Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be el...Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.展开更多
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 evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This ...Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control(n=40)and intervention(n=40)groups.The control group received conventional orthopedic treatment,whereas the intervention group received TEAS and conventional treatment.The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks.The primary out-comes were muscle thickness(MT)and cross-sectional area(CSA)of the rectus femoris and gastroc-nemius muscles,whereas the secondary outcome measure was echo intensity(EI).Data were collected before the fixation operations(baseline assessment)and 4 and 8 weeks after intervention.Results:Compared with baseline,the MT and CSA were reduced in both groups by the end of treatment,whereas EI increased in both groups.At week 4,the reduction in the rectus femoris CSA in the inter-vention group was significantly lower than that in the control group(P=0.02);however,the between-group differences in the MT and EI(all P>0.05)were not significant.No serious adverse events were observed in either group.Conclusion:Our study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA.Because this was only a pilot trial,subsequent studies will need longer follow-ups and larger sample sizes.展开更多
Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still u...Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.展开更多
Background:The aim of this study was to analyze the bi-directional causal relation-ship between lipid profile and characteristics related to muscle atrophy by using a bi-directional Mendelian randomization(MR)analysis...Background:The aim of this study was to analyze the bi-directional causal relation-ship between lipid profile and characteristics related to muscle atrophy by using a bi-directional Mendelian randomization(MR)analysis.Methods:The appendicular lean mass(ALM),whole body fat-free mass(WBFFM)and trunk fat-free mass(TFFM)were used as genome-wide association study(GWAS)data for evaluating muscle mass;the usual walking pace(UWP)and low grip strength(LGS)were used as GWAS data for evaluating muscle strength;and the triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL),low density lipo-protein cholesterol(LDL),apolipoprotein A-1(Apo A-1),and apolipoprotein B(Apo B)were used as GWAS data for evaluating lipid profile.For specific investigations,we mainly employed inverse variance weighting for causal estimation and MR-Egger for pleiotropy analysis.Results:MR results showed that the lipid profile predicted by genetic variants was negatively correlated with muscle mass,positively correlated with UWP,and was not causally correlated with LGS.On the other hand,the muscle mass predicted by genetic variants was negatively correlated with lipid profile,the UWP predicted by genetic variants was mainly positively correlated with lipid profile,while the LGS pre-dicted by genetic variants had no relevant causal relationship with lipid profile.Conclusions:Findings of this MR analysis suggest that hyperlipidemia may affect muscle mass and lead to muscle atrophy,but has no significant effect on muscle strength.On the other hand,increased muscle mass may reduce the incidence of dyslipidemia.展开更多
Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life ...Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.展开更多
Purpose: The objective of the present study was to determine whether a denervated muscle extract(DmEx) could stimulate satellite cell response in denervated muscle.Methods: Wistar rats were divided into 4 groups: norm...Purpose: The objective of the present study was to determine whether a denervated muscle extract(DmEx) could stimulate satellite cell response in denervated muscle.Methods: Wistar rats were divided into 4 groups: normal rats, normal rats treated with DmEx, denervated rats, and denervated rats treated with DmEx. The soleus muscles were examined using immunohistochemical techniques for proliferating cell nuclear antigen, desmin, and myogenic differentiation antigen(MyoD), and electron microscopy was used for analysis of the satellite cells.Results: The results indicate that while denervation causes activation of satellite cells, DmEx also induces myogenic differentiation of cells localized in the interstitial space and the formation of new muscle fibers. Although DmEx had a similar effect in nature on innervated and denervated muscles, this response was of greater magnitude in denervated vs. intact muscles.Conclusion: Our study shows that treatment of denervated rats with DmEx potentiates the myogenic response in atrophic denervated muscles.展开更多
Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mec...Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migra- tion and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of ^-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta in- hibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.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
Background:Exercise is beneficial for muscle atrophy.Peroxisome proliferator-activated receptor gamma(PPARγ) and microRNA-29 b(miR-29 b) have been reported to be responsible for angiotensinⅡ(AngⅡ)-induced muscle at...Background:Exercise is beneficial for muscle atrophy.Peroxisome proliferator-activated receptor gamma(PPARγ) and microRNA-29 b(miR-29 b) have been reported to be responsible for angiotensinⅡ(AngⅡ)-induced muscle atrophy.However,it is unclear whether exercise can protect AngⅡ-induced muscle atrophy by targeting PPARγ/miR-29 b.Methods:Skeletal muscle atrophy in both the control group and the run group was established by AngⅡ infusion;after 1 week of exercise training,the mice were sacrificed,and muscle weight was determined.Myofiber size was measured by hematoxylin-eosin and wheat-germ agglutinin staining.Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining.The expression level of muscle atrogenes,including F-box only protein 32(FBXO32,also called Atrogin-1) and muscle-specific RING-finger 1(MuRF-1),the phosphorylation level of protein kinase B(PKB,also called AKT)/forkhead box 03 A(FOX03 A)/mammalian target of rapamycin(mTOR) pathway proteins,the expression level of PPARγ and apoptosis-related proteins,including B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),cysteine-aspartic acid protease 3(caspase-3),and cleaved-caspase-3,were determined by western blot.The expression level of miR-29 b was checked by reversetranscription quantitative polymerase chain reaction.A PPARγ inhibitor(T0070907) or adeno-associated virus serotype-8(AAV8)-mediated miR-29 b overexpression was used to demonstrate whether PPARγ activation or miR-29 b inhibition mediates the beneficial effects of exercise in AngⅡ-induced muscle atrophy.Results:Exercise can significantly attenuate AngⅡ-induced muscle atrophy,which is demonstrated by increased skeletal muscle weight,cross-sectional area of myofiber,and activation of AKT/mTOR signaling and by decreased atrogenes expressions and apoptosis.In AngⅡ-induced muscle atrophy mice models,PPARγ was elevated whereas miR-29 b was decreased by exercise.The protective effects of exercise in AngⅡ-induced muscle atrophy were inhibited by a PPARγ inhibitor(T0070907) or adeno-associated virus serotype-8(AAV8)-mediated miR-29 b overexpression.Conclusion:Exercise attenuates AngⅡ-induced muscle atrophy by activation of PPARγ and suppression of miR-29 b.展开更多
BACKGROUND Muscular atrophy is the basic defect of neurogenic clubfoot.Muscle atrophy of clubfoot needs more scientific and reasonable imaging measurement parameters to evaluate.The Hippo pathway and myostatin pathway...BACKGROUND Muscular atrophy is the basic defect of neurogenic clubfoot.Muscle atrophy of clubfoot needs more scientific and reasonable imaging measurement parameters to evaluate.The Hippo pathway and myostatin pathway may be directly correlated in myogenesis.In this study,we will use congenital neurogenic clubfoot muscle atrophy model to verify in vivo.Further,the antagonistic mechanism of TAZ on myostatin was studied in the C2C12 cell differentiation model.AIM To identify muscle atrophy in fetal neurogenic clubfoot by ultrasound imaging and detect the expression of TAZ and myostatin in gastrocnemius muscle.To elucidate the possible mechanisms by which TAZ antagonizes myostatin-induced atrophy in an in vitro cell model.METHODS Muscle atrophy in eight cases of fetal unilateral clubfoot with nervous system abnormalities was identified by 2D and 3D ultrasound.Western blotting and immunostaining were performed to detect expression of myostatin and TAZ.TAZ overexpression in C2C12 myotubes and the expression of associated proteins were analyzed by western blotting.RESULTS The maximum cross-sectional area of the fetal clubfoot on the varus side was reduced compared to the contralateral side.Myostatin was elevated in the atrophied gastrocnemius muscle,while TAZ expression was decreased.They were negatively correlated.TAZ overexpression reversed the diameter reduction of the myotube,downregulated phosphorylated Akt,and increased the expression of forkhead box O4 induced by myostatin.CONCLUSION Ultrasound can detect muscle atrophy of fetal clubfoot.TAZ and myostatin are involved in the pathological process of neurogenic clubfoot muscle atrophy.TAZ antagonizes myostatin-induced myotube atrophy,potentially through regulation of the Akt/forkhead box O4 signaling pathway.展开更多
Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal mu...Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood.In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve.RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated.We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1.The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death.In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation.These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy.This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China(approval No.SYXK 2017-C023) on June 1, 2018.展开更多
OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical fo...OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical for regulating the balance between protein synthesis and degradation during disuse/inactivity-induced muscle atrophy.The present study aimed to investigate whether natural product Icaritin(ICT)required PI3K/Akt signaling to exert counteractive effect on skeletal muscle atrophy following mechanical unloading.METHODS Two oral dosages of ICT(80and 120mg·kg-1·d-1)were administrated daily to adult male rats with or without daily injection of PI3K/Akt signaling inhibitor wortmannin(15μg·kg-1·d-1)during 28-d hindlimb suspension(HS).Ex vivo muscle functional testing,histological and immunohistochemical analysis were performed to determine the changes of soleus muscle function,mean muscle fiber cross-sectional area(CSA)and fiber type distribution.Western blot and real-time PCR analysis were also performed to evaluate the protein or mRNA expression of the markers involved in PI3K/Akt signaling pathway.RESULTS After 28-d HS,soleus muscle underwent profound muscle atrophy(-52.7% muscle mass vs.pre-HS baseline).The high dose ICT treatment significantly attenuated the decreases in soleus muscle mass(+22.6% vs.HS),muscle fiber CSA(+52.8% vs.HS),as well as the muscle functional testing parameters during the unloading.Molecularly,the high dose ICT treatment significantly attenuated the decreases in protein synthesis markers at protein levels(phosphorylation of Akt and its downstream proteins)during the unloading,whereas the increases in protein degradation markers at mRNA(atrogin-1and MuRF-1)and protein(nuclear FOXO1 and FOXO3a)levels during the unloading were significantly attenuated by the high dose ICT treatment.The low dose ICT treatment moderately attenuated the above changes induced by the unloading.Mechanistically,Wortmannin could abolish the above effects of ICT.CONCLUSION ICT requires participation of PI3K/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading in a dose-dependent manner.展开更多
We examined the effect of a combination of astaxanthin （AX） supplementation, repeated heat stress, and intermittent reloading （IR） on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats （8...We examined the effect of a combination of astaxanthin （AX） supplementation, repeated heat stress, and intermittent reloading （IR） on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats （8-week-old） were divided into control, hind-limb unweighting （HU）, IR during HU, IR with AX supplementation, IR with repeated heat stress （41.0-41.5 ℃ for 30 min）, and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soteus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.展开更多
Nerve injury commonly contributes to irreversible functional impairment, reconstruction of the function of muscle is big challenge. In denervated skeletal muscle, therapid expression of MyoD mRNA and protein also occu...Nerve injury commonly contributes to irreversible functional impairment, reconstruction of the function of muscle is big challenge. In denervated skeletal muscle, therapid expression of MyoD mRNA and protein also occurs during early postdenervation, which suggested that the function of denervation-induced MyoD may be to prevent denervation-induced skeletal muscle atrophy. However, the detail mechanism is not clear. Therefore, in this study, we established a stable-transfected MyoD L6 cell line. After the operation for cutting the rats’ tibial nerve, the MyoD-L6 cells were injected in the gastrocnemius, the function of the gastronemius was monitored. It was found that injected the MyoD-L6 cells could attenuate the muscle atrophy and dysfunction. Therefore, overexpression of MyoD could serve as a new therapy strategy to cure denervation-induced dysfunction of skeletal muscle.展开更多
Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but h...Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.展开更多
AIM:To study the electromyogram and muscular pathological features of adult sp inal muscular atrophy(SMA4).METHODS:46 cases of SMA4 were evaluated based on cli nical,histopathology,enzyme histochemistry and ultrastruc...AIM:To study the electromyogram and muscular pathological features of adult sp inal muscular atrophy(SMA4).METHODS:46 cases of SMA4 were evaluated based on cli nical,histopathology,enzyme histochemistry and ultrastructure.RESULTS:A mean age of the patients with SMA4 was 38.7 years,clinical progressed was slowly.Clinic manifestations mainly appeared proximal muscular weakness and progressive muscul ar atrophy,and there was a relatively good prognosis.Laboratory found:one-fourt h of the disease had elevated serum creatine kinase levels.Eletromyogram reveale d neurogenic damages. The muscular pathological changes showed small groups of a trophy of denervation,ATPase reaction showed fibre-type grouping of renervation and hypertrophy in muscle fibers.CONCLUSION:Muscle biopsy was important;it coul d to help to establish to diagnose the disorder and provided available cases for gene study.展开更多
Intensive care unit(ICU)acquired sarcopenia and myosteatosis are increasingly recognized complications of critical illness,characterized by a rapid loss of ske-letal muscle mass,quality,and function.These conditions r...Intensive care unit(ICU)acquired sarcopenia and myosteatosis are increasingly recognized complications of critical illness,characterized by a rapid loss of ske-letal muscle mass,quality,and function.These conditions result from a complex interplay of systemic inflammation,immobilization,catabolic stress,mitochon-drial dysfunction,and immune dysregulation,often culminating in impaired recovery,prolonged hospitalization,and increased long-term mortality.First identified in survivors of sepsis and prolonged mechanical ventilation,these muscle abnormalities were initially described using computed tomography-based assessments of muscle area and density.Subsequent advances in imaging,biomarker discovery,and functional testing have enabled earlier detection and risk stratification across diverse ICU populations.While nutritional optimization and early mobilization form the cornerstone of current prevention and treatment strategies,the emergence of novel approaches,including automated artificial intelligence-based screening,neuromuscular electrical stimulation,and targeted pharmacologic therapies,has broadened the clinical scope of interventions.Despite their significant prognostic implications,ICU-acquired sarcopenia and myosteatosis remain under-recognized in routine critical care practice.This mini-review aims to synthesize current knowledge regarding their pathophysiology,available diagnostic modalities,prognostic relevance,and the evolving landscape of therapeutic strategies for long-term functional recovery in critically ill patients.展开更多
BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increas...BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.展开更多
In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial p...In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.展开更多
基金funded by research grant from National Natural Science Foundation of China(32171135).
文摘Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
基金funded by research grants from the National Natural Science Foundation of China (32171135 and 32371168)。
文摘Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in this process.Methods: 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E-5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area(CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1(Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism.Results: Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically,Prmt1 regulated the p38 mitogen-activated protein kinase(p38)/activating transcription factor 2(ATF2)pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2(AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α(PGC-1α) signaling pathway.Conclusions: Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway.
基金supported by the funded project(HYZHX M05005)in the field of space medical experiments of manned spaceflight engineering.
文摘Objective:To evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.Methods:This was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control(n=40)and intervention(n=40)groups.The control group received conventional orthopedic treatment,whereas the intervention group received TEAS and conventional treatment.The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks.The primary out-comes were muscle thickness(MT)and cross-sectional area(CSA)of the rectus femoris and gastroc-nemius muscles,whereas the secondary outcome measure was echo intensity(EI).Data were collected before the fixation operations(baseline assessment)and 4 and 8 weeks after intervention.Results:Compared with baseline,the MT and CSA were reduced in both groups by the end of treatment,whereas EI increased in both groups.At week 4,the reduction in the rectus femoris CSA in the inter-vention group was significantly lower than that in the control group(P=0.02);however,the between-group differences in the MT and EI(all P>0.05)were not significant.No serious adverse events were observed in either group.Conclusion:Our study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA.Because this was only a pilot trial,subsequent studies will need longer follow-ups and larger sample sizes.
基金supported by the National Natural Science Foundation of China(82003447,32202023)the Natural Science Foundation of Shandong Province(ZR2021QC177)the Young Scholars Program of Shandong University(2018WLJH33,2018WLJH34)。
文摘Obesity is associated with skeletal muscle mass loss and physical dysfunction.Krill oil(KO)has been shown to be beneficial in human health.However,the effect of KO on obesity-induced skeletal muscle atrophy is still unclear.In this study,the male C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to induce obesity,and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks.The results showed that KO treatment reduced body weight,fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice.Importantly,KO treatment attenuated skeletal muscle atrophy in HFD-fed mice,as evidenced by preserving skeletal muscle mass,average myofiber cross-sectional area and grip strength.KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle.Additionally,KO treatment inhibited the transcriptional activities of nuclear factor-κB(NF-κB)p65 and forkhead box O 3a(FoxO3a),and then down-regulated muscle atrophy F-box(MAFbx)and muscle-specific RING finger protein 1(MuRF1)protein levels in skeletal muscle from HFD-fed mice.KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway.Furthermore,KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1αpathway.Collectively,KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.
基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021A1515220030Hunan Provincial Clinical Medical Technology Innovation Guiding Project,Grant/Award Number:2020SK53307+2 种基金Hunan Provincial Health Commission,Grant/Award Number:20201902Natural Science Foundation of Hunan Province,Grant/Award Number:2020JJ8043Project of Hunan Provincial Health,Grant/Award Number:c2019133。
文摘Background:The aim of this study was to analyze the bi-directional causal relation-ship between lipid profile and characteristics related to muscle atrophy by using a bi-directional Mendelian randomization(MR)analysis.Methods:The appendicular lean mass(ALM),whole body fat-free mass(WBFFM)and trunk fat-free mass(TFFM)were used as genome-wide association study(GWAS)data for evaluating muscle mass;the usual walking pace(UWP)and low grip strength(LGS)were used as GWAS data for evaluating muscle strength;and the triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL),low density lipo-protein cholesterol(LDL),apolipoprotein A-1(Apo A-1),and apolipoprotein B(Apo B)were used as GWAS data for evaluating lipid profile.For specific investigations,we mainly employed inverse variance weighting for causal estimation and MR-Egger for pleiotropy analysis.Results:MR results showed that the lipid profile predicted by genetic variants was negatively correlated with muscle mass,positively correlated with UWP,and was not causally correlated with LGS.On the other hand,the muscle mass predicted by genetic variants was negatively correlated with lipid profile,the UWP predicted by genetic variants was mainly positively correlated with lipid profile,while the LGS pre-dicted by genetic variants had no relevant causal relationship with lipid profile.Conclusions:Findings of this MR analysis suggest that hyperlipidemia may affect muscle mass and lead to muscle atrophy,but has no significant effect on muscle strength.On the other hand,increased muscle mass may reduce the incidence of dyslipidemia.
基金Suzhou Science and Technology Development Planning Project,No.SYW2024048National Natural Science Foundation of China,No.81901933Major Natural Science Research Projects in Universities of Jiangsu Province,No.24KJA310007.
文摘Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.
文摘Purpose: The objective of the present study was to determine whether a denervated muscle extract(DmEx) could stimulate satellite cell response in denervated muscle.Methods: Wistar rats were divided into 4 groups: normal rats, normal rats treated with DmEx, denervated rats, and denervated rats treated with DmEx. The soleus muscles were examined using immunohistochemical techniques for proliferating cell nuclear antigen, desmin, and myogenic differentiation antigen(MyoD), and electron microscopy was used for analysis of the satellite cells.Results: The results indicate that while denervation causes activation of satellite cells, DmEx also induces myogenic differentiation of cells localized in the interstitial space and the formation of new muscle fibers. Although DmEx had a similar effect in nature on innervated and denervated muscles, this response was of greater magnitude in denervated vs. intact muscles.Conclusion: Our study shows that treatment of denervated rats with DmEx potentiates the myogenic response in atrophic denervated muscles.
基金funded by the National Basic Research Program of China(973 Program),No.2014CB542201the National High Technology Research and Development Program of China(863 Program),No.SS2015AA020501the National Natural Science Foundation of China(General Program),No.31571235,31771322,31671248,31571236,31271284,31171150,81171146,31471144,30971526,31100860,31040043,31371210,and 81372044
文摘Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migra- tion and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of ^-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta in- hibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.
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.
基金supported by grants from the National Key Research and Development Project(2020YFA0803800 to JL,2018YFE0113500 to JX)National Natural Science Foundation of China(82020108002 and 81911540486 to JX)+2 种基金Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to JX)Science and Technology Commission of Shanghai Municipality(20DZ2255400 and 18410722200 to JX)the“Dawn”Program of the Shanghai Education Commission(19SG34 to JX).
文摘Background:Exercise is beneficial for muscle atrophy.Peroxisome proliferator-activated receptor gamma(PPARγ) and microRNA-29 b(miR-29 b) have been reported to be responsible for angiotensinⅡ(AngⅡ)-induced muscle atrophy.However,it is unclear whether exercise can protect AngⅡ-induced muscle atrophy by targeting PPARγ/miR-29 b.Methods:Skeletal muscle atrophy in both the control group and the run group was established by AngⅡ infusion;after 1 week of exercise training,the mice were sacrificed,and muscle weight was determined.Myofiber size was measured by hematoxylin-eosin and wheat-germ agglutinin staining.Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining.The expression level of muscle atrogenes,including F-box only protein 32(FBXO32,also called Atrogin-1) and muscle-specific RING-finger 1(MuRF-1),the phosphorylation level of protein kinase B(PKB,also called AKT)/forkhead box 03 A(FOX03 A)/mammalian target of rapamycin(mTOR) pathway proteins,the expression level of PPARγ and apoptosis-related proteins,including B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),cysteine-aspartic acid protease 3(caspase-3),and cleaved-caspase-3,were determined by western blot.The expression level of miR-29 b was checked by reversetranscription quantitative polymerase chain reaction.A PPARγ inhibitor(T0070907) or adeno-associated virus serotype-8(AAV8)-mediated miR-29 b overexpression was used to demonstrate whether PPARγ activation or miR-29 b inhibition mediates the beneficial effects of exercise in AngⅡ-induced muscle atrophy.Results:Exercise can significantly attenuate AngⅡ-induced muscle atrophy,which is demonstrated by increased skeletal muscle weight,cross-sectional area of myofiber,and activation of AKT/mTOR signaling and by decreased atrogenes expressions and apoptosis.In AngⅡ-induced muscle atrophy mice models,PPARγ was elevated whereas miR-29 b was decreased by exercise.The protective effects of exercise in AngⅡ-induced muscle atrophy were inhibited by a PPARγ inhibitor(T0070907) or adeno-associated virus serotype-8(AAV8)-mediated miR-29 b overexpression.Conclusion:Exercise attenuates AngⅡ-induced muscle atrophy by activation of PPARγ and suppression of miR-29 b.
文摘BACKGROUND Muscular atrophy is the basic defect of neurogenic clubfoot.Muscle atrophy of clubfoot needs more scientific and reasonable imaging measurement parameters to evaluate.The Hippo pathway and myostatin pathway may be directly correlated in myogenesis.In this study,we will use congenital neurogenic clubfoot muscle atrophy model to verify in vivo.Further,the antagonistic mechanism of TAZ on myostatin was studied in the C2C12 cell differentiation model.AIM To identify muscle atrophy in fetal neurogenic clubfoot by ultrasound imaging and detect the expression of TAZ and myostatin in gastrocnemius muscle.To elucidate the possible mechanisms by which TAZ antagonizes myostatin-induced atrophy in an in vitro cell model.METHODS Muscle atrophy in eight cases of fetal unilateral clubfoot with nervous system abnormalities was identified by 2D and 3D ultrasound.Western blotting and immunostaining were performed to detect expression of myostatin and TAZ.TAZ overexpression in C2C12 myotubes and the expression of associated proteins were analyzed by western blotting.RESULTS The maximum cross-sectional area of the fetal clubfoot on the varus side was reduced compared to the contralateral side.Myostatin was elevated in the atrophied gastrocnemius muscle,while TAZ expression was decreased.They were negatively correlated.TAZ overexpression reversed the diameter reduction of the myotube,downregulated phosphorylated Akt,and increased the expression of forkhead box O4 induced by myostatin.CONCLUSION Ultrasound can detect muscle atrophy of fetal clubfoot.TAZ and myostatin are involved in the pathological process of neurogenic clubfoot muscle atrophy.TAZ antagonizes myostatin-induced myotube atrophy,potentially through regulation of the Akt/forkhead box O4 signaling pathway.
基金supported by the National Natural Science Foundation of China, Nos.31770929(to HTW), 31522029(to HTW), 81902847(to HHY)the Beijing Municipal Science and Technology Commission of China, Nos.Z181100001518001(to HTW), Z161100000216154(to HTW)。
文摘Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood.In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve.RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated.We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1.The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death.In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation.These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy.This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China(approval No.SYXK 2017-C023) on June 1, 2018.
基金The project supported by National Natural Science Foundation of China(81201406)Direct Grant for Research,The Chinese University of Hong Kong(4054138)
文摘OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical for regulating the balance between protein synthesis and degradation during disuse/inactivity-induced muscle atrophy.The present study aimed to investigate whether natural product Icaritin(ICT)required PI3K/Akt signaling to exert counteractive effect on skeletal muscle atrophy following mechanical unloading.METHODS Two oral dosages of ICT(80and 120mg·kg-1·d-1)were administrated daily to adult male rats with or without daily injection of PI3K/Akt signaling inhibitor wortmannin(15μg·kg-1·d-1)during 28-d hindlimb suspension(HS).Ex vivo muscle functional testing,histological and immunohistochemical analysis were performed to determine the changes of soleus muscle function,mean muscle fiber cross-sectional area(CSA)and fiber type distribution.Western blot and real-time PCR analysis were also performed to evaluate the protein or mRNA expression of the markers involved in PI3K/Akt signaling pathway.RESULTS After 28-d HS,soleus muscle underwent profound muscle atrophy(-52.7% muscle mass vs.pre-HS baseline).The high dose ICT treatment significantly attenuated the decreases in soleus muscle mass(+22.6% vs.HS),muscle fiber CSA(+52.8% vs.HS),as well as the muscle functional testing parameters during the unloading.Molecularly,the high dose ICT treatment significantly attenuated the decreases in protein synthesis markers at protein levels(phosphorylation of Akt and its downstream proteins)during the unloading,whereas the increases in protein degradation markers at mRNA(atrogin-1and MuRF-1)and protein(nuclear FOXO1 and FOXO3a)levels during the unloading were significantly attenuated by the high dose ICT treatment.The low dose ICT treatment moderately attenuated the above changes induced by the unloading.Mechanistically,Wortmannin could abolish the above effects of ICT.CONCLUSION ICT requires participation of PI3K/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading in a dose-dependent manner.
基金Project supported by the Japan Society for the Promotion of Science(JSPS)KA-KENHI(Nos.20500578 and 17K01765)the Ministry of Education,Culture,Sports,Science and Technology(MEXT)-Supported Program for the Strategic Research Foundation at Private Universities
文摘We examined the effect of a combination of astaxanthin （AX） supplementation, repeated heat stress, and intermittent reloading （IR） on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats （8-week-old） were divided into control, hind-limb unweighting （HU）, IR during HU, IR with AX supplementation, IR with repeated heat stress （41.0-41.5 ℃ for 30 min）, and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soteus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.
文摘Nerve injury commonly contributes to irreversible functional impairment, reconstruction of the function of muscle is big challenge. In denervated skeletal muscle, therapid expression of MyoD mRNA and protein also occurs during early postdenervation, which suggested that the function of denervation-induced MyoD may be to prevent denervation-induced skeletal muscle atrophy. However, the detail mechanism is not clear. Therefore, in this study, we established a stable-transfected MyoD L6 cell line. After the operation for cutting the rats’ tibial nerve, the MyoD-L6 cells were injected in the gastrocnemius, the function of the gastronemius was monitored. It was found that injected the MyoD-L6 cells could attenuate the muscle atrophy and dysfunction. Therefore, overexpression of MyoD could serve as a new therapy strategy to cure denervation-induced dysfunction of skeletal muscle.
文摘Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.
文摘AIM:To study the electromyogram and muscular pathological features of adult sp inal muscular atrophy(SMA4).METHODS:46 cases of SMA4 were evaluated based on cli nical,histopathology,enzyme histochemistry and ultrastructure.RESULTS:A mean age of the patients with SMA4 was 38.7 years,clinical progressed was slowly.Clinic manifestations mainly appeared proximal muscular weakness and progressive muscul ar atrophy,and there was a relatively good prognosis.Laboratory found:one-fourt h of the disease had elevated serum creatine kinase levels.Eletromyogram reveale d neurogenic damages. The muscular pathological changes showed small groups of a trophy of denervation,ATPase reaction showed fibre-type grouping of renervation and hypertrophy in muscle fibers.CONCLUSION:Muscle biopsy was important;it coul d to help to establish to diagnose the disorder and provided available cases for gene study.
文摘Intensive care unit(ICU)acquired sarcopenia and myosteatosis are increasingly recognized complications of critical illness,characterized by a rapid loss of ske-letal muscle mass,quality,and function.These conditions result from a complex interplay of systemic inflammation,immobilization,catabolic stress,mitochon-drial dysfunction,and immune dysregulation,often culminating in impaired recovery,prolonged hospitalization,and increased long-term mortality.First identified in survivors of sepsis and prolonged mechanical ventilation,these muscle abnormalities were initially described using computed tomography-based assessments of muscle area and density.Subsequent advances in imaging,biomarker discovery,and functional testing have enabled earlier detection and risk stratification across diverse ICU populations.While nutritional optimization and early mobilization form the cornerstone of current prevention and treatment strategies,the emergence of novel approaches,including automated artificial intelligence-based screening,neuromuscular electrical stimulation,and targeted pharmacologic therapies,has broadened the clinical scope of interventions.Despite their significant prognostic implications,ICU-acquired sarcopenia and myosteatosis remain under-recognized in routine critical care practice.This mini-review aims to synthesize current knowledge regarding their pathophysiology,available diagnostic modalities,prognostic relevance,and the evolving landscape of therapeutic strategies for long-term functional recovery in critically ill patients.
基金thank the staff of the accredited animal facility of the laboratory of anatomy,Histology and Embryology of Aristotle University of Thessaloniki’s veterinary school for their assistance in animal handling and care.
文摘BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.
基金supported by the National Natural Science Foundation of China,No.816019591003263(to JXW)the National Basic Research Program of China(973 Program),No.2014CB542203(to LC)
文摘In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.
