Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
BACKGROUND 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
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great o...Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great opportunity to develop advanced molecular breeding markers to efficiently improve animal meat production traits.Hippo is an important study subject because of its crucial role in the regulation of organ size.In recent years,with the increase of research on Hippo signaling pathway,the integrative application of multi-omics technologies such as genomics,transcriptomics,proteomics,and metabolomics can help promote the in-depth involvement of Hippo signaling pathway in skeletal muscle development research.The Hippo signaling pathway plays a key role in many biological events,including cell division,cell migration,cell proliferation,cell differentiation,cell apoptosis,as well as cell adhesion,cell polarity,homeostasis,maintenance of the face of mechanical overload,etc.Its influence on the development of skeletal muscle has important research value for enhancing the efficiency of animal husbandry production.In this study,we traced the origin of the Hippo pathway,comprehensively sorted out all the functional factors found in the pathway,deeply analyzed the molecular mechanism of its function,and classified it from a novel perspective based on its main functional domain and mode of action.Our aim is to systematically explore its regulatory role throughout skeletal muscle development.We specifically focus on the Hippo signaling pathway in embryonic stem cell development,muscle satellite cell fate determination,myogenesis,skeletal muscle meat production and organ size regulation,muscle hypertrophy and atrophy,muscle fiber formation and its transformation between different types,and cardiomyocytes.The roles in proliferation and regeneration are methodically summarized and analyzed comprehensively.The summary and prospect of the Hippo signaling pathway within this article will provide ideas for further improving meat production and muscle deposition and developing new molecular breeding technologies for livestock and poultry,which will be helpful for the development of animal molecular breeding.展开更多
Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challe...Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.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
Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity hav...Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.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
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
Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acup...Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion: Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.展开更多
Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.Howev...Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.展开更多
Background:Lung cancer cachexia has received widespread attention as one of the most common complications in patients with advanced lung cancer.As a multifactorial syndrome,lung cancer cachexia is characterized by a p...Background:Lung cancer cachexia has received widespread attention as one of the most common complications in patients with advanced lung cancer.As a multifactorial syndrome,lung cancer cachexia is characterized by a persistent decline in muscle mass that cannot be reversed by conventional nutrition Xiaoyan d ecoction can promote appetite and improve skeletal muscle mass in patients with lung cancer cachexia,while the third lumbar skeletal muscle index(L3-SMI)is able to determine whole-body skeletal muscle mass.To analyze the relationship between L3-SMI and hematological indexes and lung cancer cachexia,and to study the clinical efficacy of Xiaoyan decoction on skeletal muscle atrophy in lung cancer cachexia patients,with the aim of providing a reference basis for the early diagnosis and treatment of lung cancer cachexia patients and skeletal muscle atrophy.Methods:148 patients who were diagnosed with lung cancer in the Department of Oncology of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to December 2022 were included,and were divided into cachexia and non-cachexia groups according to the diagnostic criteria of cachexia,and analyzed the differences of hematological indexes and L3-SMI between cachexia patients and non-cachexia patients.And the patients with cachexia were divided into control group and treatment group,analyzed and compared the changes of body mass index(BMI),L 3-SMI,Karnofsky functional status score,albumin and other hematological indexes of the two groups before and after the treatment,and evaluated the safety of the Xiaoyan decoction in the treatment of cachexia.Results:A total of 148 lung cancer patients were included in this study,including 67 patients in the cachexia group and 81 patients in the non-cachexia group.According to the pre-treatment statistical analysis,the BMI of patients in the cachexia group was lower than that of patients in the non-cachexia group(P<0.05);among the biochemical function indexes,the proportions of creatinine(P<0.05),total protein(P<0.05),The levels of albumin in the cachexia group were significantly lower(P<0.05)compared to the non-cachexia group;in the cachexia group,both males and females had lower L3-SMIs than in the non-cachexia group(P<0.05).A total of 62 cases of lung cancer cachexia were studied,30 cases in the control group and 32 cases in the treatment group,according to statistical analysis,BMI was significantly different before and after treatment(P<0.05);L3-SMI was significantly different in the treatment group before and after treatment(P<0.05);Karnofsky significantly differed in the treatment group before and after treatment(P<0.05);and there was a significant difference in albumin before and after(P<0.05).Conclusion:Cachexia patients had significantly lower third lumbar skeletal muscle mass than non-cachexia patients,according to this study;Xiaoyan decoction was able to improve skeletal muscle mass,nutritional status as well as functional status of patients with cachexia in lung cancer,among others.展开更多
Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ...Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.展开更多
As the only source of stem cells, satellite cells play and extraordinary role in the remediation process of skeletal muscle after injury. This paper overviewed the biological characteristic of skeletal muscle satellit...As the only source of stem cells, satellite cells play and extraordinary role in the remediation process of skeletal muscle after injury. This paper overviewed the biological characteristic of skeletal muscle satellite cells and its role in repairing muscle injury, and put forward the prospects of its application in muscle trauma repair.展开更多
Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less w...Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.展开更多
The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin r...The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.展开更多
BACKGROUND： Sarcopenia and non-alcoholic fatty liver dis- ease （NAFLD） share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study invest...BACKGROUND： Sarcopenia and non-alcoholic fatty liver dis- ease （NAFLD） share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skel- etal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS： We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index （SMI） was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index （FLI） 〉60 in the absence of other chronic liver disease. RESULTS： Among the included subjects, 18.3% （SE： 1.4%） in men and 7.0% （SE： 0.7%） in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, inde- pendent of other metabolic and lifestyle parameters in both genders [males： odds ratio （OR）=1.35; 95% confidence inter- val （CI）： 1.17-1.54; females： OR=1.36; 95% CI： 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males （OR-1.50; 95% CI： 1.22-1.84） than in males less than 45 years of age （OR=1.25; 95% CI： 1.02-1.52） and in premenopausal females （OR=l.50; 95% CI： 1.12-2.03） than in postmenopausal females （OR-1.36; 95% CI： 1.20-1.54）.CONCLUSIONS： Low SMI is associated with the risk of FLI- defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ ac- cording to age group or menopausal status. Further studies are warranted to confirm this relationship.展开更多
Objective To distinguish the edema, injury, or rupture in the traumatic skeletal muscle fiber in vivo using diffusion tensor imaging （DTI） and tractography on magnetic resonance imaging （MRI）. Methods The skeleta...Objective To distinguish the edema, injury, or rupture in the traumatic skeletal muscle fiber in vivo using diffusion tensor imaging （DTI） and tractography on magnetic resonance imaging （MRI）. Methods The skeletal muscle trauma models were made in 4 rabbits （ eight hindlimbs） by iron discus （ weight 1. 0 kg, diameter 6 cm） falling down vertically from 45 cm height to rabbits＇ thighs. Conventional sequences and two-dimensional （2D） diffusion-weighted （DW） spin-echo （SE） echo planar imaging （EPI） sequence with fat suppression （ b = 600 s/mm^2 ） were performed on 1.5T MRI scanner. The grading of edema, injury, and fiber rupture in the damaged muscle were made according to their histopathological views, which was consistent with the images. The mean apparent diffusion coefficient （ADC） values and fractional anisotropy （FA） values were measured from the region of interests （ROIs） of all groups on 2D DW images used for tractography. Analysis of variance test was performed to analyze all data. Results ADC values of the areas in normal muscle, edema muscle, injury muscle, and ruptured muscle were （6. 12±1.34 ） × 10^-3, （ 6.38±1.30 ） × 10^-3, （ 8.06±0. 97 ） × 10^-3, and （ 9. 57±0. 93 ） × 10^-3 mm^2/s, respectively. There was significant difference among groups （P 〈0. 001 ）, but no difference between edema muscle and normal muscle group （P 〉0. 05）. The FA values of normal muscle, edema muscle, injury muscle, and ruptured muscle were 0. 42±0. 12, 0. 36±0. 12, 0. 26±0. 09, 0. 12±0. 08, respectively, with a significant difference among groups （ P 〈 0. 001 ）. In the edema muscle, the tracking cross-fiber could be seen but it decreased slightly. In the injury muscle, the tracking fiber decreased markedly. In the ruptured muscle, the transverse-orientation tracking fiber vanished, yet some interrupted longitudinal-orientation tracking fiber could be found. Conclsion The edema, injury, and rupture of muscle fiber in rabbit damaged skeletal muscle can be verified according to the ADC and the FA on DTI and tractography.展开更多
Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine＇s act...Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine＇s action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin （mTOR） complex-1 （mTORC1）. Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine （400 μmol·kg^-1·h^-1） for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 （S6K1） and eukaryotic initiation factor （elF） 4E-binding protein-1 （4E-BP1） phosphorylation in gastrocnemius and masseter muscles （P 〈 0.05）, but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTQRC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of elF2α and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation.展开更多
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
文摘BACKGROUND 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 NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
基金supported by the National Natural Science Foundation of China(31830090)the High-level Talent Project of Shihezi University,China(2022ZK022)the Agricultural Science and Technology Innovation Program,Chinese Academy of Agricultural Sciences(CAAS-ZDRW202006).
文摘Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great opportunity to develop advanced molecular breeding markers to efficiently improve animal meat production traits.Hippo is an important study subject because of its crucial role in the regulation of organ size.In recent years,with the increase of research on Hippo signaling pathway,the integrative application of multi-omics technologies such as genomics,transcriptomics,proteomics,and metabolomics can help promote the in-depth involvement of Hippo signaling pathway in skeletal muscle development research.The Hippo signaling pathway plays a key role in many biological events,including cell division,cell migration,cell proliferation,cell differentiation,cell apoptosis,as well as cell adhesion,cell polarity,homeostasis,maintenance of the face of mechanical overload,etc.Its influence on the development of skeletal muscle has important research value for enhancing the efficiency of animal husbandry production.In this study,we traced the origin of the Hippo pathway,comprehensively sorted out all the functional factors found in the pathway,deeply analyzed the molecular mechanism of its function,and classified it from a novel perspective based on its main functional domain and mode of action.Our aim is to systematically explore its regulatory role throughout skeletal muscle development.We specifically focus on the Hippo signaling pathway in embryonic stem cell development,muscle satellite cell fate determination,myogenesis,skeletal muscle meat production and organ size regulation,muscle hypertrophy and atrophy,muscle fiber formation and its transformation between different types,and cardiomyocytes.The roles in proliferation and regeneration are methodically summarized and analyzed comprehensively.The summary and prospect of the Hippo signaling pathway within this article will provide ideas for further improving meat production and muscle deposition and developing new molecular breeding technologies for livestock and poultry,which will be helpful for the development of animal molecular breeding.
基金supported by Shanghai Sailing Program(22YF1438700)National Key Research and Development Program of China(2021YFA1201303)+5 种基金National Natural Science Foundation of China(82172511,81972121,81972129,82072521,82011530023,and 82111530200)Sanming Project of Medicine in Shenzhen(SZSM201612078)the Introduction Project of Clinical Medicine Expert Team for Suzhou(SZYJTD201714)Shanghai Talent Development Funding Scheme 2020080Shanghai Sailing Program(21YF1404100 and 22YF1405200)Research Project of Shanghai Science and Technology Commission(22DZ2204900)。
文摘Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.
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This study was approved by the Ethics Committee of Kyushu Rosai Hospital Moji Medical Center(No:04-01,date of approval:June 2,2022).This study was conducted in compliance with the principles of the Declaration of Helsinki.
文摘Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.
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.
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supported by the National Natural Science Foundation of China(82074523)the National Natural Youth Science Foundation of China(82004448).
文摘Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion: Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.
基金the Foundation of State Key Laboratory of Component-based Chinese Medicine,No.CBCM2023107National Natural Science Foundation of China,No.81901853Specially Funded Scientific Research Project of the Fourth Affiliated Hospital of Harbin Medical University,No.HYDSYTB202126.
文摘Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.
基金National Natural Science Foundation of China(No.81303095)Tianjin Science&Technology Program(No.12ZCDZSY15800).
文摘Background:Lung cancer cachexia has received widespread attention as one of the most common complications in patients with advanced lung cancer.As a multifactorial syndrome,lung cancer cachexia is characterized by a persistent decline in muscle mass that cannot be reversed by conventional nutrition Xiaoyan d ecoction can promote appetite and improve skeletal muscle mass in patients with lung cancer cachexia,while the third lumbar skeletal muscle index(L3-SMI)is able to determine whole-body skeletal muscle mass.To analyze the relationship between L3-SMI and hematological indexes and lung cancer cachexia,and to study the clinical efficacy of Xiaoyan decoction on skeletal muscle atrophy in lung cancer cachexia patients,with the aim of providing a reference basis for the early diagnosis and treatment of lung cancer cachexia patients and skeletal muscle atrophy.Methods:148 patients who were diagnosed with lung cancer in the Department of Oncology of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to December 2022 were included,and were divided into cachexia and non-cachexia groups according to the diagnostic criteria of cachexia,and analyzed the differences of hematological indexes and L3-SMI between cachexia patients and non-cachexia patients.And the patients with cachexia were divided into control group and treatment group,analyzed and compared the changes of body mass index(BMI),L 3-SMI,Karnofsky functional status score,albumin and other hematological indexes of the two groups before and after the treatment,and evaluated the safety of the Xiaoyan decoction in the treatment of cachexia.Results:A total of 148 lung cancer patients were included in this study,including 67 patients in the cachexia group and 81 patients in the non-cachexia group.According to the pre-treatment statistical analysis,the BMI of patients in the cachexia group was lower than that of patients in the non-cachexia group(P<0.05);among the biochemical function indexes,the proportions of creatinine(P<0.05),total protein(P<0.05),The levels of albumin in the cachexia group were significantly lower(P<0.05)compared to the non-cachexia group;in the cachexia group,both males and females had lower L3-SMIs than in the non-cachexia group(P<0.05).A total of 62 cases of lung cancer cachexia were studied,30 cases in the control group and 32 cases in the treatment group,according to statistical analysis,BMI was significantly different before and after treatment(P<0.05);L3-SMI was significantly different in the treatment group before and after treatment(P<0.05);Karnofsky significantly differed in the treatment group before and after treatment(P<0.05);and there was a significant difference in albumin before and after(P<0.05).Conclusion:Cachexia patients had significantly lower third lumbar skeletal muscle mass than non-cachexia patients,according to this study;Xiaoyan decoction was able to improve skeletal muscle mass,nutritional status as well as functional status of patients with cachexia in lung cancer,among others.
文摘Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.
文摘As the only source of stem cells, satellite cells play and extraordinary role in the remediation process of skeletal muscle after injury. This paper overviewed the biological characteristic of skeletal muscle satellite cells and its role in repairing muscle injury, and put forward the prospects of its application in muscle trauma repair.
基金Supported by NIH/NIA, No.AG20407 NIH/NIAMS, No. AR47577
文摘Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.
文摘The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.
文摘BACKGROUND： Sarcopenia and non-alcoholic fatty liver dis- ease （NAFLD） share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skel- etal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS： We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index （SMI） was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index （FLI） 〉60 in the absence of other chronic liver disease. RESULTS： Among the included subjects, 18.3% （SE： 1.4%） in men and 7.0% （SE： 0.7%） in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, inde- pendent of other metabolic and lifestyle parameters in both genders [males： odds ratio （OR）=1.35; 95% confidence inter- val （CI）： 1.17-1.54; females： OR=1.36; 95% CI： 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males （OR-1.50; 95% CI： 1.22-1.84） than in males less than 45 years of age （OR=1.25; 95% CI： 1.02-1.52） and in premenopausal females （OR=l.50; 95% CI： 1.12-2.03） than in postmenopausal females （OR-1.36; 95% CI： 1.20-1.54）.CONCLUSIONS： Low SMI is associated with the risk of FLI- defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ ac- cording to age group or menopausal status. Further studies are warranted to confirm this relationship.
文摘Objective To distinguish the edema, injury, or rupture in the traumatic skeletal muscle fiber in vivo using diffusion tensor imaging （DTI） and tractography on magnetic resonance imaging （MRI）. Methods The skeletal muscle trauma models were made in 4 rabbits （ eight hindlimbs） by iron discus （ weight 1. 0 kg, diameter 6 cm） falling down vertically from 45 cm height to rabbits＇ thighs. Conventional sequences and two-dimensional （2D） diffusion-weighted （DW） spin-echo （SE） echo planar imaging （EPI） sequence with fat suppression （ b = 600 s/mm^2 ） were performed on 1.5T MRI scanner. The grading of edema, injury, and fiber rupture in the damaged muscle were made according to their histopathological views, which was consistent with the images. The mean apparent diffusion coefficient （ADC） values and fractional anisotropy （FA） values were measured from the region of interests （ROIs） of all groups on 2D DW images used for tractography. Analysis of variance test was performed to analyze all data. Results ADC values of the areas in normal muscle, edema muscle, injury muscle, and ruptured muscle were （6. 12±1.34 ） × 10^-3, （ 6.38±1.30 ） × 10^-3, （ 8.06±0. 97 ） × 10^-3, and （ 9. 57±0. 93 ） × 10^-3 mm^2/s, respectively. There was significant difference among groups （P 〈0. 001 ）, but no difference between edema muscle and normal muscle group （P 〉0. 05）. The FA values of normal muscle, edema muscle, injury muscle, and ruptured muscle were 0. 42±0. 12, 0. 36±0. 12, 0. 26±0. 09, 0. 12±0. 08, respectively, with a significant difference among groups （ P 〈 0. 001 ）. In the edema muscle, the tracking cross-fiber could be seen but it decreased slightly. In the injury muscle, the tracking fiber decreased markedly. In the ruptured muscle, the transverse-orientation tracking fiber vanished, yet some interrupted longitudinal-orientation tracking fiber could be found. Conclsion The edema, injury, and rupture of muscle fiber in rabbit damaged skeletal muscle can be verified according to the ADC and the FA on DTI and tractography.
文摘Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine＇s action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin （mTOR） complex-1 （mTORC1）. Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine （400 μmol·kg^-1·h^-1） for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 （S6K1） and eukaryotic initiation factor （elF） 4E-binding protein-1 （4E-BP1） phosphorylation in gastrocnemius and masseter muscles （P 〈 0.05）, but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTQRC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of elF2α and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation.
