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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.

All Articles (159)

Neuromuscular Mechanisms and Oxidative Stress in Skeletal Muscle Atrophy: Emerging Stem Cell and Gene-Based Therapeutic Strategies

  • Sathish Kumar Gunasekaran,
  • Mandam Amzad Khan and
  • Mohamed Sheik Tharik Abdul Azeeze
  • + 2 authors

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.

10 February 2026

Neuromuscular redox vicious cycle. Schematic representation of the feed-forward cycle in skeletal muscle atrophy. Motor neuron degeneration, NMJ instability, and RyR1-mediated Ca2+ leak converge on mitochondrial dysfunction to amplify oxidative stress, accelerating synaptic dismantling and proteolysis. Retrograde injury further destabilizes NMJ input, while oxidative modification of RyR1 drives Ca2+ overload and mitochondrial failure, reinforcing a self-perpetuating cycle of redox stress, fiber degeneration, and muscle atrophy.

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.

11 February 2026

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.

9 February 2026

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.

2 February 2026

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Muscles - ISSN 2813-0413