Muscles

This study compared elbow flexor hypertrophy and maximal strength adaptations after eight weeks of resistance training performed either to momentary muscular failure or with 1–3 repetitions in reserve (RIR). Nineteen resistance-trained adults completed a unilateral within-participant protocol in which one arm trained to failure and the contralateral arm trained with 1–3 RIR. Participants trained twice weekly using the unilateral preacher curl exercise at 70–80% one-repetition maximum (1RM). Elbow flexor muscle thickness and 1RM strength were assessed before and after the intervention. Bayesian mixed-effects models estimated between-condition differences. Both protocols increased muscle thickness and 1RM strength. The estimated between-condition differences for muscle thickness were 0.032 cm (95% highest density interval [HDI]: −0.044 to 0.113) while the estimated difference in 1RM strength was 0.588 kg (85% HDI: −0.491 to 1.66), with both 95% HDIs spanning zero and including values favoring either protocol. Sex-specific analyses showed the same general patter of responses. Overall, resistance training performed with 1–3 RIR produces similar elbow flexor hypertrophy and maximal strength adaptations to training performed to momentary muscular failures under the loading and volume conditions examined. Full article

Primary dystrophin deficiency, caused by X-chromosome mutations within the DMD gene, encompasses a continuous clinical spectrum of neurological, muscular, and cardiac disorders known as dystrophinopathies that exhibit profound phenotypic variability driven by specific mutation profiles and epigenetic factors. This comprehensive review analyzes the clinical and molecular characteristics of seven primary classifications: Duchenne muscular dystrophy (DMD), a severe childhood myopathy caused by a complete absence of the protein that leads to loss of ambulation and fatal cardiorespiratory failure in youth; Becker muscular dystrophy (BMD), a milder variant with partial protein deficiency that preserves walking capabilities into adulthood and prolongs life expectancy; pseudometabolic dystrophinopathic syndrome, featuring exercise intolerance, cramps, and recurrent rhabdomyolysis that mimics metabolic diseases; asymptomatic dystrophinopathy, representing the mild end of the spectrum identified incidentally through chronically elevated creatine kinase levels; brain dystrophin-related syndrome, where the disruption of distal isoforms like Dp140 and Dp71 results in neurodevelopmental and neuropsychiatric comorbidities such as ADHD, autism, and intellectual disability; X-linked dilated cardiomyopathy (XLDCM), a cardiac-selective condition causing severe heart failure and arrhythmias while sparing skeletal muscle function; and female dystrophin-related syndrome, distinguishing between familial carriers—who can manifest symptoms due to skewed X-chromosome inactivation—and rare sporadic females who develop an exceptional, severe, Duchenne-like phenotype due to cytogenetic accidents such as Turner syndrome or chromosomal translocations. Ultimately, advancements in molecular testing (NGS and WGS) have significantly optimized diagnostic precision, proving essential for implementing early cardioprotective care, accurate genetic counseling, and the development of future tissue-specific targeted gene therapies. The present study also discusses the psychosocial impact that the disease has on patients. Full article

Charcot–Marie–Tooth (CMT) is a rare, genetic, slowly progressive disorder that affects nerve conduction, particularly in the limbs and, therefore, the muscles. Phenotypes vary, but the impact on quality of life is always present. CMT1A is the most prevalent type. There is no pharmacological cure, so physiotherapy is essential, but nutritional and exercise aspects are rarely considered. In this case report, we demonstrate how, even in this condition, effective results can be achieved with strength training if properly supervised, coordinated with physiotherapy, and combined with an appropriate nutritional plan. Full article

Myostatin (GDF8) is a member of the transforming growth factor-β (TGF-β) superfamily. Myostatin gene mutations or inhibition of the Myostatin/Activin pathway results in increased skeletal muscle mass, demonstrating its role as a negative regulator of skeletal muscle. Myostatin blockade is a promising strategy for increasing muscle mass in myopathies such as Duchenne Muscular Dystrophy (DMD); however, it faces considerable challenges in clinical translation, in part due to the progressive nature of the disease. Here we tested the ability of JA16 monoclonal antibody-mediated myostatin blockade to improve the dystrophic phenotype in newborn mdx mice (an animal model of DMD). Myostatin inhibition led to significant increases in muscle size, fiber number and cross-sectional area along with increased absolute force alongside reduced post-eccentric contraction force drop and reduced serum creatine kinase. We used the Multiparametric Muscle Improvement Score (MMIS) to objectively quantitate benefits in this preclinical study and determined that the magnitude of improvements exceeded those reported using the exact same intervention in older mdx mice treated for the same duration. This study demonstrates an age-dependent aspect of this intervention and suggests that earlier interventions may provide greater therapeutic benefits. Full article

Background: Pathogenic variants in the DMD gene are a frequently overlooked cause of dilated cardiomyopathy (DCM) in idiopathic cases, especially when skeletal myopathy is mild or seemingly absent. Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy are at opposite ends of this clinical spectrum but result from pathogenic variants in the same gene. Cardiomyopathy is a major cause of premature death in muscular dystrophies. Case presentation: We describe a 37-year-old man who underwent orthotopic heart transplantation for presumed idiopathic DCM with refractory heart failure. He had a six-year history of progressive proximal weakness, pseudohypertrophy of the calf, a positive Gowers sign, and markedly elevated creatine kinase (6638 IU/L). Multiplex ligation-dependent probe amplification (MLPA) revealed an in-frame deletion of exons 45–47 of DMD [c. (6438+1_6439-1)_(6912+1_6913-1) del; NM_004006.2], confirming BMD. Immunofluorescence showed reduced and patchy dystrophin expression. Conclusions: To our knowledge, this is the first documented heart transplant in a patient with BMD in Mexico. This case demonstrates the value of considering muscular dystrophy in the differential diagnosis of apparently idiopathic dilated cardiomyopathy (DCM), a step that opens the door to accurate diagnosis, carrier screening, and genetic counseling, and supports the view that heart transplantation is a viable option in carefully selected patients with muscular dystrophy cardiomyopathy. Full article

Background: Sports-related musculoskeletal injuries, including tendon, ligament, muscle, and cartilage damage, often heal slowly and incompletely. Current treatments may not fully restore tissue function, necessitating regenerative therapies. Objective: This study was conducted to review the therapeutic potential of stem cell-derived extracellular vesicles (EVs) and conditioned medium (CM) as cell-free approaches to treating musculoskeletal injuries in sports medicine. Methods: A narrative review of preclinical and early clinical studies investigating the biological mechanisms and regenerative effects of mesenchymal stem/stromal cell (MSC)-derived EVs and CMs published between 2019 and 2026 was performed by searching Scopus, PubMed, Web of Science, and Google scholar. Results: EVs and CMs contain bioactive molecules, including microRNAs, cytokines, and growth factors, that modulate inflammation, promote tissue repair, enhance angiogenesis, and support extracellular matrix remodeling. Preclinical studies demonstrate improved healing of tendons, ligaments, muscles, and cartilage, while early clinical evidence suggests favorable safety and promising therapeutic outcomes. However, the variety of MSC sources, EV separation methods, characterization procedures, and treatment protocols present major challenges in determining the reliability and therapeutic efficacy of these therapies. Notably, the number of clinical studies on EV and CMs is still limited, and most of the available studies are in vitro studies. Conclusions: MSC-derived EVs and CMs represent promising cell-free regenerative therapies for sports-related musculoskeletal injuries. The available evidence, which demonstrates their ability to enhance healing while avoiding the challenges associated with cell-based therapies, highlights their translational potential. However, most of the studies that are now available are preclinical or early-stage clinical studies, and there is still a limited number of clinical trials. Further well-designed clinical studies are needed to establish standardized protocols and confirm long-term safety. Full article

Skeletal muscle dysfunction and exercise intolerance are major extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), yet their severity is not fully predicted by pulmonary impairment. This narrative review examines extracellular vesicles (EVs) as candidate mediators of lung–muscle communication within a broader network of inflammatory, metabolic, vascular, nutritional, and inactivity-related mechanisms. The evidence is asymmetrical. COPD provides direct human skeletal muscle evidence for quadriceps microRNA dysregulation, impaired protein synthesis and mitochondrial function, oxidative stress, and abnormalities of the regenerative microvascular niche; however, none of these observations demonstrates delivery of pathogenic cargo from the lung by EVs. In IPF, EV-mediated epithelial–mesenchymal signalling, fibroblast activation, and profibrotic remodelling are well supported within the lung, whereas skeletal muscle effects remain indirect. Accordingly, the lung–muscle EV axis should be viewed as a biologically plausible, evidence-weighted hypothesis rather than an established causal pathway. Progress will require experiments that identify the cellular source of EVs, trace their vascular transit and skeletal muscle uptake, and demonstrate functional cargo transfer using EV-depletion, rescue, and integrated muscle readouts. Conventional size and morphology measurements do not reliably distinguish muscle- from lung-derived EVs; source discrimination currently depends more on molecular cargo and cell-associated markers. Hypoxia and transient or sustained oxygen desaturation may modify EV release and cargo through HIF- and redox-sensitive signalling, but disease-specific evidence connecting these changes to lung-to-muscle transfer in COPD or IPF remains limited. Full article

Background: Skeletal muscle index (SMI, kg/m²) derived from bioelectrical impedance analysis (BIA) is widely used to assess muscle mass. However, SMI is influenced by extracellular fluid, potentially leading to inaccurate estimation in patients with fluid imbalance. Intracellular water normalized by height squared (ICW/height², L/m²) may reflect intracellular body cell volume and provide complementary information to BIA-derived SMI, particularly in patients with altered hydration or low nutritional reserve. Based on these considerations, we hypothesised that ICW/height² would demonstrate stronger correlations with BMI than SMI, that the SMI–ICW/height² correlation would differ significantly by sex, and that hydration status (ECW/TBW) would modulate this relationship. Objective: To compare ICW/height² with SMI and evaluate their relationships with nutritional status and hydration in hospitalized patients. Specifically, we tested the hypotheses that (1) ICW/height² correlates more strongly with BMI than SMI; (2) the SMI–ICW/height² correlation differs significantly between sexes; and (3) ECW/TBW and sex interact to modulate the SMI–ICW/height² relationship. Methods: This single-centre, retrospective, exploratory cross-sectional study included 477 hospitalized patients (232 men and 245 women) who underwent body composition assessment using BIA. SMI and ICW/height² were examined in relation to body mass index (BMI) and hydration status assessed by extracellular water to total body water ratio (ECW/TBW). Correlation analyses were performed overall and stratified by sex, BMI categories (<18.5, 18.5–24.9, ≥25 kg/m²), and ECW/TBW groups (<0.36, 0.36–0.40, >0.40). Results: ICW/height² showed a stronger correlation with BMI than SMI in both men (R² = 0.492 vs. 0.338) and women (R² = 0.354 vs. 0.121). A strong correlation between SMI and ICW/height² was observed in men (R² = 0.634), whereas the correlation was weaker in women (R² = 0.316). In BMI-stratified analyses, the correlation between SMI and ICW/height² increased with higher BMI in men (R² = 0.192, 0.467, 0.791), while in women it was markedly attenuated in the low BMI group (R² = 0.134). Stratification by ECW/TBW showed that in men, the correlation remained strong under normal hydration conditions but was attenuated in the high ECW/TBW group. In contrast, in women, the correlation was weak even within the normal ECW/TBW range (R² = 0.336) and particularly poor in the low ECW/TBW group (R² = 0.060). Among women with normal ECW/TBW, those with low BMI demonstrated clear discordance between SMI and ICW/height². Exploratory four-quadrant classification using sex-specific SMI and ICW/height² thresholds further demonstrated that patients with discordant SMI and ICW/height² values had distinct BMI profiles, and BMI differed significantly among the four groups in both men and women (Kruskal–Wallis test, p < 0.001). Conclusions: These exploratory findings suggest that ICW/height² and BIA-derived SMI may show systematic discordance under specific clinical conditions, particularly in underweight or fluid-imbalanced hospitalised patients. Prospective validation against reference-standard body-composition measures is required before any clinical application. Full article

High-intensity exercise performance is a complex phenomenon that emerges from the interaction of neuromuscular, metabolic, molecular, and biomechanical systems. While previous research has primarily examined these factors independently, a comprehensive understanding requires an integrative perspective. Therefore, this narrative review aimed to synthesize current evidence and conceptualize high-intensity exercise performance as a complex adaptive system. The review examined the effects of different training modalities, including high-intensity interval training, sprint training, resistance training, plyometric training, and concurrent training, alongside neuromuscular regulation, molecular adaptations, fatigue mechanisms, and ergogenic aids. Evidence indicates that performance improvements result from coordinated interactions among training-induced adaptations, intracellular signaling pathways, and physiological responses. Furthermore, ergogenic aids such as caffeine, creatine, beta-alanine, and dietary nitrates may enhance performance when appropriately aligned with training demands. Overall, high-intensity exercise performance should be viewed as an emergent property of interconnected physiological systems rather than the product of isolated mechanisms. This systems-based framework provides a comprehensive perspective for understanding and optimizing athletic performance. Full article

Nutrient supplementation may enhance muscle growth by supporting myogenic activity and regulating metabolic pathways involved in skeletal muscle development. However, the effect of specific nutrient supplementation on satellite cell (SC) activity and muscle-related metabolic pathways remains unclear. Two experiments were conducted to investigate dietary supplements, including guanidinoacetic acid (GAA), 5-hydroxytryptophan (5-HTP), and quercetin, on SC proliferation and differentiation in vitro and on muscle growth and transcriptomics in vivo. For the in vitro study, ovine SC were cultured with different levels (0, 12.5, 25, and 50 μmol/L) of 5-HTP, GAA, or quercetin to examine SC proliferation and differentiation. SC proliferation was greater with 5-HTP and quercetin supplementation, whereas GAA increased SC differentiation. Based on these results, 5-HTP and GAA were selected for the in vivo study because they increased proliferation and differentiation, respectively, and had a wider range of dose effectiveness (12.5 and 25 μmol/L). For the in vivo study, Texel lambs (n = 15; 33 ± 6 kg) were blocked by weight and assigned to one of three treatments: control, GAA, or 5-HTP for 28 d. Supplements were administered sublingually at a dose of 2.5 mg/kg body weight daily before feeding. GAA or 5-HTP did not influence (p > 0.05) average daily gain or dry matter intake. Longissimus muscle area was greater (p < 0.05) at the end of the study compared to the start for all treatment groups. mRNA sequencing showed that GAA supplementation altered gene expression (Padj < 0.05) compared to the control or 5-HTP. However, 5-HTP did not affect (p > 0.05) gene expression compared to the control. LC-MS also showed that plasma 5-hydroxyindoleacetic acid (5-HIAA) was elevated (p < 0.05) in the 5-HTP group. The results suggest that these dietary supplements can stimulate SC proliferation or differentiation in vitro. Short-term supplementation of GAA or 5-HTP in vivo did not alter growth performance, muscle mass, or miR-133a expression; however, GAA supplementation altered the transcriptome to promote amino acid metabolism pathways that are commonly linked to muscle growth through muscle protein synthesis and energy metabolism. Full article

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in primary sensory neurons and has been proposed as a therapeutic target for pain management. However, the effects of repeated administration of a TRPA1 antagonist on peripheral tissue morphology remain unclear. This study examined whether repeated HC-030031 administration affected the histomorphology of skeletal muscle fibers and muscle spindles in rats. Male Fischer 344 rats were assigned to a control group (Con, n = 10, 12.6 ± 3.3 weeks) or an HC-030031-treated group (HC, n = 10, 13.2 ± 3.7 weeks). HC-030031 was administered subcutaneously once weekly for four weeks. Tibialis anterior muscles were harvested and analyzed using histochemical and morphometric methods. Morphometric analyses included muscle mass, myofiber cross-sectional area (FCSA), roundness of extrafusal muscle fibers, NADH-TR staining intensity-based assessment, and structural parameters of muscle spindles and intrafusal fibers. No significant differences were observed between the groups in body weight, muscle mass, extrafusal FCSA, or fiber roundness. NADH-TR staining was used to distinguish fibers with darker or lighter staining intensity, and FCSA was compared between the Con and HC groups within each staining-based fiber subset. No group differences were detected in the FCSA of either subset. Similarly, no significant differences were observed in intrafusal FCSA, intrafusal fiber roundness, the number of intrafusal fibers per muscle spindle, or muscle spindle density. These findings indicate that repeated HC-030031 administration was not associated with detectable histomorphological alterations in skeletal muscle fibers or muscle spindles under resting conditions in young adult male rats. Full article

Understanding the direct relationship between skeletal muscle mass and strength in athletes is paramount for optimizing performance. Such a relationship has been poorly investigated in soccer players. In this work, a large number (n = 225) of elite soccer players aged 14–37 years had whole-body (WB) and regional skeletal muscle mass (SMM) estimated from Dual-energy X-ray absorptiometry (DXA) scans, together with maximal isokinetic strength of several muscle groups. Results showed a statistically significant (p < 0.001) correlation between limb SMM or muscle strength and body mass (r = 0.84–0.86; r = 0.61–0.97, respectively) and stature (r = 0.58–0.64; r = 0.61–0.93, respectively), whereas the relationship with age was much more variable. A statistically significant (p < 0.001) correlation was found between SMM and muscle strength across all muscle groups (r = 0.55–0.80). Linear regression showed that SMM explained 30% to 64% of the variance in muscle strength. ANOVA showed that playing position had a statistically significant effect (p < 0.001) on all SMM and muscle strength values. Playing position had a significant effect on relative (normalized per-limb SMM) muscle strength during knee and ankle flexion. This work showed that DXA-measured skeletal muscle mass is associated with the strength of several limb muscle groups in soccer players. This association is of variable strength across muscle groups and is partially modulated by playing position. Full article

Background: Given its practical advantages in terms of time efficiency, joint compatibility and extensive adaptability, whole-body electromyostimulation (WB-EMS) has gained considerable attention as a training method among athletes and sportspeople across numerous disciplines. The present systematic review and meta-analysis aimed to determine the impact of WB-EMS on maximum hip/lower-extremity strength and power. Methods: A systematic search of five literature databases was carried out up to 30 March 2025 in accordance with the PRISMA scheme. Effect sizes (SMD) and 95–confidence intervals (95–CI) were derived using a random-effect model incorporating the inverse heterogeneity approach. Results: Nineteen WB-EMS and 21 control groups were included. Overall, we observed favorable effects of this novel training technology on maximum strength (18 trials, SMD: 0.62, 95–CI: 0.08 to 1.16, I² = 86%)) and power (8 trials, SMD: 0.38, 95–CI: 0.06 to 0.70, I² = 15%). Subgroup analyses examining superimposed WB-EMS relative to voluntary exercise alone yielded low to moderate, yet statistically non-significant, effects on maximum strength (12 trials, 0.44, −0.20 to 1.08, I² = 85%) and power (7 trials, 0.39, −0.02 to 0.81, I² = 35%). Studies addressing the comparison of superimposed or non-superimposed WB-EMS against traditional dynamic resistance exercise reported largely equivalent outcomes for both strength and power development. Conclusion: Contingent upon the mode of application (superimposed, additional or optional), WB-EMS may exert a positive influence on maximum strength and power in sportspeople and athletes. Full article

Accurate assessment of appendicular lean mass (ALM), an essential component for evaluating sarcopenia and nutritional status, typically requires dual-energy X-ray absorptiometry (DXA); however, its widespread clinical application is limited by cost and accessibility. This study aimed to develop a simple anthropometry-based equation for estimating ALM in women with systemic lupus erythematosus (SLE) and to compare its predictive performance with existing models. This cross-sectional study included 92 female patients with SLE. A multiple regression model was developed, incorporating height, body weight, calf circumference (CC), and age. Model performance was internally validated using five-fold cross-validation, and agreement with DXA-measured ALM was assessed using out-of-fold predictions. The diagnostic performance for detecting low skeletal muscle mass index (SMI) was also evaluated and compared with previously published equations (Hwang and Santos). The predicted ALM showed good correlation with measured ALM (R² = 0.76) and moderate agreement (Lin’s concordance correlation coefficient [CCC] = 0.829), with a root mean square error of 1.38 kg. Sensitivity and specificity for detecting low SMI were 65.0% and 88.9%, respectively. The proposed equation demonstrated comparable or superior performance (CCC: Hwang 0.782; Santos 0.672) and may serve as a practical tool for estimating ALM in female patients with SLE. Full article

Background: Physical exercise is strongly recommended for breast cancer survivors due to its beneficial effects on physical function, metabolic health, and quality of life. Lactate, traditionally considered a metabolic byproduct of glycolysis, is increasingly recognized as a signaling molecule involved in metabolic regulation and exercise adaptation. However, exercise-induced circulating lactate responses in breast cancer survivors remain poorly characterized. The aim of this systematic review and exploratory meta-analysis was to synthesize and critically appraise current evidence on exercise-induced circulating lactate responses in breast cancer survivors Methods: A systematic review and exploratory meta-analysis were conducted according to PRISMA guidelines and prospectively registered in PROSPERO (CRD42024504288). PubMed, Scopus, and Web of Science were searched to identify controlled trials investigating exercise-induced changes in circulating lactate concentrations in breast cancer survivors. Random-effects meta-analysis was performed using pooled mean differences. Results: Among 173 screened records, four studies met eligibility criteria for qualitative synthesis and three contributed to quantitative analysis. Pooled results demonstrated no statistically significant effect of exercise on circulating lactate concentrations (weighted mean difference: 0.03 mmol/L; 95% CI: −0.24 to 0.31; p = 0.81), with low heterogeneity (I² = 31.1%). Considerable variation was observed across exercise protocols, intervention duration, and lactate assessment timing. Conclusions: Exercise-induced circulating lactate responses in breast cancer survivors appear modest and inconsistently reported across available studies. Current evidence remains limited by small sample sizes and methodological heterogeneity. These findings provide a physiological overview of lactate responses to exercise in breast cancer survivorship and highlight the need for standardized exercise interventions and metabolic outcome assessment in future research. Full article

Congenital Myasthenic Syndrome represents a complex and heterogeneous group of inherited neuromuscular disorders, which result from variants in genes involved in different pathophysiological mechanisms related to the neuromuscular junction. LRP4 (Low-density lipoprotein receptor-related protein 4) represents one of the most important proteins involved in this complex signaling pathway, acting in a complex with agrin and Muscle Skeletal Receptor Tyrosine Kinase (MuSK) proteins. LRP4 became known to most neurologists due to the description of anti-LRP4 antibody-related Myasthenia Gravis. There are, however, different neurological and neuromuscular disorders that result from pathogenic variants in LRP4 gene, especially a rare and potentially treatable Congenital Myasthenic Syndrome. The authors performed a detailed narrative review, including descriptions of the main pathophysiological, clinical, and therapeutic aspects of LRP4-related Congenital Myasthenic Syndromes. Full article

Hip joint position sense (JPS), a key component of neuromuscular function arising from muscle spindle and periarticular mechanoreceptor input, remains underexplored, with no standardized and reliable clinical protocol available to assess hip proprioception. This study evaluated the intra- and inter-rater reliability of a laser- and inclinometer-based active hip JPS protocol and established preliminary references in healthy adults. A two-phase reliability study was conducted in accordance with GRRAS and COSMIN guidelines: 17 participants for reliability analyses and 57 for preliminary references. Six movement directions were assessed (flexion, extension, abduction, adduction, medial and lateral rotations). Reliability was quantified using intraclass correlation coefficients with their 95% confidence intervals, using two-way random-effects models with absolute agreement (ICC(3,1) for intra-rater and ICC(2,1) for inter-rater analyses), interpreted as poor (<0.50), moderate (0.50–0.70), or good (≥0.70). Absolute measurement error was reported as standard error of measurement (SEM%) and 95% minimal detectable change (MDC95%), normalized to target amplitudes to allow direct cross-direction comparison. Intra-rater reliability ranged from poor to moderate, with experienced raters reaching ICC = 0.64 (95% CI [0.39; 0.80]) for medial rotation. Inter-rater reliability improved across sessions, peaking for medial rotation (ICC = 0.78; 95% CI [0.50; 0.91]). Rotational movements yielded the lowest SEM% (3–6%), indicating high measurement precision despite trial-to-trial variability (MDC% 9–31%). Normative errors were largest in flexion (21.4 cm) and smallest in rotations (≈2.2–2.3°). Despite overall low-to-moderate reliability, the protocol achieved clinically acceptable measurement precision (SEM% < 10%) for rotational tasks, whereas the laser-based sagittal and frontal-plane components remained exploratory. The protocol provides preliminary reference values for hip JPS in healthy adults and requires further validation before clinical use. Full article

Micronutrients are essential for optimal muscle metabolic function. We previously showed that heat-induced skeletal muscle injury is associated with depletion of nicotinamide adenine dinucleotide (NAD⁺) and magnesium (Mg²⁺), and boosting NAD⁺ abundance with the precursor nicotinamide riboside (NR) improves skeletal muscle integrity against heat stress in male mice. In this study, we hypothesized that NR supplementation would prevent heat-induced skeletal muscle injury in female mice. Female 6-week-old C57BL/6J mice were orally administered vehicle or NR (185 mg/kg body weight) daily for 10 days. Subsequently, they underwent a single sham or heat exposure experiment. No significant differences in muscle NAD⁺ content were observed between vehicle and NR groups or between sham and heat groups. Heat groups showed significantly lower muscle Mg²⁺ levels compared to sham groups. In vehicle groups, heat exposure caused significant inflammation, oxidative stress, mitochondrial impairment, and apoptosis in skeletal muscle compared to the sham condition. NR treatment significantly reduced these alterations. While neither heat exposure nor NR affected muscle NAD⁺ homeostasis, the protective effects of NR on skeletal muscle against heat stress were similar to those observed in male mice. Together, our results demonstrate the preventive effect of NR on muscle heat injury in female mice. This effect is associated with anti-inflammatory and antioxidative activities, mitochondrial protection, and anti-apoptosis without NAD⁺ homeostatic alterations. Full article

The DMD gene is best known for its product dystrophin, a large rod-shaped protein that plays a critical role in muscular membrane strength and integrity. Mutations affecting dystrophin lead to Duchenne muscular dystrophy, a fatal X-linked disease characterized by muscular weakness and breakdown. In addition to the full-length dystrophin product that is most often associated with disease, the DMD gene also encodes multiple shorter isoforms of dystrophin with diverse functions. One isoform in particular, Dp71, has been increasingly found to play a wide variety of roles throughout the body. In this narrative review, we consolidate the numerous studies on Dp71 to provide a comprehensive foundation for future work. We outline and summarize the current state of knowledge on the role of Dp71 in the brain, the retina, and skeletal muscles, identifying current knowns and unknowns in the field. We also explore Dp71-based therapies currently being tested in the pre-clinical landscape and identify potential limitations for clinical translation. Full article