Irisin and skeletal muscle mitochondrial function and sarcopenia / 中华老年医学杂志

Irisin is a muscle factor that plays a crucial role in exercise-induced metabolic responses.Recent studies have revealed that it can boost the metabolic rate of both myocytes and adipocytes, while also enhancing mitochondrial content and dynamics.This ultimately helps to safeguard skeletal muscle, promote muscle growth, and maintain optimal muscle function.Therefore, irisin has the potential to serve as both a predictor and a biomarker for sarcopenia.In this paper, we delve into the impact of irisin on skeletal muscle, specifically exploring the synergistic relationship between irisin and mitochondria.Additionally, we investigate the effectiveness of irisin in reversing and restoring muscle atrophy, ultimately establishing irisin as a valuable target for treating sarcopenia.

Estudo clínico, histológico, imunoistoquímico e da função lisossomal na miosite por corpos de inclusão / Clinical, histological, immunohistochemical and lysosomal function study in inclusion body myositis

A miosite por corpos de inclusão (inclusion body myositis - IBM), na sua forma esporádica, é considerada a miopatia adquirida mais comum após os 50 anos de idade. Embora seja incluída no grupo das miopatias inflamatórias, estudos recentes mostram um processo particular de degeneração muscular caracterizado por deposição anormal de agregados de proteínas nas fibras musculares e funcionamento anormal dos principais sistemas de degradação proteica. O objetivo deste estudo foi o de avaliar os aspectos clínicos, histológicos e imunoistoquímicos de pacientes com IBM. Avaliamos 18 casos com diagnóstico de IBM de dois dos principais centros de doenças neuromusculares do Brasil (25 biópsias musculares). Na tentativa de diferenciar os casos de IBM das outras miopatias inflamatórias, determinamos o padrão de expressão tecidual da p-tau (p62), alfa-sinucleína e TDP-43. Também foi avaliada a função lisossomal através da reação da fosfatase ácida (marcação da atividade lisossomal global) e determinação da marcação para LC3B (marcador de autofagia). Foi observado que a IBM predominou no sexo masculino (61% dos casos), da cor branca, com início das manifestações clínicas ao redor dos 59 anos de idade e os sintomas mais frequentes foram fraqueza muscular, instabilidade postural com quedas da própria altura, disfagia e perda ponderal, podendo ainda apresentar dispneia. O diagnóstico demorou em média 7,4 anos após o início dos sintomas e frequentemente esteve associada às seguintes comorbidades: hipertensão arterial sistêmica, diabetes mellitus tipo 2, osteopenia / osteoporose, dislipidemia e hiperuricemia / gota. O padrão de comprometimento muscular na IBM foi caracterizado por tetraparesia de predomínio proximal em membros inferiores e distal em membros superiores. Os valores séricos da creatinofosfoquinase em pelo menos uma das medições foram elevados em todos os pacientes, porém sem ultrapassar 10 vezes o limite superior da normalidade. O uso de...

Sporadic inclusion body myositis (sIBM) is considered the most common acquired myopathy affecting adults aged over 50 years. Although included in the group of inflammatory myopathies, recent studies show a particular process of muscle degeneration characterized by abnormal deposit of protein aggregates in muscle fibers and abnormal operation of the main protein degradation systems. The aim of this study was to evaluate the clinical, histological and immunohistochemical patients with IBM. We evaluated 18 cases with IBM diagnostic of two of the main centers of neuromuscular diseases in Brazil (25 muscle biopsies). In an attempt to differentiate the IBM cases of other inflammatory myopathies, we determined the pattern of tissue expression of p-tau (p62), alfa-synuclein and TDP-43. Also evaluated the lysosomal function by acid phosphatase reaction (marking global lysosomal activity) and determining the markup for LC3B (autophagy marker). It was observed that IBM was predominant in males (61% of cases), white colored, with onset of clinical manifestations around 59 years old and the most common symptoms are muscle weakness, postural instability with high falls, dysphagia and weight loss, and may also present dyspnea. The diagnosis took an average of 7.4 years after the onset of symptoms and was often associated with the following comorbidities: hypertension, type 2 diabetes mellitus, osteopenia / osteoporosis, dyslipidemia and hyperuricemia / gout. The muscular damage pattern at IBM was characterized by tetraparesis predominantly proximal lower limbs and distal upper limbs. Serum creatine kinase levels in at least one of the measurements were elevated in all patients, but not exceeding 10 times normal. Immunosuppression was not effective in patients with IBM. The IBM histological findings included diversify dystrophic changes, endomysial inflammation, as well as the occurrence of rimmed vacuoles, in addition to high frequency of mitochondrial changes. Other...

Effects and mechanisms of calorie restriction on the contractile function of skeletal muscle from rats / 中国医师杂志

Objective To investigate the effects of calorie restriction (CR) for 4 weeks on twitch tension,titanic tension,and fatigue contraction induced by electrical stimulation in different kind skeletal muscles from rats and explore the possible mechanisms.Methods The rat model of CR was established by a limitation of 40％ calorie intake of control rats for 4 weeks,and then oral glucose tolerance test (OGTT) was performed.The soleus (SOL) and extensor digitorum longus (EDL) were isolated under anesthetization to detect twitch tension,titanic tension,and fatigue contraction induced by electrical stimulation.Adenosine triphosphate (ATP) content was measured by fluorescent enzymatic methods to reflect mitochondrial function.The ratio of mitochondrial gene COX Ⅰ and nuclear gene β-actin copy number was analyzed to evaluate mitochondrial biogenesis.Furthermore,the transcriptions of peroxisome proliferatoractivated receptor γ coactivator-1 (PGC-1α) and nuclear respiratory factor 1 (NRF1) genes,expressions of phosphorylated adenosine 5'-monophosphate-activated protein kinase (AMPK) and nitric oxide synthase (NOS) proteins,and nitric oxide (NO) content were determined in skeletal muscle.Results The blood glucose level at 30 min and area under the curve of blood glucose levels at various time points during OGTT were significantly decreased in the CR group compared to the control group.The twitch tension [(2.5 ± 0.15)N/cm2 vs (1.24±0.12)N/cm2,(2.66 ±0.21)N/cm2 vs (1.69 ±0.17)N/cm2,P ＜ 0.05],titanic tension [(10.43 ± 0.36) N/cm2 vs (8.06 ± 0.19) N/cm2,(11.35 ± 1.02) N/cm2 vs (8.12 ± 0.23) N/cm2,P ＜ 0.05],and fatigue contraction force in SOL and EDL from CR rats were significantly increased in association with increases of ATP content [(34.82 ±4.31)) mnol/mg protein vs (15.32 ± 1.94) nmol/mg protein,(30.82 ± 2.15) nmol/mg protein vs (12.32 ± 0.97) nmol/mg protein,P ＜ 0.05] and mitochondrial biogenesis (2.75 ± 0.20 vs 1.52 ± 0.06,1.32 ± 0.10 vs 0.84 ± 0.11,P ＜ 0.05) compared to control rats.CR for 4 weeks upregulated the transcriptions of PGC-1α and NRF genes as well as the phosphorylation of AMPK protein in SOL but not in EDL.Furthermore,CR also enhanced NOS expression and NO content in both skeletal muscles.Conclusions CR for 4 weeks can strengthen the contractile function of SOL and DL from rats,and the underlying mechanisms might be related to the upregulation of PGC-1α transcription and AMPK activation,resulting in the enhances of mitochondrial biogenesis and mitochondrial function in skeletal muscles.

Perfil de auto-anticorpos detectados em substrato rim-estômago de rato no Hospital São Lucas da PUCRS / Autoantibody profile in rat kidney-stomach substrate in the São Lucas Hospital of PUCRS

Objetivo:O trabalho descreve o perfil de autoanticorpos utilizando-se o substrato rim-estômago de rato em um centro de saúde terciário no período de um ano. Material e métodos: O estudo foi de série de casos, com dados obtidos do banco de dados do Setor de Imunologia do Laboratório de Patologia Clínica do Hospital São Lucas da PUCRS. Resultados: Em 262 pacientes (68% do sexo feminino) previamente selecionados por triagem clínica, avaliou-se o perfil de auto-anticorpos em substrato rim-estômago de rato através de imunofluorescência indireta. Anticorpos antimúsculo liso prevaleceram (31%), seguidos por anticorpos anti-reticulina (27%), anticorpos antimitocondriais (24%), anticélulas parietais gástricas (21%), anticorpos anti-"brush border" (4%) e antiLKM (liver-kidney microsome) (0,4%). A maioria dos pacientes com teste positivo para anticorpos antimúsculo liso cursou com titulações inferiores a 1/80 (ponto de corte para hepatite auto-imune). Anticorpos anti-ribossomais não foram detectados em quaisquer pacientes. À exceção do anticorpo antiLKM (presente apenas em um caso, sexo masculino), observou-se predominância do sexo feminino nos auto-anticorpos analisados; tal predomínio, entretanto, só alcançou significância estatística para anticorpos antimitocondriais (P = 0,04). Conclusão: O achado corrobora a possível relação entre fatores genéticos e hormonais na auto-imunidade.

Objective: This article describes the autoantibody profile using rat kidney-stomach substrate in a tertiary center in a year period. Material and methods: The design was a case series, being results obtained from the data bank of the Immunology Section of the Clinical Pathology Laboratory of Saint Lucas Hospital of PUCRS. Results: In 262 patients (68% females) previosly selected by clinical trial, we evaluated the antibody profile in rat kidney-stomach substrate by indirect immunofluorescence. Anti-smooth muscle antibodies predominated (31%), followed by anti-reticulin antibodies (27%), antimitochondrial antibodies (24%), anti-gastric parietal cells antibodies (21%), anti-"brush border" antibodies (4%) and liver-kidney microsome antibodies (0.4%). The majority of patients with a positive test for anti-smooth muscle antibodies had titers below 1/80 (cutoff for autoimmune hepatitis). Anti-ribosome antibodies were not detected in any patient. Apart from the liverkidney microsome antibody (seen in one male), a female predominance was observed for the other autoantibodies described; this predominance, nevertheless, was statistically significant only for antimitochondrial antibodies (P = 0.04). Conclusion: This finding corroborates a possible relationship of genetic and hormonal factors in autoimmunity.