Muscles

Exercise-induced muscle injury and the subsequent release of Damage-Associated Molecular Patterns (DAMP) result in soreness and inflammation. Dietary supplements may accelerate the rate of recovery by supporting resolution of inflammation. The purpose of this study was to determine if methylsulfonylmethane (MSM) supplementation (30 d prior to exercise and during recovery) altered mRNA expression in LPS-exposed blood leukocytes after a bout of downhill running. Exercise consisted of 60 min of downhill running (−15% grade). Blood (baseline, pre-exercise, 4, 24, 48, and 72 h post-exercise) was diluted (1:10) and combined with LPS (20 µg/mL) for 24 h. Total RNA was isolated from leukocytes and analyzed for 574 immune-associated mRNA (Nanostring nCounter; ROSALIND.BIO). Data were expressed as log2 fold change from baseline for each condition (MSM and placebo). Compared to placebo, MSM supplementation was associated with an improved inflammation response (15 mRNA) and viral immune response (2 mRNA). The largest number of changes were found at 4 and 24 h post-exercise. The key finding in the present study is that MSM supplementation can improve inflammation management and the innate immune response after exercise. Full article

The skeletal muscle is a highly plastic tissue that shows a remarkable adaptive capacity in response to acute and resistance exercise, and modifies its composition to adapt to use and disuse, a process referred to as muscle plasticity. Heat shock proteins (HSPs), a class of evolutionarily conserved molecular chaperones, have been implicated in the regulation of skeletal muscle plasticity. Here, we summarize key findings supporting the notion that HSPs are important components required to maintain skeletal muscle integrity and functionality. HSPs participate in the transcriptional program required for myogenesis and are activated following muscle exercise and injury. Their dysfunction, either as a consequence of improper expression or genetic mutations, contributes to muscle atrophy and leads to the development of myopathies and peripheral motor neuropathies. Denervation/reinnervation and repeated rounds of nerve degeneration/regeneration have been observed in motor neuropathies, suggesting that an imbalance in HSP expression and function may impair the repair of the neuromuscular junctions. Boosting HSP activity may help preventing muscle atrophy by promoting muscle differentiation and helping the repair of NMJs. Boosting HSP function may also help to combat the development of rhabdomyosarcoma (RMS), a highly aggressive type of pediatric soft tissue sarcoma whose cells have skeletal muscle features but are unable to fully differentiate into skeletal muscle cells. Full article

We describe two cases of myofibrillar myopathies, due to different gene mutations. The first was a girl with cardiomyopathy and sensory axonal neuropathy that underwent cardiac transplantation at 15 years and suffers from rotatory scoliosis due to BAG3 mutation. The second is a male patient, with evident limb-girdle weakness since age 3. Two muscle biopsies were performed at ages 3 and 15, with muscle MRI, and LDB3 gene sequence analysis also carried out. Muscle biopsies revealed the presence of dystrophic changes in the first biopsy and myopathic abnormalities in the second, and the MRI images of the lower limbs showed an asymmetrical involvement in the thigh of quadriceps muscles and in the calf of gastrocnemius muscles. The patient was responsive to treatment with an intermittent steroid regimen and muscle-strengthening exercises. Considerations on both muscle–bone interaction and psychological and socioeconomic conditions are carried out for both cases. Full article

Limb-girdle muscular dystrophies (LGMDs) represent a group of muscle diseases due to monogenic mutations encoding muscle proteins that are defective for heterozygous and homozygous mutations prevalent in certain regions. Advances in knowledge of their pathophysiology have shed light on these rare diseases, which were, until recently, difficult to diagnose. This paper has described the process of diagnosis in autosomal recessive limb-girdle dystrophy that in Tunisia are due to the c.521del mutation in gamma-sarcoglycanopathy and to ethnically specific mutations in other countries such as Italy. The epidemiology, pathophysiology clinical features, and the main socioeconomic needs as well as research progress are discussed. We discuss an Italian case for its psychosocial impact and socioeconomic consideration and compare this case with Tunisian patients. Full article

Musculoskeletal health is directly linked to independence and longevity, but disease and aging impairs muscle mass and health. Complete repair after a pathological or physiological muscle injury is critical for maintaining muscle function, yet muscle repair is compromised after disuse, or in conditions such as metabolic diseases, cancer, and aging. Regeneration of damaged tissue is critically dependent upon achieving the optimal function of satellite cells (muscle stem cells, MSCs). MSC remodeling in muscle repair is highly dependent upon its microenvironment, and metabolic health of MSCs, which is dependent on the functional capacity of their mitochondria. Muscle repair is energy demanding and mitochondria provide the primary source for energy production during regeneration. However, disease and aging induce mitochondrial dysfunction, which limits energy production during muscle regeneration. Nevertheless, the role of mitochondria in muscle repair likely extends beyond the production of ATP and mitochondria could provide potentially important regulatory signaling to MSCs during repair from injury. The scope of current research in muscle regeneration extends from molecules to exosomes, largely with the goal of understanding ways to improve MSC function. This review focuses on the role of mitochondria in skeletal muscle myogenesis/regeneration and repair. A therapeutic strategy for improving muscle mitochondrial number and health will be discussed as a means for enhancing muscle regeneration. Highlights: (a). Mitochondrial dysfunction limits muscle regeneration; (b). Muscle stem cell (MSC) function can be modulated by mitochondria; (c). Enhancing mitochondria in MSCs may provide a strategy for improving muscle regeneration after an injury. Full article

This study examines the relationships between ultrasonography measurements of skeletal muscle size and echo intensity (EI) with muscle strength and local muscle endurance in a habitually resistance-trained population. Twenty young, healthy participants underwent imaging of the biceps brachii in the sagittal and transverse planes and with the extended field of view (EFOV) technique. Linear regression was used to examine measures of muscle thickness (MT), muscle cross-sectional area (mCSA), EI, and corrected EI (cEI) in each scanning plane for their associations with strength (1RM biceps curl) and local muscle endurance (4x failure @ 50%1RM). The strongest predictor of 1RM strength and local muscle endurance was sagittal MT (adj. R² = 0.682) and sagittal cEI (adj. R² = 0.449), respectively. Strength and transverse MT (R² = 0.661) and the EFOV mCSA (R² = 0.643) demonstrated a positive relationship. Local muscle endurance and cEI in the transverse plane (R² = 0.265) and the EFOV scan (R² = 0.309) demonstrated a negative relationship. No associations were shown with uncorrected EI. While each scanning plane supports the muscle size-strength and echogenicity-endurance relationships, sagittal plane imaging demonstrated the strongest associations with muscle fitness. These findings provide important methodological insights regarding ultrasound imaging and muscle fitness relationships. Full article

Background: This study sought to investigate whether different physical function tests (objective measures of physical performance) may identify a low physical resilience in breast cancer survivors (BCS). Methods: This analytical cross-sectional study evaluated 146 BCS and 69 age-matched women without breast cancer history. The different times after the end of treatment were used as criteria for group division. Participants were divided into four groups: control (CT: n = 69–women without breast cancer history); <1.0 years after the end of treatment (<1 YAT: n = 60); 1–3.9 years after the end of treatment (1–3.9 YAT: n = 45); and ≥4 years after the end of treatment (>4 YAT: n = 41). Physical function was evaluated by 4 m walk test (4-MWT), five-times-sit-to-stand test (FTSST), timed up and go test (TUG), and short physical performance battery (SPPB). Age, menopausal status, smoking, number of medications, level of physical activity, body mass index, and muscle strength were used as confounding variables in ANCOVA. Results: All groups that underwent cancer treatment (<1 YAT, 1–3.9 YAT and ≥4 YAT) had lower physical performance (p < 0.001) identified by 4 MWT, TUG, and FTSST when compared to the CT group. For the SPPB, the <1 YAT and ≥4 YAT groups had lower performance (p = 0.005) when compared to the CT. Conclusions: The different physical function tests can be used to identify a low physical resilience in BCS. Full article

Skeletal muscle physiology is regulated by microRNA that are localized within skeletal muscle (myomiRs). This study investigated how the expression of myomiRs and genes regulating skeletal muscle mass and myogenesis are influenced in response to acute and consecutive days of exercise-related signaling using the exercise mimetic, formoterol, in vitro. Human skeletal muscle cells were proliferated and differentiated for 6 days. Experimental conditions included: (a) control, (b) acute formoterol stimulation (AFS), and (c) consecutive days of formoterol stimulation (CFS). For AFS, myotubes were treated with 30 nM of formoterol for three hours on day 6 of differentiation, and this was immediately followed by RNA extraction. For CFS, myotubes were treated with 30 nM of formoterol for three hours on two or three consecutive days, with RNA extracted immediately following the final three-hour formoterol treatment. We observed increased myomiR expression for both AFS and CFS. AFS appeared to promote myogenesis, but this effect was lost with CFS. Additionally, we observed increased expression of genes involved in metabolism, mitochondrial biogenesis, and muscle protein degradation in response to AFS. myomiR and gene expression appear to be sensitive to acute and long-term exercise-related stimuli, and this likely contributes to the regulation of skeletal muscle mass. Full article

The diagnosis of primary mitochondrial myopathy is often delayed by years due to non-specific clinical symptoms as well as variable testing of mitochondrial disorders. The aim of this review is to summarize and discuss the collective findings and novel insights regarding the diagnosing, testing, and clinical presentation of primary mitochondrial myopathy (PMM). PMM results from a disruption of the oxidative phosphorylation (OXPHOS) chain in mitochondria due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Although there are many named syndromes caused by mitochondrial mutations, this review will focus on PMM, which are mitochondrial disorders mainly affecting, but not limited to, the skeletal muscle. Clinical presentation may include muscle weakness, exercise intolerance, myalgia, and rhabdomyolysis. Although skeletal muscle and respiratory function are most frequently affected due to their high energy demand, multisystem dysfunction may also occur, which may lead to the inclusion of mitochondrial myopathies on the differential. Currently, there are no effective disease-modifying treatments, and treatment programs typically only focus on managing the symptomatic manifestations of the disease. Although the field has a large unmet need regarding treatment options, diagnostic pathways are better understood and can help shorten the diagnostic journey to aid in disease management and clinical trial enrollment. Full article

Amyotrophic lateral sclerosis (ALS) is a complex systemic disease that primarily involves motor neuron dysfunction and skeletal muscle atrophy. One commonly used mouse model to study ALS was generated by transgenic expression of a mutant form of human superoxide dismutase 1 (SOD1) gene harboring a single amino acid substitution of glycine to alanine at codon 93 (G93A*SOD1). Although mutant-SOD1 is ubiquitously expressed in G93A*SOD1 mice, a detailed analysis of the skeletal muscle expression pattern of the mutant protein and the resultant muscle pathology were never performed. Using different skeletal muscles isolated from G93A*SOD1 mice, we extensively characterized the pathological sequelae of histological, molecular, ultrastructural, and biochemical alterations. Muscle atrophy in G93A*SOD1 mice was associated with increased and differential expression of mutant-SOD1 across myofibers and increased MuRF1 protein level. In addition, high collagen deposition and myopathic changes sections accompanied the reduced muscle strength in the G93A*SOD1 mice. Furthermore, all the muscles in G93A*SOD1 mice showed altered protein levels associated with different signaling pathways, including inflammation, mitochondrial membrane transport, mitochondrial lipid uptake, and antioxidant enzymes. In addition, the mutant-SOD1 protein was found in the mitochondrial fraction in the muscles from G93A*SOD1 mice, which was accompanied by vacuolized and abnormal mitochondria, altered OXPHOS and PDH complex protein levels, and defects in mitochondrial respiration. Overall, we reported the pathological sequelae observed in the skeletal muscles of G93A*SOD1 mice resulting from the whole-body mutant-SOD1 protein expression. Full article

It is well known that muscular dystrophy disease severity is controlled by genetic modifiers. The expectation is that by identifying these modifiers, we can illuminate additional therapeutic targets with which to combat the disease. To this end we have been investigating the MRL mouse strain, which is highly resistant to muscular dystrophy-mediated fibrosis. The MRL mouse strain contains two mitochondrial-encoded, naturally occurring heteroplasmies: T3900C in tRNA-Met, and variable adenine insertions at 9821 in tRNA-Arg. Heteroplasmies are mitochondrial mutations that are variably present in a cell’s mitochondria. Therefore, MRL cells can contain 0 to 100% of each mitochondrial mutation. We have chosen the severely affected ϒ-sarcoglycan (Sgcg–/–) deficient mice on the DBA2/J background as our muscular dystrophy model to demonstrate the effects of these mitochondrial heteroplasmies on disease severity. Mice from the (Sgcg–/–) DBA2/J (D) and wildtype MRL (M) strains were crossed for more than 10 generations to establish two separate, pure breeding mouse lines: Sgcg+/–Nuc^DMito^%M and Sgcg+/–Nuc^MMito^%M. The Sgcg–/– mice from these separate lines were analyzed at 8 weeks old for membrane permeability, hydroxyproline content, pAMPK content, fibronectin content, and percentage of each heteroplasmy. We have identified that the MRL mitochondrial mutation T3900C confers a portion of the fibrosis resistance identified in the MRL mouse strain. These results have been extended to significantly correlate increased MRL mitochondria with increased pAMPK and decreased muscular dystrophy fibrosis. The beneficial mechanisms controlled by the MRL mitochondria will be discussed. We are establishing metabolic aspects of muscular dystrophy pathogenesis. These metabolic pathways will now be investigated for therapeutic targets. Full article

We have previously shown that hypothermia leads to an increase in the synaptic modulating effects of ATP but not of adenosine in several different animal skeletal muscles. In this paper, we studied the effect of ATP on the amplitude–time parameters of single and tetanic contractions of rats’ isolated fast (1) and slow (2) muscles at different temperatures. We found that when muscles were stimulated by the electrical field (0.1 Hz, 0.5 ms, 10 V), with a decrease in the bath temperature from 37 °C to 14 °C (3), there was an increase in the half-relaxation time of the slow muscle (m. soleus), but not of the fast muscle (m. EDL). Similar effects were observed using a carbachol-induced contraction technique, which suggests the postsynaptic (4) nature of the expansion of the contractile response of the slow muscle induced by ATP (5). To confirm the postsynaptic nature of the observed phenomenon, experiments were performed at a high calcium level (7.2 mM), in which the presynaptic effects of ATP were shown to be offset. We found that the hypercalcium condition did not significantly change the effects of ATP on the measured parameters in both muscles. To record muscle tetanic contractions, we gradually increased the frequency of electrical impulses with the increment of 2.5 Hz to achieve the fusion frequencies of 12.5 Hz for m. soleus and 17.5 Hz for m. EDL at normal temperatures. ATP (100 μM) did not change the fusion frequency for both muscles at a normal temperature but decreased this parameter for the slow muscle to 5 Hz at 14 °C without affecting that for the fast muscle. We conclude that ATP potentiates a hypothermia-induced increase in the half-relaxation time of the contraction of rats’ slow, but not fast, skeletal muscles by acting on postsynaptic P2 receptors (6). Full article

Purpose: To analyze the muscle activation of the rectus femoris (RF), vastus lateralis (VL), gluteus maximus (GM), and biceps femoris (BF) in concentric and eccentric actions in the squat at 90° and 140° range of motion. Methods: Thirty-five women (32.9 ± 7.4 years; 64.5 ± 11.5 kg; 1.63 ± 0.1 m; BMI: 24.2 ± 2.9 kg/m²; %fat: 24.9 ± 6.5%) experienced exercise for at least eight weeks. Electrodes were positioned in standardized locations. The signals were acquired by an A/D SAS1000 V8 converter and the electromyographic activity normalized in the percentage of the highest produced value (%RMS). The data were analyzed using repeated measures two-way ANOVA, with effect size (η²) and differences calculated in percentage points (∆ p.p.). Results: The RF (p = 0.001; ∆ = 5.1 p.p.) and BF activation (p = 0.020; ∆ = 4.0 p.p.) was higher at 90° in the eccentric action. The RF showed an interaction between the range of motion and %RMS, with a large effect size (F = 37.9; p = 0.001; η² = 0.485). The VL activation was higher at 140° (p = 0.005; ∆ = 3.9 p.p.) in the concentric action and higher at 90° (p = 0.006; ∆ = 3.7 p.p.) in the eccentric action, with a large effect size significant interaction (F = 21.3; p = 0.001; η² = 0.485). The GM activation was higher at 90° in the concentric (p = 0.020; ∆ = 5.4 p.p.) and eccentric action (p = 0.022; ∆ = 41 p.p.). Conclusions: The biarticular muscles were influenced by the squat range only in the eccentric action of the movement, while the monoarticular muscles were influenced by the squat in both concentric and eccentric muscle action. Full article

(1) Introduction: Soccer players face high demand for training and games. To facilitate their performance, many studies have investigated ergogenic supplements that can assist in the recovery and performance of players. The aim of this research was to assess whether caffeine supplementation can help soccer players’ recovery and performance. (2) Methods: Professional players were given 210 mg of caffeine or placebo in seven games during the state championship, being offered placebo in three matches and caffeine in four matches, administered 30 min before the game, during the game, and after the game. Blood creatine kinase (CK) and heart rate variability (HRV) were measured. Participants rated their perceived recuperation (RPR) and exertion (RPE) on scales developed by Laurent and Borg, respectively. The time that the player spent on the field was also evaluated. t-tests and Levene’s test were used to analyze the results. In addition to mean differences, variations in the results were also analyzed. (3) Results: No significant differences were found in CK, HRV, RPR, RPE, or minutes on the field when comparing caffeine supplementation with the placebo. (4) Conclusion: Caffeine supplementation throughout the championship appears to have had no ergogenic effect on athlete performance and recovery. Full article

The sarco(endo)plasmic reticulum Ca²⁺ ATPase (SERCA) actively transports Ca²⁺ into the sarcoplasmic reticulum to facilitate cardiac muscle relaxation. Phospholamban (PLN) allosterically inhibits SERCA, and an imbalance of SERCA2a, dominant cardiac isoform, and PLN content disrupts Ca²⁺ homeostasis and cardiac contractility. A previous study has shown that ovariectomized (OVX) rats have reduced SERCA activity due to lowered SERCA2a and increased PLN content. Furthermore, it was found that forced treadmill running in OVX rats restored SERCA activity and protein content levels. Here, we investigated whether voluntary wheel running (VWR) would produce similar effects on cardiac SERCA function in OVX mice. Female mice were divided into the following groups for 8 weeks: SHAM; OVX; SHAM + VWR; and OVX + VWR (n = 10/group). SERCA activity and Ca²⁺ uptake assays were performed in cardiac muscle homogenates. Protein levels of SERCA2, PLN, and pPLN were determined via Western blot analysis. We found statistical interactions for Ca²⁺ uptake, maximal SERCA activity, and SERCA2a content where VWR increased these parameters in SHAM mice but not in OVX mice. We detected a main effect of OVX on PLN content, and main effects of OVX and VWR on pPLN content. The OVX mice ran significantly less than the SHAM mice, suggesting that estrogen deprivation and lack of regular exercise may blunt the effects of voluntary aerobic exercise on cardiac SERCA function. Full article

Progressive supranuclear palsy (PSP) manifests with the loss of skeletal muscle mass, but the longitudinal changes have not been investigated. We studied changes in body composition, including in skeletal muscle mass, in patients with PSP twice, approximately 1 year or more apart, and we compared these measurements with those of patients with Parkinson’s disease (PD). The total number of participants was 42: 10 men had PD, 13 men had PSP, 8 women had PD, and 11 women had PSP. Using a body composition analyzer, we measured such parameters as body mass index (BMI), skeletal muscle mass, basal metabolic rate (BMR), body fat percentage (BFP), and the ratio of extracellular water to total body water. We also calculated the skeletal muscle mass index (SMI). We measured the Barthel index to assess activities of daily living. The Barthel index was lower in patients with PSP than in those with PD at the first evaluation, and it worsened by the time of the second evaluation. In men with PSP, skeletal muscle mass was far more reduced than in those with PD, but no such changes were found among women with either disease. The SMI of men with PSP was correlated significantly with BMI, BMR, BFP, and the Barthel index. Skeletal muscle mass diminished faster in patients with PSP, especially in men, than in patients with PD, probably because of inactivity. Full article

Introduction: Electromechanical delay (ED) and time to peak force (TPF) could be used to investigate the central or peripheral sources of performance decline in fatiguing tasks. Exercise with partial blood flow restriction (BFR) has been shown to induce fatigue, but the repercussions of exercise with partial BFR on ED and TPF are unclear. The present study aimed to compare the ED and TPF after an intermittent isometric task until failure with BFR and free blood flow (FBF). Methods: In this crossover randomized clinical trial, 15 healthy and physically active men volunteered in this study. Volunteers performed two intermittent isometric handgrip exercise (IIHE) to failure (72 h apart), combined with either BFR or FBF. Maximum voluntary isometric force (MVIF) concomitant with the electromyographic activity of the wrist and finger flexor muscles were assessed before (PRE) and one minute after (POST) the task failure. Within (PRE vs. POST) and between comparisons (eFBF vs. eBFR) of peak force, time to peak force, rate of force development (RFDpeak) and ED were carried out. Results: No significant between-intervention differences were identified pre- or post-exercise. Peak force and RFDpeak reduced significantly after both blood flow conditions (p < 0.05), but without between-condition difference. TPF was statistically higher after exercise only in the FBF intervention (p < 0.05). None of the interventions induced a significant change in the ED after IIHE. Conclusion: ED and TPF were similar after BFR and FBF, indicating both conditions induce similar acute performance impairments after IIHE, which seems not to be caused by local (i.e., muscular) factors, but probably by central (i.e., neural) factors. Full article

Creatine monohydrate supplementation in females is largely under-represented in the literature, and their potentially differential hemodynamic responses are unknown. Methods: Twenty-eight resistance-trained women (25.5 ± 6.1 years, 59.7 ± 6.3 kg, 163 ± 5 cm) were randomly assigned to the supplement creatine monohydrate (CRE; 5 g creatine monohydrate + 5 g dextrose) or placebo (PLA; 10 g dextrose) four times per day for 7 days in a double-blind fashion. Each subject subsequently completed resistance training sessions (3 × week) for four weeks with four sets to muscular failure of both half-squat and leg press exercises. The change in body mass (BM), exercise repetition number (REP), rated perceived exertion (RPE), and cardiovascular variables were assessed (sessions 1, 6, and 12). Statistical analyses were performed at a significance level of p ≤ 0.05. Results: Analyses revealed a significant CRE-specific BM increase (p = 0.013), as well as significantly greater half-squat (p = 0.006) and leg press (p = 0.017) REP per set versus PLA. Additionally, CRE demonstrated significantly lower relative RPE values at session 12 compared with previous sessions. Any significant main or interaction effects were observed for the studied cardiovascular variable. Conclusions: The present data substantiate the creatine’s efficacy to improve muscular performance in females while demonstrating the safety of combined creatine monohydrate supplementation and resistance training on cardiovascular parameters. Full article