Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.

Cancer cachexia is a multifactorial syndrome that is identified by ongoing muscle atrophy, along with functional impairment, anorexia, weakness, fatigue, anemia, reduced tolerance to antitumor treatments. Thus, reducing the patients’ quality of life. Cachexia alone causes about 22-25% of cancer deaths. This review covers the symptoms, mediators, available treatment, and prospects of 3D bioprinting for cancer cachexia. Studies about cachexia have shown several factors that drive this disease – protein breakdown, inflammatory cytokines activation, and mitochondrial alteration. Even with proper nutrition, physical exercises, anti-inflammatory agents, chemotherapy, and grafting attempts, standard treatment has been unsuccessful for cachexia. But the use of 3D bioprinting shows much promise compared to conventional methods by attempting to fabricate 3D constructs mimicking the native muscle tissues. In this review, some 3D bioprinting techniques with their advantages and drawbacks, along with their achievements and challenges in in-vivo applications have been discussed. Constructs with neural integration or muscle-tendon units aim to repair muscle atrophy. But it is still difficult to properly bio-print these complex muscles. Although progress can be made by developing new bio-inks or 3D printers to fabricate high-resolution constructs. Using secondary data, this review study shows prospects of why 3D bioprinting can be a good alternate approach to fight cachexia.

Muscle is one of the most critical organs for mammals, which governs multiple movement and physiological functions. Circular RNA (circRNA) is a kind of novel endogenous RNA without 5'-Caps and 3'-poly(A) structures formed by pre-mRNA's back-splicing. RNA binding proteins (RBPs) control the production and degradation of circRNA, help nucleus-cytoplasm transport and locate circRNA, and regulate circRNA translation. Therefore, circRNAs and the chaperoned RBPs play critical roles in muscle growth, development, and disease progression. In this review, we systematically characterize the possible molecular mechanism of circRNA-protein interactions. Also, we summarize the latest researches on circRNA-protein interactions in muscle development and diseases. Besides, we provide several valid prediction methods and experimental verification approaches. Our review reveals the importance of circRNAs and their protein chaperones and provides a reference for further study in this field.

Anterior Cruciate Ligament (ACL) tear is currently a main issue in all of sports communities. Although the number of ACL injuries in football remains low, it’s consequences on both professional and personal lives remain a major concern of rehabilitation. If practitioners often require more time to bring athletes in the best condition, the fact remains that this concept of time before return to sport is nowadays considered as obsolete. Indeed, the better understanding of the mechanisms of lesion and the strains placed on the graft after reconstruction, allow us to establish a personalized program based on clinical criteria and the patient's objectives. The current scientific literature allows us today to optimize the return to play and performance by the use of neuromotor and neurocognitive approaches, muscle strengthening methods and a preventive program necessary to cover the previous level of the players while taking into account physiological and psychological changes due to ACL reconstruction. Indeed, it is important to have a systemic approach centered on the patient, the sports movement, as close as possible to the field in order to find an optimal function of the knee in interaction with its environment.If there is a risk of reinjury of the ACL, it appears important to be able to identify the risk factors so that the player can return to play in optimal conditions.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d >0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d <0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Preventing muscle wasting in certain chronic diseases including cancer is an ongoing challenge. Studies have shown that polyphenols derived from fruits and vegetables show promise in reducing muscle loss in cellular and animal models of muscle wasting. We hypothesized that polyphenols derived from plum (Prunus domestica) could have anabolic and anti-catabolic benefits on skeletal muscle. The effects of a polyphenol-enriched plum extract (PE60) were evaluated in vitro on C2C12 and Colon-26 cancer cells. Treatment of myocytes with plum extract increased the cell size by ~3-fold (p<0.05) and stimulated myoblast differentiation by ~2-fold (p<0.05). Plum extract induced total protein synthesis by ~50% (p<0.05), reduced serum deprivation- induced total protein degradation by ~30% (P<0.05), and increased expression of IGF-1 by ~2-fold (p<0.05). Plum extract also reduced TNFα-induced NFkB activation by 80% (p<0.05) in A549/NFkB-luc cells. In addition, plum extract inhibited growth of Colon-26 cancer cells, and attenuated cytotoxicity in C2C12 myoblasts induced by soluble factors released from Colon-26 cells. In conclusion, our data suggest that plum extract may have pluripotent health benefits on muscle based on its demonstrated ability to promote myogenesis, stimulate muscle protein synthesis, and inhibit protein degradation. It also appears to protect muscle cell from tumor-induced cytotoxicity.

Background: The maximal one-repetition test (1-RM) is widely used in scientific research; however, there are conflict results regarding its reproducibility in elderly population. The present study aimed to analyze the reproducibility the test both before and after a 12 week training period by using the bench press and leg press 45° 1-RM tests in the elderly taking into consideration the training experience and strength level of the women. Methods: Elderly women (n = 376; age, 68.5 ± 14.1 years; height, 162.7 ± 5.5 cm; body mass, 71.2 ± 16.0 kg) who underwent ≥3 months of resistance training performed an initial week of familiarization and a second week of testing and retest, with a 48–72 hour interval. Results: The results showed maximal and relative load strength of 39.3 kg and 0.59 kg/body mass for lower limbs and 20.9 kg and 0.31 kg/body mass for upper limbs. The Kappa indices were 0.93 and 0.95, and the intraclass correlation coefficients were 0.99 and 0.99 for the lower and upper limbs, respectively. Conclusion: Therefore, the present study confirms that the 1-RM test has high reliability and reproducibility in the elderly, for both upper and lower limbs.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

Recently, selection in pigs has been focused on improving the lean meat content in carcasses; this focus has been most evident in breeds constituting a paternal component in breeding. Such sire-breeds are used to improve the meat quantity of cross-breed pig lines. However, even in one breed, a significant variation in the meatiness level can be observed. In the present study, the comprehensive analysis of genes and microRNA expression profiles in porcine muscle tissue was applied to identify the genetic background of meat content. The comparison was performed between whole gene expression and miRNA profiles of muscle tissue collected from two sire-line pig breeds (Piertain, Hampshire). The RNA-seq approach allowed the identification of 627 and 416 differentially expressed genes (DEGs) between pig groups differing in terms of loin weight between Pietrain and Hampshire breeds, respectively. The comparison of miRNA profiles showed differential expression of 57 microRNAs for Hampshire and 34 miRNAs for Pietrain pigs. Next, 43 genes and 18 miRNAs were selected as differentially expressed in both breeds and potentially related to muscle development. According to Gene Ontology analysis, identified DEGs and microRNAs were involved in the regulation of the cell cycle, fatty acid biosynthesis and regulation of the actin cytoskeleton. The most deregulated pathways dependent on muscle mass were the Hippo signalling pathway connected with the TGF-beta signalling pathway and controlling organ size via the regulation of ubiquitin-mediated proteolysis, cell proliferation and apoptosis. The identified target genes were also involved in pathways such as the FoxO signalling pathway, signalling pathways regulating pluripotency of stem cells and the PI3K-Akt signalling pathway. The obtained results indicate molecular mechanisms controlling porcine muscle growth and development. Identified genes (SOX2, SIRT1, KLF4, PAX6 and genes belonging to the transforming growth factor beta superfamily) could be considered candidate genes for determining muscle mass in pigs.

Nine crossbred finishing barrows randomly assigned to 3 dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient, lysine-adequate, or lysine-excess diet for 5 weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. A total of 674 transcripts were differentially expressed (P ≤ 0.05); 60 out of 131 transcripts (P ≤ 0.01) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA, (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA, (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA, and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA, and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA.

Characterized in biomedical terms, stretching exercises have been defined as movements applied by external and/or internal forces – to increase muscle and joint flexibility, decrease muscle stiffness, to elevate joint range of motion (ROM), to increase the length of the morpho-functional unit “muscle-tendon”, to improve joint, muscle and tendon movements, contraction and relaxa-tion. The present review examines and summarizes the initial and recent literature data related to the biomechanical, physiological and therapeutic effects of static stretching (SS) on flexibility and other physiological characteristics of the main structural and functional unit “joint-ligaments-tendon-muscle”. The healing and therapeutic effects of SS, soon combined with other rehabilitation techniques (massage, foam rolling – with and without vibrations; hot/cold therapy, etc.) are discussed in relationship to creation of individual (patient-specific) or group programs for treatment and prevention of joint injuries as well as for improving performance in sports. From a theoretical point of view, the role of SS as positively affecting the composition of the connective tissue matrix is pointed out: type I-III collagen synthesis, hyaluronic acid and glucosaminoglycans (GAGs) turnover – under influence of the transforming growth factor beta-1 (TGF-β-1). Different variables as collagen type, biochemistry, elongation and elasticity are used as molecular biomarkers. Recent studies evaluated that the static progressive stretching therapy could prevent/reduce the development of arthrogenic contractures, joint capsule fibrosis, muscle stiffness and need new clinical applications. Combined stretch techniques are proposed and ap-plied in medicine and sports, depending on their long- and short-term effects on variables such as ROM, EMG activity, muscle stiffness, etc. The results obtained are of theoretical and practical interest for development of new experimental, mathematical and computational models and creation of efficient therapeutic programs. The healing SS effects on the main structural and functional unit – “joint-ligament-tendon-muscle” need further investigations, which could clarify and evaluate benefits of SS in prophylaxis and treatment of joint injuries - in healthy and ill in-dividuals, in older adults, as compared to young, active and well-trained persons, as well as to professional athletes.

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. Back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA recovered at 20 weeks. SDH staining was lower in CKD than control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time.

Background: Parity and vaginal delivery may contribute to female urinary incontinence prev-alence. The aim of this study was to evaluate the impact of parity and type of child delivery on pelvic floor muscle strength (PFMS). Material and Methods: 140 healthy women were prospectively evaluated and distributed into 4 groups: G1 (n=34) 30-40 years old; G2 (n=38) 41-50; G3 (n=35) 51-60 and G4 (n=33) over 60. De-mographic data, and body mass index (BMI) were obtained using a clinical questionnaire. Sub-jective PFMS assessments were performed using transvaginal digital palpation (TDP), and ob-jective evaluation was obtained using a portable perineometer. Results: BMI was significantly higher in G4 compared to G1. There was a positive linear rela-tionship between age and BMI. The number of pregnancies was higher in G4 compared to G2 and vaginal delivery was more frequent in G4 compared to G1 and G3. There was no statistical correlation among different groups in PFMS assessed either by TDP and perineometer. Like-wise, we did not observe any negative linear relationship between PFMS and parity or number of vaginal deliveries. Conclusion: Our data demonstrates that both the number of pregnancies and of vaginal deliv-eries had no impact on PFMS in continent women.

Colorectal cancer is third most common malignancy. For metastasis of rectal cancer, metastasis to skeletal muscle tissue is rare. In this case report, we describe a 51-year-old male patient with rectal cancer with neoadjuvant concurrent radiotherapy and chemotherapy followed by transanal total mesorectal excision with ileostomy. However, he had deep venous thrombosis of left leg after operation and skeletal muscle metastasis was diagnosed via tissue proof. Therefore, less possibility of metastasis increased included brain, duodenum, bone, and nervous system. The prognosis of metastasis to skeletal muscle is poor in contrast to liver or lung metastasis.

Succinate is proposed to be a mediator of muscle exercise-induced adaptations. We studied metabolic health and changes of muscle mass in 6-month-old male mice after 12 weeks of feeding regular diet (RD, 13.4 kcal% fat, 66.8 kcal% carbohydrate, 29.8 kcal% protein), high fat diet (HFD, 60 kcal% fat, 20 kcal% carbohydrates, 20 kcal% protein) and ketogenic diet (KD, 80 kcal% fat, &lt;1 kcal% carbohydrates, 20 kcal% protein) with or without 2% succinate supplements (SUS) in drinking water (n=8-12 per group). Functional overloading of the plantaris muscle (PL) was induced in a group of mice by denervation of the gastrocnemius and soleus muscles at week 6 of feeding different diets. HFD induced the greatest (p &lt; 0.001) increase in body and fat mass. HFD and KD lead to significant (p &lt; 0.01) impairment in glucose tolerance compared to RD. SUS blunted (p &lt; 0.01) initial surge in energy intake when mice were switched from RD to HFD, but did not influence any measures of metabolic health after 12 weeks of the study. Functional overloading lead to ~25% increase in PL mass which was not affected by diet or SUS. In conclusion, SUS does not have a long-term effect on metabolic health or muscle mass.

This review delves into the growing field of flexible and stretchable strain sensors utilized in human gait analysis, focusing on determining knee bending angle and muscle activities when a human subject walks. Recent advancements have enabled these sensors to accurately capture biomechanical parameters while accommodating the body's natural movements. We examine the principles underlying these sensors' design and fabrication techniques, emphasizing their flexibility, stretchability, and biocompatibility for seamless integration into wearable systems. Through critical evaluation of existing methodologies, we assess the reliability and validity of these sensors in quantifying gait parameters. Furthermore, we discuss this technology's clinical and research implications, highlighting its potential in personalized rehabilitation and sports performance optimization. We provide an overview of flexible strain sensors and their application for analyzing human walking gait, especially for observing walking gait in rehabilitation programs. First, we present the basic working principles of various flexible strain sensors. Second, by the application of flexible strain sensors as walking gait monitoring. Finally, current challenges and future opportunities in this research area are discussed. By synthesizing current knowledge and outlining future directions, this review aims to provide insights for researchers and practitioners seeking to leverage flexible and stretchable strain sensors for comprehensive human gait analysis.

In the last three decades the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because of their role in signalling acting. Here we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling both in physiological and pathological conditions.

TMEM16A is a Ca2+-activated Cl- channel expressed in various species and tissues. In mammalian skeletal muscle precursors, the activity of these channels is still poorly investigated. Here, we characterized TMEM16A channels and investigated if the pharmacological activation of Piezo1 channels could modulate the TMEM16A currents in mouse myogenic precursors. Whole-cell patch-clamp recordings combined with the pharmacological agents Ani9, T16inh-A01 and Yoda1 were used to characterize TMEM16A-mediated currents and the possible modulatory effect of Piezo1 activity on TMEM16A channels. Western blot analysis was also carried out to confirm the expression of TMEM16A and Piezo1 channel proteins. We found that TMEM16A channels were functionally expressed in fusion-competent mouse myogenic precursors. The pharmacological blockage of TMEM16A inhibited myocyte fusion into myotubes. Moreover, the specific Piezo1 antagonist Yoda1 positively regulated TMEM16A currents. The findings demonstrate, for the first time, a sarcolemmal TMEM16A channel activity and its involvement at the early stage of mammalian skeletal muscle differentiation. In addition, the results suggest a possible role of mechanosensitive Piezo1 channels in the modulation of TMEM16A currents.

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in the elderly, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants of the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between Low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyzes were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived after a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pain. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise Lower ASM was moderately associated with LBP and knee pain, while higher ASM correlated with engagement in regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pain. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

Treatment options for sarcopenia are currently limited, primarily relying on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. Our objective is to investigate the relationship between nutrient intake and lean mass, function, and strength. Data were derived from the Gothenburg H70 birth cohort study in Sweden, including 719 70-year-olds born in 1944 (54,1 % females). For independent variables, the diet history method (face-to-face interviews) was used to estimate habitual food intake during the preceding three months. Dependent variables were gait speed (muscle performance), hand grip strength (muscle strength) and appendicular lean soft tissue index (ALSTI). Linear regression analyses were performed to analyze the relationship between the dependent variables and each of the covariates. Several nutrients were positively associated with ALSTI, such as polyunsaturated fatty acids (DHA, EPA), selenium, zinc, riboflavin, niacin equivalent, vitamin B12, vitamin D, iron, and protein. After correction for multiple tests, there were no remaining correlations with handgrip and gait speed. Findings of positive correlations for some nutrients with lean mass suggest a role for these nutrients for maintaining muscle volume. These results can be used to inform clinical trials to expand the preventive strategies and treatment options for individuals at risk of muscle loss and sarcopenia.

Functional ankle instability (FAI) results from multiple ankle sprains, causing a perceived sense of joint instability due to muscle and ligament imbalances. Neuromuscular training (NMT) is employed to enhance ankle stability in individuals with FAI. The study included 24 male university students with FAI, who underwent ankle NMT on three surfaces. OpenSim musculoskeletal model analyzed the effects on ankle muscle activity, kinetics, and kinematics. Utilizing repeated measures analysis of variance (ANOVA) and one-dimensional statistical non-parametric mapping (SNPM1d) to identify distinctions between training surfaces. NMT on foam cushion (FC) significantly enhanced tibialis anterior (TA) and gastrocnemius medial (GM) activation during walking compared to level-ground (LG) and artificial turf (AT) (p&lt;0.05). However, no differences observed for peroneus longus (PL), gastrocnemius lateral (GL), and peak ankle plantarflexion (PF). During jogging and fast running, post FC training increased TA, PL, GM, GL activation, and peak ankle PF moment (p&lt;0.05). Additionally, post FC training, subtalar mobility was significantly reduced (p&lt;0.05), and ankle joints exhibited greater dorsiflexion (DF) angles during jogging and fast running (p&lt;0.05). Consequently, selecting FC for short-term ankle NMT proves more advantageous in enhancing ankle stability among individuals with FAI, yielding a more positive impact on FAI improvement.

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17β-estradiol, a major estrogen component, directly affects energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 3D 31P FID-MRSI to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases when their blood 17β-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17β-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17β-estradiol but display a high correlation between EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC).The robust association we have identified between ATP-referenced PCr and 17β-estradiol suggests that 17β-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

Epicatechin has been described as a polyphenol compound that promotes skeletal muscle restructuring, by expressing muscle regulation factors, activation of satellite cells and modulation of the main pathways associated with catabolism. However, the literature shows contrasting results of therapeutic effects and treatment protocols. Thus, the aim of this systematic review was to analyze the current literature addressing the molecular mechanism and clinical protocol of epicatechin on skeletal muscular atrophy in humans and animals. A search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library databases. The qualitative analysis showed a prevalence of the inhibitory action of epicatechin in myostatin expression and atrogenes FOXO, MAFbx and MuRF1. Epicatechin showed positive effects on increased follistatin and on the activation of the myogenic regulatory factors (Myf5, MyoD and myogenin). In addition, the studies evidenced the impact of epicatechin on the mitochondrias' biosynthesis in muscle fibers, activation of the signaling pathway of AKT/mTOR protein synthesis, and improvement of skeletal musculature performance, particularly when associated with physical training. Epicatechin showed promising clinical applicability through beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization allowing to draw more specific conclusions on its therapeutic use.

Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation on airway remodeling in asthma. We conducted a comprehensive search of electronic databases and identified experimental studies and randomized controlled trials that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, and regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to influence many of the pathways central to asthma progression, indicating a promising potential in asthma management and prevenation of asthma progression.

Targets for finished livestock are often determined by expected fat, either subcutaneous or intramuscular. These targets are used frequently to improve the chances of acceptable eating quality. Lower intramuscular fat, lack of product uniformity, and reduced or insufficient tenderness can negatively impact beef acceptability. This study aimed to investigate differences in gene expression that potentially alter subsequent metabolism and intercellular signaling in the muscle and proximate intermuscular and subcutaneous adipose tissue in beef carcasses at different fat endpoints. In this study, Longissimus thoracis muscle samples and associated adipose tissue were collected at harvest. RNA was harvested from both tissues, and individual samples were sequenced using RNAseq. Differential expression was determined using edgeR, and p-values were adjusted using the Benjamini-Hochberg method. A corrected p-value of 0.005 and log₂ (fold change) of 1 was set as the threshold to identify differential expression of genes. Comparison between intermuscular fat and subcutaneous fat showed no differences between the genes activated in the two adipose tissue depots, suggesting that subcutaneous fat could be sampled to evaluate changes in adipose tissue. Carcass data allowed the classification of carcasses by projected USDA quality grades (marbling targets). In the comparison between muscle from Standard and Choice carcasses, 15 genes were downregulated, and 20 were upregulated. The insulin receptor substrate 1 (IRS 1) gene was the only known functionally important gene to be differentially expressed. There were 49 downregulated genes and 113 upregulated genes in the comparison between adipose tissue from Standard and Choice carcasses. These genes are mostly related to the metabolism of fat and energy. This potentially indicates that muscle is not changing at the transcript level as much as the adipose tissue at the sampled endpoints. Also, subcutaneous fat can be used to evaluate transcript changes in both subcutaneous and intermuscular fat. However, it is not clear if these fat tissues can be used as surrogates for intramuscular fat or marbling.

Carbon fiber insole (CFI), which is lightweight and stiff to reduce energy loss and help wearers perform better in sports, has recently been introduced. However, there are scarce reports on the effects of CFI on sports performance, muscle fatigue and wearing comfort. This study investigat-ed the short-term effects of CFI on sports performance, lower extremity muscle activity, and sub-jective comfort. Thirty young healthy males performed various sports tasks and treadmill runs with wearable sensors under two experimental insole conditions (benchmark insole as a baseline, CFI). The results showed that compared to the benchmark insole, CFI significantly improved sports performance in terms of power generation and agility. However, it activated more of the Tibialis Anterior and Gastrocnemius Medialis muscles and was perceived stiffer, and less com-fortable. These findings suggested that CFI can improve sports performance, but it could cause more lower extremity muscle fatigue and subjective discomfort.

Recently, fasting has been spotlighted from a healthcare perspective. However, the de-tailed biological mechanisms and significance by which the effects of fasting confer health benefits are not yet clear. Due to certain advantages of zebrafish, as a vertebrate model widely utilized in biological studies, we used mRNA-sequencing and bioinformatics analysis to examine comprehensive gene expression changes in skeletal muscle tissues during fasting-refeeding. Our results produced a novel set of nutrition-related genes under a fasting-refeeding protocol. We found five dramatically upregulated genes in each fasting (for 24 hours) and refeeding (after 3 hours), exhibiting a rapid response to the provided conditional changes. The assessment of the gene length revealed, the gene set whose expression was elevated only after 3 hours of refeeding had a shorter length, suggesting that nutrition-related gene function is associated with gene length. Taken together, our results from bioinformatics analyses provide new insights into biological mechanisms induced by fasting-refeeding conditions within zebrafish skeletal muscle.

Background: This study aimed to clarify trunk muscle activity during jump header shooting and examine the immediate effects of trunk stabilization exercises on trunk muscle activity. Methods: Nineteen male college students who had played soccer in junior high and high school clubs and youth sports teams for over 5 years were assigned to either the trunk stabilization exercise group (n = 10) or the control group (n = 9). Muscle activity during jump header shooting was measured before and after intervention. The intervention in the trunk stabilization exercise group was trunk muscle training, whereas that in the control group was sitting. The phases of jump header shooting and the effects of the interventions were compared. Results: The internal oblique activity during the push-off phase and early floating phase was significantly greater than that during the late floating phase. The muscle activity of the internal oblique increased from the push-off phase, prior to the increase in muscle activity of the rectus abdominis and external oblique, whereas the muscle activity of all abdominal muscles increased immediately after take-off. The trunk stabilization exercise intervention decreased the muscle activity of the erector spinae during jump header shooting. Conclusions: These results provide useful coaching-related insights for jump header shooting.

We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 µg/day of H2) or H2-depleted placebo (1500 mg/day) for 3 consecutive days. They performed cycling incremental exercise starting at 20-watts work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (VE) and CO2 output (VCO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved-NIRS in the vastus lateralis (VL) and rectus femoris (RF). Blood gases' pH, lactate, and HCO3− concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower VE, VCO2, and higher HCO3−, PCO2 versus placebo. During exercise, a significant pH decrease and greater HCO3− continued until 240-watts work rate in HCP. The VE was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of VCO2 or oxygen uptake (VO2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Oxidative stress is a major contributor to muscle aging and loss of muscle tissue. Jakyakgamcho-tang has been used in traditional Eastern medicine to treat muscle pain. Here, we compared various solvent-based Jakyakgamcho-tang extracts in terms of their effects against hydrogen peroxide-induced oxidative stress in murine C2C12 skeletal muscle cells. Total phenolic content and total flavonoid content in 30% ethanol extracts of Jakyakgamcho-tang were higher than those of water extracts of Jakyakgamcho-tang. Ethanol extracts of Jakyakgamcho-tang had stronger antioxidant and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and 2,2´-diphenyl-1-picrylhydrazyl-scavenging activity than water extracts of Jakyakgamcho-tang. The ethanol extract of Jakyakgamcho-tang inhibited peroxide-induced cell viability and intracellular reactive oxygen species generation more effectively than the water extract of Jakyakgamcho-tang in a dose-dependent manner. These results suggest that the ethanol extract of Jakyakgamcho-tang is relatively more efficacious at protecting against oxidative stress-induced muscle cell death because it prevents reactive oxygen species generation in C2C12 cells. Moreover, the current study indicated that the effective dose of the ethanol extract of Jakyakgamcho-tang required to alleviate muscle pain might be lower than that required for Jakyakgamcho-tang.

Background: The relationship between adherence to the Mediterranean Diet (MD) and both physical fitness (PF) and physical activity (PA) level has been analysed in several studies. The aim of this research was to describe, compare and analyse the level of PF and PA in schoolchildren aged 6-13 in the Region of Murcia, according to adherence to the MD. Methods: A descriptive and cross-sectional study was performed. A total of 370 schoolchildren (44.9% girls) aged 6-13 (8.7±1.8) from six primary schools in the Region of Murcia (Spain). Results: Only 25.9% of the schoolchildren had optimal adherence to the MD. Regarding the scores of the different PF tests in MD groups, only statistically significant differences were found for CRF (p=0.048) in boys. PA level, showed statistically significant differences in both boys (p=0.040) and girls (p=0.016). A positive relationship was found between the KIDMED index and CRF (ρ=.127), standing broad jump (ρ=.133) and PA level (ρ=.235). A higher probability of having a greater CRF (OR=1.17; CI95%=1.02–1.34) and PA level (OR=7.84; CI95%=2.84–21.60) was found in High MD group. Conclusion: These results suggest that an optimal adherence to the MD is associated with higher CRF and PA level in the selected schoolchildren.

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, neurodegenerative disorder caused by degeneration of upper and lower motor neurons. The disease process leads from lower motor neuron involvement to progressive muscle atrophy, weakness, fasciculations for the upper motor neuron involvement to spasticity. Muscle atrophy in ALS is caused by a dysregulation in the molecular network controlling fast and slow muscle fibres. Denervation and reinnervation processes in skeletal muscle occur in the course of ALS and are modulated by rehabilitation. MicroRNAs (miRNAs) are small non-coding RNAs that modulate a wide range of biological functions under various pathophysiological conditions. MiRNAs can be secreted by various cell types and they are markedly stable in body fluids. MiR-1, miR-133 a, miR-133b, and miR-206 are called “myomiRs” and are considered markers of myogenesis during muscle regeneration and neuromuscular junction stabilization or sprouting. We observed a positive effect of a standard aerobic exercise rehabilitative protocol conducted for six weeks in 18 ALS patients during hospitalization in our center. We correlated clinical scales with molecular data on myomiRs. After six weeks of moderate aerobic exercise, myomiRNAs were down-regulated, suggesting an active proliferation of satellite cells in muscle and increased neuromuscular junctions. Our data suggest that circulating miRNAs modulate during skeletal muscle recovery in response to physical rehabilitation in ALS.

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.

Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA [nDNA] and mitochondrial DNA [mtDNA]) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various -omics platforms in unraveling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype-phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field.

Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.

The stiffness of the myosin cross-bridges is a key factor in analysing possible scenarios to explain myosin head changes during force generation in active muscles. The seminal study of Huxley and Simmons (1971: Nature 233: 533) suggested that most of the observed half-sarcomere instantaneous compliance (=1/stiffness) resides in the myosin heads. They showed with a so-called T₁ plot that, after a very fast release, the half-sarcomere tension reduced to zero after a step size of about 60Å (later with improved experiments reduced to 40Å). However, later X-ray diffraction studies showed that myosin and actin filaments themselves stretch slightly under tension, which means that most (at least two-thirds) of the half sarcomere compliance comes from the filaments and not from cross-bridges. Here we have used a different approach, namely to model the compliances in a virtual half sarcomere structure in silico. We confirm that the T₁ curve comes almost entirely from length changes in the myosin and actin filaments, because the calculated cross-bridge stiffness (probably greater than 0.4 pN/Å) is higher than previous studies have suggested. In the light of this, we present a plausible modified scenario to describe aspects of the myosin cross-bridge cycle in active muscle. In particular, we suggest that, apart from the filament compliances, most of the cross-bridge contribution to the instantaneous T₁ response comes from weakly-bound myosin heads, not myosin heads in strongly attached states. The strongly attached heads would still contribute to the T₁ curve, but only in a very minor way, with a stiffness that we postulate could be around 0.1 pN/Å, a value which would generate a working stroke close to 100 Å from the hydrolysis of one ATP molecule. The new program can serve as a tool to calculate sarcomere elastic properties for any vertebrate striated muscle once various parameters have been determined (e.g. tension, T₁ intercept, temperature, X-ray diffraction spacing results).

The aim of this study was to analyze the effects of the playing position (backs vs. pivots vs. wings) and the player role (starter vs. non-starter) on internal match-load and well-being status of female handball players after official matches. Fourteen female handball players from the Spanish 2^nd Division were monitored during a half-season (13 matches, n = 102 individual observations) using rate of perceived exertion (match-RPE) and the Hooper questionnaire in MD+1 and MD+2. Differences between playing positions and player role were determined by Kruskal-Wallis and Mann-Whitney U test, respectively. Furthermore, epsilon-squared (ε²) and Cohen's d (ES) were calculated and interpreted using Hopkins' categorization criteria. The results reveal that backs registered moderately more match-RPE compared to pivots (p < 0.05, ES = 0.84). In contrast, wings experienced the highest values of fatigue and muscle soreness in MD+1 and MD+2 compared to all other playing positions (p < 0.05, ES = 0.66-0.93). Also, wings reported moderately more Hooper index in MD+1 and MD+2 than backs (p < 0.01, ES = 0.73-0.77). Furthermore, starters reported higher absolute values of match-RPE, fatigue, muscle soreness and Hooper index in MD+1 compared to non-starters (p < 0.05, ES = 0.25-0.29). However, no differences were found in MD+2. Therefore, handball coaches and practitioners should consider the internal match-load and the well-being status of the players to implement different training stimulus (e.g., recovery or compensatory strategies) in MD+1 according to playing positions and player role to equalize the total weekly load of the players.

The dietary proteins are one of the most important factors determining health conditions in human. The sufficient digestion and absorption of dietary proteins in the digestive tract have positive effects on performance and recovery in sportspeople or athletes. Improving of protein digestibility is a strategy for maintaining health status and optimal performance in sport or exercise activities. The hypothesis of the present study is that Weizmannia coagulans BC 99 (BC99) can increase muscle mass and strength. This randomized double-blind, controlled trial assigned 72 male college students to receive probiotics (n = 36, 20.25±1.03 years; 1.79±5.94 cm; 73.55±8.73 kg, protein powder with BC99) or placebo (n = 36, 20.19±0.79 years; 179.25±5.16 cm; 73.61±8.24 kg, protein powder) for 12-week. At the baseline and final stages of the study, strength tests and body composition assessment were performed; Blood and stool samples were taken at the end of the 12-week intervention, digestive enzymatic activity of stool samples, biochemical parameters, amino acids and hormone level of plasma were analyzed. BC99 administration significantly improved strength performance, skeletal muscle mass, activity of pepsin and trypsin, the concentrations of branched chain amino acids and essential amino acids, reduced activities of creatine kinase and lactic dehydrogenase and urea nitrogen (BUN) level, and increased testosterone and glucagon-like peptide-1 level in male college students. Therefore, BC99 supplementation can be an important nutritional strategy to improve strength performance, body composition, protein digestion and body metabolism in various groups of individuals.

Background/Objectives: This study aimed to evaluate the effects of an 8-week combined plyometric and resistance training program on the physical fitness of adolescent girls aged 12 to 15 years. The objective was to determine whether combined training (CT) would yield greater improvements in performance measures compared to resistance training (RT) alone. Methods: Forty-seven adolescent girls were randomly assigned to either the CT group or the RT group. Performance measures such as the 20-meter sprint, squat jump, vertical jump, handgrip strength, and flexibility (sit and reach test) were assessed before and after the 8-week interven-tion. Changes in these measures were analyzed to compare the effects of the two training ap-proaches. Results: The CT group showed a significant reduction in sprint time (-6.5%) compared to the RT group (-4.1%), although the difference was not statistically significant. Squat jump height im-proved significantly by 5.6% in the CT group compared to 1.1% in the RT group (p < 0.05). Simi-larly, vertical jump height increased by 6.7% in the CT group and by 2.4% in the RT group (p < 0.05). Handgrip strength improved by 7.5% in the CT group and 4.6% in the RT group, with no significant differences between the groups. Flexibility showed slight, non-significant improve-ments in both groups. Conclusions: The findings suggest that combined plyometric and resistance training is more ef-fective in enhancing explosive power, specifically squat and vertical jump performance, in ado-lescent girls compared to resistance training alone. These results highlight the potential of com-bined training programs for improving overall physical performance in this population.

While adeno-associated viral (AAV) vectors are successfully used in a variety of in vivo gene therapy applications, they continue to be hampered by the immune system. Here, we sought to identify innate and cytokine signaling pathways that promote CD8+ T cell responses against the transgene product upon vector administration to murine skeletal muscle. Eliminating just one of several pathways (including DNA sensing via TLR9, IL-1 receptor signaling, and possibly endosomal sensing of double-stranded RNA) substantially reduced the CD8+ T cell response at lower vector doses but was surprisingly ineffective at higher doses. Using genetic, antibody-mediated, and vector engineering approaches, we show that blockade of at least two innate pathways is required to achieve an effect at higher vector doses. Concurrent blockade of IL-1R1>MyD88 and TLR9>MyD88>IFN I>IFNaR pathways was often but not always synergistic and had limited utility in preventing antibody formation against the transgene product. We further provide evidence that CpG depletion of vector genomes and inclusion of TLR9 inhibitory sequences can have a synergistic effect. However, even low-frequency CD8+ T cell responses could eliminate transgene expression. Thus, innate immune avoidance/blockade strategies, albeit helpful, may not be sufficient to prevent destructive cellular responses in muscle gene transfer because of redundancy of immune activating pathways.

Larrea tridentata is an endemic plant from the Mexican highlands used in traditional medicine to treat hypertension and kidney stones, among many ailments. This study evaluated a vasorelaxant compound: 5- Hydroxy-2-(4-hydroxy-3-methoxyphenyl)-6,7,8-trimethoxy-4H-1-benzopyran-4-one (also known as 8-Methoxycirsilineol: 8-M) which we purified from an extract of this plant. Mesenteric artery rings were isolated from male guinea pigs for isometric force measurements. Freshly isolated smooth muscle cells from mesenteric artery were used for ionic current measurement for calcium and potassium. 10 μM 8-M completely relaxed vascular rings contracted with phenylephrine in a dose-dependent fashion with an EC50 = 4.26 ± 1.16 10-6 M and 4.56 ± 1.64 10-6 M for endothelium intact and endothelium-free tissue, respectively. The relaxant effect of 8-M was not affected by maximal doses of nifedipine, verapamil or iberiotoxin. Nevertheless, the relaxant effect was partially abolished by addition of 10 mM Tetraethylammonium (TEA). In accordance to this, calcium currents evoked by depolarization were not affected by 8-M, whereas TEA-sensitive potassium currents, were increased upon its addition. Vasorelaxation due to 8-M is partly due to activation of KV currents in an endothelium independent mode.

This study investigates the effects of home-based Kakao health care breathing exercises and stretching on respiratory function and fatigue in COVID-19 cured patients. A total of 35 participants performed four movements of home-based breathing exercise and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using FVC, FEV1, FEV1/FVC, and PEF. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using Independent Samples and Paired Samples T-tests in SPSS 24, with a significance level set at p &lt; 0.05. After four weeks of Home based Kakao health care Breathing Exercise, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p &lt; 0.05). Such an increase was observed when comparing these values with the pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function outcomes before and after exercise in the control group (C.G.) (p &gt; 0.05). The FSS scores were statistically significant within the training group (T.G.). (p &gt;0.05). The 4-week Kakao health care Breathing Exercise was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.

Background/Objectives: High-intensity anaerobic physical training frequently results in muscle damage among boxers and kickboxers, which can impede performance and recovery. Vibrational therapy (VT) and passive rest (PR) have been employed as methods to enhance muscular recovery and performance. This study evaluates the effectiveness of these two recovery methods on upper limb muscle strength and lactate levels in plasma after high-intensity exertion. Methods: Eighteen elite boxers and kickboxers, aged 19-32 years, underwent tests employing VT and PR as recovery methods in a controlled, crossover study. Muscle performance was assessed via isokinetic dynamometry, and lactate levels were measured pre-exercise, post-exercise, and post-recovery. The study adhered to the Declaration of Helsinki guidelines and was approved by the relevant bioethics committee. Results: The results showed that VT led to a faster recruitment of muscle fibers and improved muscle endurance as indicated by decreased fatigue work indices compared to PR. However, no significant differences were observed in peak torque or lactate levels between the two recovery methods. The VT group exhibited quicker recovery times in torque generation and better performance in fatigue resistance. Conclusions: VT appears to provide superior muscular recovery compared to PR following intense anaerobic effort, particularly in terms of muscle strength endurance and activation speed. These findings support the potential of VT in sports recovery protocols, although similar lactate response suggests that metabolic recovery rates are not significantly affected.

Skeletal muscle (SKM), despite comprising ~40% of body mass, is rare. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer.

This study analyzes the efficacy of trapezius muscle electromyography (EMG) in discerning mental states, namely stress and meditation. Fifteen healthy participants were monitored to assess their physiological responses to mental stressors and meditation. Sensors were affixed to both the right and left trapezius muscles to capture EMG signals, while simultaneous electroencephalography (EEG) was conducted to validate cognitive states. Our analysis of various EMG features, considering frequency ranges and sensor positioning, revealed significant changes in trapezius muscle activity during stress and meditation. Notably, low-frequency EMG features facilitated enhanced stress detection. For accurate stress identification, sensor configurations can be limited to the right trapezius muscle. Furthermore, the introduction of a novel method for determining asymmetry in EMG features suggests that applying sensors on bilateral trapezius muscles can improve the detection of mental states. This research presents a promising avenue for efficient cognitive state monitoring through compact and convenient sensing.

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Muscle fatigue caused by using staplers affects the surgical procedures of surgeons. Compared to manual staplers, electric staplers decrease the muscle fatigue by replacing repeated gripping and releasing with automatic model. Still powered by the battery, the electric staplers are confronted with new operation fatigue due to the extra weight of the battery. The weight and manual operation of the electric stapler can cause user's muscle fatigue. To tackle the unsettled fatigue issue, the study is to propose a new design method to offset the influence of extra weight of the battery attached to the electrical stapler by changing the opening and closing of the stapler end clamp to electric control. The purpose of this study is to verify whether the design of this electric stapler can offset the impact of weight. Experiments are set up to test the feasibility of the design on 12 male Chinese surgeons. The muscle fatigue is indicated by measuring the EMG (electromyography) signal, and the stapler's working effect is indicated by measuring the end movement of the stapler. The result shows the new-designed stapler reduce the operation fatigue, counteracting the impact of the battery weight.

Resistance training is beneficial to adults for improving muscle strength and reducing the body composition. Nevertheless, little is known regarding online resistance training on anthropometric parameters and muscular strength (MS) in overweight female adolescents. This study aimed to examine the effects of online resistance training on anthropometric parameters and muscular strength (MS) in overweight female adolescents. This prospective, single-center, single-blinded, randomized controlled study included 60 overweight female adolescents who were divided into a control group (n=30) and an intervention group (n=30). The intervention group performed online resistance training, which focused on body weight training of 12 components (4 sets, 12 repetitions) for 45 min, three times per week, for 12 weeks. The intensity of training was 65–75%. Anthropometric parameters, including body weight (BW), body mass index (BMI), body circumference measurements (BCM), and muscle strength (MS), were assessed. All parameters were measured at weeks 0, 8, and 12. Within-group and between-group comparisons were performed. The results revealed improvements in MS, BW, BMI, and BCM in the intervention group. However, chest circumference was not significant. These findings suggest that online resistance training was effective in improving MS and reducing the body composition and circumference.

Background: Muscle wasting is a common phenomenon in oncology and appears to be alleviated by exercise training. This study aims to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles, and whether exercise training can attenuate this muscle dysfunction. Methods: Fifty Sprague-Dawley rats were randomly assigned to four experimental groups, two control groups (sedentary and exercised) and two breast cancer model groups (sedentary and exercised) induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training the animals were sacrificed and the gastrocnemius and soleus muscles were harvested for morphometric analysis. Results: A significant reduction in cross-sectional area (P < 0.05) was found in both muscles of sedentary tumor-bearing animals. Interstitial fibrosis was significantly higher in the gastrocnemius of sedentary tumor-bearing animals (P < 0.05), but not in the soleus. A shift from large to small fibers was observed in the gastrocnemius of sedentary tumor-bearing animals. Long-term exercise training was able to prevent this cancer-related mus-cle dysfunction. Conclusions: The Gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and marked interstitial fibrosis in sedentary animals with tumors. The soleus muscle showed a less pronounced but significant reduction in cross-sectional area, and collagen deposition did not differ between tumor groups. These contrasting results confirm that can-cer-induced muscle wasting can affect specific fiber types, and specific muscles, namely fast glycolytic muscles, and that exercise training can act to improve it.

Previous studies have found that individuals with limited motor capabilities due to acquired neurological injury (e.g., spinal cord injury and stroke) can make accurate action possibility judgements for neurologically healthy individuals. Previous studies have shown that people with limited motor capabilities may rely on previous motor experience (i.e., pre-injury) when making action possibility judgments for others. In the present study, we examined whether having severely limited previous motor experience from birth, as a consequence of spinal muscle atrophy (SMA), alters the action possibility judgments made for neurologically healthy individuals. Participants with SMA and Neurologically Healthy (NH) sex- and age-matched controls performed a perceptual-motor judgment task using the Fitts’s law paradigm (see Fitts, 1954). Participants observed apparent motion videos of reciprocal aiming movements with varying indices of difficulty (ID, see: Manson et al., 2014). For each movement, participants predicted the shortest movement time (MT) at which a neurologically healthy young adult could perform the task while maintaining accuracy. Between-group comparisons revealed that participants with SMA predicted significantly longer MTs compared to controls. Regression analyses revealed that predicted MTs of both NH and SMA participants exhibited a Fitts’s law relationship (i.e., the predicted MTs significantly increased as movement difficulty increased). A supplementary analysis on the SMA group revealed no differences in predicted MTs between the participants with some and no motor function as assessed by the SMA health index. Overall, these results provide evidence that participants with SMA who have limited or no motor experience may make more conservative action possibility judgments for others. Critically, our finding that the pattern of action possibility judgements (e.g., the slopes of the regression lines) were not different between SMA and NH groups provides evidence that limited previous motor experience may not completely impair action possibility judgements.

Cellular senescence is characterized by permanent proliferation and migration arrest, senescence-associated secretory phenotype (SASP), and oxidative stress. Senescent vascular smooth muscle cells (VSMCs) contribute to cardiovascular diseases and atherosclerotic plaque instability. To establish and characterize a model of replicative senescence (RS), human aortic VSMCs were serially passaged to represent different stages of RS such as young proliferating cells and old/senescent non-proliferating cells. More than 50% of old cells stained positive for the senescence-associated β-galactosidase compared to 20% of young cells. Old cells have a slower proliferation rate, a migratory activity reduced by 50%, but increased levels of TP53 and of cell cycle inhibitors p21/p16 expression, and accumulate in the G1 phase. Old cells showed a flattened appearance and enlarged and regular nuclei, and downregulation of the expression of LMNB1 and HMGB1. Old cells showed also an increased expression of SASP molecules (IL1β, IL6, IL8, and MMP3). Moreover, among a set of 12 manually selected long non-coding RNAs (lncRNAs), we detected significant upregulation of PURPL and NEAT1. We observed also increased levels of RRAD mRNA. The detection of novel molecular markers of senescence, such as RRAD, PURPL, and NEAT1, could be helpful for future studies on potential anti-aging factors.

In China, the demand for rabbit meat is also increasing, and the production for rabbit meat is important. However, the underlying mechanisms of regulate skeletal muscle growth and development in rabbits remain unclear. The purpose of this study was to identify candidate genes related to skeletal muscle growth in rabbits and explore their potential regulatory mechanisms. RNA-seq technique was used to compare the differences of skeletal muscle transcriptome in Fujian white rabbits at different developmental stages (day 20 and 26 of embryos and birth 1, 30 and 60-day-olds) with a total of 25 individual selected. A total of 9737 DEGs that were acquired from the five groups were annotated into three ontologies of the GO database: biological process (BP), cell component (CC), and molecular function (MF). For KEGG analysis, there are 8249 genes were enriched in 1148 pathways, of which 67 pathways were significantly enriched, mainly in Hypertrophic cardiomyopathy (HCM), the PPAR signaling pathway, MAPK signaling pathway. Among all comparison groups, SE was the most abundant AS event. Real-time PCR verified that the expression patterns of differential genes were consistent with the transcriptome sequencing results. These results will provide a molecular regulation mechanism of muscle growth and development in Fujian white rabbits, and should serve an important theoretical basis for improving meat performance and growth rate of Chinese local meat rabbit breeds.

Our prior studies have shown that B type Natriuretic Peptide (BNP) decreases absorption from the gastrointestinal (GI) tract. Since non-muscle myosin-type II (NMM-II) is known to have a role in epithelial tight junction regulation, we aimed to test whether BNP has an effect on the localization and expression of NMM-II in the intestinal villi. We treated wild type mice with a 10 ng/g intravenous bolus of BNP followed by infusion of BNP at 1ng/g/minute vs. vehicle control. The mice were then euthanized and intestinal tissue isolated and sectioned. The tissue was immune-stained for NMM-II and examined using fluorescence microscopy. The tissue section not treated with antibody to NMM-II was used as a methodological control to evaluate the non-specific binding. Scanning electron micrographic images were taken to compare structural differences between the two groups. Western blotting was performed to compare the regional protein expression of NMM-II and associated proteins including smooth muscle actin, kinesin, and E cadherin in small intestinal tissue between BNP vs. vehicle infused mice. Fluorescence microscopy revealed markedly increased localization of NMM-II at the crypts and core of intestinal villi of the jejunum, ileum and colon of BNP treated mice compared to vehicle. Transmission electron microscopy revealed that the microvilli of BNP treated mice assumed the distinctive appearance of ‘relaxed’ microvilli compared to vehicle. Such decrease in contractility was previously shown to decrease para-cellular permeability of epithelia. Our observation indicates that BNP alters the localization of NMM-II in intestinal villi and makes the intestinal villi structures assume a state of decreased permeability of the apical junctional complex. Further characterization of this process and understanding the specific mediators involved could lead to the identification of novel therapeutic targets for various disease states such as heart failure and malabsorption.

The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4±6.4 years; 1RM back squat 139.1±26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls, aiming to hit a target 3 meters high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24h, 48h and 72h after the session. The CK concentration 24h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; effect size: 0.74; p≤0.05). At 48h and 72h following exercise, CK concentration had returned to baseline levels. The PRS general and of the lower limbs were lower in the 24-hours post-exercise compared to pre-exercise (PRS general: 4.7 ±1.5 and 7.9 ±1.7 mmol/L; and PRS of the lower limbs: 4.0 ±2.5 and 7.9 ±0.8, respectively). The PRS general, lower, and upper limbs were reduced at 48-post exercise compared to 72-hours post-exercise scores. Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches effectively design the daily session.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low levels of a constant current via scalp electrodes to specifically targeted areas of the brain. The effects of tDCS on whole-body exercise performance has been of interest in recent literature. The purpose of the current investigation was to investigate if tDCS, administered via Halo Sport, influences time trial performance in trained cyclists, and if changes in exercise performance are associated with prefrontal cortex (PFC) activation and/or muscle oxygenation (SmO2). Methods: Twelve recreationally trained cyclists volunteered to participate in two 10-kilometer time trials following 20 minutes of tDCS or a sham condition. Results: T-tests showed there was no significant difference in performance (time to completion) or physiological measures (BLa-, HR, SmO2, PFC oxygenation) between the Halo and sham conditions. Conclusions: These results indicate that the application of tDCS via Halo Sport does not induce changes in exercise performance or related physiological parameters during a 10-kilometer cycling time trial.

(1) Background: The aim of the present study was to evaluate the effect of different types of warm-ups on the strength and skin temperature of Paralympic powerlifting athletes; (2) Methods: The participants were 15 male Paralympic powerlifting athletes. It was analyzed the effects of three different types of warm-up (without warm-up (WW), traditional warm-up (TW), or stretching warm-up (SW)) on static and dynamic strength tests as well as in the skin temperature, which was monitored by thermal imaging; (3) Results: show no differences in the dynamic and static indicators of the force in relation to the different types of warm-up. No significant differences were found in relation to the Peak Torque (p = 0.055, F=4.560, η2p= 0.246 medium effect), and 1-Repetition Maximum (p = 0.139, F=3.191, η2p = 0.186, medium effect) between the different types of warm-up. In the thermographic analysis, there was a significant difference only in the Pectoral muscle clavicular portion between the TW (33.04 ± 0.71ºC) and the WW (32.51 ± 0.74ºC) (p = 0.038). The TW method also presented slightly higher values than the SW and WW in the Pectoral Muscles Sternal portion and in the Deltoid anterior portion, but with p-value &gt; 0.05; (4) Conclusions: that the types of warm-up studied do not seem to interfere with the performance of Paralympic Powerlifting athletes. However, the thermal images showed that traditional warm-up best meets the objectives expected for this preparation phase.

An informative probe of myosin crossbridge behaviour in active muscle is a mechanical transient experiment where, for example, a fully active muscle initially held at constant length is suddenly shortened to a new fixed length giving a force transient, or has its load suddenly reduced giving a length transient. We describe the simplest crossbridge mechanical cycle we could find to model these transients. We show using the statistical mechanics of 50,000 crossbridges that a simple cycle with two actin-attached cross-bridge states, one producing no force and the other producing force, will explain much of what has been observed experimentally and we discuss the implications of this modelling for our understanding of how muscle works. We show that this same simple model will explain reasonably well the isotonic mechanical and X-ray transients under different loads observed by Reconditi et al (2004, Nature 428, 578) and that there is no need to invoke different crossbridge step sizes under these different conditions; a step size of 100 Å works well for all loads. We do not claim that this model provides a total mechanical explanation of how muscle works. But we do suggest that only if there are other observations that cannot be explained by this simple model should something more complicated be considered.

Oleuropein, glycosylated secoiridoid present in olive leaves is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process in a genomic and epigenomic manner by functioning as an efficient antioxidant.

Oleuropein, glycosylated secoiridoid present in olive leaves is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process in a genomic and epigenomic manner by functioning as an efficient antioxidant.

Gross strap muscle invasion (gSMI) in patients with differentiated thyroid cancer (DTC) was defined as high-risk recurrent group in the 2015 American Thyroid Association guidelines. However, controversy persists because several studies suggested gSMI had little effect on disease outcome. Herein, a systematic review and meta-analysis was conducted to investigate impact of gSMI on outcome of DTC. Methods: A systematic search of electronic databases (PubMed, EMBASE, Cochrane Library, and MEDLINE) for studies published until February 2020 was performed. Case-control studies and randomized controlled trials that studied the impact of gSMI on outcome of DTC were included. Results: Six studies (all retrospective studies) involving 13639 patients met final inclusion criteria. Compared with no extrathyroidal extension (ETE), patients with gSMI were associated with increased risk of recurrence (P=0.0004,OR, 1.46; 95% CI: 1.18 to 1.80) and lymph node metastasis (LNM) (P<0.00001,OR 4.19;95% CI. 2.53 to 6.96). For mortality (P=0.34,OR 1.47;95% CI:0.67 to 3.25), ten-year disease-specific survival (P=0.80, OR 0.91;95% CI:0.44 to 1.88) and distant metastasis (DM) (P=0.21, OR 2.94;95% CI. 0.54 to 15.93), there was no significant difference between gSMI and no ETE group. In contrast with maximal ETE, patients with gSMI were associated with decreased risk of recurrence (P<0.0001,OR, 0.58; 95% CI: 0.44 to 0.76) , mortality (P=0.0003,OR 0.20;95% CI:0.08 to 0.48), LNM (P=0.0003,OR 0.64;95% CI. 0.50 to 0.81) and DM (P=0.0009,OR 0.28;95% CI. 0.13 to 0.59). Conclusions: DTC patients with gSMI had a higher risk of recurrence and LNM than those without ETE. However, in contrast with maximal ETE, a much better prognosis was observed in DTC patients with only gSMI. The findings of our meta-analysis provide supportive evidence for the validity of the T category changes in the 8th edition American Joint Committee on Cancer system. The actual impact of gSMI should be re-evaluated and revised in the recurrent risk stratification system in the future.

Background and Aims: We aimed to investigate cross-sectional relationships of relative handgrip strength (RHGS) with presence of diabetes and hypertension in a community setting. Methods and Results: Between 2016 and 2018, we enrolled 601 consecutive women with an average age of 70.7 ± 6.9 years (mean ± SD). Nutritional status was evaluated by the Mini Nutritional Assessment (MNA) score. Muscular strength and level of fitness were assessed by handgrip strength (HGS) and other standardized physical functional tests. The majority of participants were overweight or obese (80% with BMI > 25). Prevalence of diabetes and hypertension was 13 and 60%, respectively. Participants in the lowest quartile of HGS adjusted for BMI (RHGS) had significantly higher prevalence of diabetes and hypertension compared with those in the lower quartile (20.7 vs. 5.3% and 49.3 vs. 39.3%, respectively, p < 0.01 for both), whereas differences in nutritional status were not observed. Likelihood of having diabetes was significantly reduced in women with higher RHGS values (OR 0.77; 0.59–0.86 CI95%; p=0.002), independently of age, abdominal adiposity and presence of hypertension. RHGS was positively correlated with most of the physical functional tests performed. Conclusion: RHGS is an easy-to-obtain and inexpensive measure of muscular strength, independently associated with presence of diabetes in overweight elderly women. Prospective studies are required to assess its predictive value in individuals at risk of new onset or progression of diabetes.

Oleuropein, glycosylated secoiridoid present in the olive leaves, is known as an important antioxidant phenolic compound. We studied the antioxidant effect of low dose of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggest that growth arrest and cell dead of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects myogenesis of C2C12 cells; because the MyoD mRNA levels and the differentiation process are restored after treatment with 3,4-DHPEA-EA(P). Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process by functioning as an efficient antioxidant.

Statins prevent cardiovascular diseases, yet their use is limited by the muscle disturbances they cause. Rarely, statin-induced myopathy is autoimmune, but more commonly it is due to direct muscle toxicity. Available evidence suggests that statin-induced creatine deficiency may be a major cause of this toxicity, and that creatine supplementation prevents it. Statins inhibit guanidinoacetate methyl transferase (GAMT), the last enzyme in the synthesis of creatine, thus they decrease its intracellular content. Such decreased content could cause mitochondrial impairment, since creatine is the final acceptor of the phosphate group of adenosine triphosphate (ATP) at the end of mitochondrial oxidative phosphorylation. Decreased cellular synthesis of adenosine triphosphate (ATP) would follow. Accordingly, ATP synthesis is decreased in statin-treated cells. In vitro, creatine supplementation prevents the opening of mitochondrial permeability transition pore caused by statins. Clinically, creatine administration prevents statin myopathy in statin-intolerant patients. Additional research is warranted to hopefully confirm these findings. However, creatine is widely used by athletes with no adverse events, and has demonstrated to be safe even in double-blind, placebo-controlled trials of elder individuals. Thus, it should be trialed, under medical supervision, in patients who cannot assume statin due to the occurrence of muscular symptoms.

NIRS uses the relative absorption of light at 850nm and 760nm, to determine skeletal muscle oxygen saturation. Previous studies have used the ratio of both signals to report muscle oxygen saturation. Purpose: To evaluate the different approaches used to represent muscle oxygen saturation, and to evaluate the pulsations of the O₂heme and Heme signal. Method: Twelve participants, ages 20-29years were tested on the forearm flexor muscles using continuous wave NIRS at rest. Measurements were taken during 2-3mins rest, during physiological calibration (5-minuts Ischemia) and during reperfusion. Results: There was a significant difference in pulse size between O₂heme and Heme signal at the three locations (p < 0.05). Resting oxygen saturation was 58.8+9.2%, 69.6+3.9%, and 89.2+6.9% when calibrated using O₂heme, TSI, and Heme, respectively. Conclusion: The difference in magnitude of O₂heme and Heme pulse with each heartbeat might suggest different anatomical locations of these signals, which propose calibrating with just one of the signals instead of the ratio of both. Calculations of physiological calibration must account for increased blood volume in the tissue, because of the changes in blood volume which appear to be primarily from the O₂heme signal. Resting oxygen levels calibrated with Heme agrees with theoretical oxygen saturation.

Background/Objectives: To describe the effects of muscle-targeted oral nutritional supplementation (MT-ONS) on nutrition, functional capacity, and other health outcomes in patients after femur fracture surgery; Methods: A prospective, open-label, single-center study was conducted. Patients aged 80+ post-femur fracture were recruited. They were assessed at baseline and after 90 days with MT-ONS, 100% whey protein enriched with leucine and vitamin D. Demographics, clinical and nutritional status (MNA®-SF), functional capacity [Barthel Index (BI), Lawton &amp; Brody (LB) scale], muscle strength (dynamometry), cognition [Global Deterioration Scale (GDS)], tolerability, and satisfaction data were collected. Descriptive statistics were performed. Ethical approval was obtained; Results: Thirty-one patients (74% women, mean age 87 ± 3.99 years) were enrolled. At baseline, 32% were malnourished and 65% at risk. After ≥90 days of MT-ONS, malnutrition decreased to 13% and well-nourishment increased to 32%. Ninety percent gained weight, with significant muscle strength improvements (+2 kg, p&lt;0.001). Eighty-one percent achieved a BI score ≥60 points [mean 84.8 (± 17.82)]. BI score improvements correlated with higher baseline muscle strength (rho=0.413, p=0.021) and better nutritional status (rho=0.464, p=0.009). LB mean score was 4.84 (± 2.26). Improvements correlated with pre-fracture BI score (rho=0.475, p=0.007). Positive correlations were noted between nutritional status, muscle strength, and functional outcomes. Cognition remained stable (GDS=1 in 67.7% patients). Tolerability and satisfaction with MT-ONS were high at 90%; Conclusions: MT-ONS, 100% whey protein enriched with leucine and vitamin D for ≥90 days, enhances nutritional status and functional recovery in patients after femur fracture surgery.

Maximal athletic performance can be limited by various factors, including restricted respiratory function. These limitations can be mitigated through targeted respiratory muscle training, as supported by numerous studies. However, the full potential of respiratory training in competitive finswimming has not been fully investigated. This case study aims to evaluate performance variability during underwater phases in an elite Bi-Fins swimmer (current world record holder and multiple world championship medallist) over a 200m race simulation after an eight-week respiratory training using Airofit PRO™. Performance variability was assessed based on pre-test, inter-test, and post-test data. Each measurement included pulmonary function, body composition, and swim performance evaluations. The swimmer followed a 28-day training program with the AiroFit PRO™ respiratory trainer between tests. Significant improvements were observed in Wilcoxon paired-sample test between the pre-test and post-test in underwater distance (p=0.012; d=1.26), underwater time (p=0.012; d=1.26), and number of underwater kicks (p=0.043; d=1.01), resulting in a 14.23% longer underwater distance, 14.08% longer underwater time, and 14.94% increase in underwater kicks. Despite increased distance and time, underwater velocity remained stable, indicating improved underwater performance efficiency. The results suggest that the AiroFit PRO™ respiratory trainer has practical applications in finswimming training programs.

This paper presents an interpretable support vector machine (SVM) and its application to rehabilitation assessment. We introduce the concept of nearest boundary point to standardize the one-class SVM decision function and determine the shortest path for data from abnormal cases to become those from normal cases. This analytical approach is computationally simple and provides a unique solution. The nearest boundary point of abnormal data can also be used to analyze the cause of abnormal classification and indicate countermeasures for normalization. These properties render the proposed interpretable SVM valuable for medical assessment applications and other problems that require careful consideration of classification results for treatment. Simulation and application results demonstrate the feasibility and effectiveness of the proposed method.

This study investigates the collapse of the medial longitudinal arch (MLA) as a risk factor for medial tibial stress syndrome (MTSS), hypothesizing that overuse of extrinsic foot muscles to prevent MLA collapse can lead to disability. Twenty healthy adults (39 feet) with a foot posture index score below 6 and no recent lower extremity orthopedic history participated. Ultrasonog-raphy measured foot muscle cross-sectional areas, while three-dimensional motion analysis us-ing VICON assessed foot kinematics during gait, focusing on navicular height at initial contact (ICNH) and dynamic navicular drop (DND) during the stance phase. Hierarchical cluster analy-sis based on ICNH and DND compared muscle cross-sectional areas between clusters using ANOVA or Kruskal–Wallis test. The analysis indicated that ICNH was lower in clusters 1 and 3 than in cluster 2, and DND was smaller in clusters 1 and 2 than in cluster 3. Although there was no significant difference in muscle cross-sectional area between the clusters, the flexor hallucis longus tended to be thicker in cluster 1 than in cluster 3 (p = 0.051). The findings suggest that the flexor hallucis longus may help prevent MLA compression during loading, indicating that over-use of extrinsic foot muscles may contribute to MTSS development.

Background: This study investigates microvascular changes in the dermis and muscle following a balneotherapy regimen prescribed by therapeutic protocols. Methods: Thirty-five inpatients participated in a two-week balneal course involving the application of mud and hypersaline water. Mud was applied outdoors in the summer as cold mud ointment and indoors year-round as mud packs or mud baths alternated with hypersaline water baths. Biopsies of the skin and muscle were obtained twenty-four hours post-discharge and prepared histologically. Results: Analysis focused on the epidermis, dermis, and muscle. Microvascular changes observed included increased caliber and number of open capillaries, as well as the presence of angiogenesis vessels. Statistical analysis showed significant differences in angiogenesis vessels between cold mud ointment and mud pack treatments compared to control and mud bath groups. A higher number of angiogenesis vessels were observed in the dermis in the mud pack group and in the muscle with mud cold ointment. Repeated thermal stimulation with mud and hypersaline water over two weeks produced histologically evident tissue modifications, persisting in the dermis and muscle at least twenty-four hours post-treatment completion.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration of gemcitabine and docetaxel (Gem/Doce) as the first-line treatment in BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed treatment protocol set by the University of Iowa. Follow-up assessments were con-ducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with T1HG bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of CIS+T1HG. Median time to first recurrence in T1HG, CIS and T1HG+CIS groups was 11, 10.5 and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2% and 80.8% at 6, 9 and 12 months, respectively. The rate of progression-free survival was 100%, 98.1% and 92.3% at 6, 9 and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-up, as well as direct comparison of Gem/Doce and other anticancer agents, are essential.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.

Abstract: A progressive neurological disorder was observed in a male neutered Weimaraner. Clinical signs included fecal incontinence, lethargy, moderate paraparesis, proprioceptive pelvic limb ataxia, falling, cognitive decline, incoordination, decreased interest in food, changes in posture, and episodes of trance-like behavior. Neurologic signs were first observed at approximately 4 years, 10 months of age and progressed slowly. Magnetic resonance imaging showed generalized brain atrophy with areas of white matter pathology. Humane euthanasia was elected at 6 years, 7 months of age due to increasing severity of the neurological signs. Autoflorescent intracellular granules were observed in the cerebral and cerebellar cortexes, optic nerve, and cardiac muscle of the affected dog. These abnormal inclusions in the cerebral cortex and cardiac muscle immunolabeled with antibodies to mitochondrial ATP synthase subunit c protein, like that observed in the neuronal ceroid lipofuscinosis group of lysosomal storage diseases. Immunolabeling also demonstrated pronounced neuroinflammation in brain tissues. The ultrastructural appearances of the disease-related inclusion bodies in the brain and optic nerve were quite variable. The ultrastructure and locations of many of the inclusions in the nervous tissues suggested that they were derived, at least in part, from the myelin surrounding axons. The storage bodies in the cardiac muscle were located in mitochondria-rich regions and consisted of parallel arrays of membrane-like components interspersed with electron-dense flocculent material. The disease was characterized by pronounced abnormalities in the myelin of the brain and optic nerve consisting of distinctive areas of ballooning between the layers of myelin. The whole genome sequence generated from the affected dog contained a homozygous G-to-A missense mutation in CNP, which encodes proteins with CNPase enzyme activity and a structural role in myelin. The mutation predicts a Thr42Met amino acid sequence substitution. Genotyping of archived Weimaraner DNA samples identified an additional G>A variant homozygote with a clinical history and brain lesions similar to those of the proband. Of 292 Weimaraners and over 4,000 other dogs of various breeds, the proband and the other Weimaraner that exhibited similar signs were the only two that were homozygous for the CNP missense variant. CNPase immunolabeling was widespread in brain tissues from normal dogs but was undetectable in the same tissues from the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the late-onset Weimaraner disorder likely results from the missense mutation that results in CNPase deficiency, leading to myelin abnormalities, accumulation of lysosomal storage bodies, and brain atrophy. Similar disorders have been associated with different CNP variants in Dalmatians and in human subjects.

This paper presents a thorough review of Electrical Muscle Stimulation (EMS) in the context of Augmented Reality (AR) and Virtual Reality (VR), specifically focusing on its application in providing kinesthetic feedback. Our systematic review of 17 studies reveals the growing interest and potential of EMS in this domain, as evidenced by the growing body of literature and citations. Key elements presented in our review encompass a catalog of the applications developed to date, specifics of the stimulation parameters used, the participant demographics of the studies, and the types of measures used in these research efforts. We discovered that EMS offers a versatile range of applications in AR/VR, from simulating physical interactions like touching virtual walls or objects, to replicating the sensation of weight and impact. Notably, EMS has shown effectiveness in areas such as object handling and musical rhythm learning, indicating its broader potential beyond conventional haptic feedback mechanisms. However, our review also highlights major challenges in the research, such as inconsistent reporting of EMS parameters and a lack of diversity in study participants. These issues underscore the need for improved reporting standards and more inclusive research approaches to ensure wider applicability and reproducibility of results.

Epigenetic modifications play a significant role in determining the fate of AFSC in terms of differentiation into multiple lineages. There is a tight correlation among DNA methylation, histone modifications, and small noncoding RNAs during the epigenetic control of stem cells differentiation. The present study investigates the role of miRNAs in differentiation of AFSC and addresses how their unique signatures contribute to lineage-specific differentiation. miRNAs profile was assessed in AFSC after 4 weeks of endothelial and muscular differentiation. Our results showed a decreased expression of for 5 miRNAs (miR-125b-5p, hsa-miR-18a-5p, hsa-miR-137, hsa-miR-21-5p and hsa-let-7a-5p) and an increased expression for 12 miRNAs (miR-134-5p, miR-103a-3p, let-7i-5p, miR-214-3p, let-7c-5p, miR-129-5p, miR-210-3p, let-7d-5p, miR-375, miR-181-5p, miR-125a-5p, hsa-let-7e-5p) in EPC compared with undifferentiated AFSC. Smooth muscle differentiation of AFSC revealed significant changes in 9 miRNAs from total of 84 tested; 3 were downregulated (miR-18a-5p, miR-137, sa-miR-21-5p) and 6 were upregulated (miR-155-5p, miR-20a-5p, let-7i-5p, hsa-miR-134-5p, hsa-miR-214-3p, hsa-miR-375). miRNAs are molecular regulators of cell fate and differentiation, recent advances in molecular biology techniques revealed miRNA regulatory networks that can provide us information of endothelial and muscle cell biology in terms of homeostasis, growth, differentiation, and vascular function.

Abstract: Sarcopenia poses a significant challenge to public health and can severely impact the quality of life of aging populations. Despite extensive efforts to study muscle degeneration using traditional animal models, there is still a lack of effective diagnostic tools, precise biomarkers, and treatments for sarcopenia. Zebrafish models have emerged as powerful tools in biomedical research, providing unique insights into age-related muscle disorders like sarcopenia. The advantages of using zebrafish models include their rapid growth outside of the embryo, optical transparency during early developmental stages, high reproductive potential, ease of husbandry, compact size, and genetic tractability. By deepening our understanding of the molecular processes underlying sarcopenia, we may develop novel diagnostic tools and effective treatments that can improve the lives of aging individuals affected by this condition. This review aims to explore the unique advantages of zebrafish as a model for sarcopenia research, highlight recent breakthroughs, outline potential avenues for future investigations, and emphasize the distinctive contributions that zebrafish models offer. Our research endeavors to contribute significantly to addressing the urgent need for practical solutions to the impact of sarcopenia on aging populations, ultimately striving to enhance the quality of life for individuals affected by this condition.

Despite limited research on the effects of a combined physical exercises on static and proactive postural control and neuromuscular functions in older adults with sarcopenic obesity (SO), this study addresses the gap by examining the efficacy of a 4-month Total Mobility Plus (TMP) regimen. The study enrolled 40 older adults with SO, split into an intervention group (n=25, mean age = 76.1 ± 3.5 years; mean BMI = 34.4 ± 4.0 kg/m²) and a control group (n=25, mean age = 75.9 ± 5.4 years; mean BMI = 32.9 ± 2.3 kg/m²). Participants in the IG engaged in 60-minute TMP sessions three times a week for four months, while the CG maintained their typical daily activities. Standardized evaluations were performed before and after the intervention, including the Romberg and Timed Up and Go (TUG) tests, Center of pressure (CoP) parameters during different conditions, muscle activation and strength of plantar and dorsal flexors. Post-intervention results revealed significant reduction of the standing time measured in the Romberg (-15.6%, p<0.05), and TUG (-34.6%, p<0.05) tests. Additionally, CoP area and velocity, were notably reduced in various conditions (p<0.05). Postural control improvements were associated with an increase of strength and decrease of ankle muscle activation. These findings validate the TMP program as a safe and effective method for enhancing static and proactive postural control and neuromuscular capabilities in older adults with SO.

Pigs are susceptible to cold stress due to the absence of brown fat caused by the partial deletion of uncoupling protein 1 during their evolution. Some local pig breeds in China, exhibit potential cold adaptability, but research has primarily focused on fat and intestinal tissues. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, yet the molecular mechanism of cold adaptation in porcine skeletal muscle remains poorly understood. This study investigated the cold adaptability of two pig breeds, Mashen pigs (MS) and Large White pigs (LW), in a 4-day cold (4°C) or room temperature (25°C) environment. We recorded phenotypic changes and collected blood, and longissimus dorsi muscle for transcriptome sequencing. Finally, a candidate gene was randomly selected for functional exploration in porcine skeletal muscle satellite cells. A decrease in body temperature and body weight in both LW and MS pigs under cold stress, accompanied by increased shivering frequency and respiratory frequency. However, MS pigs demonstrated stable physiological homeostasis, indicating a certain level of cold adaptability. LW pigs primarily responded to cold stress by regulating heat production and Glycolipid energy metabolism. MS pigs exhibited a distinct response to cold stress, involving regulation of heat production, energy metabolism pathways, robust fatty acid oxidation ability, and stronger immune response. Furthermore, the functional exploration of PRSS8 in porcine skeletal muscle satellite cells revealed it affected cellular energy metabolism and thermogenesis by regulating ERK phosphorylation. These findings shed light on the diverse transcriptional responses of skeletal muscle in LW and MS pigs under cold stress, offering valuable insights into the molecular mechanisms underlying cold adaptation in pigs.

This study aimed to investigate the influence of cranio-cervical position on the electromyographical activity of the core muscles during the prone plank exercise. Twenty healthy participants were enrolled in this study. Muscle activation was registered using surface electromyography (sEMG) in the rectus abdominis (RA), external oblique (EO), internal oblique (IO) and lumbar portion of erector spinae (LES). Three prone plank conditions were randomly evaluated, varying the position of the cranio-cervical segment during the prone plank performance (NEUTRAL, FLEXION and EXTENSION). sEMG signals of each individual muscle, Total Intensity (TI) and ratings of perceived exertion (RPE) were analysed with statistical significance set at P&lt;0.05. FLEXION revealed significantly higher TI values compared to NEUTRAL and EXTENSION (p = 0.000; effect size (ES) &gt; 0.90). The RA presented larger activation in FLEXION compared to the other variations (p &lt; 0.05; ES &gt;0.70). FLEXION elicited a greater response compared to NEUTRAL for both sides of EO when compared to EXTENSION, and also for both sides of IO compared to the other conditions. Both FLEXION and EXTENSION reported higher RPE values compared to NEUTRAL. Cranio-cervical segment position influenced the electromyographical activation of core musculature, showing highest values when performing prone plank in a cranio-cervical flexion.

Background: This systematic review aimed to provide a comprehensive overview of the effects of Functional Electrical Stimulation (FES) on gait characteristics in healthy individuals. Methods: Six electronic databases (PubMed, Embase, Epistemonikos, PEDro, COCHRANE Library, Scopus) were searched for studies evaluating the effects of FES on spatiotemporal, kinematic and kinetic gait parameters in healthy individuals. Two examiners evaluated the eligibility and quality of included studies using the PEDro scale. Results: A total of 15 studies met the inclusion criteria. Findings from the literature reveal that FES can be used to modify lower-limb joint kinematics, i.e., to increase or reduce the range of motion of hip, knee and ankle joints. In addition, FES can be used to alter kinetics parameters, including ground reaction forces, center of pressure trajectory, or knee joint reaction force. As a consequence of these kinetics and kinematics changes, FES can lead to changes in spatiotemporal gait parameters, such as gait speed, step cadence, and stance duration. Conclusion: The findings of this review improve our understanding of the effects of FES on gait biomechanics in healthy individuals, and highlight the potential of this technology as a training or assistive solution for improving gait performance in this population.

The development of sarcopenia in the elderly is associated to many potential factors and/or processes, that impair the renovation and the maintenance of skeletal muscle mass and strength as ageing progresses. Among them, a defect by skeletal muscle to respond to anabolic stimuli is to be considered. Common anabolic stimuli/signals in skeletal muscle are hormones (insulin, growth hormones, IGF-1, androgens, β-agonists such epinephrine), substrates (amino acids as protein precursors on top, but also glucose and fat, as source of energy), metabolites (such as β-agonists and HMB), some cytokines, various biochemical/ intracellular mediators), physical exercise, neurogenic and immune-modulating factors, etc. Each of them may exhibit a reduced effect upon skeletal muscle as ageing progresses. In this review article, we will concisely overview the effects of anabolic signals on muscle metabolism, as well as currently available evidence of a resistance, at skeletal muscle level, to any of the above-mentioned anabolic factors, from both in vitro and in vivo studies.

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of functional impairments on altered muscle growth remains unclear. This prospective longitudinal study modelled the morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III=47/22/18). Repeated ultrasound assessments were performed during 2-year (y) follow-up with an interval of minimal 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I versus GMFCS-II&amp;III. MV and CSA growth trajectories showed piecewise model with 2 breakpoints, with the highest growth before 2y and negative growth rates after 6-9y. Before 2y, children with GMFCS-II&amp;III already showed lower growth rates compared to GMFCS-I. From 2-9y, the growth rates did not differ between GMFCS-levels. After 9y, a more pronounced reduction in normalized CSA was observed in GMFCS-II&amp;III. Different trajectories in ML growth were shown between the GMFCS-level subgroups. These longitudinal trajectories could be used to monitor the SCP muscle pathology during childhood and to optimize treatment planning and goals aiming to stimulate muscle growth

The combined muscle-skeletal traumas (MST) are very frequent over the last few years. The emergency care try to save the life of the patient and to receive resuscitation treatment. The role of Trauma surgeon is to choose the right moment for surgery. Aim: To present the management of patient with combined height injury, fracture stabilization, partial foot amputation, local flaps, skin grafting and HIFU – thermotherapy as scar treatment. Materials and methods: 40 years old mail patient, injured after a fall from 8 meters in an elevator shaft. After resuscitation treatment to control the shock the Imaging results are: burst fracture of L3 with spinal canal stenosis, fracture of the sacral bone Denis I, fracture of the right humerus in the proximal third, Monteggia fracture of the left arm, fracture of the proximal third of the right tibia as well as comminuted fractures of both calves and of both heel bones. Results: After a few operations his final result was well healed bone fractures and a good quality soft tissue coverage allowing the patient a satisfactory quality of life. Conclusions: Combined traumas of the muscle- skeletal system are severe, serious and difficult to manage. The good outcome in their treatment requires a team approach between the different medical specialists.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

This study explored the development of neuromuscular fatigue responses during progressive cycling exercise. The sample comprised 32 participants aged 22.0 ± 0.54 years who were assigned into three groups: endurance-trained group (END, triathletes, n = 10), strength-trained group (STR, body-builders, n = 10), and control group (CON, recreationally active students, n = 12). The incremental cycling exercise was performed using a progressive protocol starting with a 3 min resting measurement and then 50 W workload with subsequent constant increments of 50 W every 3 minutes until 200 W. Surface electromyography (SEMG) of rectus femoris muscles was recorded during the final 30 s of each of the four workloads. During the final 15 s of each workload, participants rated their overall perception of effort using the 20-point RPE scale. Post-hoc Tukey’s HSD testing showed significant differences between END and STR groups in MF and MPF across all workloads (p < 0.001 and p < 0.01, respectively). Athletes from END group had significantly lower AEMG responses than those from STR (p = 0.0093) and CON group (p = 0.0006). Increasing RPE points from 50 to 200 W were significantly higher in STR than in END group (p < 0.001). In conclusion, there is a significant variation in neuromuscular fatigue profiles between athletes with different training backgrounds when a cycling exercise is applied. The approximately linear trend of the SEMG and RPE values of both groups of athletes with increasing workload support the increased skeletal muscle recruitment with perceived exertion or fatiguing effect.

In several mammalian species including humans, complex stimulation patterns such as cognitive challenge and physical exercise lead to improvements in organ function, organism health and performance, as well as possibly longer lifespans. The hypothesis is presented here that activity-dependent transcriptional programs, induced by these environmental stimuli, temporarily and lightly de-differentiate somatic cells such as neurons and muscle cells into a state that resembles functionally younger cells to allow cellular remodeling and adaptation of the organism to environmental change. This cellular adaptation program targets several process classes that are heavily implicated in aging, such as mitochondrial metabolism, cell-cell communication, intracellular signaling and epigenetic information processing and leads to functional improvements in these areas. I reverse engineer these activity-dependent gene programs, identify critical molecular nexus points such as CREB, MEF2 and cFos and speculate as to how one might leverage them to prevent and attenuate human aging-related decline of body function, enhance human performance and restore more youthful levels of function and morphology. The findings presented here can serve as a basis for the study and development of effective longevity efforts as the underlying gene programs could be used as markers for treatment success and as targets for therapy development.

Branched-chain amino acid (BCAA) levels are associated with skeletal muscle cross-sectional area (CSA). Serum BCAA levels are enhanced by whey protein supplementation (WPS), and evidence in clinical populations suggests an association of single nucleotide polymorphisms (SNPs) with BCAA metabolite levels. It is not known whether the same SNPs are associated with the ability to catabolise BCAAs from exogenous sources, such as WPS. The present study investigated whether possessing a higher number of alleles associated with increased BCAA metabolites correlates with muscle fiber CSA of m. vastus lateralis in physically active participants, and whether any relationship is enhanced by WPS. Endurance-trained participants (n=75) were grouped by self-reported habitual WPS consumption and genotyped for 5 SNPs (PPM1K rss1440580, APOA5 rs2072560, CBLN1 rs1420601, DDX19B rs12325419, TRMT61A rs58101275). Body mass, BMI and fat percentage were significantly lower and muscle mass higher in the WPS group (n=22) compared to Non-WPS (n=53). The number of BCAA-increasing alleles was correlated with fiber CSA in the WPS group (r=0.75, p&lt;0.0001) and was stronger for fast-twitch fibers (p=0.001) than slow-twitch fibers (p=0.048). Similar results remained when corrected for multiple covariates (age, physical activity, meat and dairy intake). No correlation was found in the Non-WPS group. This study presents novel evidence of a positive relationship between BCAA-increasing alleles and muscle fiber CSA in athletes habitually consuming WPS. We suggest that a high number of BCAA-increasing alleles improves the efficiency of WPS by stimulation of muscle protein synthesis, and contributes to greater fiber CSA.

The proper regulation of RNA processing is critical for muscle development and the fine-tuning of contractile ability between muscle fiber-types. RNA binding proteins (RBPs) regulate the diverse steps in RNA processing including alternative splicing, which generates fiber-type specific isoforms of structural proteins that confer contractile sarcomeres with distinct biomechanical properties. Alternative splicing is disrupted in muscle diseases such as myotonic dystrophy and dilated cardiomyopathy, and is altered after intense exercise as well as with aging. It is therefore important to understand splicing and RBP function, but currently only a small fraction of the hundreds of annotated RBPs expressed in muscle have been characterized. Here we demonstrate the utility of Drosophila as a genetic model system to investigate basic developmental mechanisms of RBP function in myogenesis. We find that RBPs exhibit dynamic temporal and fiber-type specific expression patterns in mRNA-Seq data and display muscle-specific phenotypes. We performed knockdown with 105 RNAi hairpins targeting 35 RBPs and report associated lethality, flight, myofiber and sarcomere defects, including flight muscle phenotypes for Doa, Rm62, mub, mbl, sbr, and clu. Interestingly, knockdown phenotypes of spliceosome components, as highlighted by phenotypes for A-complex components SF1 and Hrb87F (hnRNPA1), revealed level- and temporal-dependent myofibril defects. We further show that splicing mediated by SF1 and Hrb87F is necessary for Z-disc stability and proper myofibril development, and strong knockdown of either gene results in impaired localization of Kettin to the Z-disc. Our results expand the number of RBPs with a described phenotype in muscle and underscore the diversity in myofibril and transcriptomic phenotypes associated with splicing defects. Drosophila is thus a useful model to gain disease-relevant insight into cellular and molecular phenotypes observed when expression levels of splicing factors, spliceosome components and splicing dynamics are altered.

Introduction: The Elevation Training Mask 2.0 (ETM) has been introduced as a novel tool to allow for respiratory muscle training and altitude exposure during exercise that can improve performance and hematological markers in elite and well-trained athletes. Thus, the aim of the present study was to assess the effect of wearing ETM while training on erythropoietin (EPO), vascular endothelial growth factor (VEGF), peak oxygen consumption (VO2max), lactate, and 1000-m kayaking performance in elite Kayaking girls. Methods: Thirty elite Kayaking girls (14 to 18-year-old) were equally and randomly assigned into mask, no mask, and control groups. The mask and no-mask groups completed 8 weeks of repeated sprint training, while the control group performed their routine kayaking training programs. Pre- and post-training tests included EPO, VEGF, VO2max, lactate, and 1000-m kayaking performance. Results: 1000-m time trial significantly decreased for mask (p < 0.001) and control (p = 0.035) groups, and was significantly lower in mask group than control (p = 0.014) and no mask (p = 0.009) groups. EPO did not show any significant changes for all groups. VEGF was increased significantly for mask (p = 0.04) and no mask (p = 0.014) groups. Lactate was decreased significantly for mask group (p = 0.025). VO2max increased significantly for no mask group (p = 0.021). Conclusion: Wearing the ETM while participating in 8 weeks of repeated sprint training might improve specific blood markers and endurance performance, especially anaerobic pathways. Performing repeated sprint training while wearing ETM has the potential to enhance performance in Kayak racing.

We explored the hypothesis that progesterone direct effect on Trichinella spiralis might be mediated indeed by a new steroid-binding parasite protein. Our first results showed that Progesterone decreases the parasite molting rate. We amplify, isolated, cloned and sequenced the PGRMC2 sequence using specific primers from known species. Furthermore, we expressed the protein and developed an antibody to performance immunofluorescent confocal microscopy, where detected that parasite cells showed expression of a P4-binding protein exclusively located at the oocyte and the parasite´s cuticle. Presence of the PGRMC2 protein in these cells was also confirmed by western blot and flow cytometry. Molecular modeling studies accompanied by computer docking using the sequenced protein showed that PGRMC2 is potentially able to bind steroid hormones such as progesterone, estradiol, testosterone, and dihydrodrotestosterone with different affinities. Phylogenetic analysis and sequence alignment clearly demonstrated that Trichinella spiralis PGRMC2 is related to a steroid-binding protein of another platyhelminths. Progesterone may probably act upon Trichinella spiralis oocytes probably by binding to PGRMC2. This research has implications in the field of host-parasite co-evolution as well as the sex-associated susceptibility to this infection. In a more practical matter, present results may contribute to the molecular design of new drugs with anti-parasite actions.

Heart attacks and strokes are one of the leading causes of death in the world today, and heart attacks caused by clogged arteries that carry blood to the heart muscle are a significant part of these strokes. These are caused by the accumulation of fat particles in the walls of the arteries and the reduction of blood flow through it over a long process. The process of fat penetration in the underlying layers of the Artery wall has been the focus of many researchers, and various researches and Simulations have been done on it, in each of them, the effect of specific parameters has been considered. In the present study, the effect of blood flow rate on the flow pattern in a bifurcate artery with two ducts has been investigated using FLUENT software with Computation fluid dynamic Method. The effect of the angle between the two ducts of the Artery on the flow pattern has been investigated.

Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15-day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-κB subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated bidirectional relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass &lt;0.789 in men and &lt;0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs=1.213, 95% CIs=1.050–1.402). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs=1.564, 95% CIs=1.378–1.775). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a bidirectional relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

The effect of prostaglandin E1 (PGE1) encapsulated in nanoparticles (Nano PGE1) on motor dysfunction and muscle atrophy induced by sciatic nerve injury (SNI) was investigated in rats, and was compared with PGE1 encapsulated in lipid microspheres (Lipo PGE1) or PGE1 clathrated in cyclodextrin (PGE1-CD). The hind limb muscle weight ratio decreased until 2 weeks after SNI. All 3 PGE1 formulations significantly improved SNI-induced motor dysfunction. Nano PGE1 significantly promoted recovery from muscle atrophy at 2 and 3 weeks after SNI. Lipo PGE1 was also effective, but multiple doses were required. Compared with the SNI control group, the Nano PGE1 group showed upregulation of vascular endothelial growth factor (VEGF) and agrin expression in the injured sciatic nerve and atrophic muscles. Nano PGE1 accumulated prominently at the site of nerve injury and persisted for longer than Lipo PGE1 or PGE1-CD. Expression of all EP receptors was detected in the normal sciatic nerve, and EP2 expression increased after SNI. Finally, Nano PGE1 promoted ERK1/2 and Akt phosphorylation. These findings suggest that PGE1 released from nanoparticles accumulates at sites of nerve injury and increases VEGF production by augmenting ERK1/2 phosphorylation via EP receptor signaling, thus promoting tissue repair and regeneration.

Introduction: Increases in contralateral range of motion (ROM) have been shown following acute high-intensity and high-duration static stretching (SS) with no significant change in contralateral force, power, and muscle activation. There are currently no studies comparing the effects of a high-intensity, low-duration (HILD) or low-intensity, high-duration (LIHD) SS on contralateral performance. Purpose: The aim of this study was to examine how HILD and LIHD SS of the dominant leg hamstrings influence contralateral limb performance. Methods: Sixteen trained participants (8 females, 8 males) completed three SS interventions of the dominant leg hamstrings; 1) HILD (6x10s at maximal point of discomfort (POD)), 2) LIHD (6x30s at initial POD), and 3) control. Dominant and non-dominant ROM, maximal voluntary isometric contraction (MVIC) forces, muscle activation (electromyography (EMG)), unilateral CMJ and DJ heights were recorded pre-test and 1-minute post-test. Results: There were no significant contralateral ROM or performance changes. Following the HILD condition, the post-test ROM for the stretched leg (110.612.60) exceeded the pre-test (106.09.00) by 4.2% (p=0.008). Similarly, with LIHD, the stretched leg post-test (112.216.50) also exceeded (p=0.06) the pre-test ROM (109.316.20) by 2.6%. There were large magnitude impairments, evidenced by main effects for testing time for force, instantaneous strength, and associated EMG. A significant ROM interaction (p=0.02) showed that with LIHD, the stretched leg significantly (p=0.05) exceeded the contralateral leg by 13.4% post-test. Conclusion: The results showing no significant increase in contralateral ROM with either HILD or LIHD SS suggesting the interventions may not have been effective in promoting crossover effects.