The role of proteasome in muscle wasting of experimental arthritis

Abstract Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. Methods Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMβ5, PMSβ6, PSMβ7, PSMβ8, PSMβ9, and PSMβ10), and protein (PSMβ1, PSMβ5, PSMβ1i, PSMβ5i) expression of proteasome subunits. Results Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMβ8 and PSMβ9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSβ6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMβ5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMβ5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit β1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). Conclusions The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMβ8 and PSMβ9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting.

The effects of light exposure on skeletal muscle wasting in rats with endotoxemia / 医学研究生学报

Objective Constant light exposure can lead to hypercatabolism. The aim of this study was to investigate the effects of different light rhythm on skeletal muscle metabolism in endotoxemia rats, and looked for the optimal light rhythm that could reduce skeletal muscle consumption and enhance the recovery of patients with sepsis. Methods 54 adult male S-D rats were randomly divided into 3 groups on average：Control group (intraperitoneal injection of normal saline +12h/12h light-dark cycle for 7 days), LPS- regular light group (intraperitoneal injection of lipopolysaccharide(LPS) +12h/12h light-dark cycle for 7 days) and LPS-constant light group (intraperitoneal injection of LPS + constant light for 7 days). All experimental animals were sacrificed on the 8th day. The level of skeletal muscle metabolites 3-methylhistidine (3-mh) and tyrosine, atrophy genes MAFbx and murf-1 mRNA and hypothalamic clock genes BMAL1, CLOCK and neuropeptide POMC were also detected. Results The food intake, weight growth ratio and the ratio of extensor digitorum longus/weight in the LPS-constant light group were significantly lower than those in the LPS-regular light group (P <0.05), and both groups were significantly lower than those in the control group (P <0.01). The skeletal muscle metabolites 3-methylhistidine(nmol/g) and tyrosine(nmol/g) in the LPS-constant light group rats (6.200±0.273 and 461.039±13.292) were significantly higher than those in the LPS- regular light group (5.197±0.263 and 375.744±20.308) and the control group (3.244±0.275 and 290.935±19.065,all P <0.05). The expression levels of atrophic genes MAFbx and murf-1 mRNA and tnf-alpha and il-1 mRNA in hypothalamus in the LPS-constant light group were significantly higher than those in the LPS- regular light group(P <0.05), and both groups were significantly higher than those in the control group (P <0.05). The expression of the clock genes(BMAL1 and CLOCK) in the showed obvious rhythm (SE (A) /A<0.3) in the LPS-regular light group and the control group. The expression of BMAL1 was highest at the beginning of the illumination period, while the expression of CLOCK was high during the illumination period and decreased during the darkness period. In the LPS-constant light group, the expression of BMAL1 and CLOCK rhythm lost rhythm. Conclusion Normal light rhythm can maintain the normal rhythm expression of hypothalamic clock gene in rats with endotoxemia and reduce POMC-mediated skeletal muscle consumption, which may be of positive significance for the enhanced recovery of sepsis.

Effects of dexmedetomidine on the expressions of hypothalamus neuropeptide and skeletal muscle atrophy gene in endotoxemic rats / 医学研究生学报

Objective Sepsis is often accompanied by serious disorder of energy metabolism, which is characterized by high catabolism, leading to irreversible acute skeletal muscle decomposition. As a new sedative, dexmedetomidine can alleviate the hypercatabolism of sepsis to a certain extent, so it has the potential to improve acute skeletal muscle decomposition. The present work aims to investigate the effects of dexmedetomidine on the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.Methods Thirty-six male Sprague Dawley rats were randomly divided into three groups (n=12): control group(group CON),-model group(group LPS-CON) and intervention group(group LPS-DEX). The endotoxemic rat model was established by injecting lipopolysaccharide (LPS) intraperitoneally. After 24 hours intervention, the expressions of hypothalamic neuropeptide (POMC, CART, AgRP and NPY) mRNA as well as MuRF-1 and MAFbx mRNA in skeletal muscle in rats were detected by RT-PCR.Results Compared with control group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly up-regulated (P＜0.05), while the expression of AgRP mRNA was significantly down-regulated in-model group (P＜0.05). Compared with-model group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly down-regulated (P＜0.05), while the expression of AgRP mRNA was significantly up-regulated in intervention group (P＜0.05).Conclusion Dexmedetomidine could regulate the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.

Mechanism of cell autophagy for regulating skeletal muscle wasting of rats after severe burns / 中华烧伤杂志

Objective@#To investigate the mechanism of cell autophagy for regulating skeletal muscle wasting of rats after severe burns.@*Methods@#Seventy-two Sprague-Dawley rats were collected and divided into sham injury group, simple burn group, burn+ phosphate buffer solution (PBS) group, and burn+ 3-methyladenine (3-MA) group according to the random number table, with 18 rats in each group. Rats in simple burn group, burn+ PBS group, and burn+ 3-MA group were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burns). Rats in sham injury group were sham injured. Immediately after burns and fluid resuscitation, rats in burn+ PBS group were intraperitoneally injected with 1 mL PBS, and rats in burn+ 3-MA group were intraperitoneally injected with 1 mL 3-MA (125 g/L). On post injury day 3 and 7, the weights of anterior tibial muscle of right hind limbs and body of rats were measured to calculate percentage of anterior tibial muscle of right hind limbs weight. Protein expressions of microtubule related protein 1 light chain 3A (LC3A) and Beclin-1 of anterior tibial muscle were observed by immunofluorescence method and detected by Western blotting, and ratio of microtubule related protein 1 LC3A-Ⅱ to LC3A-Ⅰ was calculated. Data were processed with analysis of variance of factorial design, one-way analysis of variance, t-test and Bonferroni correction.@*Results@#On post injury day 3 and 7, percentages of anterior tibial muscle of right hind limbs weight of rats in simple burn group were (0.148±0.009)% and (0.134±0.018)%, respectively, which were significantly lower than those in sham injury group [(0.203±0.009)%, (0.181±0.015)%, t=10.585, 4.913, P<0.01]. Percentages of anterior tibial muscle of right hind limbs weight of rats in burn+ 3-MA group were (0.187±0.004)% and (0.192±0.009)%, respectively, which were obviously higher than those in burn+ PBS group [(0.162±0.005)%, (0.167±0.005)%, t=9.564, 5.948, P<0.01]. On post injury day 3 and 7, protein expressions of Beclin-1 and microtubule related protein 1 LC3A of anterior tibial muscle of rats in simple burn group were significantly higher than those in sham injury group, while protein expressions of Beclin-1 and microtubule related protein 1 LC3A of anterior tibial muscle of rats in burn+ 3-MA group were significantly lower than those in burn+ PBS group. Ratios of microtubule related protein 1 LC3A-Ⅱ to LC3A-Ⅰ of anterior tibial muscle of rats in simple burn group were significantly higher than those in sham injury group (t=3.461, 3.353, P<0.05), while ratios of microtubule related protein 1 LC3A-Ⅱ to LC3A-Ⅰ of anterior tibial muscle of rats in burn+ 3-MA group were significantly lower than those in burn+ PBS group (t=3.129, 3.977, P<0.05).@*Conclusions@#Cell autophagy induced by severe burns is involved in the process of skeletal muscle wasting of rats, and inhibition of cell autophagy may contribute to the remission of skeletal muscle wasting of rats induced by burns.

Fasting: a major limitation for resistance exercise training effects in rodents

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P<0.001). After the longer RET protocol, no difference was observed for body mass, extensor digitorum longus (EDL) morphology or skeletal muscle function (P>0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01). Altogether, these data indicate that fasting is a major limitation for RET in rats.

Ultrasonografía del musculoesquelético como valoración nutricional en el paciente crítico / Skeletal muscle ultrasound as a nutritional assessment in the critically ill patient / Ultra-som muscúlo esquelético como valoração nutricional no paciente crítico

Resumen: Introducción: El paciente crítico se caracteriza por una respuesta catabólica aumentada de origen multifactorial, la cual incrementa la pérdida muscular. El ultrasonido a la cabecera del paciente es una herramienta útil para medir el desgaste muscular, evaluar y dar seguimiento nutricional. Material y métodos: Estudio prospectivo y descriptivo con una intervención diagnóstica de bajo riesgo. Se realizaron mediciones del grosor del músculo cuádriceps de una muestra de 20 pacientes consecutivos, se dividieron dos grupos, el grupo 1 con 11 pacientes que tuvieron desgaste muscular representado en porcentaje y en el grupo 2 nueve pacientes sin desgaste muscular. Resultados: En el análisis univariado sólo se observó diferencia entre ambos grupos en el día en que se lograron las metas de nutrición, fue tardío en el grupo de pacientes con desgaste muscular (5 [5-5.5, IC 95%] y 3 [2.5-5, IC 95%] con p = 0.02). En el análisis multivariado se corrobora la misma asociación, pero sin significancia estadística (RM 10.8 [0.93-125-68, IC 95%]). En el análisis de correlación se encontró una relación inversa entre el puntaje de SOFA y el porcentaje de desgaste muscular (r = -0.48 y r2 = 0.23). Conclusiones: El estudio reveló una posible asociación entre la presencia de desgaste muscular en el paciente crítico y el retraso en alcanzar las metas de nutrición. Y una relación inversa entre el valor del puntaje de SOFA y el porcentaje de pérdida muscular.

Abstract: Introduction: The critically ill patient is characterized by an increases catabolic response whith multifactorial origin, which increases muscle loss. Ultrasound at the bedside is a useful tool for measuring muscle wasting, and assess nutritional goals. Material and methods: A prospective study with a low risk diagnostic intervention. We measure the thickness of the quadriceps muscle of a sample of 20 consecutive patients. Two groups were divided, in group 1 with 11 patients who had muscle wasting represented in percentage and group 2 with 9 patients without muscle wasting. Results: In univariate analysis only difference was found between the two groups on the day they were achieved nutrition goals, and was late for the group of patients with muscle wasting (5 [5-5.5; 95%] and 3 [2.5-5, 95% CI] p = 0.02). In multivariate analysis corroborates the same association, but without statistical significance (RM 10.8 [0.93-125-68, 95% CI]). For the correlation analysis an inverse relationship between SOFA score and the percentage of muscle wasting (r = -0.48 and r2 = 0.23) was found. Conclusions: In the study a possible association was met between the presence of muscle wasting in critically ill patients and delay in achieving nutrition goals. And inverse relationship between the value of SOFA score and the percentage of muscle loss.

Resumo: Introdução: O paciente crítico se caracteriza por um aumento da resposta catabólica multifatorial, o que aumenta a perda de massa muscular. O ultra-som à beira do leito é uma ferramenta útil para medir a perda de massa muscular, avaliar e dar monitoramento nutricional. Material e métodos: Estudo prospectivo descritivo com uma intervenção diagnóstica de baixo risco. Realizaram-se medições da espessura do músculo quadríceps de uma amostra de 20 pacientes consecutivos, foram divididos em dois grupos, grupo 1 com 11 pacientes que tiveram perda de massa muscular representada em porcentagem e no grupo 2 com 9 pacientes sem perda de massa muscular. Resultados: A análise univariada só encontrou diferença entre os dois grupos no dia em que foram alcançadas as metas nutricionais, foi tardío para o grupo de pacientes com perda de massa muscular (5 [5-5.5, IC 95%] e 3 [2.5-5, IC 95%] com p = 0.02). A análise multivariada comprova a mesma associação, mas sem significado estatístico (RM 10.8[0.93-125-68, IC 95%]). Para a análise de correlação encontrou-se uma relação inversa entre SOFA escore e a percentagem de perda de massa muscular (r = -0.48 e r2 = 0.23). Conclusões: Encontrou-se uma possível associação entre a presença da perda de massa muscular em pacientes críticos e o atraso em lograr as metas de nutrição. E relação inversa entre o valor SOFA escore e a porcentagem da perda de massa muscular.

Sarcopenia Predicts Reduced Survival in Patients with Hepatocellular Carcinoma at First Diagnosis

Abstract: Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. Aim. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Material and methods. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. Results. Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). Conclusions. This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

Cardiac Cachexia: Perspectives for Prevention and Treatment / Caquexia Cardíaca: Perspectivas para a Prevenção e Tratamento

Abstract Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.

Resumo Caquexia é condição patológica prevalente em pacientes com insuficiência cardíaca (IC) associada. Sua ocorrência constitui marcador de gravidade da doença e está associada a aumento da morbidade e mortalidade independentemente de variáveis clínicas importantes como idade, função ventricular ou classe funcional da IC. As consequências clínicas da caquexia dependem tanto da perda de peso como da inflamação sistêmica que acompanha seu desenvolvimento. Perda da musculatura esquelética é importante componente da caquexia; ela frequentemente precede o desenvolvimento desta condição e está associada a mau prognóstico da IC. A caquexia afeta vários órgãos e sistemas. Sua origem é multifatorial; como os mecanismos fisiopatológicos envolvidos em seu desenvolvimento não estão completamente entendidos, há grande dificuldade no desenvolvimento de terapia específica para a prevenção e tratamento. Estratégias para a prevenção visam, principalmente, a preservação da massa muscular. Diferentes opções de tratamento têm sido descritas, a maioria delas avaliada em estudos experimentais ou pequenos estudos clínicos. Estas incluem suporte nutricional, bloqueio de sistemas neuro-hormonais, redução de translocação bacteriana intestinal, tratamento da anemia e ferrodeficiência, estimulantes de apetite, agentes imunomodulatórios, hormônios anabólicos, e diferentes programas de exercícios físicos. Atualmente, a terapia não farmacológica como o suporte nutricional e exercícios físicos tem sido considerada de grande importância na prevenção e tratamento da caquexia associada à IC.

Bilateral spontaneous anterior shoulder dislocation: A missed orthopedic injury mistaken as proximal neuropathy / 中华创伤杂志(英文版)

A number of orthopedic injuries can occur during epileptic seizures. Anterior shoulder dislocation is one such orthopedic injury that is quite rare. The shoulder dislocation may injure the brachial plexus. Besides seizures, the nerves can also be damaged by anticonvulsive therapy. Muscle wasting following a seizure can misguide a clinician to investigate only neural or muscular pathologies. We report here an individual with epilepsy who was referred to us for electrodiagnostic evaluation of proximal muscle wasting related to a suspected proximal neuropathy. He was found to have a normal electrodiagnostic evaluation and later on discovered to have had bilateral shoulder dislocation on X-rays. This report advocates a thorough clinical appraisal, radiographs, and electrodiagnostic evaluation in a case with muscle wasting following a seizure.

Efeito do exercício aeróbico em modelo experimental de artrite / Effect of aerobic exercise on an experimental model of arthritis

INTRODUÇÃO: A artrite reumatoide é uma doença inflamatória sistêmica autoimune que acomete preferencialmente as articulações, mas também outros tecidos, como o músculo esquelético. A perda de massa muscular determina uma grande repercussão na funcionalidade e qualidade de vida desses pacientes e o exercício físico surge como uma alternativa terapêutica para esse acometimento. OBJETIVO: Avaliar o efeito do exercício físico aeróbico moderado sobre a perda muscular em artrite induzida por colágeno (CIA). MÉTODOS: Esse é um estudo-piloto em que CIA foi induzida em camundongos machos DBA1/J divididos em dois grupos: (i) animais com exercício (EXE, n=5), (ii) animais sem exercício (semEXE, n=4). Foram avaliados o escore clínico, o edema da pata traseira, o peso do animal e a locomoção espontânea periodicamente. Após a morte, a histopatologia da articulação tibiotarsal e a área da miofibra dos músculos gastrocnêmio e tibial anterior foram avaliados. Significância foi considerada se p<0,05.RESULTADOS: Não foi observada diferença significativa entre os grupos nos parâmetros de atividade da doença, peso e locomoção espontânea. Entretanto, a histopatologia da articulação demonstrou redução da erosão cartilaginosa no grupo EXE. Também se observou aumento significativo na área seccional da miofibra do grupo EXE, representando uma diferença média de 24%. CONCLUSÃO: Este é o primeiro estudo com exercício aeróbico moderado em esteira em modelo experimental de artrite. O protocolo de exercício testado não parece impactar no desenvolvimento clínico da doença, mas demonstrou benefício sobre a perda muscular consequente da artrite, reduzindo a atrofia da miofibra.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease that affects primarily the joints, but also other tissues such as skeletal muscle. Muscle wasting significantly impairs the functionality and quality of life of patients with RA and physical exercise is an alternative therapy for this outcome. AIM: To evaluate the effect of moderate aerobic physical exercise on muscle loss caused by collagen-induced arthritis (CIA). METHODS: This is a pilot study in which CIA was induced in DBA/1J mice divided into two groups: (i) animals which exercised (EXE, n=5), (ii) animals which did not exercise (semEXE, n=4). Clinical score, hind paw swelling, weight, and spontaneous locomotion were evaluated periodically. After death, the histopathological score of the ankle and the myofiber area of the gastrocnemius and tibialis anterior muscles were evaluated. Significance was considered when p<0.05. RESULTS: No significant difference was observed between groups regarding clinical parameters of disease activity, animal weight, and spontaneous locomotion. However, joint histopathology demonstrated a decrease in cartilage erosion in the EXE group. There was also significant difference in the myofiber sectional area, with a 24% increase in the EXE group. CONCLUSION: This is the first interventional study with moderate aerobic exercise on a treadmill in an arthritis experimental model. The tested exercise program does not seem to have a clinical impact on the process of arthritis. However, it has a positive effect on muscle wasting caused by arthritis, demonstrated mainly by the reduction of myofiber atrophy.

Camurati-Engelmann Disease.

Camurati-Engelmann disease (CED) is a very rare autosomal dominant genetic disorder that causes characteristic anomalies in the skeleton. It is a connective tissue disorder known for marked variability of its clinical presentation. The authors report CED in a 25-year-old male with atypical involvement of metacarpals (acrosclerosis) and features of neuromuscular disease along with the classical features of the disease.

Mechanisms of Muscle Wasting in Patients with Sepsis / 대한구급학회지

Muscle wasting is commonly seen in patients with sepsis as a consequence of the catabolic response in skeletal muscle. Muscle wasting can occur in cases that have an imbalance between degradation and synthesis of muscle proteins. Although decrements in the synthesis of muscle proteins may contribute to sepsis-induced muscle wasting, it has been recognized that increments in its degradation play a more essential role in muscle wasting. Muscle wasting in sepsis patients has some significant clinical consequences such as reduced ambulation and exercise tolerance, and an increased risk for pulmonary and thromboembolic complications. Several mechanisms have been proposed for sepsis-induced muscle wasting. Increased proteolysis via the ubiquitin-proteasome pathway and the calpains system is one of the principal mechanisms of muscle wasting induced by sepsis. Calpains are activated by calcium, which increases in patients with sepsis. The activation of the calpains system disrupts the sarcomere of the myofibrils, resulting in the release of myofilaments that are subsequently ubiquitinated and degraded by the 26S proteasome complex. Recent studies have suggested that transcriptional factors such as NF-kappaB and FoxO, and the apoptosis and autophagy-lysosome pathways may also be involved in sepsis-induced muscle wasting. This review briefly summarizes the contribution of these mechanisms of muscle wasting in patients with sepsis and the possible therapeutic agents to treat it.