The integrated stress response (ISR) and mitochondrial unfolded protein response (UPRmt) plays a vital role in myogenic differentiation of muscle satellite cells. In this study, chronic ISR and UPRmt was induced with impaired myogenic differentiation and cluster of differentiation 36 (CD36) was highly expressed and localized on the mitochondria in aging muscle. Little is known about the interplay of CD36 and ISR during differentiation. Knocking down CD36 expression at day 3 in differentiated C2C12 myoblasts indicated that the expression levels of Activating transcription factor 4 (ATF4), and other ISR - related proteins decreased, but the expression levels of UPRmt - related proteins Activating transcription factor 5 (ATF5), Heat Shock Protein 60(HSP60) and Heat Shock Protein 10(HSP10) increased with mRNA level of HSP60 increased. Meanwhile Myogenin (MyoG) expression level was increased but Myosin heavy chain 1 (Myh1) expression level was decreased. Following CD36 knockdown, mito-nuclear protein imbalance and mitochondrial dysfunction occurred. Interaction between CD36 and Mammalian Target of Rapamycin (mTOR) was observed in aging muscle. Collectively, CD36 was localized on the mitochondria in aging muscle, while CD36 was associated with ISR and UPRmt early during myogenic differentiation in C2C12 myoblasts, which could have implications for the development of new strategies to treat sarcopenia.

S-ketamine is recognized as a rapid-acting antidepressant, exerting its effects primarily through activation of the mTOR signaling pathway in the brain, which plays a key role in neuroplasticity. Given the shared molecular mechanisms between brain and skeletal muscle, we investigated whether S-ketamine can also modulate regulatory proteins involved in muscle protein synthesis (MPS) and muscle protein breakdown (MPB) in skeletal muscle. Adult female Flinders Sensitive Line rats received a single intraperitoneal injection of S-ketamine (20mg/kg) or saline, and soleus and extensor digitorum longus (EDL) muscles were collected two hours post-injection for protein analysis using Western blot. S-ketamine significantly increased phosphorylated mTOR (p-mTORSer2448) in both soleus and EDL, while total ULK1 protein expression was elevated in soleus. These findings suggest that S-ketamine can stimulate mTOR-related signaling in skeletal muscle, potentially enhancing MPS, although the activation was limited to specific signaling proteins. The results provide novel insights into the peripheral effects of S-ketamine beyond the central nervous system, highlighting the potential relevance for skeletal muscle physiology and anabolic regulation. Future studies are warranted to determine the temporal dynamics of these effects, the dose-dependence, and the impact of repeated administration on muscle hypertrophy. Overall, this study expands understanding of S-ketamine's systemic actions and raises new questions regarding its potential as a modulator of skeletal muscle protein metabolism.

This study has used acoustic myography as a technique to assess not only the number of active fibres and their firing frequency, but also the efficiency with which they are recruited, to re-examine age-related changes in movement. It is known that ageing results in less precise and controlled muscle movements, changes that also occur with some neurological diseases. The aim of this study was therefore to look at the control with which two muscles, an extensor and a flexor, are activated and determine how, as well as which, changes occur with increasing age. In the upper limb it appears that the flexor declines later than the extensor muscle (m.Biceps vs. m.Triceps). This study lends support to the published evidence that proprioception and postural stability are regulated to some extent by muscle spindles and that this process is age-related. The changes are identifiable in the acoustic myography parameters (E-score and ST-score) and are observed in a muscle-specific manner.

Microtubule acetylation is known to promote autophagic degradation; however, its therapeutic potential in resolving exercise-induced autophagic flux blockage and facilitating injured muscle recovery remains unclear. In this study, Sprague-Dawley rats were treated with Tubastatin A for 3 consecutive days to enhance microtubule acetylation. Subsequently, the rats underwent a 90-minute downhill run at a gradient of -16°and a speed of 16m·min⁻¹. Soleus muscles were sampled at 12h post-exercise. Single muscle fibers were isolated and labelled with α-tubulin, acetylated α-tubulin (AcK40 α-tubulin), cytoplasmic dynein intermediate chain (dynein), or LC3 for immunofluorescent analysis. Protein expression of α-tubulin, AcK40 α-tubulin, dynein, LC3, p62, Myf5, Myod, and Myogenin were detected by Western blot. The results showed that Tubastatin A treatment significantly upregulated the expression of AcK40 α-tubulin and dynein. It also increased the amount of dynein on α-tubulin and promoted the retrograde transport of autophagosomes. In response to downhill running, Tubastatin A-treated rats exhibited enhanced autolysosome formation, along with reduced LC3-II and p62 expression. Additionally, Tubastatin A further potentiated the increases in MyoD and Myogenin induced by downhill running. These findings suggest that enhancing microtubule acetylation through Tubastatin A can mitigate the impairment of autophagosome degradation caused by downhill running and promote the myogenic program in skeletal muscle.

Corilagin is a type of ellagitannin that exhibits inhibitory effects on the proliferation of vascular smooth muscle cells (VSMCs). However, the mechanism underlying this inhibition remains unclear. The study utilized a balloon injury-induced rat carotid artery model to investigate the effects of corilagin on the prevention of restenosis following vascular injury. VSMCs were isolated from the carotid arteries of rats post-balloon injury and treated with PDGF-BB and various concentrations of corilagin. Western blotting was employed to assess the phosphorylation levels of MAPK in VSMCs. Two weeks of treatment with corilagin or a control vehicle was conducted on the injury model, and the area of neointima formation and collagen density in the intima were evaluated histopathologically. Our results revealed that corilagin dose-dependently inhibited VSMCs migration and phenotypic transformation, suppressing extracellular matrix deposition by upregulating matrix metalloproteinases (MMPs) and reducing collagen (COL) protein synthesis. In vivo, this result showed a significantly lower intimal thickness and intima/media ratio in the corilagin group compared to the control group. Corilagin inhibits the proliferation and migration of VSMCs by reducing the phosphorylation of ERK, p38, and JNK, and this effect can be weakened by the ERK/MAPK pathway activator C6 ceramide. Corilagin may be a promising drug that could provide a new approach to preventing and treating post-interventional restenosis.

The aim of this study was to determine the impact of myostatin deficiency on the mechanical and contractile adaptations of the soleus muscle to functional overload (FO). Using a cross-sectional design, we compared the control and FO soleus muscles of myostatin-deficient (BEHcc) and myostatin-functional (BEH⁺⁺) mice. FO was induced by 28 days of gastrocnemius ablation. Soleus muscles were isolated and subjected to an isometric-eccentric contraction protocol to analyse contractile performance and tissue mechanical behaviour. FO significantly increased muscle mass, tetanic force, and stiffness, in BEH⁺⁺ mice (p < 0.05), but not in BEHcc where absolute force was even reduced (p < 0.05). These findings indicate that myostatin plays an important role in successful skeletal muscle adaptations and preservation of muscle function under chronic loading.

Polystyrene microplastic (PS-MP), known as a white pollutant, exhibited adverse effects on aquatic and terrestrial animals. The present study aims to evaluate the dose-dependent effect of polystyrene microplastics on skeletal muscle energy metabolism in Wistar rats. PS-MP was administered orally in Wistar rats at doses of 0.5mg/L, 5mg/L, and 50mg/L in drinking water for 28 days daily. After the treatment, metabolic profile and tissue histological analyses were performed. Average food consumption by the treated rats was decreased by PS-MPs. Glycogen and pyruvate contents were depleted in a dose-responsive fashion. Lactate dehydrogenase and transaminase activities were decreased by PS-MP exposure. Free amino nitrogen was mobilized from blood to skeletal muscle in response to stress. Protein content depleted in the muscular tissue whereas enhanced carbonylated protein formation. Pronase and cathepsin activities were increased by PS-MP. Inhibited TCA cycle enzyme activities were observed in the target tissue. Moreover, muscle hypertrophy, nuclear migration, and fibrillation were seen in histological sections. Decreased food consumption by PS-MP exposure could promote glucose scarcity in blood. Depletion of muscular glycogen may result from increased glycogenolysis to replenish loss of blood glucose. Reduction in pyruvate content may result from decreased glycolysis which could perturb the lactate dehydrogenase function. Lack of transaminase in the target tissue was indicative of tissue damage. Muscular protein breakdown might be due to oxidative denaturation of native proteins as well as increased proteolysis. Due to less pyruvate production, the TCA cycle enzyme functions were suppressed. Histopathological studies established significant degenerative changes in muscular morphology following PS-MP exposure. The present study suggests that PS-MP perturbed skeleto-muscular energy metabolism and promoted muscle fiber degeneration following sub-acute exposure.

Cell proliferation plays a crucial role in muscle atrophy-regeneration. However, the functional roles of Long non-coding RNA X-inactive specific transcript (lncRNA Xist) in C2C12 cell proliferation remain poorly characterized.We identified lncRNA Xist as a regulator of cell proliferation kinetics by acting as a competing endogenous RNA (ceRNA) in C2C12 cells. Downregulation or overexpression of lncRNA Xist correlated with enhanced or impaired cell proliferation, respectively. Mechanistically, lncRNA Xist sponges miR-486-5p to regulate serine/threonine kinase 4 (Stk4) expression, thereby modulating C2C12 cell proliferation in vitro.The lncRNA Xist/miR-486-5p/Stk4 ceRNA network plays an essential role in C2C12 proliferation, suggesting lncRNA Xist as a potential therapeutic target for muscle atrophy.

Marfan syndrome is an autosomal dominant multisystemic connective tissue disorder caused by mutations in the FBN1 gene. Although clinical changes in the cardiovascular, ocular, and skeletal systems have been described in detail in Marfan syndrome patients, investigations about skeletal muscle alterations are still incipient. This systematic review describes cellular, molecular, and functional changes in skeletal muscles of patients and mice with Marfan syndrome. Study selection (from EMBASE, MEDLINE, and Web of Science databases), data extraction, and quality appraisal were performed by two independent reviewers. A total of 2634 articles were identified; 26 were included in the analysis based on the selection criteria. The risk of bias was evaluated using the Critical Appraisal Skills Programme and Joanna Briggs Institute Critical Appraisal tool for human studies and the Systematic Review Centre for Laboratory Animal Experimentation RoB tool for animal studies. The findings indicate that skeletal muscle alterations in Marfan syndrome are characterized by fibrosis, reduced muscle mass and myofiber size, compromised muscle regeneration, and impaired muscle function. Future studies are warranted to investigate the mechanisms involved in the development of this muscle phenotype to help develop effective strategies to improve skeletal muscle function and the quality of life of individuals with Marfan syndrome.