Complete tissue recovery following traumatic injury remains a major clinical challenge. While tissue adhesives show promise for managing traumatic injuries, developing materials with robust wet adhesion and high biocompatibility remains difficult. Decellularized extracellular matrix (ECM)-derived materials are widely utilized in tissue engineering due to their superior biocompatibility and bioactivity. In this study, a wet adhesive is developed by functionalizing ECM with dopamine. The resulting ECM-dopamine exhibits strong wet adhesion and excellent biocompatibility. Furthermore, ECM-dopamine can be engineered into a drug delivery platform for small agents and macromolecules. Solid lipid nanoparticles (SLNs) are incorporated into ECM-dopamine to enable sustained release of small molecules. The ECM-dopamine-SLN system ensures sustained drug release for at least one week upon adhesion to target tissues. ECM-dopamine-SLN loaded with antimicrobials accelerates wound healing and promotes angiogenesis by modulating the inflammatory response in a mouse skin excision model. Additionally, ECM-dopamine can deliver bioactive macromolecules to injured tissue. ECM-dopamine loaded with insulin-like growth factor-1 promotes skeletal muscle regeneration in a mouse volumetric muscle loss model, likely through the modulation of M2-like macrophage polarization. The dual functionality of ECM-dopamine as both a wet adhesive and a drug delivery platform offers significant potential for regenerative medicine applications.

Despite the growing interest in the use of probiotics in broilers as feed additives, studies conducted to investigate the effect of probiotic administration on acute phase responses and the impact on muscle growth parameters in broilers are still limited. In this study, we investigated the effect of Bacillus amyloliquefaciens CECT 5940 on relative gene expression for growth factors involved in muscle development (insulin-like growth factors, myogenic factor 5, paired-box transcription factor), percentage of proliferating antigen cell nuclei in breast muscle, and secretion of acute phase proteins (serum amyloid A, haptoglobin, alpha1-acid glycoprotein) in the peripheral blood of broilers. Sixty one-day-old chicks from the experimental group were sprayed with a probiotic containing B. amyloliquefaciens at a dose of 1 × 1010 CFU/g directly after hatching and received the probiotic in drinking water (50 × 1010 CFU/1000 L) for 5 consecutive days of life. Sampling was performed on the 5th, 8th, and 12th day of life of the chicks. From the obtained results, we can conclude that B. amyloliquefaciens modulated the gene expression of selected growth parameters in the pectoral muscle, thereby increasing the number of satellite cells, however, their uptake into muscle fibers and thus increased hypertrophic growth was not proven at the time of the last sampling. At the same time, it demonstrated a potentiating effect on PCNA expression in chicken breast muscles in the early intensive growth phase of broiler chickens and modulated the production of acute phase proteins, which may contribute to improving adaptive processes during the growth and development of broilers.

The increasing global aging population has brought greater focus to age-related diseases, particularly muscle-brain comorbidities such as sarcopenia and late-life depression. Sarcopenia, defined by the gradual loss of muscle mass and function, is notably prevalent among older individuals, while late-life depression profoundly affects their mental health and overall well-being. Epidemiological evidence suggests a high co-occurrence of these two conditions, although the precise biological mechanisms linking them remain inadequately understood. This review synthesizes the existing body of literature on sarcopenia and late-life depression, examining their definitions, prevalence, clinical presentations, and available treatments. The goal is to clarify the potential connections between these comorbidities and offer a theoretical framework for the development of future preventive and therapeutic strategies.

In the treatment and management of type 2 diabetes mellitus (T2DM), exercise therapy has received increasing attention due to its accessibility and cost-effectiveness. Regular physical exercise improves glycemic control by ameliorating insulin resistance (IR) and reducing the risk of complications. However, the distinct mechanisms underlying the efficacy of endurance training (ET) and resistance training (RT) in T2DM remain incompletely understood. This review systematically compares the molecular pathways through which ET and RT improve IR, focusing on epigenetic regulation, metabolic reprogramming, and anti-inflammatory effects. We highlight that RT enhances protein synthesis via the IGF-1/PI3K/AKT/mTOR pathway, while ET predominantly improves mitochondrial biogenesis and lipid oxidation through AMPK/SIRT1/PGC-1α signaling. Additionally, ET exerts immunomodulatory effects by suppressing pro-inflammatory cytokines (e.g., TNF-α) and elevating anti-inflammatory myokines (e.g., IL-6). These findings provide a mechanistic basis for personalized exercise prescriptions in T2DM management.

This study investigates the effects of Moringa oleifera leaf powder (MOLP) supplementation on growth performance and the expression of MYF5 and IGF-1 genes in Japanese quails. A total of 116 quails were assigned to four dietary treatments: Control, Moringa-1 (2% MOLP), Moringa-2 (4% MOLP), and Moringa-3 (6% MOLP). Body weights were recorded weekly, and gene expression levels were analysed using quantitative real-time PCR. The results showed significant improvements in body weight and feed efficiency in the Moringa-2 and Moringa-3 groups compared to the Control group (p < 0.05). Additionally, the expression levels of MYF5 and IGF-1 increased dose-dependent, with the highest expression observed in the Moringa-3 group. These findings demonstrate the potential of MOL as a natural feed additive to enhance growth performance and modulate molecular pathways related to muscle development in poultry. This study provides valuable insights for sustainable poultry production and highlights the need for further research on optimal inclusion levels and the long-term effects of MOL supplementation.

Skeletal muscle mass is significantly negatively regulated by glucocorticoids. Following glucocorticoid administration, the balance between protein synthesis and breakdown in skeletal muscle is disrupted, shifting towards a predominance of catabolic metabolism. Short-chain fatty acids like sodium butyrate have been found to regulate inflammatory reactions and successively activate signaling pathways. The preventive benefits of sodium butyrate against dexamethasone-induced skeletal muscle atrophy and myotube atrophy models were examined in this work, and the underlying mechanism was clarified. A total of 32 6-week-old C57BL/6 inbred male mice were randomly assigned to one of four groups and treated with dexamethasone to induce muscle atrophy and sodium butyrate. We found that sodium succinate alleviated dexamethasone-induced myotube atrophy in the myotube atrophy model by lowering the gene expression of two E3 ubiquitin ligases, Atrogin-1 and MURF1, and activating the AKT/mTOR signaling pathway. Pertussis toxin reversed this effect, indicating that G protein-coupled receptors were involved in sodium butyrate's action as a mediator. Additionally, pre-treatment with sodium butyrate lowered weight and muscle mass loss in a mouse model of skeletal muscle atrophy, dramatically decreased the MURF1 gene expression and decreased the nuclear translocation of the glucocorticoid receptor. In conclusion, this study shows that sodium butyrate inhibits the expression of atrophy genes, thus preventing the breakdown of proteins and the loss of muscle mass, while also inhibiting weight loss, in animal models.

Insulin regulates glucose uptake and metabolism in muscle via the insulin receptor. Here, we show that Lrtm1 (leucine-rich repeat and transmembrane domain 1), a protein of unknown function enriched in insulin-responsive metabolic tissues, senses changes in insulin signaling in muscle and serves as a regulator of metabolic response. Thus, whole-body Lrtm1-deficient mice exhibit a reduced percentage of fat mass, an increased percentage of lean mass, and an enhanced glucose tolerance and insulin sensitivity compared with control mice under both chow and high-fat diet conditions. Lrtm1 whole-body deficiency also affects dopamine signaling in the brain, leading to hyperactivity. The improvements in glucose and insulin tolerance, but not behavioral or body composition changes, are also observed in skeletal muscle-specific Lrtm1 knockout mice. These effects occur with no change in classical insulin receptor-Akt signaling. Thus, Lrtm1 senses changes in insulin receptor signaling and serves as a novel postreceptor regulator of metabolic and behavioral activity.

Cultivated meat may be an ethical, environmentally friendly, antibiotic-free meat alternative of the future. As of now, one of the main limiting factors for bringing cultivated meat to the market is the high cost of the cell culture media and their great dependency on serum albumins, production of which is predicted to become a major bottleneck of this industry. Here, using bovine muscle stem cells, we optimized serum free B8/B9 medium. We identified several food grade, low-price medium stabilizers, exhibiting comparable or even superior stabilization of the B8 medium in short- and long-term cultivations, as compared to recombinant human serum albumin. We show transferability of our approach to other satellite cells (porcine, chicken) and CHO cells, though significant cell-line specific differences in response to stabilizers were observed. Thus, we provide an alternative to serum albumin, enabling up to an overall 73% reduction of medium price for certain cell lines.

Stunting is a major global health concern, particularly in low- and middle-income countries, due to its persistently high prevalence. It often originates from chronic malnutrition during the critical first 1000 days of life. Maternal and child nutrition are critical determinants of a child's growth and development. This article aimed to explore the impact, causes, and evidence-based strategies to accelerate the reduction of stunting incidence worldwide. This review was undertaken with sources from PubMed, Scopus, Google Scholar, Science Direct, and MEDLINE from October 2024 to January 2025. This review was undertaken with sources from PubMed, Scopus, Google Scholar, Science Direct, and MEDLINE from October 2024 to January 2025 using the keyword "Stunting", "Causes of stunting", "Stunting Impact", "Stunting Intervention", and "Stunting Prevention". The findings highlight the multifactorial causes of stunting, including maternal malnutrition, inadequate breastfeeding and complementary feeding, poor sanitation, and socioeconomic factors. Stunting is associated with impaired linear growth, cognitive deficits, gut dysbiosis, endocrine disruption, anemia, and increased risk of chronic diseases later in life. Addressing stunting demands multisectoral strategies focusing on maternal and child nutrition, infection prevention, improved WASH (Water, Sanitation, and Hygiene) practices, and socioeconomic support. The evidence presented may guide policy development and targeted interventions to prevent stunting and its long-term effects.

Skeletal muscle atrophy is associated with denervation, cancer, diabetes, aging, immobilization, and inflammation, which can significantly impair mobility. It is primarily attributable to increased protein catabolism alongside reduced protein synthesis, although the precise mechanisms underlying this process are not yet fully known. Unlike in the pathway driving increased catabolism, fewer studies have explored the mechanism underpinning muscle atrophy under reduced protein synthesis. Therefore, this study aimed to focus on summarizing relevant studies on the reduction of protein synthesis leading to skeletal muscle atrophy, as driven by alterations in pathways such as the insulin-like growth factor-1-phosphatidylinositol 3-kinase-protein kinase B-rapamycin signaling pathway, glycogen synthase kinase-3, glucocorticoids, 5'-adenosine monophosphate-activated protein kinase, branched-chain amino acid sensors, myostatin, long-term proinflammatory factors, oxidative stress and mitochondrial dysfunction, calciumion concentration, activating transcription factor 4, and glycyl-tRNA synthetase alterations. Consolidating these data will provide a foundation and theoretical basis for further investigation into the mechanisms of muscle atrophy from the perspective of reduced protein synthesis pathways.

Background/Objectives: High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, and promoting muscle health. This study investigates the combined effects of HIIT and TRF on the AKT-IGF-1-mTOR signaling pathway in the muscle tissue of type 2 diabetic (T2D) rats. Methods: 42 male Wistar rats (4-5 weeks of age) were included in the study. The animals were randomly divided into two groups: 1. Standard diet (SD) non-diabetic (n = 7) and 2. High-fat diet (HFD n = 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) of streptozotocin (STZ) at 35 mg/kg. Animals with blood glucose levels ≥ 250 mg/dL were considered diabetic. Diabetic rats were randomly divided into five groups (n = 7): 1. Diabetes-HIIT (D-HIIT), 2. Diabetes-TRF (D-T), 3. Diabetes-combined TRF and HIIT (D-T+HIIT), 4. Diabetes-Untreated Control (D), and 5. Diabetes with metformin (D-MET). The HIIT protocol and TRF regimen were followed for 10 weeks. Muscle tissue was collected for histological analysis, and the expression of proteins related to the AKT-IGF-1-mTOR pathway was measured. Results: Blood glucose levels, insulin resistance (IR), and markers of muscle degradation were significantly improved in the D-T+HIIT and D-MET groups compared to the non-diabetes group. Furthermore, the activation of the AKT and mTOR signaling proteins, as well as increased IGF-1 expression, was significantly elevated in the D-T+HIIT group compared to the diabetic control group and other treatment groups, and approached levels observed in the non-diabetes group. Additionally, muscle fiber size and overall tissue structure were improved in the treatment groups, particularly in the D-T+HIIT group. Conclusions: The combination of HIIT and TRF appears to offer superior benefits in improving muscle protein synthesis, and glucose regulation in T2D rats, as compared to either HIIT or TRF alone. These findings highlight the potential of this combined approach for addressing muscle-related complications in T2D.

Accelerated recovery from bone injuries is a paramount health-care goal with substantial impacts on physical status and overall well-being. The aim of this study was to evaluate the impact of colostrum supplementation on bone healing in patients with a traumatic extracapsular hip fracture (ECF).

Patients with an ECF undergoing internal fixation were randomly assigned to receive either bovine colostrum or whey protein. Bone healing was assessed using the Radiographic Union Score for Hip (RUSH). Physical rehabilitation was evaluated using the Harris hip score (HHS) and the Short Musculoskeletal Functional Assessment (SMFA) within 3 months postoperatively. A generalized estimating equation (GEE) was used to assess the time-by-group interactions of these longitudinal variables. Patients were monitored for postoperative complications for 12 months, with the risk difference (RD) and risk ratio (RR) calculated.

A total of 116 patients with an ECF were included in the final analysis (colostrum group, n = 59; whey group, n = 57). Baseline characteristics, including age, gender, ethnicity, and body mass index, were similar between the groups (p > 0.05 for all). The colostrum group had a significantly greater increase in the RUSH score (β = 0.88; p = 0.001) and HHS (β = 1.2; p = 0.001) over time compared with the whey group. SMFA dysfunction and bother indices demonstrated significantly greater decreases over time in the colostrum group compared with the whey group (β = -1.2 and -2.4, respectively; p < 0.001 for both).

The present study provides preliminary evidence suggesting that colostrum may accelerate bone healing and enhance short-term physical rehabilitation outcomes more effectively than whey protein.

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Stem cell therapy is a promising approach for tissue regeneration after traumatic injury, yet current applications are limited by inadequate control over the fate of stem cells after transplantation. Here we introduce a bioconstruct engineered for the staged release of growth factors, tailored to direct different phases of muscle regeneration. The bioconstruct is composed of a decellularized extracellular matrix containing polymeric nanocapsules sequentially releasing basic fibroblast growth factor and insulin-like growth factor 1, which promote the proliferation and differentiation of muscle stem cells, respectively. When applied to a volumetric muscle loss defect in an animal model, the bioconstruct enhances myofibre formation, angiogenesis, innervation and functional restoration. Further, it promotes functional muscle formation with human or aged murine muscle stem cells, highlighting the translational potential of this bioconstruct. Overall, these results highlight the potential of bioconstructs with orchestrated growth factor release for stem cell therapies in traumatic injury.

Cirrhosis is an important cause of morbidity and death in patients with chronic liver disease. It can be divided into compensatory and decompensated stages. During the decompensation period, complications such as esophageal and gastric varices hemorrhage, hepatic encephalopathy, infection, and hepatorenal syndrome are often incurred, which has a high mortality rate and leverages huge economic burden on society, healthcare resources, and individuals. Sarcopenia and frailty are common in patients with cirrhosis. The pathogenesis of sarcopenia and frailty in the context of cirrhosis is complicated and multifactorial, including overwhelming systemic inflammation, imbalance of muscle protein metabolism, malnutrition, endocrine and metabolic dysfunctions, intestinal microecological disorders, lack of physical exercise, and other aspects. Notably, accumulating evidence implicates that many patients experience sarcopenia/frailty even before the onset of liver cirrhosis. In this regard, the magnitude of liver fibrosis is closely linked to the progression of sarcopenia with reciprocal impact. In conclusion, this review article will shed light on the pathogenesis of cirrhosis complicated with sarcopenia/frailty, aimed at facilitating early diagnosis and effective management.

Emerin, a ubiquitously expressed inner nuclear membrane protein, plays a central role in maintaining nuclear structure and genomic organization, and in regulating gene expression and cellular signaling pathways. These functions are critical for proper myogenic differentiation and are closely linked to the pathology of Emery-Dreifuss muscular dystrophy 1 (EDMD1), a laminopathy caused by mutations in the EMD gene. Emerin, along with other nuclear lamina proteins, modulates chromatin organization, cell signaling, gene expression, and cellular mechanotransduction, processes essential for muscle development and homeostasis. Loss of emerin function disrupts chromatin localization, causes dysregulated gene expression, and alters nucleoskeletal organization, resulting in impaired myogenic differentiation. Recent findings suggest that emerin tethers repressive chromatin at the nuclear envelope, a process essential for robust myogenesis. This review provides an in-depth discussion of emerin's multifaceted roles in nuclear organization, gene regulation, and cellular signaling, highlighting its importance in myogenic differentiation and disease progression.

Skeletal muscle satellite cells (SMSCs) are quiescent stem cells located in skeletal muscle tissue and function as the primary reservoir of myogenic progenitors for muscle growth and regeneration. However, the molecular and metabolic mechanisms governing their differentiation in geese remain largely unexplored. This study comprehensively examined the morphological, transcriptional, and metabolic dynamics of goose SMSCs across three critical differentiation stages: the quiescent stage (DD0), the differentiation stage (DD4), and the late differentiation stage (DD6). By integrating transcriptomic and metabolomic analyses, stage-specific molecular signatures and regulatory networks involved in SMSC differentiation were identified. Principal component analysis revealed distinct clustering patterns in gene expression and metabolite profiles across these stages, highlighting dynamic shifts in lipid metabolism and myogenesis. The PPAR signaling pathway emerged as a key regulator, with crucial genes such as PPARG, IGF1, ACSL5, FABP5, and PLIN1 exhibiting differentiation-dependent expression patterns. Notably, PPARG and IGF1 displayed negative correlations with adenosine and L-carnitine levels, suggesting their role in metabolic reprogramming during myotube formation. Additionally, MYOM2 and MYBPC1 exhibited stage-specific regulation and positively correlated with 2,3-dimethoxyphenylamine. This study provides a foundational framework for understanding muscle development and regeneration, offering valuable insights for both agricultural and biomedical research.

Study of fish skeletal muscle is essential to understand physiological or metabolic processes, and to develop programs searching for increased muscle mass and meat production. Amino acids (AA) and IGF1 stimulate processes that lead to muscle growth, but their signaling pathways and molecular regulation need further clarification in fish. We obtained the proteome of pacu (Piaractus mesopotamicus) cultured muscle cells treated with AA or IGF1, which induced the differential abundance of 67 and 53 proteins, respectively. Enrichment analyses showed that AA modulated histone methylation, cell differentiation, and metabolism, while IGF1 modulated ATP production and protein synthesis. In addition, we identified molecular networks with candidate markers that commonly regulate fish muscle cells: FN1B and EIF3C, respectively up- and down-regulated by both treatments. FN1B was related to cell proliferation, protein synthesis, and muscle repair, while EIF3C connected with negative regulators of muscle growth. Their gene expression was evaluated in pacu and Nile tilapia (Oreochromis niloticus) after nutrient manipulation, with fn1b increased during refeeding and eif3c increased during fasting in both species. Our work helps clarify the molecular regulation by AA or IGF1 and suggests that FN1B and EIF3C could be potential stimulatory and inhibitory biomarkers of fish muscle growth.

Silent Information Regulator 5 (SIRT5) has been established as a crucial regulator of cellular alanylation modification. Furthermore, accumulating evidence suggests that SIRT5 plays a significant regulatory role in key metabolic pathways, including glycolysis, the tricarboxylic acid (TCA) cycle, and fatty acid oxidation, all of which are closely associated with cellular lipid metabolism. Despite these advancements, the specific role of SIRT5 in regulating intramuscular fat (IMF) deposition in goats, as well as the underlying molecular mechanisms, remains largely unexplored. In this study, we cloned the complete coding sequence of the goat SIRT5 gene and, through amino acid sequence alignment, demonstrated its closest phylogenetic relationship with sheep. Additionally, we characterized the higher expression of SIRT5 during the differentiation of goat intramuscular precursor adipocytes. The silencing of SIRT5 by siRNA-mediated knockdown significantly upregulated the expression of lipogenesis-related genes and enhanced lipid deposition in goat intramuscular preadipocytes. Concurrently, SIRT5 deficiency led to the inhibition of cell proliferation and a marked reduction in apoptosis. Interestingly, although overexpression of SIRT5 promoted cell proliferation, it did not significantly alter lipid deposition in goat intramuscular precursor adipocytes. RNA sequencing (RNA-seq) analysis identified a total of 106 differentially expressed genes (DEGs) following SIRT5 silencing in goat preadipocytes, predominantly involved in the Focal adhesion, HIF-1, PI3K-Akt, and MAPK signaling pathways by KEGG pathway enrichment analysis. Notably, we successfully reversed the phenotypic effects observed in SIRT5 knockdown goat precursor adipocytes by inhibiting the PI3K-Akt and MAPK signaling pathways using the AKT inhibitor LY294002 and the p38 MAPK pathway inhibitor PD169316, respectively. In conclusion, our findings demonstrated that SIRT5 may modulate intramuscular fat deposition in goats through PI3k-Akt and MAPK signaling pathways. These results expand the gene regulatory network associated with IMF formation and provide a theoretical foundation for improving meat quality by targeting IMF deposition.

Background: Orthopedic surgery and the corresponding events (i.e., immobilization and muscle disuse) result in a cascade of biological events to promote healing but can come with the loss of skeletal muscle mass and strength. A good nutritional status of patients is associated with positive post-surgical outcomes, with macronutrients receiving the majority of emphasis in the research literature. However, beyond the surgical literature, there are other nutrients and nutritional supplements that have been established or postulated to improve skeletal muscle mass and strength. Objective: The purpose of this narrative review is to provide evidence for the utility of using creatine, vitamin D, omega-3 fatty acids, glutamine, essential amino acids-branched chain amino acids (EAA-BCAA) and beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the role they may play in minimizing muscle atrophy and strength loss following orthopedic surgery. The review will also highlight areas of future research to support a better understanding of the efficacy of supplementing with these substances pre- and/or post-surgery.

Blood flow restriction training (BFRT) is a tool utilized in rehabilitation and injury prevention to improve muscle strength and size, particularly in load-compromised individuals. BFRT facilitates gains in muscular strength and hypertrophy at lower loads, allowing for accelerated recovery and less disuse atrophy. BFRT must be applied appropriately and with caution, particularly in individuals with cardiovascular concerns. There are applications for BFRT across a wide spectrum of human performance training and in rehabilitation of both lower and upper extremity conditions, providing a high-quality adjunct to improve muscle strength, power, and endurance.

Level V, expert opinion.

Peripheral nerve injury is common clinically and can lead to neuronal degeneration and atrophy and fibrosis of the target muscle. The molecular mechanisms of muscle atrophy induced by denervation are complex and not fully understood. Inflammation and oxidative stress play an important triggering role in denervated muscle atrophy. Astragaloside IV (ASIV), a monomeric compound purified from astragalus membranaceus, has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effect of ASIV on denervated muscle atrophy and its molecular mechanism, so as to provide a new potential therapeutic target for the prevention and treatment of denervated muscle atrophy. In this study, an ICR mouse model of muscle atrophy was generated through sciatic nerve dissection. We found that ASIV significantly inhibited the reduction of tibialis anterior muscle mass and muscle fiber cross-sectional area in denervated mice, reducing ROS and oxidative stress-related protein levels. Furthermore, ASIV inhibits the increase in inflammation-associated proteins and infiltration of inflammatory cells, protecting the denervated microvessels in skeletal muscle. We also found that ASIV reduced the expression levels of MAFbx, MuRF1 and FoxO3a, while decreasing the expression levels of autophagy-related proteins, it inhibited the activation of ubiquitin-proteasome and autophagy-lysosome hydrolysis systems and the slow-to-fast myofiber shift. Our results show that ASIV inhibits oxidative stress and inflammatory responses in skeletal muscle due to denervation, inhibits mitophagy and proteolysis, improves microvascular circulation and reverses the transition of muscle fiber types; Therefore, the process of skeletal muscle atrophy caused by denervation can be effectively delayed.

Gaping is a recently described condition that affects the Pectoralis minor (tender) muscle of broiler chickens, characterized by post-mortem separation of myofiber that leads to meat depreciation and economic losses. In this study, we aimed at understanding prevalence, morphological features, and transcriptomics signatures of this poorly understood myopathy. Between July 2022 and January 2023, a total of 5,180 chicken tenders were collected from 32 flocks across two plants in the USA, handling light (2.7 kg) and heavy (4.1 kg) birds. The prevalence of moderate and severe gaping was 24.8 % and 53.7 %, respectively. The light bird plant had a lower prevalence of moderate gaping (P < 0.001), while the heavy bird plant had a lower prevalence of severe gaping (P < 0.001). Spaghetti meat prevalence from 8,000 fillets was 46.9 % for moderate and 8.3 % for severe cases, with no significant inter-plant differences. Use of peracetic acid treatment at the poultry plants significantly increased the prevalence of severe gaping. Physical and histological features, along with gene expression, were evaluated in 120 samples representative of three gaping severity tiers. Severely gaped tenders showed greater width compared to normal and moderately gaped tenders in both light and heavy birds (P < 0.05). An increase of 1 cm in tender width was associated with a 1.99-fold increase in the odds of classification into a more severe gaping category (95 % CI: 1.15 - 3.46). Affected muscles revealed histological evidence of myodegeneration, inflammation, and lipidosis with fibrosis. For one-unit increase in the myodegeneration score, samples had a 1.75-fold increase in the odds of being classified into a more severe gaping category (95 % CI: 1.37 - 2.23). Gene expression analysis using droplet digital PCR showed differential expression of 19 genes involved in oxidative stress response, cellular signaling, muscle development, and collagen formation between weight groups and myopathy categories. Notably, 21 out of 22 differentially expressed genes showed higher expression in light birds. This study provides the comprehensive description of gaping in broiler chickens and lays a crucial benchmark for assessment of future mitigating strategies.

Weddell seal (Leptonychotes weddellii) females lose substantial body mass across an intensive, nutritionally restricted lactation period and then must rapidly recover mass during the short Antarctic summer. In this study, we examined endocrine dynamics associated with mass loss across lactation and subsequent realimentation in Weddell seals, comparing patterns between seals that recently gave birth and demographically similar non-reproductive females (skip females) in McMurdo Sound, Antarctica. Postpartum seals near weaning (∼35 days postpartum, n = 64) and skip females (n = 32) were handled during early austral summer (November/December) and rehandled in late summer (January/February). Body mass, body composition (% lipid), and a suite of metabolic hormones (growth hormone (GH), insulin-like growth factor (IGF)-I, cortisol, total thyroxine (tT4), free thyroxine (fT4), and total triiodothyronine (tT3) and IGF binding protein (IGFBP)-2 and -3) were measured. Postpartum seals gained mass after weaning (0.98 ± 0.56 kg·day-1 (mean ± SD)), primarily as lean tissue rather than lipid, while their serum concentrations of tT4 and fT4, IGF-I, and cortisol increased. Their circulating GH and IGFBP-2 concentrations decreased and correlated negatively with mass. Skip females had greater body masses and lipid stores than postpartum seals at the end of the lactation period in early summer, but they lost mass (-1.03 ± 0.35 kg·day-1) and lipid stores over summer while their serum cortisol concentrations increased. Overall, body mass and composition of postpartum and skip females converged across summer. This convergence, likely driven in large part by contrasting endocrine profiles between the groups, may allow female Weddell seals to reach an advantageous seasonal body mass "set point" by onset of winter.

Skeletal muscle is the most abundant tissue in the human body and is responsible for movement, metabolism, energy production and longevity. Muscle atrophy is a frequent complication of several diseases and occurs when protein degradation exceeds protein synthesis. Genetics, ageing, nerve injury, weightlessness, cancer, chronic diseases, the accumulation of metabolic byproducts and other stimuli can lead to muscle atrophy. Muscular dystrophy is a neuromuscular disorder, part of which is caused by the deficiency of dystrophin protein and is mostly related to genetics. Muscle atrophy and muscular dystrophy are accompanied by dynamic changes in transcriptomic, translational and epigenetic regulation. Multiple signalling pathways, such as the transforming growth factor-β (TGF-β) signalling pathway, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, inflammatory signalling pathways, neuromechanical signalling pathways, endoplasmic reticulum stress and glucocorticoids signalling pathways, regulate muscle atrophy. A large number of long noncoding RNAs (lncRNAs) have been found to be abnormally expressed in atrophic muscles and dystrophic muscles and regulate the balance of muscle protein synthesis and degradation or dystrophin protein expression. These lncRNAs may serve as potential targets for treating muscle atrophy and muscular dystrophy. In this review, we summarized the known lncRNAs related to muscular dystrophy and muscle atrophy induced by denervation, ageing, weightlessness, cachexia and abnormal myogenesis, along with their molecular mechanisms. Finally, we explored the potential of using these lncRNAs as therapeutic targets for muscle atrophy and muscular dystrophy, including the methods of discovery and clinical application prospects for functional lncRNAs.

Type 2 diabetes is a chronic metabolic disorder characterised by insulin resistance and sustained hyperglycaemia, and is a major cause of blindness, kidney failure, heart attacks and stroke. Our team has recently identified hexosaminidase A (HEXA) as an endocrine factor secreted by the liver that regulates sphingolipid metabolism in skeletal muscle. Specifically, HEXA converts GM2 to GM3 gangliosides within cell-surface lipid rafts. Remodelling of ganglioside composition by HEXA enhances IGF1 signalling in skeletal muscle, increasing muscle glucose uptake and improving blood glucose control.

We produced a long-acting HEXA-FC fusion protein (murine HEXA and the fragment crystallisable [FC] region from IgG1) and evaluated the effects of chronic bi-weekly HEXA-FC administration (1 mg/kg body weight) on glycaemic control in C57BL/6 mice with diet-induced obesity and insulin resistance and the db/db mouse model of severe type 2 diabetes. Outcome measures included glucose and insulin tolerance, including a stable isotope-labelled GTT and assessment of tissue-specific glucose disposal, as well as proteomics analysis to define changes in skeletal muscle metabolism.

Chronic administration of a long-acting recombinant HEXA-FC fusion protein led to improvements in random blood glucose, fasting blood glucose and glucose tolerance, driven by increased glucose disposal into skeletal muscle, effects that were associated with enhancement of IGF1 signalling in muscle.

Given that skeletal muscle is a primary site of insulin resistance in individuals with type 2 diabetes, HEXA-FC protein therapy may open new avenues for therapeutic advancement in type 2 diabetes.

The aim of this review is to discuss and evaluate diabetic sarcopenia (DS) and its relationship with nutrition by discussing the mechanisms of diabetic sarcopenia in detail and comprehensively reviewing the literature.

Type 2 diabetes (T2DM) affects approximately 25% of people aged 50 years and over and indicates a significant the cost of health for the elderly. Nutrition is an important part of these treatment approaches, and in this review, the literature was comprehensively reviewed, focusing on understanding the mechanisms of DS and discussing its relationship with nutrition. A comprehensive search was conducted on Web of Science, Google Scholar, Scopus, Science Direct, and PubMed from inception up to July 2024. The aim of nutritional treatment for DS is to improve muscle mass, muscle strength and physical performance while improving diabetes-related metabolic risk and glucose levels. In this context, it is important to determine energy intake in individuals with DS according to calorie intake exceeding 30 kcal/kg. For these individuals, a protein intake of at least 1-1.2 g/kg/day is recommended, with an emphasis on the number and timing of meals and a nutritional pattern rich in branched chain amino acids (BCAA). In addition, it is important to adopt a diet rich in antioxidants and to choose diet patterns that contain sufficient levels of macro and micronutrients. The Mediterranean diet model can be a good diet option for individuals with DS. Comprehensive studies in this field are needed so that clinicians can make specific dietary recommendations for DS.

Medium cut-off (MCO) dialyzers are designed to provide clearance of large-middle molecular weight uremic toxins and cytokines that are also responsible for the pathogenesis of sarcopenia.

To investigate the short- and long-term effects of MCO dialyzers on fat and muscle mass.

This single-center prospective, cross-over study includes 20 maintenance hemodialysis (MHD) patients treated with low-flux (LF) dialyzers. Baseline parameters were measured under LF dialyzers and repeated at 2nd week and 6th month after switching to MCO dialyzers. Fat tissues were measured with a skinfold caliper and mid-upper arm circumference. Muscle thickness and strength parameters were measured with ultrasound and handgrip tests.

Median skinfold thickness showed a statistically significant increase in the second week of HD with MCO dialyzers [15 mm (10, 17) to 16 mm (13.3, 19.8), p = 0.04] and remained similar in the 6th month (p = 0.08). There was a gradual increase in median mid-upper arm circumference with a significant increase in the 6th month [28 (27, 29.5), 28.5 cm (27, 30), and 30.6 cm (26.7, 32), respectively, p = 0.03]. Significant increases were detected in the measurements of all four abdominal muscle groups (p = 0.03 for rectus abdominis and external oblique; p = 0.002 for internal oblique and transversus abdominis) in the 2nd week of MCO dialyzers and remained similar in the 6th month. Median RF and GCM thicknesses also significantly increased in the 2nd week (p = 0.001 and p < 0.001, respectively). The thicknesses of the external oblique, internal oblique, transversus abdominis, and rectus femoris muscles showed no significant differences in the 6th month. We also observed significant increases in the median GCM fibril length and GCM fibril pennation (p = 0.01 and p = 0.008, respectively) in the 2nd week, which also remained similar in the 6th month. The handgrip strength test showed a gradual increase at each time point without statistical significance.

MCO dialyzers provide increased fat and muscle mass, which might be due to their better clearance of uremic toxins compared to low-flux dialyzers. This study serves as a hypothesis-generating investigation; larger randomized controlled trials are required to validate the hypothesis.

Neurological disorders, marked by progressive neuronal degeneration, impair essential cognitive functions like memory and motor coordination… This manuscript explores the significant roles of glial cell line-derived neurotrophic factor (GDNF), its co-receptors (GFRA1), and the receptor tyrosine kinase (RET) in mediating neuronal survival and function in various neurodegenerative conditions. The interplay between pivotal signaling pathways-PI3K/AKT and ERK1/2-facilitated by GDNF/GFRA1/RET, is emphasized for its neuroprotective effects. Dysregulation of these pathways is implicated in neurodegenerative and neuropsychiatric processes, with overactivation of GSK3β contributing to neuronal damage and apoptosis. Experimental evidence supports that activation of the RET receptor by GDNF enhances AKT signaling, promoting cell survival by inhibiting apoptotic pathways-therapeutic strategies incorporating GDNF delivery and RET activation present promising neuronal protection and regeneration options. Furthermore, inhibition of GSK3β demonstrates potential in ameliorating tau-related pathologies, while small molecule RET agonists may enhance therapeutic efficacy. This review explores the knowledge of GDNF/GFRA1/RET and PI3K/AKT/ERK1/2 associated signaling cascades, underscoring their significance in neuroprotection and therapeutic targeting to combat neurodegenerative diseases. Emerging approaches such as gene therapy and small-molecule RET agonists may offer novel avenues for treatment, although challenges like targeted delivery across the blood-brain barrier remain pertinent.

Sarcopenia is a condition characterized by the loss of muscle fibers and excessive deposition of extracellular matrix proteins. The interplay between muscle atrophy and fibrosis is a central feature of sarcopenia. While the mechanisms underlying skeletal muscle aging and fibrosis remain incompletely understood, cellular senescence has emerged as a key contributor. This study investigates the role of D-galactose (D-gal) in inducing fibroblasts senescence and skeletal muscle fibrosis, and aims to find the key regulator of the process to serve as a therapeutical target.

To discover the role of D-gal in inducing cellular senescence and fibrosis, the senescence markers and the expression of fibrosis-related proteins were assessed after introducing D-gal among fibroblasts, and muscle strength and mass. The severity of muscle atrophy and fibrosis were also verified by using H&E staining and Masson trichrome staining after D-gal treatment via subcutaneous injection among mice. Subsequently, mRNA sequencing (RNA-seq) was performed and the differential expressed genes were identified between under D-gal or control treatment, to discover the key regulator of D-GAL-driven fibroblasts senescence and fibrosis. The role of the key regulator IGFBP5 were then validated in D-GAL treated IGFBP5-knockdown fibroblasts in vitro by analyzing the level of senescence and fibrosis-related markers. And the results were further confirmed in vivo in IGFBP5-knockdown SAMP8 mice with histological examinations.

D-gal treatment effectively induced cellular senescence and fibrosis in fibroblasts, as well as skeletal muscle atrophy, fibrosis and loss in muscle mass and function in mice. IGFBP5 was identified as a key regulator of D-GAL induced senescence and fibrosis among fibroblasts using RNA-seq. And further validation tests showed that IGFBP5-knockdown could alleviate D-GAL-induced fibroblast cellular senescence and fibrosis, as well as the severity of muscle atrophy and fibrosis in SAMP8 mice.

IGFBP5 emerging as a key regulator of D-GAL-induced fibroblast cellular senescence and fibrosis. The findings provide new insights into the molecular mechanisms underlying age-related skeletal muscle fibrosis and highlight IGFBP5 as a potential therapeutic target. Further research is needed to validate these findings and explore related clinical applications.

Circular RNAs (circRNAs) are post-transcriptional regulators generated from backsplicing of pre-mRNAs of host genes. A major circRNA regulatory mechanism involves microRNA (miRNA) sequestering, relieving miRNA-blocked mRNAs for translation and functions. To investigate possible circRNA-host gene relationship, skeletal myogenesis is chosen as a study model for its developmental importance and for readily available muscle tissues from farm animals for studies at different myogenic stages. This review aims to provide an integrated interpretations on methodologies, regulatory mechanisms and possible host gene-circRNA synergistic functional relationships in skeletal myogenesis, focusing on myoblast differentiation and proliferation, core drivers of muscle formation in myogenesis, while other myogenic processes that play supportive roles in the structure, maintenance and function of muscle tissues are also briefly discussed. On literature review,thirty-two circRNAs derived from thirty-one host genes involved in various myogenic stages are identified; twenty-two (68.6 %) of these circRNAs regulate myogenesis by sequestering miRNAs to engage PI3K/AKT and other signaling pathways while four (12.5 %) are translated into proteins for functions. In circRNA-host gene relationship,ten (32.3 %) host genes are shown to regulate myogenesis,nine (29.0 %) are specific to skeletal muscle functions,and twelve (38.8 %) are linked to skeletal muscle disorders.Our analysis of skeletal myogenesis suggests that circRNAs and host genes act synergistically to regulate cellular functions. Such circRNA-host gene functional synergism may also be found in other major cellular processes. CircRNAs may have evolved later than miRNAs to counteract the suppressive effects of miRNAs and to augment host gene functions to further fine-tune gene regulation.

The functionality of probiotics is highly influenced by culture and processing conditions, making batch stability validation through human or mouse trials impractical. Here, we employed a comprehensive approach using Caenorhabditis elegans, mouse and human models to elucidate the beneficial effects of Lactiplantibacillus plantarum TWK10 (TWK10). In C. elegans, TWK10 administration significantly prolonged lifespan by 26.1 ± 11.9 % (p < 0.05), enhanced locomotion (p < 0.01) and muscle mass (p < 0.001), elevated glycogen storage (p < 0.05), and reduced lipid accumulation (p < 0.001), outperforming Lacticaseibacillus rhamnosus GG and L. plantarum type strain ATCC 14917T. We also confirmed the equivalence of laboratory-prepared and mass-produced TWK10 in ergogenic efficacy using C. elegans assay. In mice, oral administration of mass-produced TWK10 significantly enhanced exercise performance and glycogen storage in muscle and liver in a dose-dependent manner. In a clinical study involving healthy male adults, significant improvements in grip strength (1.1-fold, p < 0.01) and exhaustion time (1.27-fold, p < 0.01), and significant reductions in circulating lactate and ammonia levels were observed in the TWK10 group (1 × 1010 colony-forming unit/day) compared to the control group. Both humans and mice receiving mass-produced TWK10 showed improved body composition with increased muscle mass and reduced fat mass. In conclusion, TWK10 demonstrates superior longevous and ergogenic effects in C. elegans compared to reference strains. The consistent ergogenic efficacy of mass-produced TWK10 across C. elegans, mice, and humans, highlights the utility of C. elegans as a reliable model for probiotic research and industrial application.

Chemotherapy remains a central component of breast cancer treatment, significantly improving patient survival rates. However, its toxic side effects, along with cancer-related paraneoplastic syndromes, can lead to the loss of skeletal muscle mass and function, impairing physical abilities and increasing the risk of complications during treatment. Chemotherapeutic agents directly impact skeletal muscle cells by promoting protein degradation, inhibiting protein synthesis, and triggering systemic inflammation, all of which contribute to muscle atrophy. Additionally, these drugs can interfere with the proliferation and differentiation of stem cells, such as satellite cells, disrupting muscle regeneration and repair while inducing abnormal differentiation of intermuscular tissue, thereby worsening muscle wasting. These effects not only reduce the effectiveness of chemotherapy but also negatively affect patients' quality of life and disease prognosis. Recent studies have emphasized the role of exercise as an effective non-pharmacological strategy for preventing muscle loss and preserving muscle mass in cancer patients. This review examines the clinical manifestations of muscle dysfunction following breast cancer chemotherapy, the potential mechanisms underlying these changes, and the evidence supporting exercise as a therapeutic approach for improving muscle function.

Androgen is widely acknowledged to regulate skeletal muscle mass. However, the specific mechanism driving muscle atrophy resulting from androgen deficiency remains elusive. Systemic androgen receptor knockout (ARKO) mice exhibit reduction in both muscle strength and muscle mass while skeletal muscle fiber specific ARKO mice have decreased muscle strength without affecting skeletal muscle mass in the limbs. Therefore, androgens may indirectly regulate skeletal muscle mass through effects on non-myofibers. Considering this, our investigation focused on blood fluid factors that might play a role in the regulation of skeletal muscle mass under the influence of androgens. Using a male mouse model of sham, orchidectomy and DHT replacement, mass spectrometry for serum samples of each group identified epidermal growth factor receptor (EGFR) as a candidate protein involving the regulation of skeletal muscle mass affected by androgens. Egfr expression in both liver and epididymal white adipose tissue correlated with androgen levels. Furthermore, Egfr expression in these tissues was predominantly elevated in male compared to female mice. Interestingly, male mice exhibited significantly elevated serum EGFR concentrations compared to their female counterparts, suggesting a connection with androgen levels. Treatment of EGFR to C2C12 cells promoted phosphorylation of AKT and its downstream S6K, and enhanced the protein synthesis in vitro. Furthermore, the administration of EGFR to female mice revealed a potential role in promoting an increase in skeletal muscle mass. These findings collectively enhance our understanding of the complex interplay among androgens, EGFR, and the regulation of skeletal muscle mass.

Feeding frequency represents a potential strategy to improve the utilization of protein sources by fish. This study investigated its impact on the utilization of protein blend in gibel carp. The dietary fishmeal was totally substituted with three protein blends consisting of Tenebrio molitor meal, Chlorella meal, Clostridium autoethanogenum protein, cottonseed protein concentrate, at ratios of 1:1:8:2, 1:1:6:4, and 1:1:4:6, respectively. During an 8-week feeding trial, a total of 960 healthy fish (18.10 g) were randomly assigned to eight groups, each with three replicates. Then they were fed either twice daily (two meals per day) or four times daily (four meals per day) with four different diets. Higher feeding frequency increased feed intake and intestinal trypsin activity (P < 0.05), and up-regulated the expression levels of genes related to amino acid or peptide transporter (pept1, y + lat2) and sensory receptors (casr, gprc6a, mglur4) in intestine (P < 0.05). Moreover, it accelerated muscle protein turnover by increasing free amino acid content, aspartate aminotransferase activity and akt1 transcript levels (P < 0.05), ultimately promoting growth. However, higher feeding frequency reduced protein apparent digestibility and feed efficiency (P < 0.05). Dietary blended proteins elevated trypsin and chymotrypsin activities (P < 0.01). Notably, the adverse effects observed with blended proteins (ratio at 1:1:8:2) on total essential amino acid digestibility and muscle protein metabolism-related gene expression were mitigated with increased feeding frequency, thus alleviating growth inhibition. Furthermore, the blended proteins at a ratio of 1:1:6:4 increased protein apparent digestibility (P < 0.05), down-regulated mstn expression level (P < 0.05), and up-regulated expression levels of genes related to protein synthesis (akt1, mtor, s6k1, eif4b, eif4e; P < 0.05); thereby promoting protein utilization and muscle growth at four meals per day. Overall, feeding frequency interacted synergistically with blended proteins to influence growth and protein utilization in gibel carp, and a protein blend with a ratio of 1:1:6:4 was a superior alternative to fishmeal at both feeding frequencies. Future strategies aimed at replacing dietary fishmeal should consider the role of feeding frequency as a critical factor.

Traditional transcriptomic studies often overlook the complex heterogeneity of skeletal muscle, as they typically isolate RNA from mixed muscle fibre and cell populations, resulting in an averaged transcriptomic profile that obscures fibre type-specific differences. This study assessed the potential of the recently developed Xenium platform for high-resolution spatial transcriptomic analysis of human skeletal muscle histological sections. Human vastus lateralis muscle samples from two individuals were analysed using the Xenium platform and Human Multi-Tissue and Cancer Panel targeting 377 genes complemented by staining of successive sections for Myosin Heavy Chain isoforms to differentiate between type 1 and type 2 muscle fibres. Manual segmentation of muscle fibres allowed accurate comparisons of transcript densities across fibre types and subcellular regions, overcoming limitations in the platform's automated segmentation. The analysis revealed higher transcript density in type 1 fibres, particularly in nuclear and perinuclear areas, and identified 191 out of 377 genes with differential expression between muscle fibres and perimysium. Genes such as PROX1, S100A1, LGR5, ACTA2, and LPL exhibited higher expression in type 1 fibres, whereas PEBP4, CAVIN1, GATM, and PVALB in type 2 fibres. We demonstrated that the Xenium platform is capable of high-resolution spatial in situ transcriptomic analysis of skeletal muscle histological sections. This study demonstrates that, with manual segmentation, the Xenium platform effectively performs fibre type-specific transcriptomic analysis, providing new insights into skeletal muscle biology.

Low vitamin D status is associated with either low muscle mass or impaired muscle function in dialysis patients. However, there is no consensus on how best to correct hypovitaminosis D, defined as serum 25-hydroxyvitamin D level <30 ng/mL, in patients with end-stage kidney disease (ESKD). This study investigated the effect of different vitamin D supplementation regimens on sarcopenia outcomes in dialysis patients.

This was a prospective randomized controlled trial. ESKD patients treated with maintenance hemodialysis (HD) or peritoneal dialysis with low vitamin D status on a ratio of 1:1, were randomized to either receive oral ergocalciferol utilizing a severity-dependent treatment protocol for low vitamin D status suggested by the Kidney Disease Outcomes Quality Initiative as a control group or a fixed-dose regimen of 20,000 international units/week. The changes in muscle mass were measured by bioimpedance spectroscopy, muscle strength was assessed by a hand grip dynamometer, physical performance was determined by gait speed, and muscle-related biomarkers were examined.

A total of 76 dialysis patients were randomized (HD = 43.4%). Baseline characteristics, including age, dialysis vintage, and muscle parameters were similar. After supplementation, the average serum 25-hydroxyvitamin D levels in the severity-dependent and fixed-dose groups were significantly elevated from 14.5 ± 7.3 to 27.2 ± 13.2 ng/mL, P < .001 and from 15.1 ± 6.4 to 28.8 ± 11.5 ng/mL, P < .001, respectively, and did not differ between groups at 6 months (P = .60). Despite comparable energy and protein intake, the mean bioimpedance spectroscopy-derived total body muscle mass normalized to height squared was significantly increased at 6 months in the fixed-dose group (14.5 ± 3.3 to 15.3 ± 3.0 kg/m2, P = .03) compared with the severity-dependent protocol (13.5 ± 2.7 to 13.7 ± 2.9 kg/m2, P = .58). In the subgroup analysis, muscle mass improvement was statistically elevated in peritoneal dialysis patients (P = .01) while unaltered among HD patients (P = .88) in the fixed-dose group. Muscle strength, gait speed, and serum insulin-like growth factor-1 level, as the mediators of muscle cell growth, were not different between the two groups at 6 months (P > .05). Neither hypercalcemia nor hyperphosphatemia was found throughout the study.

A fixed-dose ergocalciferol supplementation demonstrates similar performance in the correction of low vitamin D status but better muscle mass improvement than a severity-dependent protocol among ESKD patients. Regular dosing intervals of weekly vitamin D supplementation appear to be a promising treatment for sarcopenia among patients undergoing dialysis.

Cancer cachexia (CC) is characterized by significant skeletal muscle wasting, and contributes to diminished quality of life, while being associated with poorer response to treatment and with reduced survival. Chronic inflammation plays a central role in driving CC progression, within a complex interplay favoring catabolism. Although cachexia cannot be fully reversed by conventional nutritional support, nutritional intervention shows promise for the prevention and treatment of the syndrome. Of special interest are nutrients with antioxidant and anti-inflammatory potential and those that activate pathways involved in muscle mass synthesis and/or in the inhibition of muscle wasting. Extensive research has been carried out on novel nutritional supplements' power to mitigate CC impact, while the mechanisms through which some nutrients or bioactive compounds exert beneficial effects on muscle mass are still not totally clear. Here, we discuss the most studied supplements and nutritional strategies for dealing with muscle loss in CC.

Skeletal muscle exhibits remarkable plasticity in response to diverse stimuli, with exercise serving as a potent trigger. Varied exercise modalities, including moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), induce distinct structural and functional adaptations on skeletal muscle. However, the underlying molecular mechanisms governing these adaptations remain poorly understood. In this study, we utilized RNA-seq to characterize the transcriptomic profile of murine gastrocnemius muscle following 8-week treadmill-based MICT (M group) and HIIT (H group). A total of 1052 DEGs were screened in H vs. M. Among the top 10 significant DEGs, Foxo1 and Myod1 are closely related to muscular physiology. Through KEGG pathway analysis, distinct adaptations were primarily identified in the FoxO, MAPK, and PI3K-AKT pathways. By analyzing the expression of myokines, a significantly higher Igf-1 expression level was observed in the M group compared to the H group. Therefore, IGF-1, a well-known upstream regulator of both the PI3K-AKT-FoxO and MAPK pathways, might drive distinct muscle adaptations through variations in Igf-1 expression induced by these two exercise modalities.

Skeletal muscle atrophy is a major comorbidity associated with chronic obstructive pulmonary disease caused by exposure to cigarette smoke (CS). CS-activated macrophages and pyroptosis play an important role in skeletal muscle atrophy, but its specific molecular mechanism remains unclear. This study investigated the role and mechanisms of pyroptosis and activated macrophages in CS-induced skeletal muscle atrophy.

In the in vivo model, mice were exposed to either CS or air for 24 weeks, and in the in vitro model, C2C12 murine skeletal muscle cells were co-cultured with macrophages in Transwell chambers. Western blotting, real-time PCR, ELISA, and other methods were used to detect pyroptosis-related markers to investigate the mechanism of CSE-activated macrophages on skeletal muscle atrophy and pyroptosis.

In vivo, CS-induced atrophy of the mouse gastrocnemius muscle was accompanied by increased expression of pyroptosis-related markers, including NLRP3 inflammasome, cleaved Caspase-1, the GSDMD N-terminal domain, and interleukin (IL)-18. In vitro, CS extract (CSE)-activated macrophages mediates pyroptosis of skeletal muscle cells and induces myotube atrophy. Further studies demonstrated that macrophage-derived TNF-α is the initiating factor of skeletal muscle pyroptosis, and this process appears to be mediated through TNF-α activating the TNFR1/NLRP3/caspase-1/GSDMD signaling pathway.

TNF-α released by CSE-activated macrophages can promote skeletal muscle pyroptosis by activating the TNFR1/NLRP3/Caspase-1/GSDMD signaling pathway, which likely contributes to skeletal muscle atrophy. These findings provide more insight into the mechanisms underlying skeletal muscle atrophy in COPD.

Background/Objectives: Our previous study demonstrated that 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) administration improved grip strength and reduced blood urea nitrogen levels, but its underlying mechanisms remain unclear. This study aimed to investigate the effects of HMPA on oxidative stress and muscle fiber composition, emphasizing its potential role in modulating redox signaling pathways and influencing muscle development. Methods: Eight-week-old male C57BL/6 mice were orally administered HMPA solution (50 or 500 mg/kg/day) or distilled water (10 mL/kg) for 14 days, and then divided into sedentary and exhaustive exercise groups to evaluate oxidative stress status, myosin heavy chain (MHC) isoform expression, and underlying mechanisms. Results: Both low and high doses of HMPA reduced oxidative stress by decreasing plasma reactive oxygen metabolites. High-dose HMPA reduced plasma nitrite/nitrate levels and enhanced antioxidant capacity post-exercise, accompanied by changes in the mRNA abundance of antioxidant enzymes (e.g., Sod1 and Nqo1) and reductions in the mRNA abundance of nitric oxide synthases (e.g., Nos2 and Nos3) in the soleus. Additionally, high-dose HMPA administration increased the protein expression of MYH4 in the soleus, while low-dose HMPA enhanced the gene expression of Myh4 and Igf1, suggesting that HMPA may promote fast-twitch fiber hypertrophy through the activation of the IGF-1 pathway. Furthermore, low-dose HMPA significantly increased the gene expression of Sirt1 and Nrf1, as well as AMPK phosphorylation post-exercise, suggesting low-dose HMPA may improve mitochondrial biogenesis and exercise adaptation. Conclusions: These findings suggest that HMPA may serve as a dietary supplement to regulate redox balance, enhance antioxidant defenses, and promote the formation of fast-twitch fibers.