Search Results (586)

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

Skeletal muscle regeneration requires a reliable source of myogenic progenitor cells capable of forming new fibers and creating a self-renewing satellite cell pool. Human induced pluripotent stem cell (hiPSC)-derived teratomas have emerged as a novel in vivo platform for generating skeletal myogenic progenitors, although in vivo studies to date have provided only an early single-time-point snapshot. In this study, we isolated a specific population of CD82⁺ ERBB3⁺ NGFR⁺ cells from human iPSC-derived teratomas and verified their long-term in vivo regenerative capacity following transplantation into NSG-mdx^4Cv mice. Transplanted cells engrafted, expanded, and generated human Dystrophin⁺ muscle fibers that increased in size over time and persisted stably long-term. A dynamic population of PAX7⁺ human satellite cells was established, initially expanding post-transplantation and declining moderately between 4 and 8 months as fibers matured. MyHC isoform analysis revealed a time-based shift from embryonic to neonatal and slow fiber types, indicating a slow progressive maturation of the graft. We further show that these progenitors can be cryopreserved and maintain their engraftment potential. Together, these findings give insight into the evolution of teratoma-derived human myogenic stem cell grafts, and highlight the long-term regenerative potential of teratoma-derived human skeletal myogenic progenitors. Full article

Prolonged high-dose administration of synthetic glucocorticoids (GCs) leads to limb muscle atrophy and weakness, yet its underlying mechanisms remain incompletely understood. Muscle fibers and muscle satellite cells (MSCs) are essential for skeletal muscle development and associated pathologies. This study demonstrates that dexamethasone (Dex) induced MSC-derived extracellular vesicles (EVs) impair myogenesis in muscle fiber-like cells (MFLCs) via inducible nitric oxide synthase (iNOS) suppression. High-throughput sequencing revealed a marked upregulation of miR-335-5p in MSC-derived EVs following Dex treatment. Mechanistically, EV miR-335-5p targeted MAPK11, leading to iNOS downregulation and subsequent UPS activation in MFLCs, which directly promoted muscle protein degradation. Collectively, our findings identify the EV miR-335-5p/MAPK11/iNOS axis as a critical mediator of GC-induced muscle atrophy, offering novel insights into therapeutic strategies targeting EV-mediated signaling in muscle wasting disorders. Full article

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

Background: Aerobic exercise induces a range of complex molecular adaptations in skeletal muscle. However, a complete understanding of the specific transcriptional changes following exercise warrants further research. Methods: This study aimed to identify gene expression patterns following acute aerobic exercise by analyzing Gene Expression Omnibus (GEO) datasets. We performed a comparative analysis of transcriptional profiles of related genes in two independent studies, focusing on both established and novel genes involved in muscle physiology. Results: Our analysis revealed ten consistently upregulated and eight downregulated genes across both datasets. The upregulated genes were predominantly associated with mitochondrial function and cellular respiration, including MDH1, ATP5MC1, ATP5IB, and ATP5F1A. Conversely, downregulated genes such as YTHDC1, CDK5RAP2, and PALS2 were implicated in vascular structure and cellular organization. Importantly, our findings also revealed novel exercise-responsive genes not previously characterized in this context. Among these, MRPL41 and VEGF were significantly upregulated and are associated with p53-mediated apoptotic signaling and fatty acid metabolism, respectively. Novel downregulated genes included LIMCH1, CMYA5, and FOXJ3, which are putatively involved in cytoskeletal dynamics and muscle fiber type specification. Conclusions: These findings enhance our understanding of the transcriptional landscape of skeletal muscle following acute aerobic exercise and identify novel molecular targets for further investigation in the fields of exercise physiology and metabolic health. Full article

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. Full article

The decline in differentiation capacity during skeletal muscle (SkM) aging contributes to the deterioration of skeletal muscle function and impairs regenerative ability. Epicatechin gallate (ECG), a major functional component of catechins found in tea, has an unclear role in aging-related sarcopenia. In vivo experiments in 54-week-old C57BL/6J mice showed that ECG treatment improved exercise performance, muscle mass, and fiber morphology and downregulated the expression of the testosterone metabolic enzyme gene UGT2A3 in aged mice. In vitro experiments with Leydig cells (TM3) demonstrated that ECG upregulated the mRNA and protein expression levels of testosterone synthase genes, including StAR, P450scc, 3β-HSD, CYP17a1, and 17β-HSD. Network pharmacology analysis further suggested that ECG can influence testosterone secretion through the regulation of cytokines, thereby promoting skeletal muscle differentiation. These findings indicate that ECG enhances the differentiation of skeletal muscle cells by modulating testosterone levels, which helps alleviate age-related muscle function decline. Full article

Medical phantoms are essential to imaging calibration, clinician training, and the validation of therapeutic procedures. However, most ultrasound phantoms prioritize acoustic realism while neglecting the viscoelastic and anisotropic properties of fibrous soft tissues. This gap limits their effectiveness in modeling realistic biomechanical behavior, especially in wave-based diagnostics and therapeutic ultrasound. Current materials like gelatine and agarose fall short in reproducing the complex interplay between the solid and fluid components found in biological tissues. To address this, we developed a soft, anisotropic composite whose dynamic mechanical properties resemble fibrous biological tissues such as skin and skeletal muscle. This material enables wave propagation and vibration studies in controllably anisotropic media, which are rare and highly valuable. We demonstrate the tunability of damping and stiffness aligned with fiber orientation, providing a versatile platform for modeling soft-tissue dynamics and validating biomechanical simulations. The phantoms achieved Young’s moduli of 7.16–11.04 MPa for skin and 0.494–1.743 MPa for muscles, shear wave speeds of 1.51–5.93 m/s, longitudinal wave speeds of 1086–1127 m/s, and sound absorption coefficients of 0.13–0.76 dB/cm/MHz, with storage, loss, and complex moduli reaching 1.035–6.652 kPa, 0.1831–0.8546 kPa, and 2.138–10.82 kPa. These values reveal anisotropic response patterns analogous to native tissues. This novel natural fibrous composite system affords sustainable, low-cost ultrasound phantoms that support both mechanical fidelity and acoustic realism. Our approach offers a route to next-gen tissue-mimicking phantoms for elastography, wave propagation studies, and dynamic calibration across diverse clinical and research applications. Full article

Skeletal muscle function is determinant for maintaining functional performance and independence in older adults. Muscle is a primary target of aging and insulin resistance (IR)—two conditions associated with functional decline. Sex-related differences may influence these effects at structural and functional levels. We aimed to evaluate the individual and combined effects of aging and IR on the function and structure of extensor digitorum longus (EDL) and soleus muscles in male and female rats. Animals aged 3 and 20 months were studied, with IR induced by 8 weeks of 20% fructose in drinking water. Muscle contractility was assessed alongside histological and hormonal analyses. In males, aging impaired EDL and soleus contractile force, free testosterone levels, and muscle mass. IR decreased muscle function only in young animals. In females, aging led to muscle loss without affecting contractile strength, but the combination of aging and IR reduced muscle contraction, decreased estradiol and exacerbated muscle loss. Both sexes showed aging-related loss of EDL glycolytic fibers, altered regenerative capacity, and increased fibrosis. IR alone reduced glycolytic fibers in young animals of both sexes but increased fibrosis only in males. These results highlight sex-specific effects of aging and IR on muscle function, relevant for targeted strategies to prevent and treat age- and IR-related muscle function decline. Full article

Cardiac cachexia (CC) is an advanced stage of heart failure (HF) characterized by structural and functional abnormalities in skeletal muscle, leading to muscle loss. Aerobic training provides benefits; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the therapeutic effects of aerobic training on transcriptomic alterations associated with disease progression in cachectic skeletal muscle. HF was induced in male Wistar rats by a single monocrotaline injection (60 mg/Kg). Aerobic training consisted of 30 min treadmill running at ~55% of maximal capacity, 5×/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA-seq analysis was performed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs. Enrichment pathways analyses and weighted gene co-expression network analysis (WGCNA) identified potential key genes involved in disrupted lipid metabolism in sedentary cachectic rats, which were not observed in the exercised cachectic rats. Validation of DEGs related to lipid metabolism confirmed that Dgat2 gene expression was modulated by aerobic training in CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid metabolism in rats with CC, highlighting its therapeutic potential. Full article

Background: Myofascial trigger points (MTrPs) are hyperirritable spots within taut bands of skeletal muscle fibers, often developing in overloaded muscles. Ischemic compression (IC) is a frequently used therapeutic technique for MTrP treatment. Material and Methods: Seventy-nine participants with MTrPs in the upper trapezius muscle were included. Three IC protocols were used. In group 1, the compression force was increased once; in group 2, twice; and in group 3, three times—each time up to the pain threshold, then held constant until the pain subsided. Evaluations included pressure pain threshold (PPT), pressure pain perception (PPP), and myotonometric measurements. Results: PPT values increased significantly in group 2 (p = 0.009) and group 3 (p = 0.009), while PPP values decreased significantly in both groups (group 2: p = 0.016; group 3: p = 0.041) post-intervention. Group 1 showed a significant reduction in muscle tone (p < 0.001), and group 2 in muscle stiffness (p = 0.036). Muscle elasticity significantly improved in all groups: group 1 (p = 0.022), group 2 (p = 0.001), and group 3 (p = 0.042). Conclusions: IC applied with a constant force at the individual’s pain perception threshold effectively elevates the pain threshold and enhances the biomechanical parameters of muscle fibers in the trigger point area. Full article

Skeletal muscle fiber type composition critically influences lamb meat quality. This study examined the relationships between muscle fiber types and key quality traits, including tenderness, color, lipid and amino acid profiles, and volatile flavor compounds. MyHC I (slow-twitch oxidative fibers) positively correlated with desirable traits such as increased redness, water-holding capacity, unsaturated fatty acids, and essential amino acids. Conversely, MyHC IIb (fast glycolytic fibers) was linked to reduced tenderness and higher levels of off-flavor compounds. MyHC IIa and IIx showed minimal effects. Untargeted metabolomics comparing muscles with high versus low slow-twitch fiber proportions revealed differential metabolites enriched in sphingolipid and arginine-proline metabolism pathways. These results suggest that a higher proportion of oxidative fibers enhances both the sensory and nutritional qualities of lamb meat by modulating lipid metabolism, amino acid availability, and flavor formation. Full article

Skeletal muscle is one of the largest tissues in the body. It is of great significance to analyze the molecular mechanism of skeletal muscle development for the further study of meat quality improvement and muscle diseases. CircRNA has been reported to be involved in many biological processes, but further research is needed in skeletal muscle. In this study, we detected the authenticity, stability, and spatio-temporal expression characteristics of circHOMER1 and its effect on the proliferation, apoptosis, and differentiation of muscle cells, and analyzed its possible molecular mechanism. The results showed that circHOMER1 exists in the skeletal muscle of the Ningxiang pig, is more stable than linear RNA, and is significantly upregulated in adipose tissue and during the early growth of myoblasts. In terms of function, overexpression of circHOMER1 significantly promoted the expression levels of proliferation marker genes and proteins and significantly increased the EdU positive cell rate, optical density (OD) value (at 450 nm), and proportion of S-phase cells. Overexpression of circHOMER1 also significantly promoted the expression levels of apoptosis marker genes and proteins and significantly increased the proportions of cells in Q2 (with late apoptosis) and Q3 (with early apoptosis). Overexpression of circHOMER1 significantly inhibited the expression levels of differentiation marker genes and proteins, significantly inhibited the differentiation index, and decreased the proportion of 5-nucleus muscle fibers. Conversely, opposite results were obtained after circHOMER1 interference. In terms of molecules mechanism, subcellular localization analysis showed that circHOMER1 was mainly distributed in cytoplasm, and mechanism analysis showed that circHOMER1 participated in myoblast development by forming a 4-element interaction network with 4 miRNAs, 2 lncRNAs, and 20 mRNAs, and possibly regulated myoblast development by encoding 79 amino acids. To sum up, we verified that circHOMER1 promoted the proliferation and apoptosis of myoblasts and inhibited their differentiation. It may regulate the development of myoblasts through ceRNA or by encoding small peptides. These results provided a reference for the regulation mechanism of muscle development and the breeding of Ningxiang pigs. Full article

Heart failure with preserved ejection fraction (HFpEF) shows diverse disease patterns, with various combinations of comorbidities and symptoms. A common hallmark is exercise intolerance, caused by alterations in the peripheral skeletal muscle (SKM) including a recently indicated titin hyperphosphorylation. Our aim is to compare a metabolic syndrome- (ZSF-1 rats) and a hypertension-driven (Dahl salt-sensitive (DSS) rats) HFpEF rat-model in relation to SKM function and titin phosphorylation. Obese ZSF-1 and high-salt fed DSS rats (HFpEF) were compared to lean ZSF-1 and low-salt fed rats (con). HFpEF was confirmed by echocardiography and invasive haemodynamic measurements. SKM atrophy, in vitro force measurements, titin- and contractile protein expression were evaluated. Obese ZSF-1 HFpEF rats showed muscle atrophy, reduced muscle force and increased titin phosphorylation compared to controls, which was not detected in hypertensive DSS rats. Fiber type specific troponins, myostatin and four and a half LIM domain 1 were differently regulated between the two models. Altogether, our results show that both animal models of HFpEF exhibit different SKM phenotypes, probably based on the divergent disease etiologies, which may help to define the most suitable animal model for HFpEF to test potential treatment regimens. Full article

Background/Objectives: Chestnut inner shells, traditionally used in Korean and Chinese herbal medicine, contain antioxidant and anti-inflammatory compounds that contribute to complementary medicine. This study aimed to explore the therapeutic effects of chestnut inner-shell extract (CIE) on skeletal muscle injury and atrophy using both in vivo and in vitro models. Methods: We used three experimental models representing distinct pathological mechanisms: (1) barium chloride (BaCl₂)-induced muscle injury to model acute myofiber damage, (2) sciatic nerve transection to model chronic neurogenic muscle atrophy, and (3) H₂O₂-treated C2C12 myoblasts to model oxidative-stress-related myogenic impairment. Histological analyses (e.g., hematoxylin and eosin staining and cross-sectional area measurement) and molecular analyses were performed to evaluate the effects of CIE on muscle structure, apoptosis, and oxidative stress. Results: In the BaCl₂ injury model, CIE treatment significantly restored the muscle fiber structure, with muscle protein levels returning to near-normal levels. In the denervation-induced muscle atrophy model, CIE treatment led to a dose-dependent decrease in apoptosis-related factors (especially cleaved caspase-3) and mitigated the Akt/mTOR signaling pathway. In the in vitro oxidative stress model, CIE suppressed the expression of NRF2 and HO-1, which are key oxidative stress response regulators. Conclusions: These findings suggest that CIE may offer therapeutic potential for mitigating skeletal muscle damage, atrophy, and oxidative stress. Full article