Search Results (67)

In skeletal muscle, there are two main progenitor populations crucial for growth, maintenance, and repair: satellite cells (SCs) and interstitial cells, of which fibro-adipogenic progenitor cells (FAPs) are the best characterized fraction. However, data on how specific diseases or physiological conditions affect the biological properties of FAPs are limited. In this review we analyze data obtained with FAPs purified from skeletal muscle tissue from Duchenne muscular dystrophy (both human patients and mdx mice models), hindlimb functional unloading (rats), and type 2 diabetes (T2DM, human patients). Here we discuss how disuse/disease affect FAP’s properties: the adaptive metabolic remodeling; the alterations in adipogenic differentiation in vitro; the possible role of particular subpopulations of FAPs in disease development; the role of FAPs in cell-to-cell interactions during skeletal muscle degeneration and regeneration. Current research has outlined how different physiological and pathological conditions alter FAPs’ behavior, highlighting FAPs as a potential target for clinical protocols aimed at treating or mitigating skeletal muscle disorders. Future studies should clarify how FAPs govern cell-to-cell interactions during skeletal muscle degeneration and regeneration, offering critical insights for therapies targeting diverse neuromuscular diseases. Full article

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in mammalian skeletal muscle development, moving beyond their initial characterization as transcriptional “noise”. Unlike previous reviews that focus primarily on individual IncRNA catalogues, this review systematically integrates recent advances across five dimensions: (1) molecular characteristics and multidimensional classification of muscle related lncRNAs; (2) stage-specific expression patterns spanning embryonic myogenesis, postnatal growth, adult maintenance, and regeneration; (3) underlying molecular mechanisms including chromatin remodeling, ceRNA networks, IncRNA protein interactions, and nucleocytoplasmic trafficking; (4) pathological implications in muscular dystrophy, atrophy, and neuromuscular diseases; (5) translational applications in precision animal breeding. We critically evaluate the controversial ceRNA hypothesis and highlight quantitative limitations in current evidence. By integrating existing knowledge into a multi-layer regulatory network model and addressing current technical challenges and controversies (e.g., the ceRNA stoichiometry debate), this review provides a comprehensive roadmap for future basic research and translational applications in muscle biology. Full article

Aging is characterized by progressive degeneration of neuromuscular junctions (NMJs), which significantly contributes to muscle weakness and the development of sarcopenia. Photobiomodulation (PBM), a non-invasive therapeutic method based on the use of low-intensity light, has shown promising results in mitigating muscle degeneration in both experimental and clinical studies. The aim of this study was to evaluate the ultrastructural effects of photobiomodulation on neuromuscular junctions and skeletal muscle fibers in the m. vastus lateralis muscle of aged rats using light and transmission electron microscopy. Male Wistar rats (18 months old, body weight 650–800 g, n = 10) were subjected to photobiomodulation of the right m. vastus lateralis muscle (650 nm, 6 J/cm², four consecutive daily sessions of 3 min each). The contralateral left limb served as an untreated control. Muscle samples were analyzed by light and transmission electron microscopy. Histological examination revealed typical age-related changes in control muscles, including variability in muscle fiber diameter, centrally located nuclei, and an increased volume of connective tissue. Ultrastructural analysis confirmed signs of skeletal muscle aging, such as myofibril fragmentation, sarcomere disorganization, lipofuscin accumulation, and tubular aggregate formation. Morphometric analysis of neuromuscular junctions after photobiomodulation showed an increase in the number of active zones on the presynaptic membrane, elongation of the postsynaptic membrane, and a reduction in the width of the synaptic cleft. In addition, mitochondrial hyperplasia was observed in presynaptic terminals, while the total number of synaptic vesicles decreased. These findings indicate a compensatory reorganization of neuromuscular junctions and suggest that photobiomodulation can enhance their functional activity in aged skeletal muscle. Full article

Sarcopenia is a progressive and multifactorial muscle disorder associated with diminished strength, reduced functional capacity, and increased risk of adverse health outcomes including frailty, falls, and mortality. Despite its clinical burden, the molecular pathogenesis of sarcopenia remains poorly understood, which hinders the development of precise therapeutic strategies. This review examines emerging evidence linking anabolic resistance, mitochondrial dysfunction, neuromuscular instability, and chronic inflammation to impaired regeneration and disrupted proteostasis. While nutritional interventions such as high-quality protein, leucine metabolites, and vitamin D supplementation preserve lean mass, they fail to consistently restore function independently. Although exercise remains the cornerstone therapy, its benefits are often constrained in patients with multimorbidity or reduced mobility. Given the biological heterogeneity of sarcopenia, there is a need to shift from generic supportive care to stratified, mechanism-based therapy. Emerging omics technologies including transcriptomic, proteomic, and metabolic profiling offer a promising avenue to define molecular endotypes. This will guide the development of precision-based management strategies. Full article

Orthobiologic treatments such as platelet-rich plasma and stem cell therapies are increasingly used to support the healing of tendons, ligaments, and joints. This perspective proposes applying periodization—a structured, progressive model borrowed from athletic training—to rehabilitation following orthobiologic interventions in order to improve functional outcomes. The framework is organized into sequential phases that align with biological stages of healing. Early phases emphasize pain control, inflammation management, and safe, controlled mobility. Rehabilitation then progresses toward gradually increasing load bearing and strength, and toward more specific exercises to promote tissue regeneration while reducing the risk of re-injury. In later phases (mesocycles), the model highlights the importance of neuroplastic adaptations for sustained functional recovery, including neurogenesis, synaptic plasticity, and functional remodeling to safer RTP for athletes. A key advantage of this approach is its adaptability: progression can be individualized according to a patient’s recovery trajectory and response to loading. By aligning rehabilitation progression with intrinsic healing processes and integrating physiological and neuromuscular goals, the proposed model aims to maximize regenerative potential across both athletic and non-athletic populations. Overall, this neuroplastic periodized approach offers a practical, evidence-informed structure to guide clinicians in delivering patient-centered regenerative rehabilitation and may help standardize care after orthobiologic procedures. Full article

Mutations in the Mitofusin 2 (MFN2) gene cause Charcot–Marie–Tooth type 2A (CMT2A). Neurotrophin 3 (NT-3) is an autocrine factor that supports Schwann cell survival and differentiation, axon regeneration and myelination, neuromuscular junction (NMJ) integrity, and mitochondrial function. In this study, we assessed the efficacy of NT-3 gene therapy using the AAVrh74 serotype in the Mfn2^+/− mouse model for CMT2A. Although haploinsufficiency is not reported in CMT2A patients, our model shows some features of CMT2A, including axonal atrophy, muscle atrophy, length-dependent axon loss, and abnormal mitochondria, in muscle in the enzyme histochemistry. Eight-month-old Mfn2^+/− mice received a 3 × 10¹¹ vector genome dose of AAVrh74.tMCK.NT-3 intramuscularly, and functional, electrophysiological, and histological outcomes were assessed six months post-treatment. NT-3 gene therapy in Mfn2^+/− mice significantly improved grip strength and rotarod performance, and ameliorated electrophysiological abnormalities and NMJ denervation in lumbrical muscles. Additionally, our therapeutic approach improved muscle histopathology with reductions in mitochondrial abnormalities and oxidative stress. NT-3 further remodeled carbohydrate metabolism in muscle. Our study indicated that AAV.NT-3 gene therapy has a disease-modifying effect in the Mfn2^+/− model of CMT2A, providing further support for the translational potential of this surrogate gene therapy approach to CMT2A patients. Full article

Neuromuscular junctions (NMJs) are highly specialized synapses that enable efficient communication between motor neurons and skeletal muscle fibers. Impaired formation or maintenance of NMJs is implicated in the pathogenesis of multiple neuromuscular disorders and contributes to age-related declines in skeletal muscle mass and strength. NMJ functionality is governed by complex regulatory crosstalk among different cells and is mediated by a diverse network of proteins. Moreover, immune cells often reside at NMJs and exhibit phenotypically different characteristics depending on the regenerative state of the muscle. These complex interfaces have posed a significant challenge for elucidating pathogenic mechanisms and developing biomarkers or effective targeted treatments. Many animal models have been developed to address this challenge by characterizing the fundamental structural features of neuromuscular junctions (NMJs) and their transmission capacity under both healthy and disease conditions. In contrast, studies of human NMJs remain limited, although emerging evidence is increasingly revealing substantial morphological and functional differences from animal NMJs. This review provides an overview of animal research on NMJs over the past decades, highlighting interspecies differences and key advances in our understanding of human NMJs. Full article

Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-β, and a growth-factor receptor—performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration. Full article

Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine. Full article

Skeletal muscle dysfunction is a major systemic manifestation of COPD that shapes symptoms, exercise tolerance and mortality. Current evidence can be integrated within a Damage–Regeneration–Remodeling framework linking mechanics and biology to clinical phenotypes. Pulmonary hyperinflation and chest wall geometry chronically load the diaphragm and other respiratory muscles in COPD, whereas inactivity and exacerbation-related disuse underload locomotor muscles. Across muscle compartments, oxidative/nitrosative stress, activation of proteolytic pathways, mitochondrial and endoplasmic reticulum stress, microvascular limitations, neuromuscular junction instability, and myosteatosis degrade muscle quality. The diaphragm adapts with a fast-to-slow fiber shift, greater oxidative capacity, and sarcomere foreshortening, improving endurance, whereas limb muscles show atrophy, a glycolytic shift, reduced oxidative enzymes, extracellular matrix accrual, and fat infiltration. Translational levers that address these mechanisms include: (I) Reduce damage: bronchodilation, lung-volume reduction, oxygen, non-invasive ventilation, early mobilization, pulmonary rehabilitation, neuromuscular stimulation, and corticosteroid stewardship; (II) Enable regeneration: progressive resistance plus high-intensity/heavy-load endurance training; adequate protein and vitamin-D intake, and endocrine correction; and (III) Steer remodeling: increase physical activity (with/without coaching/telecoaching), functional assessment and CT or MRI monitoring, inspiratory-muscle training, and phenotype-guided adjuncts in selected cases. This framework clarifies why lung deflation strategies benefit inspiratory mechanics, whereas limb recovery requires behavioral and metabolic interventions layered onto systemic optimization. Full article

Background/Objectives. Despite growing interest in capacitive-resistive electric transfer TECAR) and Vibration therapy (VT), their comparative effectiveness in sports recovery remains unclear. This study aimed to evaluate and contrast the short-term effects of TECAR and VT on neuromuscular recovery following eccentric muscle fatigue, relative to passive rest, in active young adults. We hypothesized that both interventions would accelerate recovery and potentially reduce injury risk. Methods. Forty-one participants were randomized into two groups: TECAR therapy (Group 1) and VT (Group 2). Neuromuscular function was assessed at baseline, post-exercise, and post-intervention using tensiomyography (TMG) and electromyography (EMG). Results. Both groups showed a significant increase in EMG MDF intercept after exercise. Post-intervention, VT induced a further rise in this parameter, whereas TECAR stabilized values without significant change. In the contralateral resting limb, increases persisted after exercise and passive recovery. Between-limb differences were significant only in the TECAR group. TMG analysis revealed a non-significant but large-effect increase in contraction delay (Td) post-exercise, followed by significant reductions after both interventions. In the left limb, Td changes were not significant. For maximal displacement (Dm), both VMO and VLO muscles demonstrated a significant decrease post-exercise and a marked recovery after both therapies. Other TMG parameters (Ts, Tc, Tr) showed no significant changes. Conclusions. Both TECAR and VT effectively enhanced neuromuscular recovery after eccentric exercise. TECAR demonstrated a modest but consistent advantage, particularly in normalizing muscle recruitment and restoring mechanical properties, making it suitable in contexts requiring rapid recovery. VT, however, remains a more accessible and cost-effective modality. These findings support the application of both techniques in sports recovery, while highlighting the need for further research in professional athletes and diverse exercise settings to optimize regeneration strategies and reduce injury risk. Full article

Background: Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody is a rare but critical complication usually triggered by statin use. However, the comprehensive characterization and long-term outcomes of anti-HMGCR-positive IMNM remain underexplored. This study aimed to examine the clinical characteristics, diagnostic challenges, treatment responses, and long-term outcomes of patients with anti-HMGCR-positive IMNM. Methods: A retrospective review was conducted at a single institution between 2019 and 2025 to analyze the data of patients diagnosed with anti-HMGCR-positive IMNM. Diagnoses were confirmed by detecting anti-HMGCR antibodies and meeting the criteria for IMNM of the European Neuromuscular Center. The analyzed data included demographics, clinical presentation, laboratory findings, imaging results, muscle biopsy characteristics, treatment regimens, and follow-up outcomes. Results: Ten patients (six women and four men) with a median age of 58 (range, 33–86) years were included. Nine patients had a history of statin use for a median duration of two years. The average diagnostic delay was 233 days after the onset of symptoms. The initial creatine kinase (CK) levels ranged from 1438 to over 13,000 IU/L. Muscle biopsies revealed necrosis and regeneration of muscle fibers. CK levels fluctuated and trended downward over 180 days post-treatment. Treatment included corticosteroids, methotrexate, azathioprine, tacrolimus, mycophenolate, intravenous immunoglobulin, and rituximab. Delayed treatment initiation from symptom onset was correlated with prolonged treatment time until the first remission. Conclusions: The prognosis of anti-HMGCR-positive IMNM is less favorable when treatment is delayed after symptom onset. Further research is warranted to identify poor prognostic markers and develop relevant treatments. Full article

Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits, we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 gene overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue in the closely related Pteronotus parnellii to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules—glucose utilization, lipid handling, and nutrient signaling—that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Full article

Background: Botulinum toxin type A (BoNT/A) is widely used in both clinical and aesthetic settings to induce temporary neuromuscular paralysis by inhibiting acetylcholine release. Although generally regarded as safe and effective, complications such as iatrogenic ptosis or facial asymmetry may occur and persist for several weeks or even months, with no standardized method currently available to accelerate recovery. Objective: This article explores the hypothesis that photobiomodulation (PBM)—a non-invasive modality recognized for its neuroregenerative potential—may facilitate the reversal of BoNT/A-induced neuromuscular blockade. Discussion: PBM enhances mitochondrial activity by stimulating cytochrome c oxidase in nerve and muscle tissues, thereby increasing ATP production and modulating intracellular signaling pathways associated with neuroplasticity, cell survival, and synaptogenesis. Preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects. While controlled clinical trials for this specific application are currently lacking, anecdotal clinical reports suggest that PBM may accelerate functional recovery in cases of BoNT/A-related complications. Conclusions: Although this approach has not yet been tested in clinical trials, we propose that photobiomodulation may hypothetically serve as a supportive strategy to promote neuromuscular recovery in patients experiencing adverse effects from BoNT/A. This hypothesis is grounded in robust preclinical evidence but requires validation through translational and clinical research. Full article

This paper proposes an adaptive human–robot concurrent control scheme that achieves the appropriate gait trajectory for a robotic leg prosthesis to improve the wearer’s comfort in various tasks. To accommodate different wearers, a neuromuscular-force-based impedance method was developed using muscle activation to reshape gait trajectory. To eliminate the use of sensors for torque measurement, a disturbance observer was established to estimate the interaction force between the human residual limb and the prosthetic receptacle. The cost function was combined with the interaction force and tracking errors of the joints. We aim to reduce the cost function by minimally changing the control weight of the gait trajectory generated by the Central Pattern Generator (CPG). The control scheme was primarily based on human-in-the-loop optimization to search for a suitable control weight to regenerate the appropriate gait trajectory. To handle the uncertainties and unknown coupling of the motors, an adaptive law was designed to estimate the unknown parameters of the system. Through a stability analysis, the control framework was verified by semi-globally uniformly ultimately bounded stability. Experimental results are discussed, and the effectiveness of the adaptive control framework is demonstrated. In Case 1, the mean error (MEAN) of the tracking performance was $3.6°$ and $3.3°$, respectively. And the minimized mean square errors (MSEs) of the tracking performance were $2.3°$ and $2.8°$, respectively. In Case 2, the mean error (MEAN) of the tracking performance is $2.7°$ and $3.1°$, respectively. And the minimized mean square errors (MSEs) of the tracking performance are $1.8°$ and $2.4°$, respectively. In Case 3, the mean errors (MEANs) of the tracking performance for subject1 and 2 are $2.4°$, $2.9°$, $3.4°$, and $2.2°$, $2.8°$, $3.1°$, respectively. The minimized mean square errors (MSEs) of the tracking performance for subject1 and 2 were $1.6°$, $2.3°$, $2.6°$, and $1.3°$, $1.7°$, $2.2°$, respectively. Full article