Search Results (5,973)

Background/Objectives: The external validity of sarcopenia screening questionnaires in the elderly has been examined in several conditions but rarely evaluated in patients with rheumatoid arthritis (RA). This study aimed to determine the performance of five Thai versions of sarcopenia screening questionnaires (SARC-F [Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls], SARC-CalF [SARC-F plus calf circumference], MSRA [Mini Sarcopenia Risk Assessment]-7, MSRA-5, and modified MSRA-5 questionnaires) in Thai RA patients, and evaluate the correlations among these instruments. Methods: In this cross-sectional study, consecutive adult RA patients (aged ≥20 years) from an outpatient rheumatology clinic completed the five sarcopenia screening questionnaires listed above. Sarcopenia was defined according to criteria of the 2019 Asian Working Group for Sarcopenia (AWGS). Appendicular skeletal muscle mass, grip strength, and physical performance were assessed using bioelectrical impedance analysis, a hand dynamometer, and a 6 m gait speed test, respectively. The cut-off values used for each sarcopenia screening questionnaire were pre-specified according to their respective established thresholds. Results: Of 299 RA patients (89.0% female, mean age of 61.3 ± 11.6 years, median [interquartile range] disease duration of 12.8 [8.2, 20.0] years), 37.5% and 27.4% of them had sarcopenia and severe sarcopenia, respectively. The areas under the receiver operating characteristic (ROC) curve for the SARC-F, SARC-CalF, MSRA-7, MSRA-5, and modified MSRA-5 questionnaires were 0.60, 0.74, 0.65, 0.62, and 0.65, respectively, with sensitivities of 34.8%, 73.2%, 77.7%, 68.8%, and 72.3% and specificities of 84.5%, 75.4%, 51.3%, 55.1%, and 58.3%, respectively. SARC-F demonstrated moderate correlations with the other questionnaires: SARC-CalF (r = 0.57), MSRA-7 (r = −0.52), MSRA-5 (r = −0.55), and modified MSRA-5 (r = −0.65), all with a p-value of <0.001. Conclusions: Sarcopenia is common among Thai RA patients. SARC-CalF had the best balance of sensitivity and specificity and is likely the most suitable sarcopenia screening questionnaire for Thai RA patients. Full article

Background and Objectives: Cancer cachexia is a debilitating metabolic syndrome highly prevalent in colorectal cancer (CRC), characterized by progressive skeletal muscle wasting. The myostatin–FOXO signaling pathway contributes to this process by activating the E3 ubiquitin ligases MuRF-1 and Atrogin-1. Exercise is a promising non-pharmacological strategy, but its effects on this pathway in CRC cachexia remain unclear. This review aimed to synthesize preclinical evidence on the impact of exercise on the myostatin–FOXO axis. Materials and Methods: A comprehensive search was performed in PubMed/MEDLINE, Scopus, Web of Science, and Science Direct from inception through August 2025. Eligible studies included murine CRC models (C26 or Apc^Min/+) exposed to aerobic, resistance, or combined exercise interventions, with outcomes assessing myostatin, FOXO, MuRF-1, or Atrogin-1. Study quality was appraised using the CAMARADES 10-item checklist. Results: eleven studies met the criteria, with quality scores ranging from 6 to 8. Aerobic exercise, particularly voluntary wheel running, most consistently reduced MuRF-1 expression and systemic inflammation, whereas resistance and eccentric training exerted stronger inhibitory effects on FOXO and Atrogin-1. Myostatin was directly measured in two studies, yielding inconsistent results. Resistance and eccentric training promoted anabolic signaling (e.g., mTORC1), whereas aerobic protocols improved oxidative capacity. Variability in exercise type, intensity, and duration contributed to heterogeneity across findings. Conclusions: Exercise attenuates skeletal muscle catabolism in CRC-induced cachexia, mainly through modulation of the myostatin–FOXO pathway and downstream ligases. However, limited direct data on myostatin and methodological heterogeneity underscore the need for standardized protocols and translational studies. This review provides the first focused synthesis of exercise-mediated regulation of this pathway in CRC cachexia. Full article

Cancer progression in skeletal muscle (SkM) is very rare, and mechanisms remain unclear. This study assessed the potential of SkM (myocyte)-derived EVs (C2C12-EVs) as anti-cancer agents. Using murine in vitro models, we showed that following treatment with C2C12-EVs, lung carcinoma cells failed to colonise SkM cells, and that C2C12-EVs selectively exerted apoptosis on cancer cells. Uptake of C2C12-EVs by carcinoma cells caused changes in lysosomal function and mitochondrial membrane properties inducing cell death with elevated caspase 3 and 9. The C2C12-EVs also inhibited cell proliferation, affecting cell cycle arrest at S phase and inhibited cell migration. Proteomic analysis of C2C12-EV cargoes highlighted functional enrichment pathways involved in lysozyme function, HIF-1 and PI3K-Akt signalling, regulation of actin cytoskeleton, pyruvate metabolism, platelet activation, and protein processing in ER. Decorin, a muscle cell-specific cytokine released from myocytes in response to stress, was significantly enriched in C2C12-EVs and may contribute to C2C12-EVs’ inhibitory activity on cancer cells. C2C12-EVs may suppress cancer and potentially be used as therapeutic agents for cancer metastasis. Full article

The C9ORF72 gene mutation is a major cause of amyotrophic lateral sclerosis (ALS). Disease mechanisms involve both loss of C9ORF72 protein function and toxic effects from hexanucleotide repeat expansions. Although its role in neurons and the immune system is well studied, the impact of C9ORF72 deficiency on skeletal muscle is not yet well understood, despite muscle involvement being a key feature in ALS pathology linked to this mutation. This study examined skeletal muscle from C9ORF72 knockout mice and found a 19.5% reduction in large muscle fibers and altered fiber composition. Ultrastructural analysis revealed mitochondrial abnormalities, including smaller size, pale matrix, and disorganized cristae. Molecular assessments showed increased expression of Atrogin-1, indicating elevated proteasomal degradation, and markers of enhanced autophagy, such as elevated LC3BII/LC3BI ratio, Beclin-1, and reduced p62. Mitochondrial quality control was impaired, with a 3.6-fold increase in PINK1, upregulation of TOM20, reduced Parkin, and decreased PGC-1α, suggesting disrupted mitophagy and mitochondrial biogenesis. These changes led to the accumulation of damaged mitochondria. Overall, the study demonstrates that C9ORF72 is critical for maintaining muscle protein and mitochondrial homeostasis. While C9orf72-haploinsufficiency does not directly compromise muscle strength in mice, it may increase the vulnerability of skeletal muscle in C9ORF72-associated ALS. Full article

Football requires repeated sprint ability for game-changing moments; however, the demand on the skeletal muscles is unknown. The aim of the current study was to determine the muscle oxygen response during duplicate sprints in professional footballers. Eight male professional footballers (age: 29 ± 5 y; height: 181 ± 8 cm; weight: 78 ± 8 kg) were recruited. Participants wore their normal GPS unit and completed their normal match warm-up before near-infrared monitors were attached to the rectus femoris and bicep femoris muscles. Participants then completed two 30 m sprints with 10 s of recovery, while GPS data and muscle oxygenation were recorded. Max speed was unaltered across the two sprints (s1: 8.4 ± 0.3 m.s⁻¹; s2: 8.4 ± 0.4 m.s⁻¹), but max acceleration (s1: 5.0 ± 1.5 m.s⁻²; s2: 3.7 ± 1.2 m.s⁻²) and time to max acceleration (s1: 1.0 ± 0.3 s; s2: 1.8 ± 0.8 s) were significantly different in sprint 2 compared with sprint 1. Change in muscle oxygenation was greater in the bicep femoris muscle than in the rectus femoris muscle in sprint 1 (right BF: 37.0 ± 14.7%; right RF: 23.4 ± 14.8%). Time to fast delay was longer in sprint 2 than in sprint 1 in the bicep femoris muscle (right BFs1: 1.6 ± 1.2 s; right BFs2: 5.2 ± 2.3 s), reflecting different recovery kinetics in the two muscles. During duplicate sprints there is a difference in oxygen response between the two muscles, and the overall recovery of the bicep femoris is much slower. This suggests poorer conditioning of the bicep femoris muscle, which may impact injury risk in professional football players. Full article

To clarify the relationship between muscle development and meat quality in Ziwuling black goats, this study used the longissimus dorsi muscle of 6-month-old and 12-month-old goats as samples. With HE staining, fast–slow myofiber immunofluorescence double staining, and transcriptome sequencing, this study analyzed muscle structure, myofiber type transformation, and molecular regulation. Results showed that 6-month-olds had higher myofiber density and smaller diameter; 12-month-olds showed myofiber hypertrophy (larger diameter); immunofluorescence revealed more fast-twitch myofibers (Type II) at 6 months and increased slow-twitch ones (Type I) at 12 months. Transcriptome sequencing identified 387 differentially expressed genes (DEGs: 156 upregulated, 231 downregulated). GO analysis indicated that DEGs are involved in skeletal muscle growth, cAMP biosynthesis, etc.; KEGG analysis showed enrichment in arginine–proline metabolism and AMPK/MAPK signaling pathways (AMPK regulates fatty acid metabolism genes like ACACB/CPT1A; arginine–proline metabolism relates to muscle maturation). WGCNA clustered genes into nine modules (MEblue correlated with myofiber density/MAPK; MEgreen correlated negatively with diameter but positively with density, involving PPARGC1A/AMPK). In conclusion, protein nutrition at 6 months (promote myofiber proliferation) and regulating energy intake at 12 months (improve meat quality) are recommended, and 12 months is the optimal slaughter age. Full article

Glycolytic potential (GP) is an important index for evaluating meat quality in the pig industry, since high muscle glycogen content generally leads to rapid postmortem glycolysis, which contributes to low meat quality. The natural differences in meat quality between Chinese local pigs (good meat quality) and Western pigs (standard meat quality) make them the ideal models for glycolysis research. Here, we investigated the mechanisms of glycolysis through comparing transcriptome and metabolome data of biceps femoris (BF) muscle between Jinhua (JH) and Landrace × Yorkshire (LY) pigs at different ages. In this research, JH pigs exhibited lower intramuscular glycogen content than LY pigs throughout the growth period (p < 0.05). Increased phosphorylated glycogen synthase (p-GS) expression indicated reduced glycogenesis capacity in JH pigs. Pathway enrichment revealed that the differentially expressed genes (DEGs) were highly enriched in glycolysis, glycogenesis, and TCA cycle pathways, but these metabolic pathways were suppressed in JH pigs. Metabolomic analysis identified increased lipids and amino acids, but carbohydrate metabolites were decreased in JH pigs. Through integrating transcriptome and metabolome data, VASH1 was identified as a biomarker of muscle glycolysis. Mechanistically, VASH1 knockdown promoted glucose metabolism through enhancing glycolysis and glycogenesis via the AMPK signaling pathway. Our findings provided novel insights into the genetic basis of meat quality and identify VASH1 as a potential target for genetic selection to improve muscle glycolytic level and pork quality. Full article

Duchenne muscular dystrophy (DMD), which results from mutations that disrupt the expression of dystrophin proteins, is characterized by progressive muscle fiber wasting and the development of skeletal muscle fibrosis. The severe pathology leads to loss of ambulation, respiratory insufficiency, cardiomyopathy, and early death in patients. Dystrophin-focused therapies based on adeno-associated viral (AAV) vector-mediated gene addition, antisense oligonucleotide-induced repair of the transcript reading frame, and chemically driven stop codon readthrough have been conditionally approved for use in subsets of patients. From trials, it is apparent that these therapies act to stabilize the disease phenotype rather than improve it significantly, meaning that early treatment results in better outcomes. AAV-mediated delivery of a form of utrophin, a structural and functional homolog of dystrophin, GALGT2, a sarcolemmal stabilizer, and Klotho, the anti-aging hormone that is silenced in a mouse model of DMD as a result of the disease pathology, have been explored in preclinical compensatory gene addition studies. Recombinant follistatin protein has been used to target the fibrosis seen. An all-in-one type of therapy is likely to provide a synergistic effect such that efficacy of the dystrophin restoration strategy would be improved. For this, CRISPRa could hold potential through the targeting of multiple relevant genes simultaneously. The suitability of targeting these genes will be discussed, as will the stages of the development of CRISPRa for DMD. A perspective on the future prospects of CRISPRa in relation to likely issues that would need addressing and how they may be overcame will be given. Full article

Disuse-induced muscle atrophy (DMA), commonly resulting from immobilization, is driven by chronic inflammation and oxidative stress, which disrupts the balance between protein synthesis and degradation. Quinic acid (QA), a natural compound with known antioxidant and anti-inflammatory properties, was investigated for its potential to counteract muscle atrophy. Using a DMA-induced immobilization model in male C57BL/6N (8 weeks) mice, we found that oral QA administration significantly restored the weight and cross-sectional area of atrophic muscles and improved muscle function, as measured by grip strength and treadmill performance. QA also reduced the expression of pro-inflammatory cytokines (Tnf, Il6, and Myostatin) and E3 ubiquitin ligases (Trim63 and Fbxo32), while increasing antioxidant enzyme levels and serum IL-15 in DMA. In tumor necrosis factor-α-stimulated L6 myotubes, QA reversed inflammation- and oxidative stress-induced gene changes, suppressed NF-ĸB activation, and downregulated protein degradation pathways mediated by FoxO3α. Furthermore, QA restored the expression of myogenesis-related genes and reactivated PI3K/Akt and mTOR/p70S6K/4EBP1 signaling pathways, enhancing protein synthesis. Collectively, our findings demonstrate that QA mitigates immobilization-induced muscle atrophy by modulating inflammation, oxidative stress, and key anabolic and catabolic signaling pathways. These results suggest that QA is a promising functional compound for preserving skeletal muscle health under conditions of disuse. Full article

Cancer survivors (CS) constitute an expanding population with underrecognized cardiometabolic risk. Despite substantial improvements in five-year survival rates, both childhood and adult survivors remain at high risk for premature morbidity and mortality. These risks are particularly pronounced following exposure to anthracyclines and/or chest radiotherapy, typically in a dose-dependent manner. In Chile, the establishment of the National Pediatric Antineoplastic Drug Program (PINDA) in 1998 marked a milestone in improving equitable access to high-quality pediatric oncology care through evidence-based treatment protocols across the public health system; the adult counterpart (PANDA) has developed diagnostic, treatment, and monitoring protocols for hematological neoplasms. Few prospective cohort or mechanistic studies have clarified risk stratification or surveillance strategies in survivor populations. The regulated, short-term activation of inflammation and innate immunity can be an adaptive and protective response to tissue injury, whereas persistent low-grade inflammation may trigger neutrophil extracellular traps formation (NETosis) and other maladaptive pathways that accelerate endothelial injury, thrombosis, and adverse cardiovascular remodeling. NETosis represents a putative immunomodulatory target for therapeutic immunomodulation in heart failure and maladaptive left ventricular remodeling in preclinical models. Concurrently, skeletal muscle-derived and hormonal mediators known as exerkines—together with increased NET activity—may modulate the pathophysiology of chronic cardiometabolic disease and contribute to cancer progression, particularly in the context of obesity, diabetes, and insulin resistance. Structured exercise is a promising non-pharmacological intervention that modulates inflammatory and metabolic pathways and may thereby help prevent non-communicable diseases, including cancer. We synthesize basic and clinical evidence to (1) define how cancer therapies promote low-grade inflammation and NETosis; (2) describe how exerkines and structured exercise influence cardiometabolic biology; and (3) evaluate exercise as a mechanistic and clinically pragmatic strategy to reduce long-term CVD risk in pediatric and adult CS. Full article

Cisplatin (CIS) is a widely used chemotherapeutic agent known for its efficacy; however, it induces several adverse effects, most notably cachexia, which is characterized by progressive loss of skeletal muscle mass, weakness, and reduced body weight. N-acetylcysteine (NAC) a compound with antioxidants properties, has been shown to mitigate CIS-induced neurotoxicity in experimental models. This study aimed to investigate the myoprotective effects of NAC during CIS treatment and explore the redox and molecular mechanisms involved in this response. For this, female Wistar rats were divided into four experimental groups: Control, NAC (300 mg/day/8 days), CIS (3 mg/kg i.p for 5 days), and NAC + CIS (NAC for 8 days, with CIS administered from day 4 onward). After treatment, muscle strength, redox status, mitochondrial biogenesis, expression of myogenic microRNAs and morphological changes were evaluated. CIS treatment caused muscle atrophy, decreased GSH/GSSG ratio, impaired cellular function, increased lipid peroxidation and altered antioxidant enzymes activity. These effects were mitigated by NAC coadministration. CIS also reduced the mtDNA/nDNA ratio; however, NAC treatment tended to increase TFAM and PGC-1α expression levels. Furthermore, CIS suppressed the expression of muscular miR-1-3p, miR-133a-3p and miR-206-3p, while NAC restored their levels when co-administered with CIS. These findings suggest that NAC may serve as a promising adjuvant therapeutic strategy to counteract CIS-induced myotoxicity through redox regulation and modulation of molecular pathways related to muscle integrity and regeneration. Full article

Objective: Obesity increases the risk of endometrial cancer (EC). In this study, we aimed to investigate the prognostic effect of sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, calculated with the help of cross-sectional imaging methods of muscle and visceral adipose tissue from body composition parameters, in EC. Methods: Patients diagnosed with EC were identified between January 2014 and June 2024. The combination of radiological markers and patient outcomes can predict prognosis. The skeletal muscle index (SMI) and visceral fat index (VFI) were calculated from computed tomography (CT) and/or abdominal magnetic resonance (MR) scans taken at the time of diagnosis at the Lumbal 3 (L3) vertebra level. The findings of these analyses demonstrate the strongest correlation with the ratio of muscle and visceral fat tissue throughout the body. The loss of muscle and fat is an unfavourable indicator in patients with EC. The present study analysed the prognostic values of sarcopenia, sarcopenic obesity, sarcopenic visceral obesity, and the visceral fat index in EC. The total skeletal muscle area was calculated in square centimetres. Body surface area (m²) was calculated using the Mosteller formula: ((height (cm) × weight (kg))/3600)^1/2. To normalize body composition components, the skeletal muscle index was calculated as cm²/m². Results: The study comprised a total of 236 EC patients. The prevalence of sarcopenia, sarcopenic obesity, and sarcopenic visceral obesity were found to be 48.31%, 33.47%, and 22.88%, respectively. The presence of sarcopenia, high VFI levels, sarcopenic obesity, and sarcopenic visceral obesity did not demonstrate statistical significance in the survival analysis. However, stage increase (p = 0.001), primary tumour localization in the lower uterine segment (p = 0.001), serous carcinoma (p = 0.001), increased grade in endometrioid carcinoma (p = 0.023), and lymphovascular invasion (p = 0.001) were significantly associated with increased mortality risk. The presence of sarcopenia was found to be significant in patients with obesity (p = 0.008) and those aged ≥ 65 years (p = 0.001). Conclusions: In EC survival, established prognostic factors such as serous histopathology, LVI positivity, and the extent of surgical staging are prioritised. The presence of these well-established markers means the potential effect of BMI-based observations, such as the ‘obesity paradox’, and even body composition measurements, such as sarcopenic obesity, are now statistically insignificant. Our findings suggest that aggressive tumour biology (serous type, LVI) and surgery, rather than metabolic variables such as sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, are the direct reason for the survival difference. This is due to the tumour’s aggressive nature and clinical characteristics (e.g., age at diagnosis, operability, stage, primary tumour localization in the lower uterine segment, serous carcinoma, grade, and LVI positivity) rather than metabolic variables. Full article

Background: Sex estimation is a basic step of human identification in both legal cases and archeological contexts. The highest accuracy for sex estimation is achieved when a complete skeleton is available, though there are situations, such as cremated, dismembered, and otherwise taphonomically altered skeletal remains, where a complete skeleton is not available. The aim of the present preliminary study was to evaluate the usefulness of four non-metric skull traits that are considered taphonomically resilient for sex estimation and their potential application in forensic cases. Methods: Non-metric skull traits of 100 skulls from the Bass Donated Skeletal Collection were analyzed. These traits included foramen magnum shape, zygomatic arch extension with respect to the external auditory canal, sigmoid notch, and gonial angle muscle attachment. A discriminant function analysis model was used to develop specific formulae for sex estimation. Results: The foramen magnum and sigmoid notch showed no significant differences between males and females. The zygomatic arch extension (ZAE) and gonial angle morphology (GO) showed strong, significant differences between the sexes. However, gonial angle morphology has shown to be affected by edentulism. Based on the ZAE, the function obtained by the discriminant function analysis was sex = 2.469*ZAE − 1.247, with a result of zero pointing to males and result of one pointing to females, which correctly classified 79.8% of the original cases. Conclusions: This study highlights the value of four different skull traits and their potential use in forensic cases. Of all the evaluated traits, zygomatic arch extension was the best indicator for sex estimation. This anatomical region corresponds to a highly resistant skeletal structure. Full article

Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disease caused by a CTG repeat expansion in the DMPK gene. The toxic mutant mRNA sequesters MBNL proteins, disrupting global RNA metabolism. Although alternative splicing in DM1 skeletal muscle pathology has been extensively studied, early-stage transcriptomic changes remained uncharacterized. To gain deeper and contextual insight into DM1 transcriptome, we performed the first Weighted Gene Co-expression Network Analysis (WGCNA) on skeletal muscle RNA sequencing data from the widely used DM1 mouse model HSA^LR (~250 CTG repeats). We identified 532 core genes using data from 16-week-old mice, an age before the onset of muscle weakness. Additional differential expression analysis across multiple HSA^LR datasets revealed 42 common up-regulated coding and non-coding genes. Within identified core genes, the pathway gene-pair signature analysis enabled contextual selection of functionally related genes involved in maintaining proteostasis, including endoplasmic reticulum (ER) protein processing, the ubiquitin-proteasome system (UPS), macroautophagy and mitophagy, and muscle contraction. The enrichment of ER protein processing with prevailing core genes related to ER-associated degradation suggests adaptive chaperone and UPS activation, while core genes such as Ambra1, Mfn2, and Usp30 indicate adaptations in mitochondrial quality control. Coordinated early alterations in processes maintaining protein homeostasis, critical for muscle mass and function, possibly reflect a response to cellular stress due to repeat expansion and appears before muscle weakness development. Although the study relies exclusively on transcriptomic analyses, it offers a comprehensive, hypothesis-generating perspective that pinpoints candidate pathways, preceding muscle weakness, for future mechanistic validation. Full article

Background: FDA-approved artificial sweeteners (ASs) are widely used in food products due to their low-calorie content and high sweetness. However, growing evidence links them to adverse metabolic effects, including stroke and coronary heart disease. The musculoskeletal system, as a key metabolic target organ, has gradually gained attention, but the potential impact of ASs on its health remains unclear. Objective: This systematic review aims to assess the effects of ASs on bone and muscle, explore the underlying biological mechanisms and provide guidance for future research. Methods: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science using relevant keywords from inception to 25 June 2025. Studies written in English, available in full text, and investigating FDA-approved ASs in relation to the musculoskeletal system were included. Two independent reviewers screened and selected the eligible studies. The findings were summarized using a narrative synthesis approach. Results: A total of 15 studies (12 preclinical, 3 clinical), covering aspartame, acesulfame potassium, sucralose, and saccharin were included from an initial pool of 662 articles identified across PubMed (168), Embase (368), and Web of Science (126). Among them, twelve studies focused on skeletal effects, four on muscles, and two on joints; three studies reported multiple outcomes. No studies investigated ligaments or tendons. Conclusions: Based on our search, this review provides a narrative synthesis of the available evidence on ASs influencing skeletal structure, development, biomechanical strength, and skeletal muscle metabolism. Potential mechanisms involve gut microbiota, oxidative stress, and signaling pathways such as SIRT1/FOXO3a and PGC-1α/UCP3. Further research is warranted to clarify these mechanisms and to assess the chronic health effects of long-term AS exposure on the musculoskeletal system in human populations. Full article