Skeletal muscle injuries are widespread in everyday life and sports. The purpose of the present study was to determine whether exposure to mild hyperbaric oxygen (MHO) after muscle injury accelerates recovery. Male 8-week-old mice were injected with 30 μL of 10 μM cardiotoxin (CTX) into the left tibialis anterior (TA) muscle and saline into the right TA muscle. The mice were then divided into a normal control (CON) and an MHO (1.3 atm with 38% oxygen) group. Four weeks after CTX injection, cross-sectional area (CSA) was higher in the CTX + MHO group than in the other groups (P < 0.05). The number of centrally nucleated fibers (%) was 11.5% lower in the CTX + MHO group than in the CTX + CON group (P < 0.05), while it was higher in the CTX groups than in the saline groups regardless of MHO exposure (P < 0.05). MHO exposure had a negative main effect on the number of Pax7-positive nuclei (P < 0.05). MHO accelerated muscle recovery, characterized by a reduced proportion of centrally nucleated fibers and increased cross-sectional area of regenerating muscle fibers.

Calcium ion (Ca2+) acts as a second messenger involved in various adaptations by activating signaling pathways. The expression of Ca2+ regulators is modified by resistance training. Thus, Ca2+ signaling may be altered during a period of resistance training. In this study, male Sprague-Dawley rats underwent repeated resistance exercise via transcutaneous electromyostimulation, and the expression of Ca2+-related factors was examined 3 h after the 1st, 5th, and 10th exercise sessions. Expression of sarcolipin (SLN) and regulator of calcineurin 1 (RCAN1) was significantly higher in exercised legs than control legs after the 5th (p < 0.001) and 10th sessions (p < 0.001). Calcineurin expression showed significant main effects of exercise (p = 0.009) and session (p < 0.001). A significant main effect of session was also observed for Ca2+/calmodulin-dependent protein kinase II (CaMKII) (p < 0.001), CaMKII α (p < 0.046), CaMKII β (p = 0.002), and CaMKII γ (p < 0.001). In contrast, expression of sarcoplasmic reticulum Ca2+-ATPase (SERCA) did not change with repeated electromyostimulation. Pearson's correlation analysis showed a significant positive correlation between the expression of SLN and RCAN1 (r = 0.630, p = 0.005) and between SLN and CaMKII γ (r = 0.471, p = 0.048), as well as a trend for a positive correlation between SLN and CaMKII (r = 0.463, p = 0.053). These results suggest that repeated sessions of electromyostimulation increase SLN expression, which may in turn contribute to enhanced Ca2+ signaling after exercise.

Essential amino acids (EAA) and resistance exercise (RE) are well-known approaches to activate muscle protein synthesis. Methionine is an EAA that stimulates mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signalling. It is believed that the lack of a single EAA could blunt protein synthesis. However, to our knowledge, no study has investigated the effects of methionine-restricted diet (MR) on RE-induced anabolic and catabolic signalling in skeletal muscle. Therefore, in this study, we aimed to investigate the effects of MR on RE-induced muscle protein synthesis and breakdown-related signalling. Male Sprague-Dawley rats were randomly divided into Control and MR group, and rats in the MR group were fed the experimental diets for 8 weeks. After the dietary intervention, RE was performed. p70S6K phosphorylation exhibited a significant main effect of RE and MR, with higher values observed across both conditions. FoxO3a Ser253 phosphorylation showed a significant main effects of both RE and MR, with lower values observed across conditions, while MuRF-1 protein expression showed a significant main effect of MR, with lower values observed in the MR condition. Furthermore, muscle protein synthesis demonstrated a significant main effect of MR, with higher values observed across MR conditions. These results suggested that the MR for 8 weeks neither attenuate RE-induced muscle anabolic response nor enhance catabolic response in rat skeletal muscle.

Loss of muscle mass is associated with muscle functional decline and mortality. The present study aimed to determine whether exposure to mild hyperbaric oxygen (MHO) during and after casting immobilization reduces muscle atrophy. We distributed eight‐week‐old rats into control (CON), cast immobilization (Cast), and Cast + MHO (1.3 atmosphere absolute with 38% oxygen) groups. Rats were cast for 2 weeks under the normal or MHO condition, followed by a two‐week recovery period under the same condition after cast removal. The plantaris muscle weight (mg/g BW) decreased by approximately 11.5% in the Cast group compared to the CON group ( p < 0.01), while there were no differences between the CON and Cast + MHO groups, suggesting that MHO enhanced the recovery of muscle atrophy. However, the soleus muscle weight (mg/g BW) decreased by casting immobilization, regardless of MHO. The enzyme activity by succinate dehydrogenase (SDH) staining in the plantaris muscle was lower in the Cast group than in the CON group ( p < 0.01), while there were no differences between the CON and Cast + MHO groups. In summary, MHO enhances the recovery of plantaris muscle atrophy and partially attenuates the decreased SDH activity after cast immobilization of hindlimb in rats.

Mild hyperbaric oxygen (MHO) attenuates the muscle atrophy caused by muscle disuse. Training cessation results in the partial or complete loss of training-induced adaptations, including mitochondrial enzyme activities. The present study aimed to determine whether exposure to MHO after running training attenuated negative adaptation induced by detraining. We allocated eight-week-old mice into training (Tr), detraining after the training period (DeTr), and detraining + mild hyperbaric oxygen (DeTr + MHO, 1.3 atm absolute with 38 % oxygen) groups. Mice underwent voluntary wheel running for four weeks, followed by a two-week detraining period under normal or MHO conditions. The soleus muscle weight (mg/g BW) decreased by approximately 30 % in the DeTr and DeTr + MHO groups compared to the Tr group (P < 0.001 and 0.01, respectively). Citrate synthase (CS) activity, the expression of mitochondrial complex IV, antioxidant-related proteins, catalase, and heme oxygenase 1 (HO-1), decreased in the DeTr and DeTr + MHO group compared to the Tr group (P < 0.05). In summary, MHO did not attenuate the detraining-induced decrease in soleus muscle weight relative to body weight, mitochondrial enzyme activity, protein, or antioxidant protein expression level in the plantaris muscle after a four-week training period using voluntary wheel running in mice.

Finland’s national vitamin D fortification policy has significantly improved the population’s vitamin D sufficiency. This study investigates the association between serum vitamin D concentration and muscle health, considering the impact of menopause and aging in Finnish cohorts. The study comprised two cohorts: 237 middle-aged women (aged 47–55 years) from the Estrogenic Regulation of Muscle Apoptosis (ERMA) study and its follow-up, and 908 older adults (aged 75, 80, and 85 years) from the Active Aging (AGNES) study. Vitamin D concentration was assessed through serum 25-hydroxyvitamin D (25(OH)D) concentrations, alongside measurements of muscle mass and function. High concentrations of 25(OH)D were observed across both cohorts, aligning with Finland’s fortification efforts. Furthermore, no significant correlations were found between 25(OH)D concentrations and indicators of muscle mass or function in either age group. Notably, middle-aged women in menopausal transition exhibited a slight increase in 25(OH)D concentrations, yet this did not translate into improved muscle outcomes. Similarly, older adults demonstrated sufficient 25(OH)D concentrations without a corresponding enhancement in muscle health. The findings indicate that, within the context of Finland’s vitamin D fortification program, serum 25(OH)D sufficiency does not directly correlate with better muscle mass or function among middle-aged and older Finnish populations. These results suggest a need for a broader approach to sarcopenia prevention, incorporating factors beyond vitamin D sufficiency. Further research is warranted to explore the multifactorial nature of muscle health during aging and the menopausal transition, to develop targeted interventions for sarcopenia prevention.

Dietary gamma-aminobutyric acid (GABA) provides physiological benefits and has been extensively studied for its metabolic effects such as reducing stress, hypertension, improving sleep and cognitive function. However, its effects, when combined with exercise training, on endurance exercise capacity remain unclear. In this study, we aimed to investigate the combined effects of dietary GABA supplementation and exercise training on endurance performance in mice and explore its underlying mechanisms. Mice were divided into four groups: (1) control (standard diet, no training), (2) GABA (GABA-supplemented diet, no training), (3) training (standard diet, treadmill training), and (4) GABA-training (GABA-supplemented diet, treadmill training). Skeletal muscle samples were analyzed for molecular and metabolic changes. The findings demonstrated that dietary GABA supplementation significantly increased the treadmill endurance time, with the most pronounced effect observed in the GABA-training group. Mechanistic analysis revealed that these endurance improvements were associated with enhanced activation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), glycogen storage, and mitochondrial biogenesis in skeletal muscle. These findings suggest that dietary GABA supplementation enhances exercise-induced adaptations and endurance performance by modulating key metabolic pathways and may serve as a valuable dietary supplement for athletes and physically active individuals seeking to improve endurance capacity.

Collagen peptides (CPTs) increase muscle mass with resistance exercise training. However, little is known regarding the effect of CPT administration on anabolic signals in skeletal muscle. In this study, we prepared two types of CPTs, one rich in hydroxyprolyl-glycine (CPT-A) and the other rich in hydroxyprolyl-glycine, prolylhydroxyproline, and alanyl-hydroxyprolyl-glycine (CPT-B) and investigated the effects of these peptides on skeletal muscle mTORC1 in mice. Initially, the effects of individual administration of each CPT were investigated. CPT-B increased the expression of phosphorylated rpS6 at 180 min post-administration which was not observed after the administration of whey protein. CPT-A did not induce any significant changes in mTORC1 signaling. Subsequently, their combined effects with whey protein were evaluated. However, the delayed activation was not observed under these conditions. These findings suggest that the CPT-B alone has the potency to activate mTORC1 progressively over time, with a slower onset than whey protein.

Hypereosinophilic syndrome (HES) is characterized by the overproduction of eosinophils and manifests as valvular disease and thrombogenesis. Herein, we report our experience with a patient with HES requiring multiple reoperations for prosthetic heart valve replacement via median sternotomy. The patient was a 54-year-old man who had undergone four valve replacement operations via median sternotomy (three mitral valve replacements and one double valve replacement) because of valvular diseases complicated by HES since he was 26 years old. All the artificial valves were bioprosthetic to prevent thrombotic events. At presentation, he had developed structural deterioration of the artificial aortic valve with severe stenosis. His prosthetic mitral valve did not fulfil the criteria for intervention, as it exhibited only mild regurgitation and no stenosis. The explanted mitral prosthetic valve at the previous (fourth) surgery had exhibited eosinophilic infiltration, resulting in the introduction of cyclosporin for poorly controlled HES. We conducted re-aortic valve replacement via a fifth median sternotomy using a bioprosthetic valve, and no eosinophilic infiltration was observed in the explanted valve. The patient was discharged on postoperative day 15 without complications. Controlling eosinophil count during the pre- and postoperative course is vital in treating patients with HES after valve replacement surgery. A holistic management and therapeutic strategy, including prosthetic valve selection and medication for HES is required to improve outcomes of patients with HES and heart valve disease.

PURPOSE OF REVIEW:The purpose of this review is to critically evaluate the effects of vitamin D on muscle mass and physical/muscle function in middle-aged and older adults, based on recent human studies, including cross-sectional, observational, and intervention studies. Vitamin D, beyond its well established role in bone health, has shown potential in influencing muscle physiology, making it a nutrient of interest in the context of sarcopenia and related chronic conditions. RECENT FINDINGS:The review states how vitamin D affects muscle function, emphasizing its role in muscle cell proliferation, differentiation, and key signaling pathways. Additionally, the review of recent human studies revealed an inconsistent relationship between vitamin D and sarcopenia and related indices, with mixed results regarding muscle mass and strength. Variability in supplementation dose, duration, and baseline 25-hydroxyvitamin D levels may contribute to these inconsistencies. SUMMARY:While animal studies indicate vitamin D's effectiveness in muscle growth, cross-sectional, observational, and intervention studies do not show clear benefits of maintaining efficient vitamin D levels on muscle mass or function in humans. Although vitamin D impacts muscle health, it is insufficient alone, emphasizing the need for a multifaceted approach to sarcopenia prevention and management.

Higher fat-to-muscle mass ratio (FMR) is reported to be a risk factor for various diseases, including type 2 diabetes and cardiovascular diseases, and mortality. Although this association suggests that reducing FMR may help to prevent certain diseases and mortality, the relationship between FMR and lifestyle factors is unclear. Therefore, we performed a cross-sectional study with the aim to elucidate this relationship. This cross-sectional study included 1518 healthy Japanese adults aged 30 to 64 years. We measured FMR in the whole body, arms, legs, and trunk and assessed various lifestyle factors. Then, we performed forced entry multiple regression analyses for FMR with the following variables: sex, age, physical activity, dietary intake, sleep quality, cigarette smoking, stress levels, and body mass index. As a result, whole-body and regional FMRs were correlated with female sex (β = 0.71); age (β = 0.06); physical activity (β = − 0.07); dietary intake of protein (β = − 0.12), carbohydrate (β = 0.04), sodium (β = 0.13), and fiber (β = − 0.16); and body mass index (β = 0.70). The results suggest that in the Japanese middle-aged population, low FMR is associated with certain lifestyle factors, i.e. higher physical activity and a diet with higher protein and fiber and lower carbohydrate and sodium, independent of age, sex, and body mass index.

[Purpose] In gastric cancer patients, low muscle mass decreases overall survival and quality of life (QOL). Resistance exercise with leucine-enriched essential amino acid (LEAA) supplementation may prevent muscle mass loss. This study was aimed at determining whether resistance exercise with LEAA supplementation prevents muscle mass loss in post-gastrectomy patients. [Participant and Methods] We conducted a single-center, open-label, randomized controlled pilot trial. Ten participants who underwent gastrectomy were divided into two groups. The intervention group underwent resistance exercise at 70% of one repetition maximum and received a supplement of 3 g of LEAA twice daily for 15 days, while the control group received standard care. We compared changes in muscle mass, physical function (muscle strength and continuous walking distance), and QOL between the groups. [Results] We found good adherence and participation rates in both groups. We failed to detect a significant difference in muscle mass between the groups. The intervention group showed significant improvements in muscle strength and QOL, while the control group showed no significant changes. [Conclusion] We failed to detect a significant difference in muscle mass due to resistance exercise with LEAA supplementation in post-gastrectomy patients. However, resistance exercise with LEAA supplementation might be beneficial for muscle strength recovery and QOL improvements.

Background Repeat surgery is common in adult congenital heart disease, and valve-related procedures are the most frequent indication for re-intervention. In these cases, problems such as advanced adhesion, deterioration and calcification of the prosthesis used, progression of cardiac dysfunction, and worsening of the general condition are often observed. Case presentation We herein report a 43-year-old patient with repaired pulmonary atresia and ventricular septal defect who experienced repeated right heart failure and protein-losing enteropathy after multiple bioprosthetic tricuspid and pulmonary valve replacements. The patient was successfully treated with a fourth pulmonary valve replacement and third tricuspid valve replacement using a mechanical valve. During surgery, peeling off and removing the right ventricular outflow conduit was risky due to dense adhesion to the ascending aorta with extremely severe calcification; thus, the mechanical pulmonary valve was implanted to a more proximal position of the right ventricular outflow tract after removing the leaflet only and leaving the stent of the bioprosthetic valve within the conduit. The right heart failure and protein-losing enteropathy were relieved with this surgery, and the patient has remained in remission for over 5 years. Conclusion Although severe adhesion and porcelain-like calcification caused by multiple surgical interventions were a major issue in this case, good surgical results were obtained. This method has a major advantage over conventional pulmonary valve replacement with right ventricle outflow tract reconstruction when the right ventricular outflow tract conduit shows severe adhesion and calcification.

AbstractSkeletal muscle mass is critical for activities of daily living. Resistance training maintains or increases muscle mass, and various strategies maximize the training adaptation. Mesenchymal stem cells (MSCs) are multipotent cells with differential potency in skeletal muscle cells and the capacity to secrete growth factors. However, little is known regarding the effect of intramuscular injection of MSCs on basal muscle protein synthesis and catabolic systems after resistance training. Here, we measured changes in basal muscle protein synthesis, the ubiquitin‐proteasome system, and autophagy‐lysosome system‐related factors after bouts of resistance exercise by intramuscular injection of MSCs. Mice performed three bouts of resistance exercise (each consisting of 50 maximal isometric contractions elicited by electrical stimulation) on the right gastrocnemius muscle every 48 h, and immediately after the first bout, mice were intramuscularly injected with either MSCs (2.0 × 106 cells) labeled with green fluorescence protein (GFP) or vehicle only placebo. Seventy‐two hours after the third exercise bout, GFP was detected only in the muscle injected with MSCs with concomitant elevation of muscle protein synthesis. The injection of MSCs also increased protein ubiquitination. These results suggest that the intramuscular injection of MSCs augmented muscle protein turnover at the basal state after consecutive resistance exercise.

Exercise training induces several skeletal muscle adaptations. Beta-guanidinopropionic acid (β-GPA) is a creatine analog that simulates the effect of exercise to induce mitochondrial biogenesis. However, the effects of β-GPA on resistance training adaptation, such as muscle hypertrophy and mitochondrial biogenesis, are unclear. Therefore, using a resistance exercise model in rats, the present study was designed to investigate the effects of β-GPA administration on resistance training adaptations.

Leucine is a branched-chain amino acid that is present in protein, and it is an essential factor in activating the mechanistic target of the rapamycin complex 1 signaling pathway and increasing muscle protein synthesis. However, the loss of digestive function after total gastrectomy leads to impaired protein absorption, potentially failing to stimulate muscle protein synthesis. Therefore, this study aimed to investigate whether muscle protein synthesis is enhanced by oral skim milk administration after total gastrectomy. Male Sprague Dawley rats were divided into total gastrectomy (TG) and sham surgery (S) groups. After five weeks postoperatively, we orally administered skim milk to achieve 3.1 g protein/kg body weight and collected blood and gastrocnemius muscle. The gastrocnemius muscle weight was significantly lower in the TG group than in the S group (p < 0.05). The increase in plasma leucine concentration was significantly lower in the TG group than in the S group (p < 0.05). The skeletal muscle protein synthesis and the phosphorylation of p70S6K and 4E-BP1 showed a similar increase in both groups. Even after TG, muscle protein synthesis was stimulated by consuming skim milk, accompanied by a sufficient rise in plasma leucine concentration.

AbstractTRPM8 agonist has been reported to promote osteogenic differentiation of mesenchymal stem cells (MSCs), therefore we evaluated whether cooling‐induced activation of TRPM8 promotes myogenic differentiation of MSCs. We used 5‐azacytidine as a myogenic differentiation inducer in murine bone marrow‐derived MSCs. Addition of menthol, a TRPM8 agonist, to the differentiation induction medium significantly, increased the percentage of MyoD‐positive cells, a specific marker of myogenic differentiation. We performed intracellular Ca2+ imaging experiments using fura‐2 to confirm TRPM8 activation by cooling stimulation. The results confirmed that intracellular Ca2+ concentration ([Ca2+]i) increases due to TRPM8 activation, and TRPM8 antagonist inhibits increase in [Ca2+]i at medium temperatures below 19°C. We also examined the effect of cooling exposure time on myogenic differentiation of MSCs using an external cooling stimulus set at 17°C. The results showed that 60 min of cooling had an acceleratory effect on differentiation (2.18 ± 0.27 times). We observed that the TRPM8 antagonist counteracted the differentiation‐promoting effect of the cooling. These results suggest that TRPM8 might modulate the multiple differentiation pathways of MSCs, and that cooling is an effective way of activating TRPM8, which regulates MSCs differentiation in vitro.