Muscles

20 pages, 2249 KB

Open AccessArticle

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

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

Open AccessArticle

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

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

Open AccessArticle

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

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

Open AccessArticle

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

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

Open AccessReview

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

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

Open AccessSystematic 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

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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15 pages, 1282 KB

Open AccessArticle

Comparing the Force–Time Characteristics Between Countermovement and Assisted Countermovement Jump with Different Landing Strategies

by Regine Y. S. Zhou, Lachlan P. James and Danny Lum

Muscles 2025, 4(4), 62; https://doi.org/10.3390/muscles4040062 - 17 Dec 2025

Abstract

Researchers comparing countermovement (CMJ) and assisted countermovement (ACMJ) jumps reported conflicting findings on the landing impact force (LIF). This was likely due to differences in the landing strategies used. As the magnitude of LIF may have implications on neuromuscular adaptations, the purpose of [...] Read more.

Researchers comparing countermovement (CMJ) and assisted countermovement (ACMJ) jumps reported conflicting findings on the landing impact force (LIF). This was likely due to differences in the landing strategies used. As the magnitude of LIF may have implications on neuromuscular adaptations, the purpose of this study was to compare the LIF between CMJ and ACMJ while adopting soft and stiff landing strategies. Thirteen resistance-trained athletes (sex: female = 5, male = 8, 26.4 ± 3.7 years, 68.4 ± 13.6 kg, 167 ± 5.1 cm) performed three CMJ and ACMJ each at 60%, 70%, 80% and 90% of bodyweight with instructions to either land soft or stiff on a force plate. Repetitions were separated by 30 s and conditions by 3 min. Resistance bands were used to induce the required weight during ACMJ. Data obtained regarding the average of the two closest trials based on jump height was analysed. Jump height significantly increased with increasing assistance during ACMJ for both landing conditions (p < 0.001). Propulsion duration (PD) was significantly shorter with increasing assistance during ACMJ for both landing conditions (p < 0.001). Peak and mean propulsion force significantly decreased with increasing assistance during ACMJ for both landing conditions (p < 0.001 and p < 0.001, respectively). The LIF was significantly greater with increasing assistance during ACMJ in the stiff-landing condition only (p < 0.001). Greater assistance allowed participants to jump higher while reducing PD. The higher LIF observed during stiff landing with greater assistance during ACMJ could be attributed to greater jump height and downward velocity during landing. Full article

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21 pages, 1426 KB

Open AccessEditor’s ChoiceSystematic Review

Effectiveness of Hyperbaric Oxygen Therapy for Musculoskeletal Pain Syndromes: A Systematic Review

by Sebastián Eustaquio Martín Pérez, Eduardo Iboleón Laynez, José Antonio Acevedo Rodríguez, María Isabel Maggioni Torres, Roberto Pérez Betancort, Antón Díaz Rodríguez, Diego Cabezos Alonso, Carlos García Camacho and Isidro Miguel Martín Pérez

Muscles 2025, 4(4), 63; https://doi.org/10.3390/muscles4040063 - 16 Dec 2025

Abstract

Background: Musculoskeletal pain syndromes (MPSs) represent a major cause of disability and reduced quality of life, and conventional therapeutic approaches often provide only partial or temporary relief. Hyperbaric oxygen therapy (HBOT) delivered as 100% oxygen at 1.3–2.5 ATA, has been proposed to modulate [...] Read more.

Background: Musculoskeletal pain syndromes (MPSs) represent a major cause of disability and reduced quality of life, and conventional therapeutic approaches often provide only partial or temporary relief. Hyperbaric oxygen therapy (HBOT) delivered as 100% oxygen at 1.3–2.5 ATA, has been proposed to modulate inflammatory processes and enhance tissue repair. This review evaluated the effectiveness of HBOT on pain, function, quality of life, and physiological outcomes in individuals with MPS. Methods: This systematic review was conducted in different databases between June 30 and 30 September 2025, following PRISMA guidelines and was previously registered in PROSPERO (CRD420251073730). Studies published in English, Spanish, or Portuguese evaluating HBOT as a standalone or adjunctive intervention were included. Methodological quality and risk of bias were assessed using PEDro, NIH, and RoB 2.0 tools, and certainty of evidence was graded with GRADE. Results: Eighteen studies (17 RCTs and 1 case series; n = 671) were included. HBOT protocols ranged from 3 to 60 sessions, lasting 60–90 min, at approximately 1.3–2.5 ATA. Consistent reductions in pain and modest functional improvements were observed in fibromyalgia and postoperative conditions such as knee arthroplasty and peripheral nerve repair, with associated improvements in quality of life and inflammatory markers. Results for delayed-onset muscle soreness and acute ligament injuries were inconsistent. Conclusions: HBOT may provide adjunctive benefits in musculoskeletal pain syndromes, yet the current evidence remains limited. Standardized treatment protocols and high-quality trials are needed to better define its clinical applicability. Full article

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12 pages, 479 KB

Open AccessEditor’s ChoiceArticle

Acute Effects of Multi-Joint Eccentric Exercise on Lower-Extremity Muscle Activation Measured During Land and Water Walking

by Brayden Worley, Brennan J. Thompson, Jon Carey and Talin Louder

Muscles 2025, 4(4), 61; https://doi.org/10.3390/muscles4040061 - 10 Dec 2025

Abstract

Falls are a leading cause of injury and loss of independence in older adults, often linked to deficits in lower-limb muscle function and gait mechanics. Eccentric exercise can improve muscular resilience, while aquatic walking offers a safe, supportive environment to retrain gait; however, [...] Read more.

Falls are a leading cause of injury and loss of independence in older adults, often linked to deficits in lower-limb muscle function and gait mechanics. Eccentric exercise can improve muscular resilience, while aquatic walking offers a safe, supportive environment to retrain gait; however, little is known about how these modalities interact at the neuromuscular level. This study compared lower-limb muscle activation during gait on land and in water, before and after an acute bout of eccentric exercise, in healthy young adults. Surface electromyography was collected from the tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL), and biceps femoris (BF) during treadmill walking on land and at equivalent speeds in chest-deep water. Results showed that aquatic walking consistently altered activation patterns relative to land walking, with increased TA activity (28%, Cohen’s d = 0.69) and reduced GM activity (−27%, Cohen’s d = −0.48) during swing, reduced VL activity during stance (−20%, Cohen’s d = −0.43), increased VL activity during swing (46%, Cohen’s d = 0.72), and increased BF activity during stance (51%, Cohen’s d = 0.63). These changes produced distinct co-activation patterns between the shank and thigh. Eccentric exercise had limited effects overall but increased thigh co-activation during swing in land walking. Findings suggest that eccentric exercise can be safely combined with aquatic walking and highlight the potential of this multimodal approach for enhancing gait mechanics relevant to fall prevention. Full article

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11 pages, 538 KB

Open AccessArticle

Effects of Acute Red Spinach Powder (VitaSpinach^®) Ingestion on Muscular Endurance and Resistance Exercise Performance

by Haley M. Nguyen, Sophia L. Porrill, Rebecca R. Rogers, Josselyn Jose-Gomez, Rachel E. Wright, Phoebe N. Spears and Christopher G. Ballmann

Muscles 2025, 4(4), 60; https://doi.org/10.3390/muscles4040060 - 3 Dec 2025

Abstract

Introduction: Red spinach powder (RSP) contains high amounts of inorganic nitrate/nitrite (NO₃/NO₂), which has been suggested to alter vascular activity, cognitive processing, and sprint exercise performance. There have been few investigations as to whether RSP serves as an ergogenic [...] Read more.

Introduction: Red spinach powder (RSP) contains high amounts of inorganic nitrate/nitrite (NO₃/NO₂), which has been suggested to alter vascular activity, cognitive processing, and sprint exercise performance. There have been few investigations as to whether RSP serves as an ergogenic aid to improve resistance exercise performance, particularly muscular endurance. Purpose: The purpose of this study was to investigate acute RSP (VitaSpinach^®) supplementation on muscular endurance and velocity during bench press exercise. Methods: In a double-blind, counterbalanced crossover manner, resistance-trained males (n = 14) were subjected to two supplement conditions as follows: (1) placebo (PL; purple sweet potato) or (2) red spinach powder (RSP; 400 mg NO₃). Supplements were consumed 2 h prior to exercise and blood was collected immediately pre-exercise to determine NO₃/NO₂ levels. To determine barbell velocity, participants completed two sets × two repetitions with maximal effort, while a rotary encoder measured mean barbell velocity. Following this, participants performed three sets × repetitions to exhaustion (RTE) at 60% of 1-Repetition Maximum (1-RM), separated by 2 min of rest, to determine muscular endurance. Local (lRPE) and global (gRPE) ratings of perceived exertion were measured after exercise. Blood NO₃/NO₂, RTE, mean velocity, lRPE, and gRPE were compared between supplement conditions. Results: RSP resulted in significantly higher blood levels of total NO₃/NO₂ (p < 0.001) compared to PL. RSP did not result in superior total RTE (p = 0.935) but increased mean velocity (p = 0.035) compared to PL. Both lRPE (p = 0.027) and gRPE (p = 0.028) were significantly reduced with RSP supplementation. Conclusions: Findings suggest acute RSP ingestion increased NO₃/NO₂ and bench press velocity. While muscular endurance remained unchanged, RSP resulted in lower perceptions of exertion. Full article

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13 pages, 248 KB

Open AccessEditor’s ChoiceReview

The Psychological Burden of Neuromuscular Diseases: A Narrative Review of Anxiety, Depression, Coping, and Quality of Life

by Valentina Baldini, Giorgia Varallo, Andi Nuredini, Rossella Tupler, Giuseppe Plazzi, Diana De Ronchi, Maria Carmela Pera, Rocco Liguori, Sandro Rubichi and Maristella Scorza

Muscles 2025, 4(4), 59; https://doi.org/10.3390/muscles4040059 - 1 Dec 2025

Abstract

Neuromuscular diseases (NMDs) include a heterogeneous group of progressive chronic conditions that frequently lead to substantial physical disability and loss of autonomy. Although motor and functional impairments of NMDs are well documented, the psychological burden remains underexplored. This narrative review synthesizes current literature [...] Read more.

Neuromuscular diseases (NMDs) include a heterogeneous group of progressive chronic conditions that frequently lead to substantial physical disability and loss of autonomy. Although motor and functional impairments of NMDs are well documented, the psychological burden remains underexplored. This narrative review synthesizes current literature regarding four psychological domains in individuals with NMDs: (i) anxiety, (ii) depression, (iii) coping strategies, and (iv) quality of life. Evidence indicates that anxiety and depressive symptoms are highly prevalent in the spectrum of NMDs, influenced by factors such as disease severity, onset age, and perceived social support. Maladaptive coping strategies, including avoidance and denial, are associated with poorer mental health outcomes and reduced involvement in rehabilitation. In contrast, adaptive strategies, such as acceptance and problem-focused coping, may help buffer psychological distress. Quality of life is consistently reported to be lower in people with NMDs compared to the general population, with psychosocial factors such as social support playing a role. Despite these findings, psychological care remains inconsistently integrated in NMD management. Full article

23 pages, 328 KB

Open AccessReview

An Update on Dermatomyositis and Related Inflammatory Myopathies: Cutaneous Clues, Skeletal Muscle Involvement, and Advances in Pathogenesis and Treatment

by Andres Parga, Dhruv Ratra and Dana Luu

Muscles 2025, 4(4), 58; https://doi.org/10.3390/muscles4040058 - 1 Dec 2025

Abstract

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to [...] Read more.

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to refine diagnosis and management. We surveyed the literature from 2000 to 2025, prioritizing randomized trials, large cohorts, and translational studies that spanned classic and juvenile DM, amyopathic/hypomyopathic variants, and overlap phenotypes. Key insights include the diagnostic weight of pathognomonic cutaneous lesions with nailfold microangiopathy; the utility of myositis-specific autoantibodies for endotyping and risk (e.g., anti-TIF1-γ/anti-NXP2 and cancer, anti-MDA5 and rapidly progressive ILD); and the value of myxovirus-resistance protein A (MxA) immunohistochemistry and muscle MRI patterning (including distinctions from immune-mediated necrotizing myopathy) when enzymes are normal, or biopsies are treatment-modified. Management is anchored in early steroid-sparing immunosuppression tailored to phenotype, with evidence for IVIG in active DM and growing support for JAK inhibition, particularly in interferon-high or anti-MDA5 ILD, alongside selective use of calcineurin inhibitors and rituximab, with plasma exchange considered for refractory, rapidly progressive ILD. We highlight risk-stratified malignancy screening (IMACS 2023) and complications, including calcinosis, lipodystrophy, and chronic cutaneous damage. Skin-led recognition coupled with antibody-guided, phenotype-directed therapy and interdisciplinary care offers a pragmatic precision framework to improve outcomes and reduce long-term disability. Full article

15 pages, 978 KB

Open AccessArticle

Establishing Ultrasound Thresholds for Sarcopenia Diagnosis in Older Brazilian Adults

by Sérgio Zabotto Dantas, Danielli Candido Munhoz Evangelista, Bruna Zampieri Nogueira Cozza, Marcelo Dib Bechara, Sandra Maria Barbalho, Eduardo Federighi Baisi Chagas, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Camila Maria de Arruda, Juliana da Silva Soares de Souza, Karina Quesada and Cláudia Rucco Penteado Detregiachi

Muscles 2025, 4(4), 57; https://doi.org/10.3390/muscles4040057 - 20 Nov 2025

Abstract

Background/Objectives: Despite the increasing use of ultrasound (US) as a tool for assessing muscle mass and diagnosing sarcopenia, its application remains limited because few studies have validated cut-off points for specific populations. This study aimed to propose US cut-off points for diagnosing [...] Read more.

Background/Objectives: Despite the increasing use of ultrasound (US) as a tool for assessing muscle mass and diagnosing sarcopenia, its application remains limited because few studies have validated cut-off points for specific populations. This study aimed to propose US cut-off points for diagnosing sarcopenia in Brazilian individuals aged 60 years and older. Methods: Patients schedule for elective abdominal computed tomography (CT) were also evaluated with musculoskeletal US of the thigh. CT images were obtained at the level of the third lumbar vertebra. US measurements included the thickness of the rectus femoris (RF) muscle and the rectus femoris combined with the vastus intermedius (RF + VI). Receiver Operating Characteristic (ROC) curves determine the sensitivity and specificity of the US cut-off points. The area under the curve (AUC) and 95% confidence intervals (CI) were calculated. Results: The study sample (n = 88) had a mean age of 71.8 ± 8.7 years, and 64% were women. The proposed cut-off points for diagnosing sarcopenia using US, based on the mean ± SD, were ≤19.1 mm and ≤15.9 mm for RF thickness and ≤31.9 mm and ≤29.2 mm for RF + VI thickness in men and women, respectively. These cut-off points demonstrated good accuracy and significant AUC values. Conclusions: This study proposes US-based cut-off points with good accuracy for suggesting sarcopenia diagnosis, particularly when assessing RF thickness. Full article

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11 pages, 328 KB

Open AccessEditor’s ChoiceArticle

Effects of Blackcurrant Extract During High-Intensity Intermittent Running: An Exploratory Study of Possible Muscle Fibre-Type Dependence

by Mark E. T. Willems, Sam D. Blacker and Ian C. Perkins

Muscles 2025, 4(4), 56; https://doi.org/10.3390/muscles4040056 - 14 Nov 2025

Abstract

Intake of anthocyanin-rich blackcurrant extract showed muscle fibre-type specific force responses during fatigue development from combined use of voluntary maximal isometric contractions and electrically evoked twitch contractions of the m. quadriceps femoris. In the present exploratory study, we examined the fibre-type specific [...] Read more.

Intake of anthocyanin-rich blackcurrant extract showed muscle fibre-type specific force responses during fatigue development from combined use of voluntary maximal isometric contractions and electrically evoked twitch contractions of the m. quadriceps femoris. In the present exploratory study, we examined the fibre-type specific effects by blackcurrant extract on high-intensity intermittent treadmill running performance to exhaustion. Active males (n = 16, age: 23 ± 3 years, height: 179 ± 5 cm, body mass: 79 ± 3 kg,

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O_2max: 55.3 ± 5.0 mL·kg⁻¹·min⁻¹) completed a fatiguing protocol with 16 voluntary maximal isometric contractions to predict muscle fibre typology. The high-intensity intermittent running protocol was completed twice following a 7-day intake of blackcurrant extract (210 mg anthocyanins per day) and twice following a placebo (PL) in a randomized, double blind, crossover design. Heart rate and lactate were recorded at exhaustion. Data were averaged for each condition. There were no significant correlations between the percentage force decline by the repeated isometric contractions (mean ± SD: 29.3 ± 12.4%) and total and high-intensity running distance. Participants were categorized into a predominant muscle fibre type I (slow-twitch, n = 3 with the lowest isometric force decline: 12 ± 9%) and type II typology (fast-twitch, n = 3 with the highest isometric force decline: 46 ± 10%). Only the individuals with a predominant type I fibre typology improved the total running and high-intensity running distance by 17 ± 12% and 15 ± 11%. At exhaustion, there were no differences between individuals with a type I or II fibre typology for heart rate and lactate. These exploratory results suggest that the ergogenic potential of anthocyanin-rich blackcurrant extract on high-intensity intermittent exercise may depend on muscle fibre type, though larger and more robust studies are needed to confirm this observation. Future work will establish whether our exploratory results contributed to our understanding of the underpinning of inter-individual responses to the intake of anthocyanin-rich nutritional ergogenic aids. Full article

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17 pages, 912 KB

Open AccessEditor’s ChoiceReview

Sarcopenia in Interventional Radiology: An Opportunistic Imaging Biomarker for Patient Outcomes and Procedural Planning

by Hyeon Yu

Muscles 2025, 4(4), 55; https://doi.org/10.3390/muscles4040055 - 13 Nov 2025

Abstract

Sarcopenia, the loss of skeletal muscle mass and function, is a common and critical comorbidity in patients with conditions frequently managed by interventional radiologists, such as liver cirrhosis and hepatocellular carcinoma (HCC). Interventional radiologists are well positioned to incorporate opportunistic screening for this [...] Read more.

Sarcopenia, the loss of skeletal muscle mass and function, is a common and critical comorbidity in patients with conditions frequently managed by interventional radiologists, such as liver cirrhosis and hepatocellular carcinoma (HCC). Interventional radiologists are well positioned to incorporate opportunistic screening for this condition during routine preprocedural cross-sectional imaging. This review summarizes the current evidence on how sarcopenia influences patient outcomes and informs procedural planning across a spectrum of interventional radiology (IR) procedures. In transarterial embolizations for HCC, sarcopenia is a robust independent predictor of increased mortality, with meta-analyses suggesting it may also predict a lower tumor response rate. Even earlier stages of muscle loss (pre-sarcopenia) are associated with worse survival, and dynamic changes in muscle mass post-treatment can serve as a biomarker for tumor progression. For patients undergoing transjugular intrahepatic portosystemic shunt, pre-procedural sarcopenia and myosteatosis are strong, independent predictors of both mortality and the development of post-procedural hepatic encephalopathy, with the presence of both conferring the highest risk. In the context of pre-surgical portal vein embolization, sarcopenia is consistently associated with impaired volumetric liver growth, although this does not always translate to worse short-term surgical outcomes, as functional liver regeneration may be preserved. Following percutaneous liver tumor ablation, sarcopenia is a powerful predictor of overall mortality, while its role in predicting tumor recurrence remains an area of active investigation. Finally, in non-oncologic interventions for peripheral arterial disease, sarcopenia is highly prevalent and is associated with worse functional status, higher mortality, and a significantly increased risk of major amputation after endovascular therapy. In conclusion, sarcopenia is a powerful and readily available biomarker that provides crucial prognostic information—often independent of standard clinical scores—across a wide spectrum of IR procedures. The consistent evidence supports integrating sarcopenia evaluation into routine practice to enhance risk stratification, improve patient counseling, and guide multidisciplinary treatment planning. Full article

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12 pages, 534 KB

Open AccessEditor’s ChoiceArticle

Muscle Oxygenation Response During Duplicate Sprints in Professional Football Players: An Original Investigation

by Andrew Usher, John Babraj and Adam Younger

Muscles 2025, 4(4), 54; https://doi.org/10.3390/muscles4040054 - 11 Nov 2025

Abstract

Football requires repeated sprint ability for game-changing moments; however, the demand on the skeletal muscles is unknown. The aim of the current study was to determine the muscle oxygen response during duplicate sprints in professional footballers. Eight male professional footballers (age: 29 ± [...] Read more.

Football requires repeated sprint ability for game-changing moments; however, the demand on the skeletal muscles is unknown. The aim of the current study was to determine the muscle oxygen response during duplicate sprints in professional footballers. Eight male professional footballers (age: 29 ± 5 y; height: 181 ± 8 cm; weight: 78 ± 8 kg) were recruited. Participants wore their normal GPS unit and completed their normal match warm-up before near-infrared monitors were attached to the rectus femoris and bicep femoris muscles. Participants then completed two 30 m sprints with 10 s of recovery, while GPS data and muscle oxygenation were recorded. Max speed was unaltered across the two sprints (s1: 8.4 ± 0.3 m.s⁻¹; s2: 8.4 ± 0.4 m.s⁻¹), but max acceleration (s1: 5.0 ± 1.5 m.s⁻²; s2: 3.7 ± 1.2 m.s⁻²) and time to max acceleration (s1: 1.0 ± 0.3 s; s2: 1.8 ± 0.8 s) were significantly different in sprint 2 compared with sprint 1. Change in muscle oxygenation was greater in the bicep femoris muscle than in the rectus femoris muscle in sprint 1 (right BF: 37.0 ± 14.7%; right RF: 23.4 ± 14.8%). Time to fast delay was longer in sprint 2 than in sprint 1 in the bicep femoris muscle (right BFs1: 1.6 ± 1.2 s; right BFs2: 5.2 ± 2.3 s), reflecting different recovery kinetics in the two muscles. During duplicate sprints there is a difference in oxygen response between the two muscles, and the overall recovery of the bicep femoris is much slower. This suggests poorer conditioning of the bicep femoris muscle, which may impact injury risk in professional football players. Full article

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15 pages, 2758 KB

Open AccessEditor’s ChoiceArticle

Altered Transcriptome Signature in Primary Human Myotubes Exposed to Inclusion Body Myositis Serum: A Pilot Case Comparison of Anti-cN1A Positive and Negative Sera

by Nataliya Slater, Abha Chopra, Ramesh Ram, Abbie Adams, Frank L. Mastaglia, Merrilee Needham and Jerome D. Coudert

Muscles 2025, 4(4), 53; https://doi.org/10.3390/muscles4040053 - 10 Nov 2025

Abstract

Inclusion body myositis (IBM) is a late-onset, treatment-resistant inflammatory myopathy. Approximately half of IBM patients develop autoantibodies against cytosolic

5^{'}

-nucleotidase 1A (cN1A), but their role in disease pathogenesis remains unclear. This pilot study examined the effects of anti-cN1A-positive IBM serum on [...] Read more.

Inclusion body myositis (IBM) is a late-onset, treatment-resistant inflammatory myopathy. Approximately half of IBM patients develop autoantibodies against cytosolic

5^{'}

-nucleotidase 1A (cN1A), but their role in disease pathogenesis remains unclear. This pilot study examined the effects of anti-cN1A-positive IBM serum on human primary myotubes’ transcriptome profile, using anti-cN1A-negative IBM and healthy sera as controls. Exposure to anti-cN1A-positive serum altered the expression of 1126 genes, with upregulation of adaptive immune response genes, notably CTSH and CTSZ, encoding cathepsins H and Z. These findings were validated using a publicly available independent dataset comprising transcriptomes from fresh muscle tissue samples. NT5C1A mRNA, which encodes cN1A, was not detected in cultured myotubes regardless of the presence of autoantibodies. The findings suggest distinct pathological mechanisms in anti-cN1A-positive IBM, independent of direct antibody-target interactions. The role of cathepsins in IBM pathogenesis warrants further investigation. Full article

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37 pages, 8035 KB

Open AccessEditor’s ChoiceReview

Dystrophin Restorative and Compensatory Gene Addition Therapies for Duchenne Muscular Dystrophy: Could CRISPRa Provide a Realistic Alternative?

by Zakaria Rostamitehrani, Rida Javed and Linda Popplewell

Muscles 2025, 4(4), 52; https://doi.org/10.3390/muscles4040052 - 10 Nov 2025

Abstract

Duchenne muscular dystrophy (DMD), which results from mutations that disrupt the expression of dystrophin proteins, is characterized by progressive muscle fiber wasting and the development of skeletal muscle fibrosis. The severe pathology leads to loss of ambulation, respiratory insufficiency, cardiomyopathy, and early death [...] Read more.

Duchenne muscular dystrophy (DMD), which results from mutations that disrupt the expression of dystrophin proteins, is characterized by progressive muscle fiber wasting and the development of skeletal muscle fibrosis. The severe pathology leads to loss of ambulation, respiratory insufficiency, cardiomyopathy, and early death in patients. Dystrophin-focused therapies based on adeno-associated viral (AAV) vector-mediated gene addition, antisense oligonucleotide-induced repair of the transcript reading frame, and chemically driven stop codon readthrough have been conditionally approved for use in subsets of patients. From trials, it is apparent that these therapies act to stabilize the disease phenotype rather than improve it significantly, meaning that early treatment results in better outcomes. AAV-mediated delivery of a form of utrophin, a structural and functional homolog of dystrophin, GALGT2, a sarcolemmal stabilizer, and Klotho, the anti-aging hormone that is silenced in a mouse model of DMD as a result of the disease pathology, have been explored in preclinical compensatory gene addition studies. Recombinant follistatin protein has been used to target the fibrosis seen. An all-in-one type of therapy is likely to provide a synergistic effect such that efficacy of the dystrophin restoration strategy would be improved. For this, CRISPRa could hold potential through the targeting of multiple relevant genes simultaneously. The suitability of targeting these genes will be discussed, as will the stages of the development of CRISPRa for DMD. A perspective on the future prospects of CRISPRa in relation to likely issues that would need addressing and how they may be overcame will be given. Full article

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14 pages, 1571 KB

Open AccessArticle

Association of Skeletal Muscle Radiodensity and Skeletal Muscle Index with Immunotherapy Response in Metastatic Non-Small Cell Lung Cancer

by Yuliia Moskalenko, Viktor Kovchun, Ihor Vynnychenko and Roman Moskalenko

Muscles 2025, 4(4), 51; https://doi.org/10.3390/muscles4040051 - 5 Nov 2025

Abstract

Sarcopenia and reduced skeletal muscle radiodensity have been proposed as potential biomarkers influencing the outcomes of immunotherapy in cancer patients. This retrospective study aimed to evaluate the prognostic significance of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), assessed by means of [...] Read more.

Sarcopenia and reduced skeletal muscle radiodensity have been proposed as potential biomarkers influencing the outcomes of immunotherapy in cancer patients. This retrospective study aimed to evaluate the prognostic significance of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), assessed by means of computed tomography imaging at the L3 level, in 76 male patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors. Patients were categorized into high and low SMI/SMD groups based on body mass index-adjusted cut-off values. Clinical outcomes included treatment response, overall survival, and immune-related adverse events. While no statistically significant differences in overall survival were observed between groups stratified by SMI or SMD, patients with higher SMD demonstrated a significantly greater disease control rate (56.22 ± 8.04 vs. 48.36 ± 10.34 HU; p = 0.031). Additionally, a statistically significant interaction was observed between PD-L1 expression and SMI (p = 0.027), indicating that muscle mass may influence the prognostic value of PD-L1. Neither SMI nor SMD were associated with immune-related adverse event incidence. Multivariate analysis identified PD-L1 expression ≥ 50% as the only independent predictor of longer overall survival (Hazard Ratio = 0.29; p = 0.001). In conclusion, while neither SMI nor SMD independently predicted overall survival, SMD was associated with treatment response. Notably, SMI modified the prognostic relevance of PD-L1 expression, suggesting a potential role for muscle mass in refining immunotherapy stratification. Full article

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