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Muscles, Volume 5, Issue 1 (March 2026) – 21 articles

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16 pages, 263 KB  
Review
Duchenne Muscular Dystrophy: Contemporary Therapeutic Options and Real-World Challenges in Treatment Selection
by Maria Tozzo Pesco, Gülru Zeynep Öztürk, Shivkumar C. Bhadola, Stephen M. Chrzanowski, Liubov V. Gushchina and Eleonora S. D’Ambrosio
Muscles 2026, 5(1), 21; https://doi.org/10.3390/muscles5010021 - 12 Mar 2026
Viewed by 670
Abstract
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by loss-of-function mutations in the dystrophin gene, leading to progressive muscle degeneration, motor decline, respiratory compromise, and cardiomyopathy. Diagnosis typically occurs in early childhood following recognition of motor delays, markedly elevated creatine [...] Read more.
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by loss-of-function mutations in the dystrophin gene, leading to progressive muscle degeneration, motor decline, respiratory compromise, and cardiomyopathy. Diagnosis typically occurs in early childhood following recognition of motor delays, markedly elevated creatine kinase, and confirmatory genetic testing. Over the past decade, the therapeutic landscape for DMD has expanded substantially, evolving from exclusively supportive care to patient-centric multifaceted treatment paradigms, including corticosteroids, mutation-specific therapies, small molecule disease-modifying approaches, and gene replacement strategies. Despite these advances, no currently available therapy restores full-length dystrophin or completely halts disease progression. This review provides a clinically oriented comprehensive overview of currently Food and Drug Administration (FDA)-approved medications for DMD, with particular emphasis on corticosteroids, exon-skipping therapies, nonsense mutation readthrough agents, recently approved gene therapy, and select ongoing gene therapy trials. We summarize mechanisms of action, clinical efficacy, safety considerations, regulatory status, and highlight the challenges of integrating these therapies into longitudinal care. Through illustrative clinical vignettes, we highlight the real-world complexity of treatment selection, shared decision-making, and longitudinal care planning in contemporary DMD management. Full article
14 pages, 2343 KB  
Article
Degenerative Gastrocnemius Muscle Changes in a Goat Tibial Ostectomy Model Persist 10 Months After Splint Removal
by Benjamin T. Baker, Rebecca E. Rifkin, Becka Klein, Brittani Lopez, Remigiusz M. Grzeskowiak, Elizabeth Croy, Xiaojuan Zhu, Pierre-Yves Mulon, David E. Anderson and Dustin L. Crouch
Muscles 2026, 5(1), 20; https://doi.org/10.3390/muscles5010020 - 4 Mar 2026
Viewed by 706
Abstract
Major orthopedic limb surgery is often accompanied by external coaptation; the combined effect of these interventions can lead to muscle atrophy and functional impairment. Large animal models, including goats, are commonly used to study orthopedic interventions, yet longitudinal data on muscle changes after [...] Read more.
Major orthopedic limb surgery is often accompanied by external coaptation; the combined effect of these interventions can lead to muscle atrophy and functional impairment. Large animal models, including goats, are commonly used to study orthopedic interventions, yet longitudinal data on muscle changes after such interventions are limited. This study quantified gastrocnemius muscle adaptations in adult Boer-cross goats undergoing a clinically representative unilateral tibial segmental ostectomy and external coaptation protocol. Muscles on the operated side exhibited statistically significant decreases in mass, length, optimal fiber length, and CSA, and increases in nucleus density compared to muscles on the contralateral, non-operated side (p < 0.05). Although muscle properties showed partial recovery over time, mass and CSA remained 20–30% lower on the operated side than on the non-operated side at 12 months post-surgery despite cast removal at about 2 months post-surgery. Muscle CSA was positively correlated with bone mineral density and peak vertical ground reaction forces measured during the in vivo study. The extent of muscle recovery in the goat model was less than that observed for other mammalian models of hindlimb remobilization. More research is needed to understand the complex interaction between surgery, external coaptation, and muscle properties in the goat model. Full article
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15 pages, 1853 KB  
Article
Phosphodiesterase 4 (PDE 4) Inhibition Reduces Ischemia–Reperfusion-Induced Leucocyte Infiltration, Apoptosis and Mitochondrial Fission Markers in Mice Skeletal Muscles Four Hours After Ischemia Onset
by Anne-Laure Charles, Liliane Tetsi, Giulia Quiring, Cindy Barnig, Margherita Giannini, Alain Meyer, Anne Lejay, Claire Lugnier and Bernard Geny
Muscles 2026, 5(1), 19; https://doi.org/10.3390/muscles5010019 - 3 Mar 2026
Viewed by 320
Abstract
Peripheral arterial disease is a leading cause of amputation and/or death worldwide. Phosphodiesterase 4 (PDE 4) inhibitors demonstrated beneficial effects in ischemia–reperfusion (IR) settings, but whether PDE 4 inhibition protects skeletal muscle against IR deleterious effects is unknown. We therefore performed limb IR [...] Read more.
Peripheral arterial disease is a leading cause of amputation and/or death worldwide. Phosphodiesterase 4 (PDE 4) inhibitors demonstrated beneficial effects in ischemia–reperfusion (IR) settings, but whether PDE 4 inhibition protects skeletal muscle against IR deleterious effects is unknown. We therefore performed limb IR (two hours each) in twenty-one male Swiss mice (12–16-week-old) treated or not with Rolipram (1 mg/kg i.p. 30 min before ischemia and 5 min before reperfusion). The muscles were analyzed 4 h after the onset of ischemia. IR significantly increased leucocyte infiltration (93.13 ± 6.886 vs. 150.1 ± 18.38 cells/mg of muscle, p < 0.05) and apoptosis (Bax/Bcl2 ratio, +239%, p < 0.05), together with enhanced mitochondrial fission transcripts (+224% for Drp1, p < 0.01 and +368%, p < 0.0001 for Fis1), and decreased mitochondrial respiration and antioxidant defense. PDE 4 inhibition reduced leucocyte infiltration (150.1 ± 18.38 vs. 55.58 ± 13.83; p < 0.01) and apoptosis (+67%, NS) in association with reduced fission markers (+91% for Drp 1 and +111%, p < 0.05, for Fis 1). Muscle mitochondrial respiration did not improve. In conclusion, PDE 4 inhibition using Rolipram partly protected skeletal muscles against IR-induced deleterious effects. These data support further studies investigating the usefulness of leucocytes modulation in lower-limb IR and a potential beneficial effect of PDE 4 inhibition in peripheral arterial disease. Full article
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14 pages, 1268 KB  
Article
Electromyographic Activation of the Pectoralis Major and Triceps Brachii Muscles During Standard, Diamond, and Wide Hand Position Push-Ups
by Konstantina Intziegianni, Epifanios Katsamis, Marcos Michaelides and Koulla Parpa
Muscles 2026, 5(1), 18; https://doi.org/10.3390/muscles5010018 - 27 Feb 2026
Viewed by 1046
Abstract
Studies examining the electromyographic activation of pectoralis major (PM) and triceps brachii (TB) muscles during push-ups of varied hand positions are limited, and findings are inconsistent. The aim was to investigate the electromyographic activation of PM and TB during standard, diamond, and wide [...] Read more.
Studies examining the electromyographic activation of pectoralis major (PM) and triceps brachii (TB) muscles during push-ups of varied hand positions are limited, and findings are inconsistent. The aim was to investigate the electromyographic activation of PM and TB during standard, diamond, and wide hand position push-ups. Twenty young males performed six repetitions of each push-up variation while the electrical activity of PM and TB was recorded, averaged, and normalized to the peak root mean square (RMS) across repetitions for each push-up. RMS (mV) and normalized RMS (%) were calculated for each muscle, push-up variation, and contraction phase (eccentric/concentric). Two separate three-way ANOVAs with Bonferroni post hoc correction were used (α = 0.05). TB demonstrated statistically significantly higher RMS (mV) and normalized RMS (%) than PM (p < 0.05), in diamond, followed by standard and wide push-ups. A statistically significant higher activation of RMS (mV) was observed in concentric compared to eccentric (p < 0.05); however, after normalizing RMS (%), contraction phase had no effect (p > 0.05) and there was no significant three-way interaction (p > 0.05). Diamond push-ups elicited the highest relative activation for both the PM and TB. Normalized RMS revealed the consistency of muscle effort in both contraction phases, sustaining near-maximal activation regardless of hand position. These findings support adaptable training strategies, with potential applications in rehabilitation and strength training contexts. Full article
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14 pages, 441 KB  
Article
Does Regional Muscle Distribution Predict Functional Capacity? Sex-Specific Insights from Bioimpedance and Performance Testing
by Elena Caso-Fontánez, Pablo López-Sierra, Carlos D. Gómez-Carmona, Sergio J. Ibáñez and Diego Muñoz
Muscles 2026, 5(1), 17; https://doi.org/10.3390/muscles5010017 - 19 Feb 2026
Viewed by 484
Abstract
Background: The relationships between segmental body composition and multidimensional performance outcomes remain insufficiently characterized in adults with limited but regular physical activity. This study examined associations between body composition parameters and functional test performance, while identifying sex-based differences. Methods: Forty-seven adults (31 women, [...] Read more.
Background: The relationships between segmental body composition and multidimensional performance outcomes remain insufficiently characterized in adults with limited but regular physical activity. This study examined associations between body composition parameters and functional test performance, while identifying sex-based differences. Methods: Forty-seven adults (31 women, 16 men; age 48.04 ± 11.33 years) underwent segmental bioelectrical impedance analysis and functional assessments including handgrip strength, isometric plank endurance, and single-leg balance. Correlations and sex comparisons statistical tests were performed. Results: Strong positive correlations were observed between segmental muscle mass and handgrip strength (r = 0.74–0.84, p < 0.05), with moderate associations for plank endurance (r = 0.30–0.32, p < 0.05). Fat mass demonstrated inverse relationships with performance, particularly for plank endurance (r = −0.36 to −0.62, p < 0.05). Males exhibited significantly greater muscle mass (p < 0.01), superior handgrip strength (p < 0.01), and longer plank times (p = 0.01). Females presented higher fat mass in lower limbs (p < 0.01). Conclusions: Segmental muscle mass shows strong associations with strength and moderate associations with core endurance, while adipose tissue exhibits inverse relationships. Pronounced sexual dimorphism exists in both body composition and functional capacity. Full article
17 pages, 2314 KB  
Article
Body Composition and Pectoralis Major Muscle Evaluation in Women Undergoing Breast Cancer Surgery: A Longitudinal Preliminary Observational Study
by Giulia Bongiorno, Nicole Salvador, Samuele De Cecco, Helena Biancuzzi, Francesca Dal Mas, Chiara Pinzini and Luca Miceli
Muscles 2026, 5(1), 16; https://doi.org/10.3390/muscles5010016 - 17 Feb 2026
Viewed by 538
Abstract
Background: The aim of this observational preliminary study is to detect any changes in body mass, muscle strength and characteristics of the pectoralis major muscle in women who have undergone breast surgery treatments. Methods: Instrumental assessments, completed before surgery and after 60 and [...] Read more.
Background: The aim of this observational preliminary study is to detect any changes in body mass, muscle strength and characteristics of the pectoralis major muscle in women who have undergone breast surgery treatments. Methods: Instrumental assessments, completed before surgery and after 60 and 120 days, included sonoelastography, dynamometric examination and surface electromyography (sEMG) of the pectoralis major muscle, hand grip test, body bioimpedance analysis; the DASH (Disability of the Arm, Shoulder and Hand) questionnaire and pain assessment using the NRS (Numerical Rating Scale). Results: An initial increase in weight and fat mass was observed, followed by a reduction related to the resumption of physical activity stimulated by physiotherapy and medical support. The IC (intracellular)/EC (extracellular) ratio showed an increase in extracellular fluids in the final phase, indicative of possible water retention and early oedema. Muscle strength and DASH scores showed a functional decline, which may be explained by reduced physical activity and the direct involvement of the pectoral muscle in surgical and radiotherapy procedures. Sonoelastography showed color variations suggestive of changes in tissue stiffness, useful for distinguishing between reinforcement processes and possible scarring. Conclusions: This multidimensional approach can be useful in the early monitoring of some tissue alterations (i.e., fat mass) as an aid to define personalized rehabilitation protocols for women who have undergone breast surgery. Full article
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22 pages, 675 KB  
Review
Cross-Platform Transcriptomic Analysis of 40 Human and Rodent Skeletal Muscle Exerkines
by Hash Brown Taha, Nathan Robbins, Firas-Shah Zoha, Shirley Zhu, Nandhana Vivek and Aleksander Bogoniewski
Muscles 2026, 5(1), 15; https://doi.org/10.3390/muscles5010015 - 13 Feb 2026
Viewed by 639
Abstract
Animal and human studies show that exercise induces organism-wide molecular adaptations that are partly mediated by exerkines which are secreted factors that enable inter-organ communication between tissues such as skeletal muscle, adipose tissue, liver and the brain. However, the tissue-specific responsiveness of individual [...] Read more.
Animal and human studies show that exercise induces organism-wide molecular adaptations that are partly mediated by exerkines which are secreted factors that enable inter-organ communication between tissues such as skeletal muscle, adipose tissue, liver and the brain. However, the tissue-specific responsiveness of individual exerkines and how these responses differ across species, exercise conditions and sexes remain poorly understood. To address this gap, we systematically analyzed skeletal muscle transcriptomic responses of 40 exerkines using three publicly available datasets including MetaMEx, Extrameta and the MoTrPAC 6-month-old rat training dataset. We reviewed exerkine-specific regulation in humans, mice and rats across acute and chronic exercise and inactivity. We determined conserved, non-conserved, and discordant exerkines across species and whether they were dependent on exercise modality or sex. Our review reveals substantial heterogeneity in skeletal muscle transcriptomic exerkine regulation with only a small subset showing conserved changes across species. Additionally, a key limitation is that our analysis was limited to transcriptomic data and may not reflect protein-level abundance, secretion, or uptake by recipient tissues. Therefore, we highlight a need for multi species and multi condition approaches when selecting exerkines as biomarkers or surrogate therapeutic targets. Full article
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15 pages, 278 KB  
Article
Examining Relationships and Differences Between the Gastrocnemius and Soleus of the Affected and Healthy Lower Limb of Athletes with Medial Tibial Stress Syndrome
by Anna Christakou, George Plakoutsis, Athanasios Gkagkalis and Eleftherios Paraskevopoulos
Muscles 2026, 5(1), 14; https://doi.org/10.3390/muscles5010014 - 11 Feb 2026
Viewed by 759
Abstract
Objectives: Medial tibial stress syndrome (MTSS) is a common overuse injury among athletes, yet limited evidence exists regarding muscle-specific deficits. This study aimed to (a) examine differences in gastrocnemius and soleus strength and endurance between the affected and healthy lower limb, and (b) [...] Read more.
Objectives: Medial tibial stress syndrome (MTSS) is a common overuse injury among athletes, yet limited evidence exists regarding muscle-specific deficits. This study aimed to (a) examine differences in gastrocnemius and soleus strength and endurance between the affected and healthy lower limb, and (b) investigate the relationships between gastrocnemius and soleus strength, endurance, and pain intensity in athletes with MTSS. Methods: Thirty athletes aged 18–40 years with MRI-confirmed MTSS, who had completed a standardized physiotherapy program, underwent isometric dynamometry and heel-rise endurance testing under knee-extended (gastrocnemius) and knee-flexed (soleus) conditions. Relative strength values and heel-rise repetitions were compared between limbs using paired t-tests. Correlations and regression analyses were performed between pain intensity, strength, and endurance of the affected limb using Pearson’s r and simple linear regression. Results: Significant deficits were found in both muscles of the affected limb, with reduced isometric strength and fewer heel-rise repetitions (gastrocnemius heel-rise: t(29) = −6.47, p < 0.001; gastrocnemius strength: t(29) = −6.27, p < 0.001; soleus heel-rise: t(29) = −5.37, p < 0.001; soleus strength: t(29) = −4.87, p < 0.001). Strong positive correlations were observed between muscle strength and endurance, while higher pain intensity was negatively associated with gastrocnemius performance. Moreover, pain intensity significantly predicted gastrocnemius strength (F(1,28) = 5.90, p = 0.022, R2 = 0.17) and endurance (F(1,28) = 7.56, p = 0.009, R2 = 0.22), but not soleus function. Physiotherapy duration, number of physiotherapy sessions, and self-reported pain improvement were not significant predictors to either soleus or gastrocnemius endurance, only training frequency emerging as the only independent variable. Conclusions: Athletes with MTSS exhibited notable impairments in plantarflexor function. These findings underscore the importance of targeted strength and endurance interventions for both the gastrocnemius and soleus muscles to optimize recovery, enhance load tolerance, and reduce recurrence risk. Future research should include pre- and post-rehabilitation assessments, larger sample sizes, and sport-specific cohorts. Full article
25 pages, 1003 KB  
Review
Neuromuscular Mechanisms and Oxidative Stress in Skeletal Muscle Atrophy: Emerging Stem Cell and Gene-Based Therapeutic Strategies
by Sathish Kumar Gunasekaran, Mandam Amzad Khan, Mehwish Mirza, Santhosh Shanthi Bhupathi and Mohamed Sheik Tharik Abdul Azeeze
Muscles 2026, 5(1), 13; https://doi.org/10.3390/muscles5010013 - 10 Feb 2026
Viewed by 801
Abstract
Skeletal muscle atrophy emerges from intertwined neuromuscular and metabolic failures, in which neuromuscular junction destabilization, excitation contraction coupling defects, and mitochondrial dysfunction collectively intensify calcium dysregulation and drive the accumulation of reactive oxygen and nitrogen species (RONS), reinforcing proteolytic and catabolic signaling programs. [...] Read more.
Skeletal muscle atrophy emerges from intertwined neuromuscular and metabolic failures, in which neuromuscular junction destabilization, excitation contraction coupling defects, and mitochondrial dysfunction collectively intensify calcium dysregulation and drive the accumulation of reactive oxygen and nitrogen species (RONS), reinforcing proteolytic and catabolic signaling programs. To integrate recent evidence on the neuromuscular redox interface and highlight therapeutic strategies that target these interdependent drivers of atrophy. RONS-mediated activation of NF-κB and FOXO pathways accelerates ubiquitin proteasome and autophagy lysosome degradation, leading to motor unit loss. Stem cell therapies (satellite cells, MSCs, and iPSC progenitors) seek to restore regenerative potential but face hurdles in engraftment and reinnervation. Gene-based interventions, including antioxidant gene delivery, Nrf2 activation, RNA modulators, and CRISPR editing, offer new avenues but remain limited by safety and delivery barriers. Bioengineering platforms such as hydrogels, decellularized scaffolds, and extracellular vesicles provide architectural, trophic, and immunomodulatory support. Translational progress requires rigorous safety pipelines, mechanistic biomarkers of motor unit recovery, and modular combination regimens that integrate cells, genes, scaffolds, and rehabilitative input. By aligning neuromuscular biology with redox control, emerging strategies hold promise to rebuild innervated, fatigue-resistant muscle across acquired and genetic atrophy syndromes. Full article
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13 pages, 970 KB  
Review
Tics, Tourette’s and Related Muscle Pain in Children: A Review
by Stuart Evans
Muscles 2026, 5(1), 12; https://doi.org/10.3390/muscles5010012 - 9 Feb 2026
Viewed by 633
Abstract
Tourette Syndrome (TS) is a neurodevelopmental disorder depicted by the occurrence of tics and accompanying behavioral problems that commonly appear during childhood. Tics, both motor and vocal, may cause musculoskeletal pain. Both acute and chronic muscle pain have been recognized as a common [...] Read more.
Tourette Syndrome (TS) is a neurodevelopmental disorder depicted by the occurrence of tics and accompanying behavioral problems that commonly appear during childhood. Tics, both motor and vocal, may cause musculoskeletal pain. Both acute and chronic muscle pain have been recognized as a common comorbid aspect of TS-related tic disorders in childhood. The pain most reported in children includes cervical, throat, shoulder, ocular, and joint pain, with most children reporting musculoskeletal pain in more than one part of the body. The impact of muscular pain caused by motor and phonic tics can negatively affect a child’s quality of life. This review describes the association and causation of musculoskeletal pain in childhood tics and TS, which are commonly under recognized and diagnosed. An analysis of the presence of musculoskeletal pain, the severity of the pain, the location of the pain and the movement incapacity due to pain in children is reviewed. Pharmacological and non-pharmacological interventions known to improve musculoskeletal pain in children are highlighted with supportive frameworks evaluated. Further research is needed to better understand musculoskeletal pain cause(s) and prevalence along with age-appropriate assessment methods and outcomes measures. Motor- and phonic-related musculoskeletal pain should be recognized as a common comorbid characteristics of TS and tic disorders in childhood. Such recognition may lead to greater therapeutic opportunities for this problematic condition. Full article
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13 pages, 231 KB  
Article
From Injury to Impact: Optimizing Return-to-Play Outcomes and Reinjury Prevention via Four-Pillar Rehabilitation Strategy in Elite Football—A Clinical Study in a Sports Scenario
by Ioannis Stathas, Nikos Koundourakis, Charalampos Christoforidis, George Kouvidis and Anna Christakou
Muscles 2026, 5(1), 11; https://doi.org/10.3390/muscles5010011 - 2 Feb 2026
Viewed by 881
Abstract
Objectives: This clinical commentary presents a four-pillar rehabilitation framework implemented in the elite football setting of OFI Crete FC and designed to facilitate the return of football players to training and competitive play. The framework is structured around five core components: (a) effective [...] Read more.
Objectives: This clinical commentary presents a four-pillar rehabilitation framework implemented in the elite football setting of OFI Crete FC and designed to facilitate the return of football players to training and competitive play. The framework is structured around five core components: (a) effective load management during training and matches, (b) individualized rehabilitation programs and injury prevention strategies integrated within the recovery phase, (c) a novel on-field rehabilitation framework, and (d) an extended secondary prevention plan. Methods: This comprehensive approach was implemented over a three-year period with the OFI Crete FC football team and involved 87 elite professional players between the ages of 17 and 35. Throughout this time, 180 injuries were documented, ranging from mild to severe injuries. Results: The outcome illustrated that only 40% of these injuries led to players missing official matches, while the recurrence or follow-up injury rate was limited to just 10%. Over the course of the three years, a steady 60% decline in injury rates was observed. Conclusions: These findings emphasize the crucial importance of training load management, the integration of injury prevention strategies throughout the rehabilitation process, and the early initiation of on-field rehabilitation. Within the clinical setting of OFI Crete FC, the implementation of this integrated rehabilitation framework was associated with favorable observations in injury incidence, player absence days, and return-to-play timelines, which may reflect that the approach has potential benefits while remaining observational in nature. Full article
10 pages, 1029 KB  
Article
The Acute Physiological Effects of Multiple Muscle Stimulation
by Rishabh Rege, Kristin M. Mendez, Riya Patel, Sydnie Keane and Kevin K. McCully
Muscles 2026, 5(1), 10; https://doi.org/10.3390/muscles5010010 - 30 Jan 2026
Viewed by 773
Abstract
Neuromuscular electrical stimulation (NMES) has been shown to provide health benefits similar to those of exercise. The aim of this study was to quantify the acute physiological effects of multiple muscle stimulation on the whole body and individual muscles. Nine healthy young adults [...] Read more.
Neuromuscular electrical stimulation (NMES) has been shown to provide health benefits similar to those of exercise. The aim of this study was to quantify the acute physiological effects of multiple muscle stimulation on the whole body and individual muscles. Nine healthy young adults were tested. NMES of eight muscle groups was performed with NMES stimulators. The vastus lateralis, biceps femoris, medial gastrocnemius, and tibialis anterior muscles of both legs were stimulated for ten minutes with twitch stimulations at the highest comfortable stimulation current. Whole-body metabolism was measured using a metabolic cart. A finger pulse oximeter and a tri-axial accelerometer were used to measure heart rate and muscle fatigue, respectively. Muscle metabolism (mVO2) was measured using near-infrared spectroscopy (NIRS) during short periods of ischemia. Femoral artery blood flow was measured using Doppler ultrasound. Whole-body VO2 and heart rate increased moderately by 36% and 22%, respectively, after 10 min of NMES. NMES increased mVO2 by 12-fold higher than resting on average, with the gastrocnemius having the smallest increase and the vastus lateralis having the greatest increase. Peak diastolic blood flow velocity was significantly reduced by 50% after 10 min of NMES. Simultaneous lower-body NMES moderately improved whole-body metabolism, muscle metabolism, and blood flow, increasing our understanding of the beneficial effects of NMES. Full article
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16 pages, 1172 KB  
Systematic Review
Muscle, Neuromuscular, and Cardiac Damage in Trail Running: A Systematic Review
by Isabel García-Valiente, Francisco Pradas, Miguel Ángel Ortega-Zayas, Carlos Castellar-Otín, Alejandro García-Giménez and Miguel Lecina
Muscles 2026, 5(1), 9; https://doi.org/10.3390/muscles5010009 - 29 Jan 2026
Viewed by 837
Abstract
Background: Trail running (TR) is an endurance discipline characterized by prolonged exercise, irregular terrain, and marked elevation changes, which increase eccentric muscular load and may induce muscular, neuromuscular, and cardiac damage. Objective: This study aimed to systematically review the evidence on [...] Read more.
Background: Trail running (TR) is an endurance discipline characterized by prolonged exercise, irregular terrain, and marked elevation changes, which increase eccentric muscular load and may induce muscular, neuromuscular, and cardiac damage. Objective: This study aimed to systematically review the evidence on muscular, neuromuscular, and cardiac damage associated with TR participation. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251135043). Five databases (PubMed, Web of Science, Scopus, SportDiscus, and ScienceDirect) were searched up to 31 August 2025. Observational, longitudinal, prospective, and case studies involving healthy adolescent or adult trail runners were included. Outcomes comprised muscle damage biomarkers (e.g., creatine kinase, alanine aminotransferase), neuromuscular function (e.g., squat jump performance, maximal voluntary isometric contraction), and cardiac biomarkers (e.g., CK-MB, cardiac troponins, NT-proBNP). Methodological quality was assessed using the National Heart, Lung, and Blood Institute Study Quality Assessment Tool. Results were synthesized qualitatively. Results: Fifteen studies met the inclusion criteria, including a total of 247 participants. Post-race analyses consistently showed marked increases in muscle damage biomarkers and significant reductions in neuromuscular performance. Transient elevations in cardiac biomarkers were also observed, suggesting acute but reversible cardiac stress following TR events. Limitations: Evidence was limited by methodological heterogeneity, small sample sizes, and underrepresentation of female athletes. Conclusions: It was found that trail running induces substantial acute muscular, neuromuscular, and cardiac stress, particularly in events with high eccentric loading. Monitoring biochemical and neuromuscular markers may support training load optimization, recovery strategies, and injury prevention. Full article
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19 pages, 936 KB  
Article
Early-Phase and Cross-Education Adaptations Following Very Short-Term Unilateral Isokinetic Forearm Extension and Flexion Training in Untrained Women
by Justin S. Pioske, Jocelyn E. Arnett, Dolores G. Ortega, Trevor D. Roberts, Robert W. Smith, Tyler J. Neltner, Richard J. Schmidt and Terry J. Housh
Muscles 2026, 5(1), 8; https://doi.org/10.3390/muscles5010008 - 28 Jan 2026
Viewed by 478
Abstract
This study: (1) Determined the time course of early-phase adaptations in average peak torque (APT), the rate of velocity development (RVD), and average power (AP) following very short-term unilateral, reciprocal, concentric isokinetic forearm extension and flexion training in untrained women; and (2) determine [...] Read more.
This study: (1) Determined the time course of early-phase adaptations in average peak torque (APT), the rate of velocity development (RVD), and average power (AP) following very short-term unilateral, reciprocal, concentric isokinetic forearm extension and flexion training in untrained women; and (2) determine whether training the non-dominant arm induced cross-education adaptations in the dominant, non-trained arm. Twelve untrained women (age: 21.7 ± 1.2 yrs) completed four testing and four training visits (pre-test and following 2, 3, and 4 days of training). The testing consisted of three maximal repetitions of the dominant and non-dominant arms at 60°, 180°, and 300°·s−1, with APT and AP calculated as the average of the 3 repetitions and RVD as the fastest repetition. The training consisted of 6 sets of 10 maximal repetitions at 180°·s−1 with the non-dominant arm. The differences in mean values across testing visits for APT, AP, and RVD were determined by separate 2 (Arm) × 2 (Muscle Action) × 3 (Velocity) × 4 (Time [across all testing visits]) repeated measures ANOVA (α ≤ 0.05) with Bonferroni-corrected post hoc comparisons. For the trained arm, there were increases in APT (p < 0.001) following four training visits and AP following three (p = 0.006) and four (p = 0.004) training visits. Furthermore, following four training visits, RVD (collapsed across Arms and Muscle Action) decreased at 180°·s−1 (p = 0.002) and 300°·s−1 (p = 0.005) following four training visits. There were no changes in APT or AP (p = 0.155–1.000) in the non-trained arm, which indicated no cross-education adaptations. These findings suggested that 3–4 days of moderate-velocity, unilateral, reciprocal, isokinetic training elicited early-phase adaptations for APT, RVD, and AP in untrained women, while cross-education adaptations for APT and AP were not observed within this timeframe. Full article
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12 pages, 612 KB  
Systematic Review
Towards a Unified Terminology for Implant-Influenced Fractures: Implications for Musculoskeletal and Muscle–Implant Interaction Research
by Giacomo Papotto, Ignazio Prestianni, Enrica Rosalia Cuffaro, Alessio Ferrara, Marco Ganci, Calogero Cicio, Alessandro Pietropaolo, Marco Montemagno, Saverio Comitini, Antonio Kory and Rocco Ortuso
Muscles 2026, 5(1), 7; https://doi.org/10.3390/muscles5010007 - 15 Jan 2026
Viewed by 360
Abstract
Background: The global increase in orthopedic implant use—both for trauma fixation and arthroplasty—has profoundly transformed musculoskeletal surgery. As a consequence, fractures occurring in the presence of implants have become more frequent and clinically relevant. Yet, these injuries are currently described using highly heterogeneous [...] Read more.
Background: The global increase in orthopedic implant use—both for trauma fixation and arthroplasty—has profoundly transformed musculoskeletal surgery. As a consequence, fractures occurring in the presence of implants have become more frequent and clinically relevant. Yet, these injuries are currently described using highly heterogeneous terminology, including periprosthetic (fracture occurring in the presence of a prosthetic joint replacement) peri-implant (fracture occurring around an osteosynthesis or fixation device), implant-related, and hardware-related fractures (umbrella terms encompassing both prosthetic and fixation devices, used descriptively rather than classificatorily). This coexistence of multiple, context-specific terminologies hinders clinical communication, complicates registry documentation, and limits research comparability across orthopedic subspecialties. Because fractures occurring in the presence of orthopedic implants significantly alter load transfer, muscle force distribution, and musculoskeletal biomechanics, a clear and unified terminology is also relevant for muscle-focused research addressing implant–tissue interaction and functional recovery. Objective: This systematic review aimed to critically analyze the terminology used to describe fractures influenced by orthopedic implants, quantify the heterogeneity of current usage across anatomical regions and publication periods, and explore the rationale for adopting a unified umbrella term—“artificial fracture.” Methods: A systematic search was performed in PubMed, Scopus, and Web of Science from January 2000 to December 2024, following PRISMA guidelines. Eligible studies included clinical investigations, reviews, registry analyses, and consensus statements explicitly employing or discussing terminology related to implant-associated fractures. Data were extracted on publication characteristics, anatomical site, terminology employed, and classification systems used. Quantitative bibliometric and qualitative thematic analyses were conducted to assess frequency patterns and conceptual trends. Results: Of 1142 records identified, 184 studies met the inclusion criteria. The most frequent descriptor in the literature was periprosthetic fracture (68%), reflecting its predominance in arthroplasty-focused studies, whereas broader and more practical terms such as implant-related and peri-implant fracture were more commonly used in musculoskeletal and fixation-related research. Terminological preferences varied according to anatomical site and implant type, and no universally accepted, cross-anatomical terminology was identified despite multiple consensus efforts. Discussion and Conclusions: The findings highlight persistent heterogeneity in terminology describing fractures influenced by orthopedic implants. A transversal, descriptive framework may facilitate communication across subspecialties and support registry-level harmonization. Beyond orthopedic traumatology, this approach may also benefit muscle and musculoskeletal research by enabling more consistent interpretation of data related to muscle–bone–implant interactions, rehabilitation strategies, and biomechanical adaptation. Full article
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20 pages, 2249 KB  
Article
Hypoxia Increases Cardiac Proteasomal Activity and Differentially Modulates Cullin-RING E3 Ligases in the Naked Mole-Rat Heterocephalus glaber
by W. Aline Ingelson-Filpula, Karen L. Kadamani, Mohammad Ojaghi, Matthew E. Pamenter and Kenneth B. Storey
Muscles 2026, 5(1), 6; https://doi.org/10.3390/muscles5010006 - 14 Jan 2026
Viewed by 627
Abstract
(1) Background: The naked mole-rat (Heterocephalus glaber) survives hypoxia–reoxygenation stresses by utilizing metabolic rate depression, achieved in part by downregulating nonessential genes and processes to conserve endogenous cellular resources and prevent buildup of toxic waste byproducts. Tight molecular control of protein [...] Read more.
(1) Background: The naked mole-rat (Heterocephalus glaber) survives hypoxia–reoxygenation stresses by utilizing metabolic rate depression, achieved in part by downregulating nonessential genes and processes to conserve endogenous cellular resources and prevent buildup of toxic waste byproducts. Tight molecular control of protein degradation (specifically the ubiquitin–proteasome system) is a potent regulatory tool for maintaining muscle integrity during hypoxia, but how this system is regulated in the heart of hypoxia-tolerant species is poorly understood. (2) Methods: The protein expression levels of cullin-RING E3 ligases (specifically CRL4 architecture), deubiquitinating enzymes, and proteasomal activity were assayed in cardiac tissues from H. glaber exposed to 24 h of normoxia or hypoxia in vivo. (3) Results: Overall, the protein expression of E3 ligases decreased, whereas expression of deubiquitinating enzymes increased during hypoxia, all of which play roles in themes of oxidative stress, heightened DNA damage repair, and the HIF-1-VHL-NFκB axis. Proteasomal activity was elevated during hypoxia, which conceivably links to the oxidative stress theory of aging and longevity of H. glaber. (4) Conclusions: Taken together, our results expand current research into protein degradation and extreme environmental stress responses, with a specific focus on cardiac mechanisms related to oxidative stress resistance along the hypoxia-longevity axis. Full article
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11 pages, 864 KB  
Article
Impact of Perceived Dorsiflexion and Plantarflexion in the Squat and Countermovement Jumps
by Flávio Ventura, Filipe Maia, Ricardo Maia Ferreira, Nuno Pimenta and Ricardo Pimenta
Muscles 2026, 5(1), 5; https://doi.org/10.3390/muscles5010005 - 12 Jan 2026
Viewed by 602
Abstract
Muscular strength plays a crucial role in sports performance and is often evaluated using vertical jump tests such as the Squat Jump (SJ) and Countermovement Jump (CMJ). Measurements based on flight time (FT) assume that takeoff and landing postures are identical, yet differences [...] Read more.
Muscular strength plays a crucial role in sports performance and is often evaluated using vertical jump tests such as the Squat Jump (SJ) and Countermovement Jump (CMJ). Measurements based on flight time (FT) assume that takeoff and landing postures are identical, yet differences in ankle position can introduce systematic errors. This study examined whether dorsiflexion (DF) or plantarflexion (PF) of the ankle during the flight phase affects jump height. Forty-three active university students completed four repetitions each of SJ and CMJ under DF and PF across two sessions. Jump heights were recorded using a Chronojump-Boscosystem platform. No significant difference was observed in SJ between DF and PF, while CMJ heights were consistently higher under DF (DF: 28.29 cm ± 7.7 cm vs. PF: 27.08 cm ± 7.03 cm, p = 0.001; d = 0.16). Notably, the effect of DF appeared more pronounced in CMJ, suggesting that higher jumps are more sensitive to postural variations. These findings could suggest that DF can artificially increase jump heights as measured on a jump platform, without reflecting true improvements in force production. Coaches and practitioners should interpret FT-derived data with caution, particularly for higher jumps. Future research combining precise motion capture with force platforms could directly track center-of-mass changes and validate this mechanism. Full article
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11 pages, 238 KB  
Article
Sex Differences in Force, Velocity, and Power Percent Changes During Countermovement Jump Performance Following a Dynamic Warm-Up
by Gabriel J. Sanders, Maura Bennett, Roger O. Kollock and Corey A. Peacock
Muscles 2026, 5(1), 4; https://doi.org/10.3390/muscles5010004 - 9 Jan 2026
Viewed by 818
Abstract
Background: The study examined sex differences in countermovement jump (CMJ) force plate metrics and neuromuscular responses to a standardized dynamic warm-up in physically active college students. Methods: Forty-one participants (21 males, 20 females) completed pre- and post-warm-up assessments of CMJ performance [...] Read more.
Background: The study examined sex differences in countermovement jump (CMJ) force plate metrics and neuromuscular responses to a standardized dynamic warm-up in physically active college students. Methods: Forty-one participants (21 males, 20 females) completed pre- and post-warm-up assessments of CMJ performance using a dual force plate system. Body composition was measured via bioelectrical impedance analysis, and performance metrics included force, velocity, power, and other jump metrics. Percent change scores were calculated for all metrics. Results: Males demonstrated significantly greater improvements in braking force metrics compared to females, including force at minimum displacement (11.4% Δ male vs. 5.7% Δ female, p = 0.043), average braking force (10.6% Δ male vs. 5.0% Δ female, p = 0.043), and peak braking force (11.5% Δ male vs. 5.7% Δ female, p = 0.043). No significant sex differences were found in velocity, power, propulsive force, or other general CMJ performance variables. Hierarchical regression analyses revealed that sex was a significant (p ≤ 0.043 for all) predictor of changes in braking force metrics, while lean body mass did not enhance model fit or independently predict force changes. The addition of lean body mass slightly attenuated the sex effect but did not contribute meaningfully to the models. Conclusions: Findings suggest males may experience greater braking force adaptation to a dynamic warm-up, while other performance outcomes appear similar between sexes. These results may inform sex-specific warm-up strategies targeting neuromuscular readiness and braking force development. Full article
12 pages, 845 KB  
Article
The Myokine FGF-21 Responds in a Time-Dependent Manner to Three Different Types of Acute Exercise
by Mikal Thrones, Thomas Rawliuk, Dean M. Cordingley and Stephen M. Cornish
Muscles 2026, 5(1), 3; https://doi.org/10.3390/muscles5010003 - 4 Jan 2026
Cited by 1 | Viewed by 681
Abstract
Background: The myokine response to various types of exercise may differ and influence the adaptations to various physiological systems in response to training. This study aimed to compare systemic myokines’ (apelin, interleukin-6 [IL-6], interleu-kin-15 [IL-15], fibroblast-growth factor-21 [FGF-21], and irisin) responses to [...] Read more.
Background: The myokine response to various types of exercise may differ and influence the adaptations to various physiological systems in response to training. This study aimed to compare systemic myokines’ (apelin, interleukin-6 [IL-6], interleu-kin-15 [IL-15], fibroblast-growth factor-21 [FGF-21], and irisin) responses to acute moderate-intensity cardiovascular exercise (MICE), high-intensity interval exercise (HIIE), or resistance exercise (RE). Methods: Six healthy, recreationally active adults (n = 4 males, n = 2 females) completed this crossover pilot study. After baseline testing, in a balanced randomized order, participants completed all three exercise sessions with one week between each of the exercise sessions. Blood samples were obtained at rest, immediately post-exercise, and 1 and 3 h post-exercise. Myokine response was analyzed using a 3 (exercise condition: MICE, HIIE, RE) × 4 (time: baseline, post-exercise, 1 and 3 h post-exercise) repeated-measures ANOVA. Results: Our results showed no significant interaction of time × exercise type in any of the analyzed myokines (all p > 0.05). A significant main effect of time was found for FGF-21, where concentrations at baseline (188.96 ± 127.34 pg/mL; p = 0.038) and immediately post-exercise (206.27 ± 135.95 pg/mL; p = 0.006) were higher than 3 h post-exercise (111.08 ± 127.65 pg/mL). No other main effects for time or exercise type were identified (all p > 0.05). Conclusions: The three exercise types, when analyzed together in this study, demonstrated a reduction in FGF-21 3 h post-exercise, suggesting this myokine was removed from the systemic circulation following exercise. The negative results of this study are inconclusive given the lower statistical power observed in this research. These preliminary results indicate the need for a larger trial to evaluate the effects of different types of exercise on the specificity of myokine responses and how acute exercise responses may translate into long-term exercise training adaptations. Full article
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28 pages, 821 KB  
Review
Mechanisms, Economy, and Performance of Advanced Footwear Technology in Endurance Running—A Review
by Daido Dagne Bruvere and Edgars Bernans
Muscles 2026, 5(1), 2; https://doi.org/10.3390/muscles5010002 - 24 Dec 2025
Viewed by 2932
Abstract
Since the introduction of advanced footwear technology (AFT) in 2017, numerous world records from 5 km to the marathon have been broken. Among these innovations, carbon-plated shoes have received particular attention. Previous research indicates improvements of 2–4% in running economy (RE), which translates [...] Read more.
Since the introduction of advanced footwear technology (AFT) in 2017, numerous world records from 5 km to the marathon have been broken. Among these innovations, carbon-plated shoes have received particular attention. Previous research indicates improvements of 2–4% in running economy (RE), which translates into an approximate 1–2% improvement in running performance when running in these shoes. The rapid progression of performance has generated significant scientific interest; however, a clear understanding of the mechanisms driving the effectiveness of AFT remains limited. Despite widespread adoption and remarkable results, the mechanisms underlying the effectiveness of AFT are still not fully understood, which is why optimising its potential benefits continues to be an ongoing challenge. This review summarises current knowledge on AFT and critically evaluates the biomechanical and physiological mechanisms underlying their effects on RE and performance. It also highlights the interaction between shoe design features and individual biomechanics, supporting evidence-based approaches to footwear selection and training strategies tailored to athletes’ needs. A clearer understanding of these mechanisms may provide valuable insights for researchers, coaches, and athletes and help maximise the potential benefits of AFT. Full article
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23 pages, 3728 KB  
Systematic Review
Impact of Exercise Modalities on Pentraxin-3 (PTX3) Levels: A Systematic Review and Meta-Analysis
by Mohammad Rahman Rahimi, Hassan Faraji, Chenour Sadeghi, George John, Ildus I. Ahmetov and Hadi Golpasandi
Muscles 2026, 5(1), 1; https://doi.org/10.3390/muscles5010001 - 23 Dec 2025
Viewed by 624
Abstract
Background: Pentraxin 3 (PTX3) is a key biomarker of innate immunity and inflammation, associated with muscle mass, metabolic syndrome, and obesity-related indicators. However, its role in training adaptations remains unclear, with studies reporting inconsistent PTX3 responses to acute and chronic exercise. This study [...] Read more.
Background: Pentraxin 3 (PTX3) is a key biomarker of innate immunity and inflammation, associated with muscle mass, metabolic syndrome, and obesity-related indicators. However, its role in training adaptations remains unclear, with studies reporting inconsistent PTX3 responses to acute and chronic exercise. This study aimed to compare the effects of aerobic exercise, resistance training, high-intensity interval training (HIIT), and acute exercise on PTX3 levels. Methods: A systematic search using Boolean logic was conducted in Web of Science, PubMed, and Google Scholar to identify randomized controlled trials examining the effects of exercise training and acute exercise on PTX3 levels. Results: Out of 3434 records published from 1992 to July 2025, 19 studies met the eligibility criteria. Meta-analysis revealed that aerobic training significantly increased PTX3 levels (SMD = 0.71; 95% CI, 0.173 to 1.252; p = 0.01; I2 = 83.14%), whereas resistance training significantly reduced them (SMD = −0.69; 95% CI, −1.025 to −0.370; p = 0.0001; I2 = 17.52%). HIIT did not elicit a significant change (SMD = 0.086; 95% CI, −0.364 to 0.535; p = 0.70; I2 = 0.00%). Notably, exercise training significantly elevated PTX3 in individuals over 50 years old (SMD = 1.124; 95% CI, 0.231 to 2.017; p = 0.014; I2 = 87.97%) but not in younger participants (SMD = −0.156; 95% CI, −0.640 to 0.327; p = 0.526; I2 = 78.80%). Conclusion: Aerobic and resistance exercise exert opposing effects on PTX3, suggesting distinct mechanisms through which different training modalities modulate inflammatory pathways relevant to muscle metabolism and repair. Acute exercise may also transiently elevate PTX3 to manage exercise-induced inflammation. Full article
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