Journal Description
Muscles
Muscles
is an international, peer-reviewed, open access journal on muscle biology and physiology published quarterly online by MDPI. The Korean Society of Physical Medicine (KSPM) is affiliated with Muscles and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), Scopus, PubMed, PMC, Embase, and other databases.
- Journal Rank: CiteScore - Q2 (General Medicine)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 35.8 days after submission; acceptance to publication is undertaken in 5.6 days (median values for papers published in this journal in the first half of 2026).
- Recognition of Reviewers: Reviewers whose reports are timely and of high quality receive an APC discount voucher for a future publication in an MDPI journal. Become a reviewer.
Impact Factor:
1.6 (2025);
5-Year Impact Factor:
1.5 (2025)
subject
Imprint Information
Open Access
ISSN: 2813-0413
Latest Articles
Congenital Clubfoot as an Early Manifestation of Duchenne Muscular Dystrophy?
Muscles 2026, 5(3), 68; https://doi.org/10.3390/muscles5030068 (registering DOI) - 19 Sep 2026
Abstract
Background: Duchenne muscular dystrophy (DMD) is the most common X-linked progressive neuromuscular disorder of childhood. The classic course of DMD is characterized by onset after a period of normal motor development. However, in recent years, evidence has been accumulating of prodromal features of
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Background: Duchenne muscular dystrophy (DMD) is the most common X-linked progressive neuromuscular disorder of childhood. The classic course of DMD is characterized by onset after a period of normal motor development. However, in recent years, evidence has been accumulating of prodromal features of the disease, including speech delays and neurocognitive impairments. Methods: This study investigates whether congenital bilateral clubfoot may represent the first clinical manifestation of DMD. Results: We present two cases of male patients with congenital bilateral clubfoot who were subsequently diagnosed with DMD. We demonstrate the high efficacy and safety of the Ponseti method for correcting foot deformities in these patients. We discuss a possible pathogenic link between dystrophin deficiency and impaired intrauterine myogenesis. Conclusions: This is the first report of an association between congenital clubfoot and DMD, highlighting the need for expanded early diagnostic protocols for boys presenting with idiopathic clubfoot.
Full article
(This article belongs to the Special Issue Muscle Function and Neuromuscular Disorders: AI and Biomechanics in Diagnosis and Rehabilitation)
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Open AccessArticle
Do Sprinters and Jumpers Differ in the Acute Countermovement-Jump Response to Isometric Conditioning Protocols? An Exploratory Study
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Atila Salaj, Hrvoje Ajman, Frane Žuvela and Petar Šušnjara
Muscles 2026, 5(3), 67; https://doi.org/10.3390/muscles5030067 (registering DOI) - 18 Sep 2026
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Sprinters and jumpers differ in their force–velocity demands, so this exploratory study compared their acute countermovement jump (CMJ) response to isometric conditioning. Methods: Twenty-two competitive track and field athletes (10 sprinters, 12 jumpers; 19.1 ± 3.3 y) were alternately allocated from a randomised
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Sprinters and jumpers differ in their force–velocity demands, so this exploratory study compared their acute countermovement jump (CMJ) response to isometric conditioning. Methods: Twenty-two competitive track and field athletes (10 sprinters, 12 jumpers; 19.1 ± 3.3 y) were alternately allocated from a randomised list to a 3 × 5 s isometric knee-extension or isometric half-squat (n = 11 each). Discipline was not manipulated, and no control condition was included. CMJ height was assessed from flight time by frame-by-frame video analysis, with take-off and landing timestamps read to the nearest 0.01 s. The best of three jumps was the primary trial summary. Percentage change (ΔCMJ) was the primary outcome. Results: Sprinters increased (+2.40 ± 4.46%) whereas jumpers decreased (−2.02 ± 6.44%). Discipline and protocol were analysed jointly in one additive model. The protocol contrast was small and imprecise (−0.25 percentage points [ISO-SQ relative to IKE], 95% CI −5.50 to 5.00; p = 0.921). The unadjusted discipline difference was non-significant (4.42 percentage points, 95% CI −0.46 to 9.30; p = 0.074) and the parallel Mann–Whitney U test was borderline and implementation-dependent (p = 0.043–0.050). After age adjustment it attenuated to +2.51 percentage points (95% CI −2.65 to 7.66; p = 0.320), whereas age remained associated with ΔCMJ (−0.86% per year; p = 0.042). Post hoc averaged trial summaries gave larger contrasts. Conclusions: The primary comparison was inconclusive and materially attenuated by age adjustment but directionally consistent across trial summaries and protocols. The observed discipline-dependent pattern is hypothesis-generating and requires confirmation in adequately powered, controlled trials.
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Open AccessSystematic Review
Effectiveness of Hip Muscle Strengthening Compared with Knee Strengthening or No Intervention in Individuals with Patellofemoral Pain Syndrome: A Systematic Review
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Carlos Contreras-Mora, Sara Cerrolaza-Tudanca, María Soledad Amor-Salamanca, Pedro Antonio Mendoza-Morón, Lara Sanchez-Suarez, María Corral-González, Arturo Cano-Uceda, Nuria Feas-Diaz, José Luis Maté-Muñoz, Pablo García-Fernández and Manuel Rozalén-Bustín
Muscles 2026, 5(3), 66; https://doi.org/10.3390/muscles5030066 (registering DOI) - 17 Sep 2026
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Background: Patellofemoral pain syndrome (PFPS) is a common musculoskeletal condition in physically active individuals. Although quadriceps strengthening has traditionally been the cornerstone of conservative management, hip-strengthening exercises have gained increasing attention because of their potential to improve lower-limb biomechanics. However, the optimal
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Background: Patellofemoral pain syndrome (PFPS) is a common musculoskeletal condition in physically active individuals. Although quadriceps strengthening has traditionally been the cornerstone of conservative management, hip-strengthening exercises have gained increasing attention because of their potential to improve lower-limb biomechanics. However, the optimal exercise prescription for PFPS remains uncertain. Objective: To evaluate the effectiveness of isolated or combined hip muscle strengthening compared with knee strengthening or no intervention on pain, physical function, and muscle strength in individuals with PFPS. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420261342475). PubMed, PEDro, the Cochrane Library, CINAHL, and Web of Science were searched from inception to 31 December 2025. Randomised controlled trials comparing hip-strengthening interventions with knee strengthening or no intervention were included. Methodological quality, risk of bias, and certainty of evidence were assessed using the PEDro scale, the Cochrane RoB 2 tool, and the GRADE approach, respectively. Results: Fifteen randomised controlled trials involving 1002 participants were included. Exercise therapy consistently improved pain, physical function and muscle strength. Both hip- and knee-strengthening programmes were superior to no intervention. Programmes incorporating hip strengthening may provide greater reductions in pain and larger improvements in proximal muscle strength than knee-focused programmes, whereas functional outcomes were generally comparable. Combined hip- and knee-strengthening programmes appeared to provide the most consistent overall clinical benefits. The overall certainty of the evidence was moderate for all outcomes. Conclusions: Current evidence supports exercise-based rehabilitation for PFPS, while evidence remains insufficient to determine whether any specific strengthening strategy provides a clear overall advantage. Further high-quality randomised controlled trials are needed to determine the optimal exercise prescription.
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Open AccessArticle
Bilateral Muscle Architecture Differences in a Rabbit Model of Unilateral Hindlimb Transtibial Amputation: A Pilot Study
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Caleb Stubbs, Patrick T. Hall, Allison J. Nelson, Samantha Z. Bratcher, Alicia A. Matavosian, Cheryl B. Greenacre, Bryce J. Burton, Stacy M. Stephenson, Remigiusz M. Grzeskowiak, Alisha P. Pedersen, Xiaojuan Zhu, David E. Anderson and Dustin L. Crouch
Muscles 2026, 5(3), 65; https://doi.org/10.3390/muscles5030065 - 16 Sep 2026
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Residual muscles after amputation experience mechanical unloading, loss of distal tendon insertion, and reduced excursion, conditions known to cause muscle degeneration. However, the architecture of residual muscles following amputation remains largely unreported. In this pilot, exploratory study, five healthy, skeletally mature, male New
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Residual muscles after amputation experience mechanical unloading, loss of distal tendon insertion, and reduced excursion, conditions known to cause muscle degeneration. However, the architecture of residual muscles following amputation remains largely unreported. In this pilot, exploratory study, five healthy, skeletally mature, male New Zealand white rabbits underwent unilateral hind-paw ankle disarticulation. The contralateral intact limb served as the within-subject control. Six hindlimb muscles that cross the intact biological ankle were harvested bilaterally at four weeks post-amputation, and muscle mass, length, fiber length, pennation angle, sarcomere length, optimal fiber length (OFL), and physiologic cross-sectional area (PCSA) were measured. All statistical comparisons were based on raw, paired differences in values between sides. Muscle mass and OFL were, on average, lower on the residual side for all muscles; raw differences between sides were significant for mass of LG (p = 0.029) and FDS (p = 0.026) and for OFL of LG (p = 0.026). Based on percent difference between sides, degeneration was most severe in the soleus, which had 63 ± 26% less mass and 51 ± 40% lower optimal fiber length in the residual limb than in the intact contralateral limb. Despite lower mass, average PCSA was generally preserved or increased (though differences were not statistically significant) across all muscles except FDS; this was possibly attributable to disproportionately greater reductions in optimal fiber length than in mass. These results have important potential implications for prosthesis function and, therefore, motivate additional research to identify influential factors and evaluate clinical strategies for preserving residual muscle architecture.
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Open AccessArticle
Balance Control and Its Correlation with Functional Capacity in People with Post-Tuberculosis Lung Disease
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Pedro Henrique Perpetuo de Lima Silva, Isabelle da Nobrega Ferreira, Alessandro dos Santos Beserra, Nielza Moreira de Souza, Estephane Ramos de Souza Penna, Alícia Sales Carneiro, Walter Costa, Bruna Cuoco Provenzano, Ana Paula Santos and Agnaldo José Lopes
Muscles 2026, 5(3), 64; https://doi.org/10.3390/muscles5030064 - 16 Sep 2026
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Background: Because falls can lead to loss of autonomy in individuals with post-tuberculosis lung disease (iwPTLD), assessing fall risk is crucial for reducing the likelihood of fractures and preventing the decline of physical function. This cross-sectional study aimed to evaluate balance control (BC)
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Background: Because falls can lead to loss of autonomy in individuals with post-tuberculosis lung disease (iwPTLD), assessing fall risk is crucial for reducing the likelihood of fractures and preventing the decline of physical function. This cross-sectional study aimed to evaluate balance control (BC) in iwPTLD and correlate it with functional capacity during exertion (FCE), pulmonary function, muscle strength, and fatigue. Methods: This cross-sectional study assessed BC in iwPTLD using the Berg Balance Scale (BBS), the Tinetti Balance Scale (TBS), and the Timed “Up and Go” Test (TUGT). Participants also underwent assessments of pulmonary function, respiratory muscle strength, handgrip strength (HGS), quadricep strength (QMS), general fatigue, and functional capacity during exertion (FCE) using the six-minute step test (6MST). Results: Of the 50 individuals with iwPTLD, 66%, 38%, and 46% had a BBS, TBS, and TUGT, respectively, indicating a moderate/high risk of falls. The degree of agreement between BC classifications was weak to poor (Kappa between 0.15 and 0.35). The BBS and TBS exhibited weak-to-moderate correlations with the QMS and 6MST. The TUGT, however, showed strong correlations with the QMS, the 6MST, and residual volume/total lung capacity ratio. Conclusions: Impaired BC appears to be common in iwPTLD, with alterations observed in up to two-thirds of cases. For these individuals, there are significant correlations of BC with peripheral muscle strength, FCE, and static pulmonary hyperinflation, especially when the TUGT is used to assess BC. Thus, the TUGT may be a tool with potential clinical applications for identifying balance impairment in patients with PTLD. However, it requires prospective validation. The BBS and TBS should be reserved for comprehensive assessments of patients with abnormal TUGT results.
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Open AccessArticle
Sex-Specific Differences in Patients with Sarcopenia and Peripheral Artery Disease
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Volker H. Schmitt, Omar Hahad, Christoph Brochhausen, Thomas Münzel, Philipp Lurz, Christine Espinola-Klein, Lukas Hobohm and Karsten Keller
Muscles 2026, 5(3), 63; https://doi.org/10.3390/muscles5030063 - 14 Sep 2026
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Background: In patients with peripheral arterial disease (PAD), the presence of sarcopenia is associated with increased morbidity and mortality. However, sarcopenia is widely underrecognized and scientifically scarcely researched in PAD. Thus, we aimed to investigate sex-specific differences in PAD patients with sarcopenia.
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Background: In patients with peripheral arterial disease (PAD), the presence of sarcopenia is associated with increased morbidity and mortality. However, sarcopenia is widely underrecognized and scientifically scarcely researched in PAD. Thus, we aimed to investigate sex-specific differences in PAD patients with sarcopenia. Methods: All hospitalizations due to PAD in Germany with additional coding for sarcopenia 2005–2020 were included in this analysis and stratified for patients’ sex. Female and male sarcopenic PAD patients were compared regarding patient characteristics, performed therapy and clinical outcome. Results: Overall, 3282 patient hospitalizations admitted due to PAD with sarcopenia were identified in Germany in 2005–2020. The majority of sarcopenic patient-cases were of male sex (N = 1821; 55.5%). Female PAD patients with sarcopenia were older (81.0 [75.0–87.0] vs. 76.0 [68.0–82.0] years, p < 0.001) and revealed a higher comorbidity burden mirrored by higher Charlson Comorbidity Index (7.0 [5.0–8.0] vs. 6.0 [3.0–8.0], p < 0.001). While surgical revascularization of the lower extremity was more often performed in hospitalizations of male sarcopenic PAD patients (17.0% vs. 14.0%, p = 0.018), interventional endovascular revascularization was similarly used in both sexes (12.7% vs. 11.8%, p = 0.429). Amputations were more often performed in male sarcopenic PAD patients (27.2% vs. 21.7%, p < 0.001). In-hospital death (8.9% vs. 6.5%, p = 0.009) and MACCE (11.0% vs. 9.1%, p = 0.070) occurred more often in female than in male sarcopenic PAD patients. Conclusions: We detected significant sex-specific differences in patient profile, performed treatment approaches, and mortality among hospitalized patients with PAD and concomitant sarcopenia. A low number of patients coded with sarcopenia indicates a remarkable under-recognition of sarcopenia in PAD.
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Open AccessReview
Lactate as a Potential Exercise-Induced Signaling Molecule: Implications for Immunometabolic Adaptation Following HIIT
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Amirhossein Ahmadi Hekmatikar, Ana M. Celorrio San Miguel, Hamid Rajabi, Farhad Daryanoosh, Enrique Roche and Diego Fernández-Lázaro
Muscles 2026, 5(3), 62; https://doi.org/10.3390/muscles5030062 - 3 Sep 2026
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High-intensity interval training (HIIT) is widely recognized as an effective strategy for improving cardiorespiratory fitness and metabolic health. Beyond these physiological benefits, growing evidence indicates that HIIT may also induce beneficial immunometabolic adaptations. A key exercise-responsive metabolite in this context is lactate, which
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High-intensity interval training (HIIT) is widely recognized as an effective strategy for improving cardiorespiratory fitness and metabolic health. Beyond these physiological benefits, growing evidence indicates that HIIT may also induce beneficial immunometabolic adaptations. A key exercise-responsive metabolite in this context is lactate, which is increasingly being recognized not as a metabolic waste product but as a bioactive signaling metabolite capable of coordinating metabolic, inflammatory, and immune processes. This narrative review examines current evidence suggesting a potential role for exercise-induced lactate in immune responses associated with HIIT. We summarize the molecular pathways through which lactate may interact with immune cells, including uptake via monocarboxylate transporters (MCT1/MCT4) and SLC5A12, receptor-dependent signaling through GPR81/HCAR1, and epigenetic regulation via histone lactylation. We further discuss the cell-specific effects of lactate on macrophages, dendritic cells, neutrophils, and T lymphocytes, highlighting how these mechanisms may influence immune-cell metabolism, inflammatory regulation, and functional remodeling. A central concept emerging from the current literature is that the biological actions of lactate are highly dependent on the kinetics, duration, and physiological context of exposure. Unlike pathological lactate elevations observed in conditions such as cancer, sepsis, or mitochondrial myopathies—the latter potentially involving an exaggerated lactate response during exercise due to impaired oxidative metabolism—HIIT generates transient systemic lactate elevations as part of a coordinated neuroendocrine and metabolic response. When combined with adequate recovery, these repeated metabolic perturbations may promote hormetic adaptations characterized by improved inflammatory regulation, enhanced immune resilience, and more efficient immunometabolic homeostasis. Conversely, excessive training loads or inadequate recovery may shift these responses toward maladaptive immune stress. Overall, current evidence suggests a paradigm shift in exercise immunology in which lactate should be regarded as one component of an integrated immunometabolic signaling network rather than simply as a marker of anaerobic metabolism. Future mechanistic studies integrating lactate kinetics, immune-cell phenotyping, transporter expression, and lactate-dependent post-translational modifications are needed to clarify the extent to which lactate may contribute to exercise-induced immune remodeling and to guide the development of immunologically informed HIIT protocols.
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Open AccessArticle
Elbow Flexor Adaptations to Failure Versus Repetitions-in-Reserve Training: A Unilateral Within-Participant Study in Resistance-Trained Adults
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Tiago Vasconcelos, Ana Ruivo Alves, Martin Charles Refalo, Gabriela Chaves Lucas, Pedro Rúben Vasconcelos, João Paulo Brito, Filipe Casanova, José Vilaça-Alves and Rafael Oliveira
Muscles 2026, 5(3), 61; https://doi.org/10.3390/muscles5030061 - 30 Aug 2026
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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
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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.
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Open AccessReview
Characterization of Dystrophin-Related Syndromes: Carriers, DMD, and BMD
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Naoufel Chabbi, Corrado Angelini, Irune García, Clara Lépée Aragón and Alicia Aurora Rodriguez
Muscles 2026, 5(3), 60; https://doi.org/10.3390/muscles5030060 - 26 Aug 2026
Abstract
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
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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.
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(This article belongs to the Collection Clinical Advances in Neuromuscular Diseases: Neurometabolic Disorders)
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Open AccessCase Report
Non-Pharmacological Management of Charcot–Marie–Tooth Disease: A Case Report
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Irene Carantini, Roberto Cannataro, Francesco Ferraro and Erika Cione
Muscles 2026, 5(3), 59; https://doi.org/10.3390/muscles5030059 - 25 Aug 2026
Abstract
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
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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
Open AccessArticle
Age-Dependent Effect of Myostatin Blockade in the mdx Mouse Model of Duchenne Muscular Dystrophy (DMD)
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Sasha Bogdanovich, Emidio E. Pistilli and Tejvir S. Khurana
Muscles 2026, 5(3), 58; https://doi.org/10.3390/muscles5030058 - 20 Aug 2026
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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
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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.
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Open AccessCase Report
Mexico’s First Heart Transplant in a Patient with Becker Muscular Dystrophy Reveals an Overlooked Cause of Idiopathic Dilated Cardiomyopathy
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Norma Alejandra Vázquez-Cárdenas, Silvia García, Martha Eunice Rodríguez Arellano, Benjamín Gómez-Díaz, Delia Carolina López Vargas and Luz Berenice López-Hernández
Muscles 2026, 5(3), 57; https://doi.org/10.3390/muscles5030057 - 11 Aug 2026
Abstract
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
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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
(This article belongs to the Collection Clinical Advances in Neuromuscular Diseases: Neurometabolic Disorders)
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Open AccessReview
Advancing Sports Injury Treatment Through Cell-Free MSC-Based Therapies: A Narrative Review
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Duaa Abuarqoub, Alqassem H. Abuarqoub, Mais Emad and Majd F. Ellauzi
Muscles 2026, 5(3), 56; https://doi.org/10.3390/muscles5030056 - 6 Aug 2026
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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)
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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.
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Open AccessReview
Skeletal Muscle Dysfunction and Exercise Intolerance in COPD and Idiopathic Pulmonary Fibrosis: Extracellular Vesicles as Candidate Mediators of a Lung–Muscle Axis
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Georgios I. Barkas, Zoe Daniil and Ourania S. Kotsiou
Muscles 2026, 5(3), 55; https://doi.org/10.3390/muscles5030055 - 3 Aug 2026
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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
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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.
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Open AccessArticle
Intracellular Water Indexed to Height Squared as a Complementary Marker to Skeletal Muscle Index Across Nutritional and Hydration Status
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Yasuhiko Nakao, Masafumi Haraguchi, Fumihiro Mawatari, Ryo Sasaki, Masanori Fukushima, Ryu Sasaki, Satoshi Miuma, Yuko Akazawa and Hisamitsu Miyaaki
Muscles 2026, 5(3), 54; https://doi.org/10.3390/muscles5030054 - 29 Jul 2026
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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
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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.
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Open AccessReview
High-Intensity Exercise Performance as a Complex Adaptive System: An Integrative Review
by
Walaa Jumah Alkasasbeh, Adam Tawfiq Amawi and Gerasimos V. Grivas
Muscles 2026, 5(3), 53; https://doi.org/10.3390/muscles5030053 - 24 Jul 2026
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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
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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.
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Open AccessArticle
Effect of Amino Acid Derivatives and Polyphenol Supplementation on Ovine Muscle Growth In Vitro and In Vivo
by
Gabriella C. Iheanacho, Aliute N. S. Udoka, James L. Klotz and Susan K. Duckett
Muscles 2026, 5(3), 52; https://doi.org/10.3390/muscles5030052 - 17 Jul 2026
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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
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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.
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Open AccessArticle
Histomorphological Effects of Repeated Administration of the TRPA1 Antagonist HC-030031 on Intrafusal and Extrafusal Muscle Fibers in Healthy Young Rats
by
Takahiro Furumi, Ryoya Oga and Hiroyuki Tamaki
Muscles 2026, 5(3), 51; https://doi.org/10.3390/muscles5030051 - 17 Jul 2026
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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.
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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.
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Open AccessArticle
Exploring the Relationship Between Skeletal Muscle Mass and Muscle Strength in the Limbs of Elite Soccer Players
by
Valentina Cavedon, Chiara Milanese and Carlo Zancanaro
Muscles 2026, 5(3), 50; https://doi.org/10.3390/muscles5030050 - 12 Jul 2026
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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
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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.
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Open AccessReview
Effects of Longitudinal Whole-Body Electromyostimulation on Maximum Strength and Power in Sportspeople and Athletes—A Systematic Review and Meta-Analysis
by
Franziska Adams, Matthias Kohl, Simon von Stengel, Andre Filipovic, Michael Uder and Wolfgang Kemmler
Muscles 2026, 5(3), 49; https://doi.org/10.3390/muscles5030049 - 8 Jul 2026
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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
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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.
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