation of China(32172697 and U23A20229)+1 种基金the Guangdong Provincial Natural Science Foundation(2021A1515011336)the Agricultural Science and Technology Innovation Program,China(CAASZDRW202406)。
文摘Genetic improvement of meat production traits has always been the primary goal of pig breeding.Geographical isolation,natural and artificial selection led to significant differences in the phenotypes of meat production traits between Chinese local pigs and Western commercial pigs.Comparative genomics and transcriptomics analysis provided powerful tools to identify genetic variants and genes associated with skeletal muscle growth.However,the number of available genetic variants and genes are still limited.In this study,a comprehensive comparison of transcriptomes showed that ribosomal protein S27-like(RPS27L)gene was highly expressed in skeletal muscle and up-regulated in Chinese local pigs when compared with Western commercial pigs.Functional analysis revealed that overexpression of RPS27L promoted myoblast proliferation and repressed differentiation in pig skeletal muscle cells.Conversely,the knockdown of RPS27L led to the inhibition of myoblast proliferation and the promotion of differentiation.Notably,a 13-bp insertion-deletion(InDel)mutation was identified within the RPS27L promoter,inserted in Chinese local breeds and predominantly deleted in Western commercial breeds.Luciferase reporter assay suggested this InDel modulated RPS27L expression by influencing transcription factor 3(TCF3)and myogenic differentiation antigen(MYOD)binding to the promoter.Furthermore,a positive correlation was observed between RPS27L expression and backfat thickness.Association studies demonstrated this InDel was significantly associated with the body weight of pigs at the age of 240 d.Together,our results suggested that RPS27L was a regulator of skeletal muscle development and growth,and was a candidate marker for improving meat production traits in pigs.This study not only provided a biomarker for animal breeding,but also was helpful for understanding skeletal muscle development and muscular disease in humans.
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.
基金supported this work,but the SMP acknowledges support from the Canada Research Chairs Program(CRC-2021-00495)MJL is supported by a Canadian Institutes of Health Research(CIHR)Postdoctoral Fellowship award(Funding Reference No.187773).
文摘Mechanical tension is widely recognized as the primary stimulus underlying the molecular mechanisms that influence muscle hypertrophy induced by resistance training.Despite this,several outdated or overstated concepts continue to persist,both in the scientific literature and in the practical application of resistance training coaching and program design.Claims that acute hormonal responses,metabolic stress,cell swelling or“the pump”meaningfully contribute to hypertrophy are not supported by scientific evidence.Additionally,the concept of sarcoplasmic hypertrophy as a distinct and functionally meaningful contributor to hypertrophy lacks strong evidence.In this review,we critically evaluate several persistent misconceptions and contrast them with evidence-based mechanistic insights into load-induced hypertrophy.Specifically,we discuss the role(or lack thereof)of systemic hormones,metabolites,and cell swelling in promoting muscle hypertrophy.We also critically review the concept of sarcoplasmic hypertrophy and propose that it is not a meaningful contributor to muscle hypertrophy.Lastly,to translate knowledge for trainees and coaches,we discuss the upper limit of muscle hypertrophy and provide readers with evidence-based,reasonable expectations for muscle hypertrophy.We aimed,through this review,to use scientific evidence to enhance our understanding of what drives muscle hypertrophy and provide an evidence-based framework for resistance exercise training.
文摘Objective： To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods： Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by early Tuina and routine Tuina. The number of satellite cells of skeletal muscles was observed. Results： The number of the satellite cells continued to grow in both groups, and it began to increase significantly 3-5 days after Tuina treatment. Early Tuina treatment produces larger number of satellite cells than routine Tuina treatment. Conclusion： Early Tuina treatment is helpful to the marked recovery of skeletal muscles by increasing the number of satellite cell.
基金supported by the National Natural Science Foundation of China[31730092,31760678 and 31402105]Hunan innovative Province construction project[2019RS3021]。
文摘The biological mechanism by which maternal undernutrition increases the metabolic disorder risk of skeletal muscles in offspring is not fully understood.We hypothesize that maternal intake restriction influences metabolic signals in the skeletal muscles of offspring via a glucagon-mediated pathway.Twentyfour pregnant goats were assigned to the control group(100%of the nutrients requirement,n=12)and restricted group(60%of the control feed allowance from pregnant days 45 to 100,n=12).Blood and Longissimus thoracis muscle were sampled from dams(100 d of gestation),fetuses(100 d of gestation),and kids(90 d after birth)in each group.The data were analyzed using the linear MIXED model,with the multiple comparison method of SIDAK applied.Intake restriction reduced(P<0.05)the total blood protein of dams and fetuses.Maternal restriction decreased(P<0.05)the cAMP-responsive element-binding protein 1(CREB1),CREB-binding protein(CREBBP),protein kinase A(PKA),aryl hydrocarbon receptor nuclear translocator-like protein 1(BMAL1),protein kinase B(AKT1),mammalian target of rapamycin(mTOR),and regulatory-associated protein of mTOR(RPTOR)mRNA expression in the fetuses,and reduced(P<0.05)the CREBBP,nuclear receptor subfamily 1 group H member 3(NR1 H3),D-box binding PAR bZIP transcription factor(DBP)and PKA mRNA levels in the kids,but increased(P<0.05)the peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC1 A)and tuberous sclerosis 2(TSC2)mRNA levels in the fetuses.The mRNA expression of clock circadian regulator(CLOCK)and TSC2 genes was increased(P<0.05)in the restricted kids.The protein expression of total PKA and phosphorylated PKA in the restricted fetuses and kids were downregulated(P<0.05),and the protein expression of total mTOR and phosphorylated mTOR were reduced(P<0.05)in the restricted fetuses and kids.Maternal intake restriction regulated fat oxidation,protein synthesis,and circadian clock expression in the muscles of the offspring probably via the glucagon-mediated PKA-CREB pathway,which reveals a noteworthy molecular pathway that maternal undernutrition leads to metabolic adaptation of skeletal muscle in offspring.
