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Background: Phase angle (PhA) is an indicator of cellular health, function, and integrity. PhA has been considered an indicator of nutritional and health status, but it is uncertain whether it could be used as a fitness or athletic performance indicator. Objective: To analyze the relationship between PhA and the fitness and athletic performance of adolescent boxers and to know whether this association is independent of body composition. Methods: Thirty-seven trained youth boxers (15–18 y old) participated in the study. Participants underwent anthropometry and bioelectrical impedance assessments. The following tests were conducted: Fitness-Gram battery; speed, agility, and quickness; ball throws; punch impact force; bench press maximal strength; and vertical and horizontal jumps. Linear regression models were estimated and adjusted by covariates. Results: The PhA was related to upper-limb strength. Nevertheless, in linear regression models, after adjusting models by body composition, only PhA remained as a predictor of relative maximal strength. The PhA was not a predictor of speed, agility, and quickness; cardiorespiratory fitness; or lower-limb power, in which adiposity was the main predictor of fitness. Conclusions: In adolescent boxers, PhA can predict upper-limb maximal strength independently of bioelectrical impedance analysis premises. However, compared with mucle mass, PhA is not a better predictor of upper-limb maximal strength. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the effects of the level of contraction during isometric shoulder abduction at different abduction angles on muscle thickness and stiffness of the shoulder girdle in asymptomatic individuals. Design: Measurement properties study. Setting: Biomechanics and motion analysis lab. Participants: Twenty individuals volunteered to participate in this study. Main Outcome Measure: The subjects were tested for morphological and mechanical properties, expressed by thickness and stiffness of the supraspinatus tendon and muscle, and upper trapezius muscle. Moreover, acromiohumeral distance was also evaluated using B-mode ultrasound and shear-wave elastography. Intervention: The thickness and stiffness of the supraspinatus and upper trapezius muscle were assessed at 3 angles of abduction (0°, 60°, and 90°) and 3 levels of contraction (0%, 10%, and 20% of the maximal voluntary isometric contraction) using ultrasonography with shear-wave imaging. Moreover, the acromiohumeral distance was measured to establish the occupation ratio during passive movement. Results: The supraspinatus and upper trapezius muscle thickness and stiffness were significantly greater at 60° shoulder abduction compared with 0°, and 90° compared with 60°, as well as significantly greater at 20% maximal voluntary isometric contraction compared with 0% and 10% maximal voluntary isometric contraction. Thickness and stiffness were significantly greater in the supraspinatus compared with the upper trapezius muscle at all 3 angles of shoulder abduction for all 3 level of contractions. The acromiohumeral distance decreased significantly from 0° to 60° and from 60° to 90°. Conclusion: Morphological and mechanical properties of the supraspinatus and upper trapezius muscles depended on the relative level of muscle contraction and the angle of shoulder abduction. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis aimed to (1) provide a comparison of peak changes in indirect markers of exercise-induced muscle damage (EIMD) in youths versus adults and (2) determine if the involved limb moderated this effect. Method: Studies were eligible for inclusion if they (1) provided a human youth versus adult comparison; (2) provided data on muscle strength, soreness, or creatine kinase markers beyond ≥24 hours; and (3) did not provide a recovery treatment. Effect sizes (ES) were presented alongside 95% confidence intervals. Results: EIMD exhibited larger effects on adults than in youths for muscle strength (ES = −2.01; P <.001), muscle soreness (ES = −1.52; P <.001), and creatine kinase (ES = −1.98; P <.001). The random effects meta-regression indicated that the effects of upper- and lower-limb exercise in youths and adults were significant for muscle soreness (coefficient estimate = 1.11; P <.001) but not for muscle strength or creatine kinase (P >.05). As such, the between-group effects for muscle soreness (ES = −2.10 vs −1.03; P <.05) were greater in the upper than lower limbs. Conclusion: The magnitude of EIMD in youths is substantially less than in their adult counterparts, and this effect is greater in upper than lower limbs for muscle soreness. These findings help guide practitioners who may be concerned about the potential impact of EIMD when training youth athletes. [ABSTRACT FROM AUTHOR]

Clinical Scenario: The fascial relationship between scapular muscles and abdominal muscles has been documented from previous studies. However, it is not yet clear whether voluntary abdominal contraction has a beneficial effect on scapular muscle activity during shoulder exercises. Clinical Question: Do scapulothoracic muscle activation levels increase if shoulder exercises are performed with voluntary abdominal activation? Summary of Key Finding: After the literature review, 4 cross-sectional studies met the inclusion criteria and were included in this critically appraised topic. Clinical Bottom Line: There is moderate evidence to support dynamic shoulder exercises with voluntary abdominal contraction can increase trapezius and serratus anterior muscle activation level in asymptomatic shoulders. Strength and Recommendation: Findings from 4 cross-sectional trials indicate that there is moderate evidence supporting that dynamic shoulder exercises performed with voluntary abdominal contraction can increase scapular muscle activity. [ABSTRACT FROM AUTHOR]

No studies have reported ground reaction force (GRF) profiles of the repeated depth jump (DJ) protocols commonly used to study exercise-induced muscle damage. Furthermore, while compression garments (CG) may accelerate recovery from exercise-induced muscle damage, any effects on the repeated bout effect are unknown. Therefore, we investigated the GRF profiles of 2 repeated bouts of damage-inducing DJs and the effects of wearing CG for recovery. Nonresistance-trained males randomly received CG (n = 9) or placebo (n = 8) for 72 hours recovery, following 20 × 20 m sprints and 10 × 10 DJs from 0.6 m. Exercise was repeated after 14 days. Using a 3-way (set × bout × group) design, changes in GRF were assessed with analysis of variance and statistical parametric mapping. Jump height, reactive strength, peak, and mean propulsive forces declined between sets (P <.001). Vertical stiffness, contact time, force at zero velocity, and propulsive duration increased (P <.05). According to statistical parametric mapping, braking (17%–25% of the movement) and propulsive forces (58%–81%) declined (P <.05). During the repeated bout, peak propulsive force and duration increased (P <.05), while mean propulsive force (P <.05) and GRF from 59% to 73% declined (P <.001). A repeated bout of DJs differed in propulsive GRF, without changes to the eccentric phase, or effects from CG. [ABSTRACT FROM AUTHOR]

Postural assessments of the lumbar spine lack valuable information about its properties. The purpose of this study was to assess neutral zone (NZ) characteristics via in vivo lumbar spine passive stiffness and relate NZ characteristics to standing lumbar lordosis. A comparison was made between those that develop low back pain during prolonged standing (pain developers) and those that do not (nonpain developers). Twenty-two participants with known pain status stood on level ground, and median lumbar lordosis angle was calculated. Participants were then placed in a near-frictionless jig to characterize their passive stiffness curve and location of their NZ. Overall, both pain developers and nonpain developers stood with a lumbar lordosis angle that was more extended than their NZ boundary. Pain developers stood slightly more extended (in comparison to nonpain developers) and had a lower moment corresponding to the location of their extension NZ boundary. Overall, in comparison to nonpain developers, pain developers displayed a lower moment corresponding to the location of their extension NZ boundary which could correspond to greater laxity in the lumbar spine. This may indicate why pain developers have a tendency to stand further beyond their NZ with greater muscle co-contraction. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) progressively impairs motor neurons, leading to muscle weakness and loss of voluntary muscle control. This study compared the effects of SOD1 mutation on masticatory and limb muscles from disease onset to death in ALS model mice. Notably, limb muscles begin to atrophy soon after ALS-like phenotype appear, whereas masticatory muscles maintain their volume and function in later stages. Our analysis showed that, unlike limb muscles, masticatory muscles retain their normal structure and cell makeup throughout most of the disease course. We found an increase in the number of muscle satellite cells (SCs), which are essential for muscle repair, in masticatory muscles. In addition, we observed no reduction in the number of muscle nuclei and no muscle fibre-type switching in masticatory muscles. This indicates that masticatory muscles have a higher resistance to ALS-related damage than limb muscles, likely because of differences in cell composition and repair mechanisms. Understanding why masticatory muscles are less affected by ALS could lead to the development of new treatments. This study highlights the importance of studying different muscle groups in ALS to clarify disease aetiology and mechanisms.

Background: Local high-frequency percussive (HFP) massage has recently found widespread application in physical therapy. Although HFP massage reportedly improves range of motion (ROM), the mechanism underlying its action has not yet been proven. This study aimed to clarify whether a 5-minute percussive massage regimen affects muscular or connective tissues, such as the deep fascia and deep intermuscular fascia and the change in joint ROM. Method: The study sample was calculated using G*Power analysis program, and this study enrolled 15 healthy men who underwent 5-minute HFP massage to the medial gastrocnemius muscle. Shear-wave elastography was used to measure tissue stiffness in the deep fascia, muscle, and deep intermuscular fascia through shear-wave velocity as well as the ROM of the volunteers' ankle joint dorsiflexion before and after the HFP massage. A value of P < .05 was used to declare statistical significance, and post hoc was used to calculate the effect size using G*Power. Results: Shear-wave velocity revealed a significant change in the deep fascia (P = .003; shear-wave velocity: -0.7 m/s) and significant increase in ROM of ankle dorsiflexion (P = .002; increase in ROM: 3.0°) after 5 minutes of HFP massage. However, the muscle and deep intermuscular fascia did not exhibit any significant changes. Conclusions: HFP massage for 5 minutes modified the stiffness of the deep fascia and concurrently improved the ankle joint-dorsiflexion ROM. This method can be used as an intervention to decrease stiffness of the deep fascia and increase the ROM efficiently. [ABSTRACT FROM AUTHOR]

Adaptations to resistance training and subsequent performance can be undermined by inadequate interset recovery. Methods typically used to monitor recovery were developed for longitudinal use, making them time-inefficient within singular exercise bouts. If valid, perceptual recovery status (PRS) may be used as an efficient and inexpensive assessment tool to monitor individual recovery. Purpose: The aim of this study was to assess the validity of PRS on monitoring recovery during a high-intensity back-squat session. Methods: Ten healthy men participated in the 2-session study (separated by at least 48 h). Session 1 included anthropometrics, PRS familiarization, and a 1-repetition-maximum back squat. Session 2 included a high-intensity protocol (5 sets of 5 repetitions; 5-min interset recovery; 85% of 1-repetition maximum). PRS was obtained before the first set and during the last 30 seconds of each 5-minute recovery; rating of perceived exertion (RPE) was also collected. A linear position transducer collected mean barbell velocity (MBV). Repeated-measures correlations assessed the common intraindividual relationships of PRS scores to intraset MBV and RPE, respectively. Results: A very large, positive correlation appeared between PRS and MBV (r [95% CI] =.778 [.613 to.878]; P <.0001). A large, negative correlation emerged between PRS and RPE (r [95% CI] = −.549 [−.737 to −.282]; P <.001). Conclusions: Results indicate that PRS can be a means for practitioners to monitor individualized recovery. PRS tracked well with RPE, strengthening its utility in a practitioner-based setting. Findings provide insight into the practicality of PRS for recovery monitoring. It could be used alongside other measures (eg, MBV and countermovement jump) to individually program and maintain performance. [ABSTRACT FROM AUTHOR]

Microgravity has been shown to lead to both muscle atrophy and impaired muscle regeneration. The purpose was to study the efficacy of microgravity to model impaired muscle regeneration in an engineered muscle platform and then to demonstrate the feasibility of performing drug screening in this model. Engineered human muscle was launched to the International Space Station National Laboratory, where the effect of microgravity exposure for 7 days was examined by transcriptomics and proteomics approaches. Gene set enrichment analysis of engineered muscle cultured in microgravity, compared to normal gravity conditions, highlighted a metabolic shift toward lipid and fatty acid metabolism, along with increased apoptotic gene expression. The addition of pro-regenerative drugs, insulin-like growth factor-1 (IGF-1) and a 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-i), partially inhibited the effects of microgravity. In summary, microgravity mimics aspects of impaired myogenesis, and the addition of these drugs could partially inhibit the effects induced by microgravity.

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Sarcospan (SSPN) is a 25-kDa transmembrane protein that is broadly expressed at the cell surface of many tissues, including, but not limited to, the myofibers from skeletal and smooth muscles, cardiomyocytes, adipocytes, kidney epithelial cells, and neurons. SSPN is a core component of the dystrophin-glycoprotein complex (DGC) that links the intracellular actin cytoskeleton with the extracellular matrix. It is also associated with integrin α7β1, the predominant integrin expressed in skeletal muscle. As a tetraspanin-like protein with four transmembrane spanning domains, SSPN functions as a scaffold to facilitate protein-protein interactions at the cell membrane. Duchenne muscular dystrophy, Becker muscular dystrophy, and X-linked dilated cardiomyopathy are caused by the loss of dystrophin at the muscle cell surface and a concomitant loss of the entire DGC, including SSPN. SSPN overexpression ameliorates Duchenne muscular dystrophy in the mdx murine model, which supports SSPN being a viable therapeutic target. Other rescue studies support SSPN as a biomarker for the proper assembly and membrane expression of the DGC. Highly specific and robust antibodies to SSPN are needed for basic research on the molecular mechanisms of SSPN rescue, pre-clinical studies, and biomarker evaluations in human samples. The development of SSPN antibodies is challenged by the presence of its four transmembrane domains and limited antigenic epitopes. To address the significant barrier presented by limited commercially available antibodies, we aimed to generate a panel of robust SSPN-specific antibodies that can serve as a resource for the research community. We created antibodies to three SSPN protein epitopes, including the intracellular N- and C-termini as well as the large extracellular loop (LEL) between transmembrane domains 3 and 4. We developed a panel of rabbit antibodies (poly- and monoclonal) against an N-terminal peptide fragment of SSPN. We used several assays to show that the rabbit antibodies recognize mouse SSPN with a high functional affinity and specificity. We developed mouse monoclonal antibodies against the C-terminal peptide and the large extracellular loop of human SSPN. These antibodies are superior to commercially available antibodies and outperform them in various applications, including immunoblotting, indirect immunofluorescence analysis, immunoprecipitation, and an ELISA. These newly developed antibodies will significantly improve the quality and ease of SSPN detection for basic and translational research.

BackgroundSkeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD.MethodsForty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype.ResultsAbnormal myofibre proportion was defined in males with COPD (n = 29) as 22% type IIx/IIax fibres and in females with COPD (n = 17) as 12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density.ConclusionsOur findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

Exercise-induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise-induced phenotypes. Using this network, we formulated a logic-based ordinary differential equation model predicting time-dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training showed that, in the model, exercise regulates cell growth and protein synthesis primarily by signalling via mechanistic target of rapamycin, which is activated by Akt and inhibited in endurance exercise by AMP-activated protein kinase. Endurance exercise preferentially activates inflammation via reactive oxygen species and nuclear factor κB signalling. Furthermore, the expected preferential activation of mitochondrial biogenesis by endurance exercise was counterbalanced in the model by protein kinase C in response to resistance training. This model provides a new tool for investigating cross-talk between skeletal muscle signalling pathways activated by endurance and resistance exercise, and the mechanisms of interactions such as the interference effects of endurance training on resistance exercise outcomes.

Context: Plantar intrinsic foot muscle strength training is difficult to master to a degree sufficient to elicit muscle hypertrophy in most individuals. It is possible that combining neuromuscular electrostimulation (NMES) and blood flow restriction (BFR) can elicit plantar intrinsic foot muscle hypertrophy regardless of the individual's technique. This study aimed to determine the effects of NMES training with BFR on acute muscle swelling in the abductor hallucis. Design: Randomized, controlled, single-blind trial design. Methods: Forty-eight participants were randomly allocated to the NMES + BFR, NMES, or Sham NMES + BFR groups. All participants received abductor hallucis NMES for 15 minutes. Participants in the NMES + BFR and Sham NMES + BFR groups received NMES with BFR. The intensity of NMES was the sensory threshold in the Sham NMES + BFR group. The cross-sectional area of the abductor hallucis was measured pretraining and posttraining using ultrasonography by a single investigator blinded to the participants' allocations. Results: After 15 minutes of training, the cross-sectional area of the abductor hallucis was significantly increased in the NMES + BFR (P<.001) and the Sham NMES + BFR (P = .004) groups. Moreover, the rate of increase was significantly higher in the NMES + BFR group than in the NMES or the Sham NMES + BFR groups (P<.001 and P = . 001, respectively). Conclusions: Since it is possible that the amount of muscle swelling immediately after training correlates with muscle hypertrophy when training is continued, the results of this study suggest that NMES training with BFR is a training method that can be expected to produce plantar intrinsic foot muscle hypertrophy. Further studies are needed to confirm the long-term effects of NMES training with BFR. [ABSTRACT FROM AUTHOR]

The study compared superficial trunk muscle activity and postural control among an active extension subgroup of people with nonspecific chronic low back pain (AE-NSCLBP) with painfree controls during functional tasks. Thirty-two people (17 people with low back pain [LBP] and 15 painfree controls) participated in this study. Muscle activity of 5 trunk muscles and postural control were investigated during both standing tasks (eyes open/closed; single/double-leg balance) and dynamic functional tasks (spinal forward flexion and return, and a sit to stand transfer). Results showed that during single-leg standing, people with AE-NSCLBP exhibit higher muscle activity than painfree controls for 3 trunk muscles, especially with their eyes closed. There were no significant differences in muscle activity between eye conditions during double-leg standing and sit to stand transfer, forward flexion, and return from flexion. The AE-NSCLBP subgroup also demonstrated significantly impaired postural control (lower time to boundary) in 4 of 8 conditions, especially during single-leg standing and with their eyes closed. These findings show people with LBP typically demonstrated greater trunk muscle activity and poorer postural control while maintaining standing posture. This pattern was most evident when the postural challenge was higher, such as single-leg standing or with eyes closed. While this study design cannot infer causality, these findings have implications for LBP rehabilitation, particularly regarding approaches which seek to alter muscle activation among people with LBP. [ABSTRACT FROM AUTHOR]

Resistance exercise training (RET) can be applied effectively to increase muscle mass and function in older adults (65–75 years). However, it has been speculated that older adults above 85 years are less responsive to the benefits of RET. This study compares the impact of RET on muscle mass and function in healthy older adults 65–75 years versus older adults above 85 years. We subjected 17 healthy older adults 65–75 years (OLDER 65–75, n = 13/4 [female/male]; 68 ± 2 years; 26.9 ± 2.3 kg/m2) and 12 healthy older adults above 85 years (OLDER 85+, n = 7/5 [female/male]; 87 ± 3 years; 26.0 ± 3.6 kg/m2) to 12 weeks of whole-body RET (three times per week). Prior to, and after 6 and 12 weeks of training, quadriceps and lumbar spine vertebra 3 muscle cross-sectional area (computed tomography scan), whole-body lean mass (dual-energy X-ray absorptiometry scan), strength (one-repetition maximum test), and physical performance (timed up and go and short physical performance battery) were assessed. Twelve weeks of RET resulted in a 10% ± 4% and 11% ± 5% increase in quadriceps cross-sectional area (from 46.5 ± 10.7 to 51.1 ± 12.1 cm2, and from 38.9 ± 6.1 to 43.1 ± 8.0 cm2, respectively; p <.001; η2 =.67); a 2% ± 3% and 2% ± 3% increase in whole-body lean mass (p =.001; η2 =.22); and a 38% ± 20% and 46% ± 14% increase in one-repetition maximum leg extension strength (p <.001; η2 =.77) in the OLDER 65–75 and OLDER 85+ groups, respectively. No differences in the responses to RET were observed between groups (Time × Group, all p >.60; all η2 ≤.012). Physical performance on the short physical performance battery and timed up and go improved (both p <.01; η2 ≥.22), with no differences between groups (Time × Group, p >.015; η2 ≤.07). Prolonged RET increases muscle mass, strength, and physical performance in the aging population, with no differences between 65–75 years and 85+ years older adults. [ABSTRACT FROM AUTHOR]

Muscle fiber conduction velocity (MFCV) can be affected by muscle fiber geometry at different joint angles and during joint movements. This study aimed to investigate MFCV during electrically evoked contraction at different joint angles, during joint movements, and during voluntary contractions. Sixteen healthy young men participated. A stimulation electrode was attached on the innervation zone of the vastus lateralis, and a linear electrode array was attached on the vastus lateralis. Under a static condition, electrically evoked electromyography signals were recorded at knee joint angles set every 15° between 0° and 105°. Under a passive movement condition, signals were recorded during knee extension and flexion passively. Under a voluntary contraction condition, signals were recorded while performing 30% or 60% of maximum voluntary contraction. MFCV was calculated using cross-correlation coefficients. Under the static condition, there were no differences in MFCV among various joint angles. Under the passive movement condition, MFCV was significantly greater during high velocity or shortening. Under the voluntary contraction condition, MFCV was significantly greater during high-intensity voluntary contraction and with a shortened muscle length. Joint angles do not influence MFCV markedly during relaxation, but it is possible to overestimate MFCV during movement or voluntary contraction. [ABSTRACT FROM AUTHOR]

A muscle's architecture, defined as the geometric arrangement of its fibers with respect to its mechanical line of action, impacts its abilities to produce force and shorten or lengthen under load. Ultrasound and other noninvasive imaging methods have contributed significantly to our understanding of these structure–function relationships. The goal of this work was to develop a MATLAB toolbox for tracking and mathematically representing muscle architecture at the fascicle scale, based on brightness-mode ultrasound imaging data. The MuscleUS_Toolbox allows user-performed segmentation of a region of interest and automated modeling of local fascicle orientation; calculation of streamlines between aponeuroses of origin and insertion; and quantification of fascicle length, pennation angle, and curvature. A method is described for optimizing the fascicle orientation modeling process, and the capabilities of the toolbox for quantifying and visualizing fascicle architecture are illustrated in the human tibialis anterior muscle. The toolbox is freely available. [ABSTRACT FROM AUTHOR]

Lower limb exoskeletons and exosuits ("exos") are traditionally designed with a strong focus on mechatronics and actuation, whereas the "human side" is often disregarded or minimally modeled. Muscle biomechanics principles and skeletal muscle response to robot-delivered loads should be incorporated in design/control of exos. In this narrative review, we summarize the advances in literature with respect to the fusion of muscle biomechanics and lower limb exoskeletons. We report methods to measure muscle biomechanics directly and indirectly and summarize the studies that have incorporated muscle measures for improved design and control of intuitive lower limb exos. Finally, we delve into articles that have studied how the human–exo interaction influences muscle biomechanics during locomotion. To support neurorehabilitation and facilitate everyday use of wearable assistive technologies, we believe that future studies should investigate and predict how exoskeleton assistance strategies would structurally remodel skeletal muscle over time. Real-time mapping of the neuromechanical origin and generation of muscle force resulting in joint torques should be combined with musculoskeletal models to address time-varying parameters such as adaptation to exos and fatigue. Development of smarter predictive controllers that steer rather than assist biological components could result in a synchronized human–machine system that optimizes the biological and electromechanical performance of the combined system. [ABSTRACT FROM AUTHOR]

In this narrative review, we explore developments in the field of computational musculoskeletal model personalization using the Physiome and Musculoskeletal Atlas Projects. Model geometry personalization; statistical shape modeling; and its impact on segmentation, classification, and model creation are explored. Examples include the trapeziometacarpal and tibiofemoral joints, Achilles tendon, gastrocnemius muscle, and pediatric lower limb bones. Finally, a more general approach to model personalization is discussed based on the idea of multiscale personalization called scaffolds. [ABSTRACT FROM AUTHOR]

Studies on postactivation performance enhancement (PAPE) have used different exercises as a conditioning activity to investigate potentiation, but exclusively in upper limbs (UL) or lower (LL) limbs, or contralateral potentiation. A single exercise capable of inducing PAPE in both UL and LL is currently unknown. The present study explored the effect of the clean and jerk (C&J) as a conditioning activity for simultaneously producing PAPE interlimbs at the fourth, seventh, and 12th minutes postintervention. Twelve male weightlifters with 1-repetition maximum (1RM) in the C&J equivalent to ≥1.15 × body mass were randomly submitted to 2 experimental conditions (C&J and control [CON]). The C&J condition consisted of general warm-up (running on a treadmill and self-selected preparatory exercises) and 4 sets of 3 repetitions of C&J with 2 minutes between them (30%1RM, 50%1RM, 65%1RM, and 80%1RM) followed by a countermovement jump and a bench-press throw on a Smith machine after 4, 7, and 12 minutes, to measure the magnitude of PAPE in UL and LL. No previous exercise preceded countermovement-jump and bench-press-throw tests in the CON besides general warm-up. The main finding was that, regardless of time, the C&J resulted in greater height on countermovement jump and Smith machine bench-press throw when compared with the CON, presenting a similar effect size between UL and LL (34.6 [3.9] vs 33.4 [4.1] cm [+3.66%]; P =.038; effect size = 0.30 and 30.3 [4.7] vs 29.0 [5.1] cm [+4.44%]; P =.039; effect size = 0.26), respectively. Thus, C&J can be useful to produce PAPE simultaneously among members. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine if hamstring-strain-injury risk factors related to muscle structure and morphology differed between rugby union players and controls. Methods: The biceps femoris long head (BFlh) fascicle length and passive muscle stiffness and relative and absolute muscle volume of knee flexors (KF) and extensors (KE) were measured in 21 male subelite rugby players and 21 male physically active nonathletes. Results: BFlh fascicle length was significantly longer (mean difference [MD] = 1.6 [1.7] cm) and BFlh passive muscle stiffness was significantly higher in rugby players (MD = 7.8 [14.8] kPa). The absolute BFlh (MD = 71.9 [73.3] cm3), KF (MD = 332.3 [337.2] cm3), and KE (MD = 956.3 [557.4] cm3) muscle volumes were also significantly higher in rugby players. There were no significant differences in the relative BFlh and KF muscle volumes. The relative KE muscle volumes were significantly higher in rugby players (MD = 2.3 [3.7] cm3/kg). However, the percentage BFlh fascicle length:KE (MD = −0.1% [0.1%]), BFlh/KE (MD = −0.9% [1.9%]), and KF:KE (MD = −4.9% [5.9%]) muscle volume ratios were significantly lower in the rugby players. BFlh muscle volume significantly correlated with BFlh fascicle length (r =.59, r2 =.35) and passive muscle stiffness (r =.46, r2 =.21). Conclusion: Future prospective studies should examine whether there are threshold values in BFlh passive muscle stiffness and BFlh fascicle length:KE, BFlh:KE, and KF:KE muscle volume ratios for predicting hamstring strain injuries. [ABSTRACT FROM AUTHOR]

Spheroids exhibit enhanced cell-cell interactions that facilitate improved survival and mimic the physiological cellular environment in vivo. Cell spheroids have been successfully used as building blocks for engineered tissues, yet the viability of this approach with skeletal muscle spheroids is poorly understood, particularly when incorporated into three-dimensional (3D) constructs. Bioprinting is a promising strategy to recapitulate the hierarchical organization of native tissue that is fundamental to its function. However, the influence of bioprinting on skeletal muscle cell spheroids and their function are yet to be interrogated. Using C2C12 mouse myoblasts and primary bovine muscle stem cells (MuSCs), we characterized spheroid formation as a function of duration and cell seeding density. We then investigated the potential of skeletal muscle spheroids entrapped in alginate bioink as tissue building blocks for bioprinting myogenic tissue. Both C2C12 and primary bovine MuSCs formed spheroids of similar sizes and remained viable after bioprinting. Spheroids of both cell types fused into larger tissue clusters over time within alginate and exhibited tissue formation comparable to monodisperse cells. Compared to monodisperse cells in alginate gels, C2C12 spheroids exhibited greater MyHC expression after 2 weeks, while cells within bovine MuSC spheroids displayed increased cell spreading. Both monodisperse and MuSC spheroids exhibited increased expression of genes denoting mid- and late-stage myogenic differentiation. Together, these data suggest that skeletal muscle spheroids have the potential for generating myogenic tissue via 3D bioprinting and reveal areas of research that could enhance myogenesis and myogenic differentiation in future studies.

Intravoxel incoherent motion (IVIM) MRI provides insight into tissue diffusion and perfusion. Here, estimates of perfusion fraction ( f ), pseudo-diffusion coefficient ( D * ), and diffusion coefficient ( D ) obtained via different fitting methods are compared to ascertain (1) the optimal analysis strategy for muscles of the lumbar spine and (2) repeatability of IVIM parameters in skeletal muscle at rest. Diffusion-weighted images were acquired in the lumbar spine at rest in 15 healthy participants. Data were fit to the bi-exponential IVIM model to estimate f , D * and D using three variably segmented approaches based on non-linear least squares fitting, and a Bayesian fitting method. Assuming that perfusion and diffusion are temporally stable in skeletal muscle at rest, and spatially uniform within a spinal segment, the optimal analysis strategy was determined as the approach with the lowest temporal or spatial variation and smallest residual between measured and fit data. Inter-session repeatability of IVIM parameters was evaluated in a subset of 11 people. Finally, simulated IVIM signal at varying signal to noise ratio were evaluated to understand precision and bias. Experimental results showed that IVIM parameter values differed depending on the fitting method. A three-step non-linear least squares fitting approach, where D , f , and D * were estimated sequentially, generally yielded the lowest spatial and temporal variation. Solving all parameters simultaneously yielded the lowest residual between measured and fit data, however there was substantial spatial and temporal variability. Results obtained by Bayesian fitting had high spatial and temporal variability in addition to a large residual between measured and fit data. Simulations showed that all fitting methods can fit the IVIM data at signal to noise ratios >35, and that D * was the most challenging to accurately obtain. Overall, this study motivates use of a three-step non-linear least squares fitting strategy to quantify IVIM parameters in skeletal muscle.

Mitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the mitophagy receptors NIX and BNIP3. Although AMP-activated protein kinase (AMPK), the energy-sensing protein kinase, can influence damaged-induced mitophagy, its role in programmed mitophagy is unclear. We found that AMPK directly inhibits NIX-dependent mitophagy by triggering 14-3-3-mediated sequestration of ULK1, via ULK1 phosphorylation at two sites: Ser556 and an additional identified site, Ser694. By contrast, AMPK activation increases Parkin phosphorylation and enhances the rate of depolarization-induced mitophagy, independently of ULK1. We show that this happens both in cultured cells and tissues in vivo , using the mito -QC mouse model. Our work unveils a mechanism whereby AMPK activation downregulates mitophagy of functional mitochondria but enhances that of dysfunctional/damaged ones. [Display omitted] • AMPK activation blocks NIX-dependent mitophagy • AMPK phosphorylates ULK1 to trigger inhibitory 14-3-3 binding • NIX-dependent mitophagy can target functioning mitochondria • Parkin-dependent mitophagy is enhanced by AMPK independently of ULK1 Under energetic stress, it is essential to balance dysfunctional versus healthy mitochondrial turnover. Longo and Bishnu et al. uncover a mechanism by which AMPK activation achieves this. They find that although AMPK enhances Parkin-mediated mitophagy upon mitochondrial damage, it blocks NIX-mediated mitophagy, which they now show can target functioning mitochondria. [ABSTRACT FROM AUTHOR]

Background The modified Thomas test (MTT) is commonly used to assess the flexibility of hip musculature, including the iliopsoas, rectus femoris, and tensor fascia latae. This measurement is important to include in a comprehensive musculoskeletal examination. However, existing research shows conflicting results regarding its reliability, particularly due to variations in controlling pelvic tilt during testing, which may lead to inaccurate measurements of hip extension when quantifying the test outcomes. Purpose/Hypothesis This study aimed to evaluate the intra- and inter-rater reliability of the Modified Thomas Test (MTT) in assessing hip flexor length using a goniometer. It was hypothesized that controlling for pelvic tilt would enhance the reliability of these measurements. Study Design Intra- and inter-rater reliability study Methods Sixty-four healthy individuals were recruited to participate in this study. The MTT was performed twice on each leg by both an experienced and a student physical therapist. Blinded goniometric measurements for hip extension range of motion (ROM) in the MTT position were taken with neutral pelvic tilt being enforced via palpation. A double-blind protocol was used where both examiners were unaware of each other's measurements and the goniometer was covered to blind the measuring therapist to the values as well. ROM values were entered into a Microsoft Excel spreadsheet and quantified using SPSS software. Statistical analysis included calculating Intraclass Correlation Coefficients (ICCs) and Standard Errors of Measurement (SEMs) using SPSS software. Results The study included 64 participants (mean age = 23.7 ± 4.34 years). The MTT demonstrated high intra-rater reliability (ICC = 0.911) and inter-rater reliability (ICC = 0.851). The SEMs indicated minimal variability around the mean scores. The average hip extension ROM measured was 5.43± 9.73 degrees. Conclusion These results suggest that the MTT is a reliable tool for assessing hip flexor length in clinical practice, particularly when pelvic tilt is controlled. These results have important implications for accurately testing orthopedic limitations that can contribute to low back, hip, and knee pain. Level of Evidence 3 [ABSTRACT FROM AUTHOR]

Exercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age‐related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that short-chain fatty acids (SCFAs) are a potential regulator of skeletal muscle energy metabolism, but the exact mechanism is unclear. OBJECTIVE: To observe the effect of SCFAs on aged rats with sarcopenia and to explore the underlying mechanism. METHODS: Sprague-Dawley rats were randomly divided into control group, sarcopenia group, and sarcopenia + SCFAs group (SCFAs group). In the latter two groups, rat models of sarcopenia were established using ovariectomized rats injected with 5 mg/kg dexamethasone for 7 days. In the control group, the abdominal cavity was only exposed but not removed, and then sutured. Rats in the SCFAs group were administered drinking water containing 150 mmol/L short-chain fatty acids, 600 mg/kg sodium acetate, 200 mg/kg sodium propionate, and 200 mg/kg sodium butyrate for 4 weeks. Rats in the control and sarcopenia groups were given the same volume of normal saline. Successful modeling was assessed by measuring the bilateral gastrocnemius muscle mass and body mass to calculate the gastrocnemius index after modeling. Food intake, body mass and grip strength of rats were measured at 0, 1, 2 and 4 weeks after successful modeling; morphological changes of gastrocnemius muscle were observed by hematoxylin-eosin staining; and the expression of p-AMPK and p-ULK1 proteins in gastrocnemius muscle was detected by western blot. RESULTS AND CONCLUSION: Compared with the control group, the sarcopenia group showed significantly decreased body mass, food intake, forelimb grip strength (P < 0.05), wet mass of gastrocnemius muscle (P < 0.05), and protein levels of p-AMPK and p-ULK1 (P < 0.05). Compared with the sarcopenia group, the SCFAs group showed a significant increase in food intake, body mass, grip strength, wet mass of gastrocnemius muscle, and protein levels of p-AMPK and p-ULK1 in gastrocnemius muscle (P < 0.05). All these findings indicate that SCFAs improve symptoms of sarcopenia in the elderly and may be associated with the upregulation of AMPK and ULK1 proteins in skeletal muscle. [ABSTRACT FROM AUTHOR]

BACKGROUND: Resistance training and weight-bearing exercise are recommended modes for patients with osteoporosis to improve bone health. High-intensity interval training is a high-impact weight-bearing exercise with obvious time-efficient characteristics; however, little attention has been paid to its impact on bones. OBJECTIVE: To observe the effect of high-intensity interval training on the bone health of ovariectomized rat models. METHODS: Thirty-six female Sprague-Dawley rats were randomly divided into sham group, model group and model exercise group (n=12 per group). Bilateral ovariectomy was used to prepare an osteoporosis rat model in the latter two groups. Six weeks after modeling, the model exercise group was subjected to a high-intensity interval training on an electric treadmill at 90% peak running speed for 2 minutes and 50% peak running speed for 1 minute as one session, a total of nine sessions, 3 days per week, for 6 weeks. Rats in the sham and model groups were raised quietly in the mouse cage during the same period. The relevant indexes were tested 48-72 hours after the final training. RESULTS AND CONCLUSION: Compared with the sham group, bone mineral density, maximal load, stiffness, elasticity, trabecular volume fraction, and trabecular number decreased (P < 0.05), while trabecular separation increased (P < 0.05); the level of irisin in the serum, gastrocnemius and femur decreased (P < 0.05); the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type III domain-containing protein 5 mRNA and protein in the gastrocnemius muscle decreased (P < 0.05); the expression of type I collagen, Osterix, and Runx2 mRNA in the femur decreased (P < 0.05); and the expression of anti-tartrate acid phosphatase, receptor activator of nuclear factor κB ligand, and osteoclast-associated receptor mRNA increased in the model group (P < 0.05). Compared with the model group, bone mineral density, fracture load, maximal load, stiffness, elasticity, average trabecular thickness, and trabecular number increased (P < 0.05), and trabecular separation decreased (P < 0.05); the level of irisin in the serum, gastrocnemius and femur increased (P < 0.05); the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type III domain-containing protein 5 mRNA and protein in gastrocnemius increased (P < 0.05); the expression of type I collagen, Osterix, and Runx2 mRNA in the femur increased (P < 0.05); and the expression of anti-tartrate acid phosphatase, receptor activator of nuclear factor κB ligand, and osteoclast-associated receptor mRNA decreased in the model exercise group (P < 0.05). To conclude, short-term high-intensity interval training may improve bone health of ovariectomized rats through up-regulating the irisin level. [ABSTRACT FROM AUTHOR]

G protein alpha q subunit (Gαq) can binds to the G protein-coupled receptor (GPCR) for signaling and is closely related to lipid metabolism. Endurance exercise is an effective means of combating acquired obesity and its complications, but the mechanisms by which endurance exercise modulates hereditary obesity and its complications are unknown. In this study, we achieved knockdown of Gαq in drosophila adipose tissue and skeletal muscle by constructing the Gαq-UAS-RNAi/Ppl-Gal4 and Gαq-UAS-RNAi/Mef2-GAl4 systems. Drosophila were subjected a three-week endurance exercise intervention, and changes in relevant indicators were detected and observed by RT-PCR, ELISA, oil red staining, immunofluorescence staining, and transmission electron microscopy. The results showed that knockdown of Gαq in both adipose tissue and skeletal muscle induced a significant increase in triglycerides accompanied by a decrease in rapid climbing ability, a decrease in Superoxide Dismutase (SOD) activity level, and a decrease in Mitochondrial respiratory chain complexI (MRCC I) content in Drosophila whole body and skeletal muscle, and down-regulated the expression of the G protein alpha q subunit (Gαq), the skeletal muscle myosin heavy chain expression gene (Mhc), mitochondrial biogenesis gene Spargal(the PGC-1alpha homologue in Drosophila). Endurance exercise significantly improved the triglyceride levels in the whole body and skeletal muscle of drosophila with Gαq knockdown in adipose tissue and skeletal muscle, as well as their ability to climb, increased SOD activity level and MRCCI content level, and up-regulated the expression of Gαq, Mhc, and Spargal(Srl). Thus, the present findings suggest that genetic defects in the Gαq gene in adipose and skeletal muscle tissues induce hereditary obesity and skeletal muscle dysfunction, and that endurance exercise attenuates this hereditary obesity and concomitant skeletal muscle dysfunction in drosophila by improving skeletal muscle fiber contractile proteins, mitochondrial function and function, and antioxidant capacity via mediating the Gαq/Mhc, Gαq/Srl/MRCC-I, and Gαq/SOD pathways. [ABSTRACT FROM AUTHOR]

Although sarcopenia has been a serious public health concern worldwide in recent years, its effective prevention and intervention measures are still lacking. The latest research has found that autophagy dysfunction is an essential mechanism in the pathogenesis of sarcopenia. And meanwhile, increasing studies have shown that phytonutrients consumption is positively correlated with the maintenance of skeletal muscle mass and strength, which involves the regulation of the autophagy pathway. However, due to the opposite environmental-dependent effect of autophagy in sarcopenia, targeting autophagy by phytonutrients as the treatment of sarcopenia is sometimes considered controversial. Thus, in this review, based on the illustration of the relationship between autophagy and skeletal muscle and the complex changes of autophagy in sarcopenia, the phytonutrients ameliorating sarcopenia by regulating autophagy are reviewed with emphasis, and the possible underlying mechanisms are systematically summarized. Despite some controversies, most current studies support the idea that maintaining basal and functional autophagy contributes to the treatment of sarcopenia. Several phytonutrients exhibit substantial beneficial effects on sarcopenia by targeting autophagy, with polyphenols (especially catechins and urolithin A) considered to be of potentially effective clinical relevance. Hence, the development of phytonutrients is a promising approach to the treatment of sarcopenia and its complications. [ABSTRACT FROM AUTHOR]

ABSTRACT Estrogen is an essential hormone for the development and functional activities of reproductive organs. Recent studies showed that estrogen signaling is also an important regulator of lipid and glucose metabolism in a number of tissues, but the molecular mechanism is not fully understood. We report here that estrogen is a stimulator of brain‐derived neurotrophic factor (BDNF) synthesis in the skeletal muscle. Estradiol (E2), but not testosterone, induces a dose‐ and time‐dependent BDNF production in cultured myotubes. Estrogen depletion in ovariectomized mice significantly reduced Bdnf expression in the glycolytic myofibers, which could be rescued after E2 administration. Mechanistically, E2 stimulation triggered the tethering of estrogen receptor (ER) α, but not ERβ, to the estrogen‐responsive element on promoter VI of the Bdnf gene in skeletal muscle. When Bdnf production was inhibited by shRNA in C2C12 myotubes, E2‐induced mitochondria activation and pyruvate dehydrogenase kinase 4 expressions were jeopardized. Collectively, our results demonstrate that BDNF is an underrecognized effector of estrogen in regulating mitochondrial activity and fuel metabolism in the skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia and rotator cuff tears are common among elderly patients. However, the role of sarcopenia in the management of rotator cuff tears has been often overlooked. This study aimed to elucidate the effects of sarcopenia-related traits on rotator cuff tears. Methods: Two-sample Mendelian randomization (MR) analyses based on genome-wide association study data were used to evaluate the causal relationships among appendicular lean mass (ALM), usual walking pace, low hand grip strength, and rotator cuff tears. Multivariate Mendelian randomization (MVMR) analyses were used to evaluate the direct effects of each muscle trait on the causal relationship. Results: Univariate MR analysis showed that ALM and usual walking pace were causally related to rotator cuff tears (odds ratio (OR) = 0.895; 95% confidence interval (CI), 0.758-0.966, P <0.001 and OR = 0.458, 95% CI, 0.276-0.762, P = 0.003, respectively), and there was no evidence of causality between low hand grip strength and rotator cuff tears (OR = 1.132, 95% CI, 0.913-1.404, P = 0.26). MVMR analysis confirmed the causal effects of ALM and walking pace on rotator cuff tears (OR = 0.918, 95% CI, 0.851-0.990, P = 0.03 and OR = 0.476, 95% CI, 0.304-0.746, P = 0.001, respectively). Conclusion: A causal genetic relationship exists between sarcopenia and rotator cuff tears. Sarcopenia-related traits including low muscle mass and physical function, increase the risk of rotator cuff tears. These findings provide new clinical insights and evidence-based medicine to optimize management of rotator cuff tears. [ABSTRACT FROM AUTHOR]

Background: In the current study, we evaluated whether atopic dermatitis (AD) affects the entire body rather than being limited to skin barrier damage and inflammation. We hypothesized that medium-term exposure of distant organs to systemic inflammatory cytokines in sub-chronic inflammatory skin diseases has detrimental effects on distant tissues. Results: Our findings demonstrated the dysregulation of genes and pathways associated with inflammation and the skin barrier, as well as genes and pathways involved in muscle development that respond to chemicals or stress in muscle tissues, all of which were reversed by hydrocortisone (Hc) administration. The expression of Ces1d showed significant differences during disease onset and after treatment in both skin and skeletal muscle, suggesting that Ces1d is likely responsible for the alleviation of subchronic AD. Conclusions: Using NC/Nga mice with AD-like symptoms, we compared the transcriptomes of the skeletal muscle (a tissue that is relatively distant from the skin) with those of the skin (the lesion induction site) before and after disease induction, after which Hc was administered. Although further study is needed to better understand the effects of Ces1d on AD, skeletal muscle was associated with AD pathogenesis, and AD-like symptoms appeared to affect the body in a systemic manner. Given the importance of evidence-based medicine and the development of precision medicine, our findings provide insights into the mechanisms of AD onset and progression. [ABSTRACT FROM AUTHOR]

The tumor microenvironment plays a pivotal role in cancer development. We recently reported that in oral squamous cell carcinoma (OSCC), adipocyte enhancer-binding protein 1 (AEBP1) is abundantly expressed in cancer-associated fibroblasts (CAFs), leading to CAF activation and inhibition of CD8 + T cell infiltration. In the present study, we investigated whether AEBP1 contributes to the destruction and atrophy of muscle tissues in OSCC. By analyzing human skeletal muscle myoblasts (HSMMs), we found that AEBP1 is downregulated during muscle cell differentiation. Transcriptome analysis revealed that AEBP1 knockdown significantly upregulates myogenesis-related genes in HSMMs, and qRT-PCR and western blot analyses confirmed the induction of muscle-related genes, including MYOG, in HSMMs after AEBP1 knockdown. Conversely, ectopic expression of AEBP1 strongly suppressed myogenesis-related genes in HSMMs. Notably, indirect co-culture of HSMMs with OSCC cells led to AEBP1 upregulation and robust suppression of muscle-related genes in HSMMs. Treatment with TGF-β1 also upregulated AEBP1 and suppressed expression of muscle-related genes in HSMMs. Our findings suggest that AEBP1 is a negative regulator of skeletal muscle cell differentiation and that OSCC cells inhibit muscle cell differentiation, at least in part, by inducing AEBP1. [ABSTRACT FROM AUTHOR]

The actin-binding protein filamin c (FLNc) is a key mediator in the response of skeletal muscle cells to mechanical stress. In addition to its function as a structural scaffold, FLNc acts as a signaling adaptor which is phosphorylated at S2234 in its mechanosensitive domain 20 (d20) through AKT. Here, we discovered a strong dephosphorylation of FLNc-pS2234 in cultured skeletal myotubes under acute mechanical stress, despite high AKT activity. We found that all three protein phosphatase 1 (PP1) isoforms are part of the FLNc d18-21 interactome. Enzymatic assays demonstrate that PP1 efficiently dephosphorylates FLNc-pS2234 and in vitro and in cells upon PP1 activation using specific modulators. FLNc-pS2234 dephosphorylation promotes the interaction with FILIP1, a mediator for filamin degradation. Altogether, we present a model in which dephosphorylation of FLNc d20 by the dominant action of PP1c prevails over AKT activity to promote the binding of the filamin degradation-inducing factor FILIP1 during acute mechanical stress. [ABSTRACT FROM AUTHOR]

Key points Increased reactive oxygen species (ROS) generation and microvascular endothelial disruptions occur with natural ageing, but often transpire before the detection of cardiometabolic conditions including hypertension. Age‐related increases in blood pressure are driven by complex systemic changes with poorly understood integrated mechanisms. The deconditioning experienced by ageing skeletal muscle from mid‐life is associated with reduced microvascular blood flow and increased peripheral resistance, suggesting that vasodilatory decrements in the muscle may precede the age‐related increases in blood pressure. Structural and functional changes within the vascular and skeletal muscle systems with advancing age can influence redox homeostasis, and vice versa, further compounding microvascular endothelial dysfunction. Therefore, comparisons between the microvascular environments of healthy and hypertensive cohorts can provide insights into the changes that occur during significant periods of functional decline. This comprehensive study protocol describes a microdialysis technique to assess the interactions of microvascular health and functional changes in the muscle, which currently cannot be otherwise addressed. Here, we detail an experimental protocol to simultaneously detect skeletal muscle ROS (H2O2 and indirect O2−), determine nutritive blood flow and assess microvascular endothelial function in response to acetylcholine stimulation. We expect that healthy middle‐aged individuals should not have increased ROS generation in the muscle at rest, compared to their hypertensive or older counterparts, but may exhibit perturbed microvascular function. The described technique allows for intricate exploration of microvascular physiology that will provide a critically novel insight into benchmarking potential age‐related mechanisms involved in the development of age‐related hypertension, and aid in early identification and prevention. Increased reactive oxygen species (ROS) production and microvascular endothelial dysfunction precede the onset of age‐related cardiometabolic and vascular conditions such as hypertension. The profound structural and functional changes that occur within the vasculature and in skeletal muscle from middle age prompt a need to mechanistically explore the microvascular environment in healthy and hypertensive individuals. Using a novel microdialysis technique, we detail an experimental protocol to simultaneously detect skeletal muscle ROS (H2O2 and indirect O2−), determine nutritive blood flow and assess microvascular endothelial function in response to acetylcholine stimulation. With this technique and study protocol, we can reveal functional insights into potential perturbations in ROS generation at rest and the microvascular endothelium, which play important roles in the development of age‐related hypertension. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Assessing upper limb muscle strength is important for understanding health outcomes, such as daily function and mortality. Ultrasound (US) is increasingly used to evaluate muscle health, but the relationship between its measures of morphology and isometric strength has not been thoroughly explored in upper limb muscles. The aim of this study was to evaluate the associations between US morphological measures and isometric strength in functionally relevant upper limb muscles in healthy adults.Twenty‐four healthy volunteers (30.0 ± 10.8 years) underwent B‐mode, axial US scans of the first dorsal interosseus (FDI), flexor pollicis longus (FPL), biceps brachii (BB), brachialis (BR), and triceps brachii lateral head (TB). Participants performed corresponding maximal voluntary contractions (MVC), including first digit distal phalanx flexion, second digit abduction, and elbow flexion and extension. US images were segmented to obtain maximal muscle thickness (MT) and cross‐sectional area (CSA).Strong positive correlations were found between muscle strength and BB MT (r = .83; p < .001), BR CSA (r = .84; p < .001), and TB MT (r = .70; p < .001). Moderate positive correlations were found for strength and FDI CSA (r = .67; p < .001), FDI MT (r = .47; p < .05), FPL CSA (r = .54; p < .01), and FPL MT (r = .42; p < .05). No significant correlation was found between strength and BR MT (r = .16; p > .05).Our data showed moderate‐to‐strong associations between US muscle morphology and strength, suggesting that US is likely a good biomarker for strength. However, its use is not “one size fits all.” Future investigations should continue to assess this relationship in different muscles and expand the generalizability to clinical populations. [ABSTRACT FROM AUTHOR]

Visual observing muscle tissue regeneration is used to measure experimental effect size in biological research to discover the mechanism of muscle strength decline due to illness or aging. Quantitative computer imaging analysis for support evaluating the recovery phase has not been established because of the localized nature of recovery and the difficulty in selecting image features for cells in regeneration. We constructed MyoRegenTrack for segmenting cells and classifying their regeneration phase in hematoxylin–eosin (HE) stained images. A straightforward approach to classification is supervised learning. However, obtaining detailed annotations for each fiber in a whole slide image is impractical in terms of cost and accuracy. Thus, we propose to learn individual recovery phase classification utilizing the proportions of cell class depending on the days after muscle injection to induce regeneration. We extract implicit multidimensional features from the HE-stained tissue images and train a classifier using weakly supervised learning, guided by their class proportion for elapsed time on recovery. We confirmed the effectiveness of MyoRegenTrack by comparing its results with expert annotations. A comparative study of the recovery relation between two different muscle injections shows that the analysis result using MyoRegenTrack is consistent with findings from previous studies. [ABSTRACT FROM AUTHOR]

Ythdf2 is known to mediate mRNA degradation in an m6A-dependent manner, and it has been shown to play a role in skeletal muscle differentiation. Recently, Ythdf2 was also found to bind to m6A-modified precursor miRNAs and regulate their maturation. However, it remains unknown whether this mechanism is related to the regulation of myogenesis by Ythdf2. Here, we observed that Ythdf2 knockdown significantly suppressed myotube formation and impacted miRNAs expression during myogenic differentiation. Through integrated analysis of miRNA and mRNA sequencing data, miR-378 and miR-378-5p were identified as important targets of Ythdf2 in myogenesis. Mechanically, Ythdf2 was found to interact with core components of the pre-miRNA processor complex, namely DICER1 and TARBP2, thereby facilitating the maturation of pre-miR-378/miR-378-5p in an m6A-dependent manner and resulting in an increase in the expression levels of mature miR-378 and miR-378-5p. Moreover, the downregulation of either miR-378 or miR-378-5p significantly inhibited myotube formation, while the forced expression of miR-378 or miR-378-5p could partially rescued Ythdf2 knockdown-induced suppression of myogenic differentiation by activating the mTOR pathway. Collectively, our results for the first time suggest that Ythdf2 regulates myogenic differentiation via mediating pre-miR-378/miR-378-5p maturation, which might provide new insights into the molecular mechanisms underlying m6A modification in the regulation of myogenesis. [ABSTRACT FROM AUTHOR]

Obesity‐induced impairment of myogenic differentiation leads to muscle loss and sarcopenia. Pyruvate dehydrogenase (PDH) plays a crucial role in glucose metabolism and is associated with muscle differentiation. However, the effect of dichloroacetate (DCA), a PDH activator, on obesity‐induced impairment of myogenic differentiation remains unknown. Here, we evaluated the effects of DCA treatment on high‐fat intake‐induced impairment of myogenic differentiation in C2C12 cells and C57BL/6 mice. In C2C12 cells, DCA treatment improved PDH activity that was reduced by palmitate (PAL) and decreased the lactate concentrations in the media. Additionally, DCA reversed PAL‐ and high‐fat diet (HFD)‐induced decrease in the expression of myoblast determination protein 1 (MyoD), myogenin (MyoG) and myosin heavy chain (MyHC) in C2C12 cells and C57BL/6 mice. To explore the possible mechanism, DCA treatment restored the levels of p‐Akt, p‐FoxO1, p‐FoxO3a and p‐p38 MAPK levels in PAL‐treated C2C12 cells. Moreover, the protective effects of DCA were reversed by treatment with the Akt inhibitor MK2206 in C2C12 cells. In summary, DCA treatment alleviated high‐fat intake‐induced impairment of myogenic differentiation via Akt signalling, suggesting its potential in treating obesity‐associated muscle loss and sarcopenia. [ABSTRACT FROM AUTHOR]

The prevalence of cardiovascular events, stroke, and diabetes worldwide underscores the urgent need for effective and minimally invasive treatments. With nearly 20 million annual casualties attributed to cardiovascular diseases and an estimated 463 million people living with diabetes in 2022. Identifying promising therapeutic candidates is paramount. MicroRNAs, short nucleic acids involved in regulating gene expression, emerge as potential game-changers. Among these, microRNA-24 (miR-24), a hypoxia-sensitive player in endothelial vessels, has protective roles against diverse vascular complications. Following heart infarction and stroke, elevating miR-24 expression proves beneficial by mitigating oxidative stress, inflammation, and apoptosis while enhancing cell survival. It reduces cardiac fibrosis in heart disease, regulates aberrant angiogenesis in cerebral hemorrhagic strokes, and enhances the functionality of cardiomyocytes and brain neurons. In diabetic conditions, augmenting miR-24 expression mitigates complications. Further, being miR-24 also expressed by the skeletal muscle (i.e., myo-miR) in response to exercise, this miRNA may participate in the complex molecular network that systemically spreads the beneficial effects of physical exercise. This review provides a comprehensive vision of the molecular mechanisms underpinning the miR-24 protective effects, offering new insights into its therapeutic potential and proposing a novel avenue for medical intervention. Highlights: miR-24 is a promising therapeutic target, sensitive to hypoxia, with diverse protective roles in cardiovascular diseases, stroke, and diabetes. miR-24's protective mechanisms, including anti-apoptotic effects and inflammation modulation, position it as a potential treatment for heart infarction, stroke, and diabetic complications. Reduced miR-24 expression in these conditions suggests its potential as an efficient treatment, pending careful evaluation in (pre)clinical trials. [ABSTRACT FROM AUTHOR]

Background: Vitamin C plays key roles in cellular homeostasis, functioning as a potent antioxidant and a positive regulator of cell differentiation. In skeletal muscle, the vitamin C/sodium co-transporter SVCT2 is preferentially expressed in oxidative slow fibers. SVCT2 is up-regulated during the early fusion of primary myoblasts and decreases during initial myotube growth, indicating the relevance of vitamin C uptake via SVCT2 for early skeletal muscle differentiation and fiber-type definition. However, our understanding of SVCT2 expression and function in adult skeletal muscles is still limited. Results: In this study, we demonstrate that SVCT2 exhibits an intracellular distribution in chicken slow skeletal muscles, following a highly organized striated pattern. A similar distribution was observed in human muscle samples, chicken cultured myotubes, and isolated mouse myofibers. Immunohistochemical analyses, combined with biochemical cell fractionation experiments, reveal a strong co-localization of SVCT2 with intracellular detergent-soluble membrane fractions at the central sarcomeric M-band, where it co-solubilizes with sarcoplasmic reticulum proteins. Remarkably, electrical stimulation of cultured myofibers induces the redistribution of SVCT2 into a vesicular pattern. Conclusions: Our results provide novel insights into the dynamic roles of SVCT2 in different intracellular compartments in response to functional demands. [ABSTRACT FROM AUTHOR]

Background: Manual therapy (MT) has been widely used in China to treat local tissue inflammation for a long time. However, there is a lack of scientific evidence for using MT in anti‐inflammatory therapy, and its anti‐inflammatory mechanism needs further clarification. Methods: We utilized MT to treat cardiotoxin (CTX) injury‐induced skeletal muscle inflammation in C57BL6/J mice. We analyzed the underlying mechanism by integrating single‐cell RNA sequencing (scRNA‐seq) with molecular techniques. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were used to assess skeletal muscle inflammation and muscle fiber cross‐sectional area (CSA). scRNA‐seq, immunofluorescence, and western blot were performed to determine cellular and molecular outcome changes. Results: Compared with CTX injury‐induced skeletal muscle inflammatory mice, MT intervention significantly reduced proinflammatory cytokines interleukin (IL)‐1β, IL‐6, and tumor necrosis factor alpha (TNF‐α) expression levels; scRNA‐seq detected that neutrophil numbers and activity were maximum proportions increased in injured skeletal muscle among macrophage, T cells, B cells, endothelial cells, fast muscle cells, fibroblasts, and skeletal muscle satellite cells; and S100A9 gene expression was supreme in neutrophils. However, after treatment with MT, S100A9 protein expression and the numbers and activity of Ly6g+/Mpo+ neutrophils were significantly inhibited, thus reducing the inflammatory cytokine levels and exerting an anti‐inflammatory effect by early clearing neutrophils. Conclusion: MT can mitigate localized inflammation induced by injured skeletal muscle, achieved by decreasing S100A9 protein expression and clearing neutrophils in mice, which may help advance therapeutic strategies for skeletal muscle localized inflammation. [ABSTRACT FROM AUTHOR]

Ex situ conservation is a complementary strategy to in situ efforts and is vital for safeguarding endangered species through maintenance and breeding in captivity with potential for reintroductions into natural environments. However, it is crucial to recognize that prolonged captivity can lead to diminished abilities of organisms over generations. Factors linked to the impact of phenotypic plasticity during development, such as restricted movement, may affect organism performance during ex situ conservation efforts, potentially making reintroduction into the wild unfeasible. Consequently, it is imperative to analyze physiological differences between captive‐bred and wild individuals. Therefore, this study investigates how captivity influences locomotor performance, morphology, and metabolic capacities of adults and juveniles of the threatened treefrog Ololygon alcatraz, in comparison to natural populations. We obtained proportional measurements of individuals and assessed their locomotor performance through jumping exercise. We also measured the metabolic capacities of the frogs by examining the activity of enzymes involved in energetic metabolic pathways in their skeletal muscle fibers. We found that wild adult frogs had larger limbs, greater jumping abilities, and a more glycolytic profile, while captive adult frogs had smaller limbs and increased aerobic enzyme activity compared to their wild counterparts. These differences probably arise from phenotypic plasticity in ontogenetic development that differs between captive and natural environments, as juveniles do not show such differences. These results highlight the need for innovative strategies in managing captive O. alcatraz populations, which will aid in their successful translocation to the wild and strengthen ex situ conservation efforts. [ABSTRACT FROM AUTHOR]

The relationship between mechanistic target of rapamycin complex 1 (mTORC1) activation after resistance exercise and acetylcholine receptor (AChR) subunit gene expression remains largely unknown. Therefore, we aimed to investigate the effect of electrical stimulation‐induced intense muscle contraction, which mimics acute resistance exercise, on the mRNA expression of AChR genes and the signalling pathways involved in neuromuscular junction (NMJ) maintenance, such as mTORC1 and muscle‐specific kinase (MuSK). The gastrocnemius muscle of male adult Sprague–Dawley rats was isometrically exercised. Upon completion of muscle contraction, the rats were euthanized in the early (after 0, 1, 3, 6 or 24 h) and late (after 48 or 72 h) recovery phases and the gastrocnemius muscles were removed. Non‐exercised control animals were euthanized in the basal state (control group). In the early recovery phase, Agrn gene expression increased whereas LRP4 decreased without any change in the protein and gene expression of AChR gene subunits. In the late recovery phase, Agrn, Musk, Chrnb1, Chrnd and Chrne gene expression were altered and agrin and MuSK protein expression increased. Moreover, mTORC1 and protein kinase B/Akt‐histone deacetylase 4 (HDAC) were activated in the early phase but not in the late recovery phase. Furthermore, rapamycin, an inhibitor of mTORC1, did not disturb changes in AChR subunit gene expression after muscle contraction. However, rapamycin addition slightly increased AChR gene expression, while insulin did not impact it in rat L6 myotube. These results suggest that changes in the AChR subunits after muscle contraction are independent of the rapamycin‐sensitive mTORC1 pathway. [ABSTRACT FROM AUTHOR]

Background: The progression of malnutrition and sarcopenia after esophagectomy for esophageal cancer negatively influences long-term prognosis. To improve nutritional status after esophagectomy, we introduced an intensified nutrition management (iNM) protocol, in which nutritional counselling by dietitians was provided more frequently. The aim of this study was to evaluate the efficacy of iNM compared with the conventional NM (cNM). Methods: We included 126 patients who underwent esophagectomy before and after NM revision, and compared nutritional status and changes in body composition after esophagectomy between the cNM and iNM groups. Nutritional parameters were assessed, and we also calculated skeletal muscle index (SMI), skeletal muscle density (SMD), and visceral fat area (VFA) using computed tomography volumetry. Results: There were no significant differences in baseline characteristics or surgical outcomes between the groups. Compared with the cNM group, nutritional counselling was provided more frequently (P < 0.001) in the iNM group, and compliance rate increased from 56.3 to 91.9% (P < 0.001). Body weight loss at 4 and 6 months and SMI reduction at 6 months were significantly improved in the iNM group compared with the cNM group (P < 0.001, P = 0.032, and P = 0.023, respectively). There were no significant differences in the changes in SMD, VFA, serum albumin level, and prealbumin level between the two groups. Conclusions: Outpatient iNM significantly mitigated the reduction in body weight and SMI 3–6 months after esophagectomy. [ABSTRACT FROM AUTHOR]

Over the course of the physical activity transition, machines have largely replaced skeletal muscle as the source of work for locomotion and other forms of occupational physical activity in industrial environments. To better characterize this transition and its effect on back muscles and the spine, we tested to what extent typical occupational activities of rural subsistence farmers demand higher magnitudes and increased variability of back muscle activity and spinal loading compared to occupational activities of urban office workers in Rwanda, and whether these differences were associated with back muscle endurance, the dominant risk factor for back pain. Using electromyography, inertial measurement units, and OpenSim musculoskeletal modeling, we measured back muscle activity and spinal loading continuously while participants performed occupational activities for one hour. We measured back muscle endurance using electromyography median frequency analysis. During occupational work, subsistence farmers activate their back muscles and load their spines at 390% higher magnitudes and with 193% greater variability than office workers. Partial correlations accounting for body mass show magnitude and variability response variables are positively associated with back muscle endurance (R = 0.39–0.90 [P < 0.001–0.210] and R = 0.54–0.72 [P = 0.007–0.071], respectively). Body mass is negatively correlated with back muscle endurance (R = -0.60, P = 0.031), suggesting higher back muscle endurance may be also partly attributable to having lower body mass. Because higher back muscle endurance is a major factor that prevents back pain, these results reinforce evidence that under-activating back muscles and under-loading spines at work increases vulnerability to back pain and may be an evolutionary mismatch. As sedentary occupations become more common, there is a need to study the extent to which occupational and leisure time physical activities that increase back muscle endurance helps prevent back pain. [ABSTRACT FROM AUTHOR]