Skeletal muscle atrophy is one of the major side effects of high dose or sustained usage of glucocorticoids. Pyroptosis is a novel form of pro-inflammatory programmed cell death that may contribute to skeletal muscle injury. Trimetazidine, a well-known anti-anginal agent, can also improve skeletal muscle performance both in human and mice. We here showed that dexamethasone induced atrophy, evidenced by the increase of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) expression , and the decrease of myotube diameter in C2C12 myotubes. Dexamethasone also induced pyroptosis, indicated by upregulated pyroptosis-related protein NLRP3, Caspase-1 and GSDMD. Knockdown of NLRP3 or GSDMD attenuated dexamethasone-induced myotube pyroptosis and atrophy. Trimetazidine administration ameliorated dexamethasone-induced muscle atrophy both in vivo and in vitro. Moreover, trimetazidine improved exercise tolerance, as evidenced by increased running distance and running time, as well as increased skeletal muscle mass in dexamethasone-treated mice. Mechanically, trimetazidine could reverse dexamethasone-induced activation of pyroptosis both in C2C12 myotubes and in mice. Taken together, our present study demonstrated that NLRP3/GSDMD pathway-mediated pyroptosis was involved in dexamethasone-induced skeletal muscle atrophy. Trimetazidine could partially alleviate dexamethasone-induced skeletal muscle atrophy, and increase the diameter of C2C12 myotubes via inhibiting pyroptosis. Thus, trimetazidine might be a potential therapeutic compound for the prevention of muscle atrophy in glucocorticoid-treated patients.

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.

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle atrophy-mediated disturbance of mitochondria that have a lipid bilayer. Tail suspension was used to establish muscle- atrophied mouse models. AX diet fed to tail-suspension mice prevented loss of muscle weight and decreased myofiber size in the soleus muscle. Additionally, AX improved down-regulation of mitochondrial respiratory chain complexes II and III in the soleus muscle after tail suspension. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial complex III-driven production of reactive oxygen species in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A-treated Sol8 myotubes. These results suggested that AX inhibited mitochondrial oxidative stress through a mitochondria-mediated apoptosis pathway and thus prevented muscle atrophy.

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.

Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interplays the contraction of actin-containing thin filaments and myosin-containing thick filaments. The breakdown product of titin has been measurable in urine as urinary titin N-fragments. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome.

In this study we used a recently developed ex vivo-in vitro model to assess the effect of feeding older adults a casein protein hydrolysate (CPH) compared with non-bioactive non-essential amino acid (NEAA) supplement on Muscle Protein Synthesis (MPS) and Breakdown (MPB). Serum from six healthy older males following overnight fast and 60 min postprandial ingestion of CPH or NEAA (0.33 g.kg^-1 body mass) was used to condition C2C12 myotube media. CPH-fed serum significantly increased MPS compared to fasted serum. In addition, CPH-fed serum induced myotube growth and markedly suppressed atrogin-1, but not MuRF1, expression. Comparatively, no change in MPS, myotube growth and gene expression was observed following NEAA-fed serum treatment. CPH-fed serum from older adults stimulated de novo MPS, suppressed markers of protein breakdown and resulted in myotube growth, indicating a potential role for CPH as a dietary protein source to prevent age-related sarcopenia.

Much has been learned about the interaction between myosin and actin through biochemistry, in vitro motility assays and cryo-electron microscopy of F-actin decorated with myosin heads. Comparatively less is known about actin-myosin interactions within the filament lattice of muscle, where myosin heads function as independent force generators and thus most measurements report an average signal from multiple biochemical and mechanical states. All of the 3-D imaging by electron microscopy that has revealed the interplay of the regular array of actin subunits and myosin heads within the filament lattice has been accomplished using the flight muscle of the large waterbug Lethocerus sp. Lethocerus flight muscle possesses a particularly favorable filament arrangement that enables all the myosin cross-bridges contacting the actin filament to be visualized in a thin section. This review covers the history of this effort and the progress toward visualizing the complex set of conformational changes that myosin heads make when binding to actin in several static states as well as fast frozen actively contracting muscle. The efforts have revealed a consistent pattern of changes to the myosin head structures determined by X-ray crystallography needed to explain the structure of the different acto-myosin interactions observed in situ.

Matrix metalloproteinases have been implicated in muscular dystrophy progression and recent studies described the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its implication in dystrophin deficient hearts is still missing. Here, we aimed at investigating MMP-10 implication in severe muscular dystrophic progression and characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We have found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, identifying a new area of investigation that could lead to future therapies for dystrophic muscles.

The purpose of the present study was to examine the relationships between bat swing speed (BSS) and muscle thickness and lateral asymmetry of the trunk and limbs in collegiate baseball players. Twenty-four collegiate baseball players participated in this study. The maximum BSS in hitting a teed ball was measured using a motion capture system. The muscle thicknesses of the trunk (upper abdominal rectus, central abdominal rectus, lower abdominal rectus, abdominal wall, and multifidus lumborum), upper limb, and lower limb were measured using a B-mode ultrasonography. Lateral asymmetry between each pair of muscles was determined as the ratio of the thickness of the dominant side to that of the non-dominant side. Significant positive correlations were observed between BSS and muscle thicknesses of the abdominal wall and multifidus lumborum on the dominant side (r = 0.426 and 0.431, respectively; p < 0.05), while nearly significant positive correlations were observed between BSS and muscle thicknesses on the non-dominant side. No significant correlations were found between BSS and lateral asymmetry of all muscles. These findings indicate the importance of the trunk muscles for bat swing, and the lack of association between BSS and lateral asymmetry of muscle size.

Background: Evaluating muscle mass and function among stroke patients is important. However, evaluating muscle volume and function is not easy due to the disturbance of consciousness and paresis. Temporal muscle thickness (TMT) has been introduced as a novel surrogate marker for muscle mass, function, and nutritional status. We herein performed a narrative literature review on temporal muscle and stroke to understand the current meaning of the TMT in the clinical stroke practice. Methods: The search was performed in PubMed, last updated in October 2021. Report on temporal muscle morphomics and stroke-related diseases or clinical entities were collected. Results: Four studies reported on TMT and subarachnoid hemorrhage, 2 intracerebral hemorrhage, 2 ischemic stroke, 2 standard TMT values, and 2 nutritional status. TMT was reported as a prognostic factor for several diseases, surrogate markers for skeletal muscle mass, and an indicator of nutritional status. Computed tomography, magnetic resonance imaging, and ultrasonography were used to measure TMT. Conclusions: TMT is gradually used as a prognostic factor of stroke or surrogate marker for skeletal muscle mass and nutritional status. Establishing standard methods to measure TMT and large prospective studies to investigate the further relationship between TMT and diseases are needed.

Near-Infrared Spectroscopy (NIRS) has been used to measure muscle mitochondrial capacity. The current method requires as many as 22 short ischemic occlusions to generate a recovery curve for mitochondrial capacity. PURPOSE: To determine the effectiveness of using a 6-occlusion analysis protocol to study muscle mitochondrial capacity. METHOD: Two independent, unidentified data sets were analyzed (bicep n=48, forearm n=41) from previous studies using a NIRS device (Artinis, Ltd.). Both data sets had two recovery tests that included 22 ischemic occlusions. A recovery rate used to indicate mitochondrial capacity was calculated two different ways (simultaneously). Each sample was analyzed with a MATLAB program; with a curve-fit for the 22 ischemic occlusions and curve matching for the first six ischemic cuffs and an end resting value. The two resulting rate constants were compared using correlations, both for the two data sets, good and bad fitting data, using the best 5 of 6 points for the 6 cuff approach. RESULTS: The rate constants were not significantly different between the 22 cmuff and 6 cuff for the total data sets: bicep (1.43+0.32min^-1, 1.44+0.35min^-1, p=0.56), forearm (1.94+0.42min^-1, 1.95+0.44min^-1, p=0.76). The average bicep rate constants, when compared to each other, had an equation of y=1.07x-0.09, R²=0.90. The average forearm rate constants, when compared to each other, had an equation of 0.98x+0.02, R²=0.93. CONCLUSIONS: The 6-Cuff analysis provided the same results as the longer 22-cuff. The 6-cuff approach is both shorter in time and uses less ischemic occlusion periods, increasing the practicality of the NIRS mitochondrial capacity test.

Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate re-habilitation and nutrition management. Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasonography, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it is mostly retrospectively conducted due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation-contraction coupling. The activity of the RyR is regulated by many intracellular factors such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for change in the cellular environment of muscles.

Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcomes measures selected: the myostatin inhibition story thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models has failed to translate into clinical benefit to patients has been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.

Background: The thoracolumbar fascia (TLF) is thought to play a role in the development of LBP, but it is not yet clear which factor of TLF changes is a cause and which is an effect. Therefore, some studies used the cross-correlation function (CCR) to reveal time-dependent relationships between biomechanical and neuromotor factors. Methods: Ten patients with acute low back pain (aLBP) were matched to healthy controls. Simultaneous recording of surface electromyography (sEMG) of the erector spinae muscle (ES) and dynamic ultrasound (US) images of TLF deformation were performed during trunk extension. CCR functions and Granger causality were used to describe the relationship between the two measures. Results: CCR time lags were significant higher in the aLBP group (p = 0.04). Granger causality (GC) showed a direct effect of TLF deformation on ES activation only in the aLBP group (p &lt; 0.03). Conclusions: The results suggest that in aLBP, ES activity is significantly affected by TLF, whereas this relation-ship is completely random in healthy subjects studied with CCR and GC comparisons of dynamic US imaging and sEMG data signals. Fascia-related disturbances in neuromotor control, particularly due to altered muscle spindle functions, are suspected as a possible mechanism behind this.

Fullerene nanomaterials exposure often causes a variety of diseases. Many studies have pointed out that fullerene nanomaterials can be studied in fish. However, there are few studies on health risk assessment of clownfish with lower doses of fullerene nanoparticles or different exposure durations. In this study, we set 1.5% and 3.0% for low- and high-dose fullerene nanomaterials exposure concentrations, respectively. Meanwhile, we performed a time-series analysis to investigate that the activation of lipid and amino acids metabolism after fullerene nanomaterials exposure in clownfish. 1368 metabolites were detected from clownfish by using liquid chromatography-mass spectrometry (LC-MS) analyses. Our results suggest that exposure to lower fullerenes nanoparticles may have a certain promoting effect on clownfish overall length, body length and weight. At the same time, the activation of potential metabolic pathways enriched by different metabolites in KEGG pathway may also indicate the positive promoting effect of fullerene nanoparticles after exposure. The present work indicates that it is particularly important to find the concentration window for fullerene nanomaterials to improve government safety guidelines, especially when these are applied to assess the health risk of human.

We have previously demonstrated that the acute ingestion of essential amino acids may augment net protein balance in the elderly. Using a double blind, randomized controlled trial, our objective was to compare an experimental meal replacement enriched with essential amino acids (EMR) compared to a commercial meal replacement (Optifast®) provided once/day (q.d.) for four weeks on body composition and physical function in older, obese participants. Twenty-seven individuals (69±5 yrs; body mass index of 32±4 kg/m2) were randomly assigned to EMR (n=13) or Optifast® (n=15) supplementation. Measurements of body composition, skeletal muscle cross-sectional area (CSA), intrahepatic lipid and physical function were completed pre- and post-supplementation. Body mass, fat mass, and visceral fat mass were reduced with EMR but not altered with Optifast®. Thigh muscle CSA increased ( 4.1 ± 1.9 cm2, P = 0.03) with EMR but not Optifast®. There was a significant increase in the distance covered during the six-minute walk test with EMR ( 21±26 m) but no change in Optifast® ( 22±54 m). Improvements in body composition and physical function support the efficacious use of EMR-based meal replacements in the obese elderly.

Objective: The purpose of this study is to compare the effects of stretching methods for flexibility, muscle activation, and pressure pain threshold in ballet dancers, and to suggest an effective stretching method. Methods: Thirty-three ballet dancers were randomized to a static stretching group (n=11), muscle energy technique stretching group (n=11), and vibration-assisted stretching group (n=11). The angle of hip joint extension in arabesque, the activation of rectus femoris in Devéloppé, and the pressure pain threshold on rectus femoris in sitting position were measured to compare the effects of different stretching methods. Results: Hip joint extension angles increased in all stretching methods (p<0.05), however, vibration-assisted stretching and muscle energy technique stretching were more effective than static stretching (p<0.05). The activation of the rectus femoris decreased in all groups (p<0.05), but the muscle energy technique stretching group and the vibration-assisted stretching group showed a significant decrease compared to the static stretching group (p<0.05). The pressure pain threshold showed significant improvement only in the static stretching group (p<0.05), and the vibration-assisted stretching group (p<0.05). Conclusion: Vibration-assisted stretching compared to static stretching and muscle energy technique stretching is a beneficial method for flexibility, muscle activation, and pressure pain threshold in ballet dancers.

Upper limb control depends on accurate internal models of limb position relative to the head and neck, accurate sensory inputs, and accurate cortical processing. Transient alterations in neck afferent feedback induced by muscle vibration may impact upper limb proprioception. This research aimed to determine the effects of neck muscle vibration on upper limb proprioception using a novel elbow repositioning task (ERT). 26 right-handed participants aged 22.21 2.64 performed the ERT consisting of three target angles between 80-90 (T1), 90-100 (T2) and 100-110 (T3). Controls (CONT) (n=13, 6F) received 10 minutes of rest and the vibration group (VIB) (n=13, 6F) received 10 minutes of 60Hz vibration over the right sternocleidomastoid and left cervical extensor muscles. Task performance was reassessed following experimental manipulation. Significant time by group interactions occurred for T1: (F1,24 = 25.330, p &lt; 0.001, p2 = 0.513) where CONT improved by 26.08% and VIB worsened by 134.27%, T2: (F1,24 = 16.157, p &lt; 0.001, p2 = 0.402) where CONT improved by 20.39% and VIB worsened by 109.54%, and T3: (F1,24 = 21.923, p &lt; 0.001, p2 = 0.447) where CONT improved by 37.11% and VIB worsened by 54.39%. Improvements in repositioning accuracy indicates improved proprioceptive ability with practice in controls. Decreased accuracy following vibration suggests that vibration altered proprioceptive inputs used to construct body schema, leading to inaccurate joint position sense and the observed changes in elbow repositioning accuracy.

The objective was to assess the instrumental validity and the test-retest reliability of a low-cost hand-held push dynamometer adapted from a load-cell based hanging scale (tHHD) to collect compressive forces in different ranges of compressive forces. Three independent raters applied 50 pre-established compressions each on the tHHD centered on a force platform in 3 distinct ranges: ~70 N, ~160 N, ~250 N. Knee isometric strength was also assessed on 19 subjects in two sessions (48h apart) using the tHHD anchored by an inelastic adjustable strap. Knee extension and flexion were assessed with the participant seated on a chair with the feet resting on the floor, knees, and hips flexed at 90°. The isometric force peaks were recorded and compared. The ICC and the Cronbach’s α showed excellent consistency and agreement for both instrumental validity and test-retest reliability, as the correlation and determination coefficients. The SEM and the MDC analysis returned adequate low values with a coefficient of variation less than 5%. The Bland-Altman results showed consistency and high levels of agreement. The tHHD is a valid method to assess the knee isometric strength, showing portability, cost-effectiveness, and user-friendly interface to provide an effective form to assess the knee isometric strength.

Tissue engineering, also called “regenerative medicine”, refers to attempt to create functional human tissue from cells in laboratory. This is a field that uses living cells, biocompatible materials, suitable biochemical and physical factors and their combinations, to create tissue-like structures.. To date, no tissue engineered skeletal muscle implants have been developed for clinical use, but it may represent a valid alternative to treat volumetric muscle loss in the near future. Herein, we reviewed the literature and showed different techniques to produce synthetic tissues with the same architectural, structural and functional properties of native tissues.

Wooden breast is a muscle disorder affecting modern commercial broiler chickens that causes a palpably firm pectoralis major muscle and severe reduction in meat quality. Most studies have focused on advanced stages of wooden breast apparent at market age, resulting in limited insights into the etiology and early pathogenesis of the myopathy. Therefore, the objective of this study was to identify early molecular signals in the wooden breast transcriptional cascade by performing gene expression analysis on the pectoralis major muscle of two-week-old birds that may later exhibit the wooden breast phenotype by market age at 7 weeks. Biopsy samples of the left pectoralis major muscle were collected from 101 birds at 14 days of age. Birds were subsequently raised to 7 weeks of age to allow sample selection based on the wooden breast phenotype at market age. RNA sequencing was performed on 5 unaffected and 8 affected female chicken samples, selected based on wooden breast scores (0 to 4) assigned at necropsy where affected birds had scores of 2 or 3 (mildly or moderately affected) while unaffected birds had scores of 0 (no apparent gross lesions). Differential expression analysis identified 60 genes found to be significant at an FDR-adjusted p value of 0.05. Of these, 26 were previously demonstrated to exhibit altered expression or genetic polymorphisms related to glucose tolerance or diabetes mellitus in mammals. Additionally, 9 genes have functions directly related to lipid metabolism and 11 genes are associated with adiposity traits such as intramuscular fat and body mass index. This study suggests that wooden breast disease is first and foremost a metabolic disorder characterized primarily by ectopic lipid accumulation in the pectoralis major.

Background: Knee joint is a common site for injury among younger people, the purpose of this study is to measure the skeletal muscle endurance and strength on people with prior knee reconstruction surgery. Methods: Young healthy female subjects were tested who reported having knee reconstruction surgery of over one year prior to testing. The skeletal muscle endurance index of the hamstring and quadriceps muscles was determined as the decline in the specific muscle acceleration in response to 2, 4, and 6 Hz electrical stimulation. Maximal isometric muscle strength (MVC) was measured in the hamstring and quadriceps muscles. Results: The hamstring muscles in the affected leg had less endurance than the non-affected leg at 6 Hz stimulation (55.5 ± 13.2% versus 78.0 ± 13.3%, P = 0.01). Muscle endurance was not reduced in the quadriceps muscles in the affected leg compared to the non-affected leg at 6 Hz stimulation (78.0 ± 13.3% versus 80.3 ± 10.0%, P = 0.69). There were no differences in MVC between the affected and non-affected legs for either the hamstring (P= 0.20) or quadriceps muscles (p = 0.67). Conclusions: Muscle endurance is reduced in the hamstring muscles at least one-year post injury, while hamstring strength is not. Reduced hamstring muscle endurance could be a result of a lack of focus on muscle endurance during rehabilitation after injury and may contribute to re-injury in the particular muscle even in people who have recovered muscle strength.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

The proliferation and differentiation of mammalian skeletal muscle satellite cells (MuSCs) are highly complicated. Apart from the regulatory signaling cascade driven by the protein-coding genes, non-coding RNAs like microRNAs (miRNA) and circular RNAs (circRNAs) play essential roles in this biological process. However, circRNA functions in MuSCs proliferation and differentiation remain largely to be elucidated. Here, we screened for an exonic circTCF4 based on our previous RNA-Seq data, specifically expressed during the development of the longest dorsal muscle in goats. Subsequently, the circular structure and whole sequence of circTCF4 were verified using Sanger sequencing. Besides, circTCF4 was spatiotemporally expressed in multiple tissues from goats but strikingly enriched in muscles. Furthermore, circTCF4 suppressed MuSCs proliferation and differentiation, independent of AGO2 binding. Finally, we conducted Poly(A) RNA-Seq using cells treated with small interfering RNA targeting circTCF4 and found that circTCF4 would affect multiple signaling pathways, including insulin signaling pathway and AMPK signaling pathway related to muscle differentiation. Our results provide additional solid evidence for circRNA regulating skeletal muscle formation.

Instep weights cause mechanical changes, modifying muscle activity and changing ground plantar support. 30 semi-professional sprinters, randomized in 3 groups [no-weight, Ascending (50, 100, 150 and 200g), Descending (200, 150, 100 and 50g)] run 6 consecutive 50-meter series at maximum speed (first and sixth without weights); partial, total times and speed were analyzed. Instep weights were safe and well tolerated. 6th series speed decreased except in men’s ascending group, who achieved a lower time in sixth compared to first series. Weights presented in ascending order in men during warm-up could improve running time. Instep weights neuromuscular effects could compensate men’s tiredness in last series; weights could be included in training methodologies. Men training weights presented in ascending order may provide better results.

Despite more than hundred years of research since Sir Sherrington’s studies on reflexes, his questions are still somehow unanswered. On what anatomical stage do the play of spinal reflex interaction take place? What are the physiological properties of this anatomical substrate? In this paper, we address these questions in light of the most advanced theory of motor control and the anatomical discoveries on the fascia that are changing how we think about control of action and perception. There are two sides of the problem: the neurological (reflex) connections that are at the base of movement, and the anatomical substrate that regulates and coordinates the movement. We recently advanced a hypothesis on how these two elements are connected and how they interplay. Here we further explain the concept of the somatic equilibrium point – SEP – and its central role in movement control and coordination. It is our belief that the concept of SEP explains how the neuro-mechanical control of movement is organized at peripheral level. At this level, intrafusal and extrafusal muscle fibres are combined in myofascial units, organized in anatomical directions. Myofascial units are closed systems whose behaviour can be affected by neural (voluntary) control or changes in external forces. SEPs represent the intrinsic equilibrium of the myofascial units, and are connected through the continuum of the fascia so that mechanical transfer of tension from segment to segment pre-adjust muscle fibers length and hence their excitation level. This is how coordination between segments is achieved. Finally, we suggest SEPs create the neurological representation of the referent configuration for action, and configurations are linked to the architecture of the fascial system.

Abstract The expression patterns of microRNAs (small non-coding RNAs) are altered in many biological processes such as myogenesis. In this study, we aimed to investigate the impact of predicted miR-202, its target genes Akt2 and Rock-1 as a potential regulator of myoblast in the myocyte differentiation process using the C2C12 cell line. After confirmation of the differentiation process induced by 3% horse serum, the expression level of miRNA and its targets were evaluated. In the following, a luciferase assay was conducted to approve the effect of miRNA on its target. Our results indicated that miR-202 and Akt2 were significantly up-regulated during differentiation, while Rock-1 was downregulated. Co-transfection of miRNA with psiCHECK2-Rock-1 significantly presented that Rock-1 was directly targeted by miR-202. On the contrary, miR-202 has failed to enforce its inhibitory effect on Akt2 expression. In particular, miR-202 seems to be a regulator of muscle differentiation pathway thought targeting Rock-1.

Ultrasound has become widely used as a mean to measure the rectus femoris muscle in the acute and chronic phase of critical illness. Despite its noninvasiveness and accessibility, its accuracy highly depends on the skills of the technician. However, few ultrasound phantoms for the confirmation of its accuracy or to improve technical skills exist. In this study, we created a novel phantom model and used it for investigating the accuracy of measurements and for training. Study 1 investigated how various conditions affect ultrasound measurements such as thickness, cross-sectional area, and echogenicity. Study 2 investigated if the phantom can be used for training of various health care providers in vitro and vivo. Study 1 showed that thickness, cross-sectional area, and echogenicity were affected by probe compression strength, probe angle, phantom compression, and varying equipment. Study 2 in vitro showed that using the phantom for training improved the accuracy of the measurements taken within phantom, and Study 2 in vivo showed the phantom training had a short-term effect on improving the measurement accuracy in a human volunteer. The new ultrasound phantom model revealed that various conditions affected ultrasound measurements, and phantom training improved the measurement accuracy.

Despite the popularity of theraphosids, detailed reports on bite symptoms are still limited to few geographic regions and subfamilies. We therefore examined 363 published bite reports and noticed muscles cramps caused by theraphosids from nearly all continents and subfamilies. Symptoms are mostly locally restricted and mild, but 12.7% of victims experience pronounced cramps with highest incidence rates by Poecilotheriinae, Harpactirinae and Stromatopelminae subfamilies. We discuss how variations in venom quantity correlate with muscle cramp prevalence.

The aim of the study was to analyze the in ovo injection of chemically and biologically synthesized silver nano-particles (Ag NPs) using Brassica oleracea L. var capitate f. Rubra, (BOL) conjugation with L-Arginine (L-Arg) on the immune, muscle growth, survivability and hatchability of the broiler chickens. L-Arg (100 μg) conjugated with 1000 µg of Ag NPs synthesized by (BOL)-extract and L-Arg (100 μg) conjugated with 100 µg of Ag NPs chemically synthesized were injected into fertile eggs at 8d, 14d and 18d of incubation. Living embryo and hatched chicks were calculated. Survivability and hatchability were not affected by the injected dose of L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) but it significantly improved when the eggs were injected on day 14 of incubation compared with those injected on days 8 or 18. Moreover, the protein expression of muscle development markers such as myogenin and myoD were significantly up-related in 14 d of incubation whereas the heat shock proteins (HSPs) such as HSP-60 and HSP-70 were significantly up-regulated in 18 d incubation. In addition, the in ovo injection on 18 d significantly increased the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) as well the immunoglobulin (IgM) levels were increased in 14d incubation period in serum at the same concentration.

The aim of the study was to analyze the in ovo injection of chemically and biologically synthesized silver nano-particles (Ag NPs) using Brassica oleracea L. var capitate f. Rubra, (BOL) conjugation with L-Arginine (L-Arg) on the immune, muscle growth, survivability and hatchability of the broiler chickens. L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) were injected into fertile eggs at 8, 14 and 18 of incubation. Survival and hatched chicks were calculated. Survivability and hatchability were unaffected by the injected dose of L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) but it significantly improved when the eggs were injected on day 14 of incubation compared with those injected on days 8 or 18. Moreover, the protein expression of muscle development markers such as myogenin and myoD were significantly up-related in 14 d incubation whereas the heat shock proteins (HSPs) such as HSP-60 and HSP-70 were significantly up-regulated in 18 d incubation. In addition, the in ovo injection on 18 d significantly increased the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) as well the immunoglobulin (IgM) levels were increased in 14-day incubation period in serum at the same concentration. Collectively, these results indicate that injecting L-Arg (100 μg) with 1000 µg of BOL-Ag NPs or L-Arg (100 μg) with 100 µg of C-Ag NPs to eggs at day 14 after incubation could improve their hatchability, survival rate, and muscle growth marker.

(1) Background: Previous systematic review suggested a beneficial effect of progressive muscle relaxation (PMR) for cancer patients receiving chemotherapy. However, poor quality of eligible studies impaired the reliability and validity of findings. Moreover, additional potential studies with good quality published in Chinese language have been published recently. The aim of the present systematic review was to investigate the value of PMR training in preventing and alleviating nausea and vomiting caused by chemotherapy among cancer patients. (2) Methods: We assigned two independent investigators to search all potential studies in PubMed, Cochrane Controlled Register of Trial (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), China Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang data. We used data extraction sheet extracted all essential information, and used the Cochrane risk of bias assessment tool to appraise the quality of eligible studies. Finally, we qualitatively summarized the results of all included studies. (3) Results: Six studies enrolling 288 patients were considered to meet our selection criteria finally. Of these 6 studies, three were labeled as moderate quality, and the remaining studies were low quality. All included studies consistently suggested that PMR has a positive impact on nausea and vomiting caused by chemotherapy among cancer patients especially alleviating the incidence, frequency and degree of delayed nausea and vomiting. (4) Conclusions: Independent studies indicated that PMR was a beneficial approach to prevent and alleviate nausea and vomiting caused by chemotherapy among cancer patients. However, further studies considering other types of primary tumors should be designed in order to increase the generality of PMR because studies included in the present systematic review mainly enrolled lung cancer and breast cancer.

This study aimed to examine the vitamin D status of professional volleyball athletes and to determine its correlation with shoulder muscle strength. We finally included 52 healthy male professional volleyball players (23.2 ± 4.5 years), who were categorized by vitamin D status (<20 ng/mL: deficiency, 20-30 ng/mL: insufficiency, and >30 ng/mL: sufficiency). We examined the strength of the internal rotator (IR) and external rotator (ER) muscles of the shoulder by using isokinetic dynamometer. Fourteen players (26.9%) had vitamin D deficiency, 24 players (46.2%) were vitamin D insufficient, and 14 players (26.9%) were vitamin D sufficient. There was no significant correlation between the vitamin D level and shoulder muscle strength at 60°/s (IR, r = 0.159, p = 0.26; ER, r = 0.245, p = 0.08), and at 180°/s (IR, r = - 0.093, p = 0.51; ER, r = - 0.037, p = 0.79). Moreover, the isokinetic shoulder strengths were not significantly different across the three groups in all settings. In conclusion, vitamin D insufficiency was common in elite volleyball players. Though not being associated with isokinetic muscle weakness, vitamin D should be regularly monitored and supplemented in young elite athletes, considering its importance on musculoskeletal health.

The purpose of the present study was to examine if 14 days of supplementation with a pine bark extract leading up to and following an exercise test would increase performance and reduce biomarkers associated with muscle damage, inflammation and oxidative stress. The study used a double-blind, placebo controlled, cross-over design. Participants ingested either 800mg pine bark extract or placebo for 14 days prior to the first exercise trial and for 2 days post-exercise. On the exercise day, participants submitted a pre-exercise blood sample, then completed a VO₂ peak test until volitional failure. A post-blood sample was collected 1 hour after completion of exercise. Participants returned at 24 & 48 hours after the exercise testing for measures of muscle pain in the lower body using an algometer. Participants then had a 7-day washout period before beginning to crossing over to the alternate treatment. Analysis via ordinal regression demonstrated a significant difference in oxidative stress in the pine bark extract group compared to placebo (ChiSq = 2.63; p = 0.05). The pine bark extract was effective at affording protection from oxidative stress post exercise. Further work should be undertaken to evaluate the findings with other exercise modes or in participants with known metabolic syndrome.

We investigated whether post-exercise capsinoids (CSN) supplementation could enhance muscle glycogen resynthesis via GLUT4/Akt expressions in human skeletal muscle. Nine male college students (aged 21.4±0.2 years, BMI 21.9±1.3 kg/m2, VO2max 47.1±1.8 ml/kg/min) participated in this crossover designed study, and completed a 60-min cycling exercise at 70% VO2max. Immediately after exercise, participants consumed high-carbohydrate diet (2 g carb/kg bodyweight) with CSN (12 mg, single dosage) or placebo. Biopsied muscle samples (vastus lateralis) were obtained immediately (0h) and 3h after exercise. Blood and expired gas samples were collected before and after exercise. We found oral CSN supplementation immediately after exercise was unable to enhance glycogen resynthesis in exercised human skeletal muscle. Despite, CSN could alter the energy reliance on fat oxidation during post-exercise recovery, based on gaseous exchange measurement (NEFA and glycerol). We further identified no significant differences in postprandial glucose/insulin area under curve in both trials. Western blot data showed no significant response of p-Akt/Akt ratio with CSN during post-exercise recovery. Inconsistent with glycogen levels, muscle GLUT4 expression was significantly elevated at 3h in CSN trial. Our findings emphasize the necessity of further evidences to confirm the ergogenic properties of CSN in connection with glycogen recovery in exercised human skeletal muscle.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

Unlike electron microscopy, which can achieve very high resolutions, but to date can only be used to study static structures, time-resolved X-ray diffraction from contracting muscles can, in principle, be used to follow the molecular movements involved in force generation on a millisecond timescale albeit at moderate resolution. However, previous X-ray diffraction studies of resting muscles have come up with structures for the head arrangements in resting myosin filaments that are different from the apparently ubiquitous interacting heads motif (IHM) found by single particle analysis of electron micrographs of isolated myosin filaments from a variety of muscle types. This head organization is supposed to represent the super-relaxed state of the myosin filaments where ATP usage is minimized. Here we have tested whether the interacting heads motif structures will satisfactorily explain the observed low-angle X-ray diffraction patterns from resting vertebrate (bony fish) and invertebrate (insect flight) muscles. We find that the interacting heads motif does not, in fact, explain what is observed. Previous X-ray models fit the observations much better. We conclude that the X-ray diffraction evidence has been well interpreted in the past and that there is more than one ordered myosin head state in resting muscle. There is, therefore, no reason to question some of the previous X-ray diffraction results on myosin filaments; time-resolved X-ray diffraction should be a reliable way to follow crossbridge action in active muscle and may be one of the few ways to follow molecular changes in myosin heads on a millisecond timescale as force is actually produced.

Calorie restriction (CR), defined as a reduction of the total calorie intake of 30% to 60% without malnutrition, is the only nutritional strategy that has proven to extend lifespan, prevent or delay the onset of age-associated diseases, and delay the functional decline in a wide range of species. However, little is known about the effects of CR when started early in life. We sought to analyze the effects of CR in the skeletal muscle of young Wistar rats. For this, 3-month-old male and female rats were subjected to 40% CR or fed ad libitum for 3 months. Gastrocnemius muscles were used to extract RNA and total protein. Western blot and RT-qPCR were performed to evaluate the expression of key markers/pathways modulated by CR and affected by aging. CR decreased body and skeletal muscle weight in both sexes. No differences were found in most senescence, antioxidant, and nutrient sensing pathways analyzed. However, we found a sexual dimorphism in markers of oxidative stress, inflammation, apoptosis, and mitochondrial function in response to CR. Our data show that young female rats treated with CR exhibit similar expression patterns of key genes/pathways associated with healthy aging when compared to old animals treated with CR, while in male rats these effects are reduced. Additional studies are needed to understand how early or later life CR exerts positive effects on health- and lifespan.

Muscle spindles are encapsulated sensory organs found in most of our muscles. Prevalent models of sensorimotor control assume the role of spindles is to reliably encode limb posture and movement. Here, I argue that the traditional view of spindles is outdated. Spindle organs can be tuned by spinal γ motor neurons that receive top-down and peripheral input, including from cutaneous afferents. A new model is presented, viewing γ motor activity as an intermediate coordinate transformation that allows multimodal information to converge on spindles, creating flexible coordinate representations at the level of the peripheral nervous system. That is, I propose that spindles play a unique overarching role in the nervous system: that of a peripheral signal-processing device that flexibly facilitates sensorimotor performance, according to task characteristics. This role is compatible with previous findings and supported by recent studies with naturalistically active humans. Such studies have so far shown that spindle tuning enables the independent preparatory control of reflex muscle stiffness, the selective extraction of information during implicit motor adaptation, and for segmental stretch reflexes to operate in joint space. Incorporation of advanced signal-processing at the periphery may well prove a critical step in the evolution of sensorimotor control theories.

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 &gt;0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d &lt;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.

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 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.

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.

Chronic pulmonary diseases such as asthma, COPD, and Idiopathic pulmonary fibrosis are significant causes of mortality and morbidity worldwide. Currently, there is no radical treatment for many chronic pulmonary diseases, and the treatment options focus on relieving the symptoms and improving lung function. Therefore, efficient therapeutic agents are highly needed. Bronchial epithelial cells and airway smooth muscle cells and their crosstalk play a significant role in the pathogenesis of these diseases. Thus, targeting the interactions of these two cell types could open the door to a new generation of effective therapeutic options. However, the studies on how these two cell types interact and how their crosstalk adds up to respiratory diseases are not well established. With the rise of modern research tools and technology, such as lab-on-chip, organoids, co-culture techniques, and advanced immunofluorescence imaging, a substantial degree of evidence about these cell interactions emerged. Hence, this contribution aims to review the growing evidence of bronchial epithelial cells and airway smooth muscle cells crosstalk under normal and pathophysiological conditions. The review first deliberates the effects of both healthy and stressed epithelial cells on airway smooth muscle cells, taking into account three themes; contraction, migration, and proliferation. Then, it discusses the impact of airway smooth muscle cells on the epithelium in inflammatory settings. Later, it examines the role of airway smooth muscle cells in the early development of bronchial epithelial cells and their recovery after injury.

While appropriate nutrient intake is important for older adults, various oral problems cause de-creased masticatory function. This cross-sectional study aimed to identify the factors associated with decreased masticatory performance in older adults. Oral examinations were performed on 80 participants (mean age: 75.10 ± 5.64 years) to determine the number of functional tooth units (FTUs). Symptoms of periodontal and temporomandibular diseases were evaluated via a ques-tionnaire. The tone, elasticity, and dynamic stiffness of the masseter muscle were measured using the Myoton® PRO device. The mixing ability test was used to assess the masticatory performance and the mixing ability index (MAI) was calculated. The analysis of covariance test was performed to adjust for confounding factors and multiple logistic regression analysis was performed to identify the risk factors affecting MAI. A lower MAI was significantly associated with higher tone (p = 0.006) and lower elasticity (p = 0.013). The number of FTUs (adjusted odds ratio [OR] = 0.724, p = 0.029), tone (adjusted OR = 1.215, p = 0.016), and elasticity (adjusted OR = 4.789, p = 0.038) were independently associated with the MAI. Muscle function training and prosthetic treatments may help increase masticatory performance in older adults, which will improve overall health.

Mesenchymal stem cells (MSCs) showed in vitro mesoderm-lineage differentiation and self-renew capacity. However, no comparative study was reported on the biological characteristics of stem cells derived from skeletal muscle (SM-MSCs), dermal skin (DS-MSCs), and adipose tissues (A-MSCs) from a single donor in camels. The present study aimed to evaluate the influence of MSCs source on stem cell characteristics. We evaluated proliferation capacity and mesoderm-lineage differentiation potential from SM-MSCs, DS-MSCs, and A-MSCs. They showed spindle-like morphology after homogenization. The proliferation ability was no significant difference in all groups. Furthermore, the portion of the cell cycle and expression of pluripotent markers (Oct4, Sox2, and Nanog) were similar in all cell lines at passage 3. The differentiation capacity of A-MSCs into adipocytes was significantly higher than that of SM-MSCs and DS-MSCs. However, the osteoblast differentiation capacity of A-MSCs was significantly lower than that of SM-MSCs and DS-MSCs. Additionally, after osteoblast differentiation, the ALP activity and calcium content was significantly decreased in A-MSCs as compared to SM-MSCs and DS-MSCs. To the best of our knowledge, we primally established MSCs from the single camel and demonstrated their comparative characteristics including expression of pluripotent factors and proliferation, and in vitro differentiation capacity into adipocytes and osteoblasts.

This study aims to explore the possibility of estimating a multitude of kinematic and dynamic quantities using subject-specific musculoskeletal models in real-time. The framework was designed to operate with marker-based and inertial measurement units enabling extensions far beyond dedicated motion capture laboratories. We present the technical details for calculating the kinematics, generalized forces, muscle forces, joint reaction loads, and predicting ground reaction wrenches during walking. Emphasis was given to reduce computational latency while maintaining accuracy as compared to the offline counterpart. Notably, we highlight the influence of adequate filtering and differentiation under noisy conditions and its importance for consequent dynamic calculations. Real-time estimates of the joint moments, muscle forces, and reaction loads closely resemble OpenSim's offline analyses. Model-based estimation of ground reaction wrenches demonstrates that even a small error can negatively affect other estimated quantities. An application of the developed system is demonstrated in the context of rehabilitation and gait retraining. We expect that such a system will find numerous applications in laboratory settings and outdoor conditions with the advent of predicting or sensing environment interactions. Therefore, we hope that this open-source framework will be a significant milestone for solving this grand challenge.

The manual muscle test (MMT) is a flexible diagnostic tool, which is used in many disciplines, applied in several ways. The main problem is the subjectivity of the test. The MMT in the version of a “break test” depends on the tester’s force rise and the patient’s ability to resist the applied force. As a first step, the investigation of the reproducibility of the testers’ force profiles is required for valid application. The study examined the force profiles of n=29 testers (n=9 experiences (Exp), n=8 little experienced (LitExp), n =12 beginners (Beg)). The testers performed 10 MMTs according to the test of hip flexors, but against a fixed leg to exclude the patient’s reaction. A handheld device recorded the temporal course of the applied force. The results show significant differences between Exp and Beg concerning the starting force (padj=0.029), the ratio of starting to maximum force (padj=0.005) and the normalized mean Euclidean distances between the 10 trials (padj=0.015). The slope is significantly higher in Exp vs. LitExp (p=0.006) and Beg (p=0.005). The results also indicate that experienced testers show inter-tester differences and partly even a low intra-tester reproducibility. That highlights the necessity of an objective MMT-assessment. Furthermore, an agreement on a standardized force profile is required – a suggestion is given.

Key features of glycogen metabolism in excitable tissues are not well-explained by current concepts. Glycogen stores in brain and skeletal muscle are generally considered to function as local glucose reserves, to be utilized during transient mismatches between glucose supply and demand; however, quantitative measures show that blood glucose supply is likely never rate-limiting for energy metabolism in either brain or muscle under physiological conditions. These tissues nevertheless do normally utilize glycogen during intervals of increased energy demand, despite the availability of free glucose, and despite the ATP cost of cycling glucose through glycogen polymer. This seemingly wasteful shunt can be explained by considering the effect of glycogenolysis on the amount of energy derived from ATP (ΔG’ATP). ΔG’ATP is diminished by elevations in Pi, such as occur at sites of rapid ATP hydrolysis and net phosphocreatine consumption. Glycogen utilization counters this effect by sequestering Pi in glycolytic metabolites (glycogen_n + Pi → glycogen_n-1 + glucose-1-phosphate → phosphorylated glycolytic intermediates), and thereby maintains the amount of energy obtained from ATP at sites of rapid ATP consumption. This thermodynamic effect may be particularly important in the narrow, spatially constricted astrocyte processes that ensheath neuronal synapses. This effect can also explain the co-localization of glycogen and cytosolic phosphocreatine in brain astrocytes, glycolytic super-compensation in brain when glycogen is not available, and aspects of exercise physiology in muscle glycogen phosphorylase deficiency (McArdle’s disease).

Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this preliminary study, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for controls). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S individuals was defined by higher levels of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older individuals with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.

Background: Even though a number of studies have verified the positive effect of physical activity (PA) on self-related health (SRH) no previous research has examined this association among pediatric patients with Type 1 diabetes mellitus (T1DM). Objective: The purpose of this study was to investigate the association between regular physical activity (PA) and self-rated health (SRH) in pediatric patients with Type 1 diabetes mellitus (T1DM) who lacked diabetes care. Methods: We conducted a retrospective study among pediatric patients with T1DM who lacked diabetes care and were enrolled in a diabetes education program between January 2011 to January 2015 at the endocrinology clinic of Seoul National University Children’s Hospital in South Korea. The eligible participants for this study were 37 pediatric patients with T1DM aged 9 to 17 years. PA was divided into regular PA and muscle strength exercise to analyze the relationship with SRH using binomial logistic regression analysis. Results: The results showed SRH of pediatric patients with T1DM who did not engage in regular PA was significantly lower than those who did (OR in regular PA = .199 [95% CI: .040, .995]; OR in regular muscle strength exercise = .097 [95% CI: .023, .825]). Conclusions: In conclusion, regular PA and muscle strength exercise in pediatric patients with T1DM who lacked diabetes care were effective in improving their SRH. A systematic plan is required to enhance regular PA for pediatric patients with T1DM.

Although fragility fractures, osteoporosis, sarcopenia and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral bone and muscle physiology the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently before. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass – FFM), grip strength and bone density (BMD) in 156,575 men and women aged 39-72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and expressed as the percentage of body weight (FFM%) or divided by body mass index (FFM_BMI). Adjusted mean grip strength, FFM%, FFM_BMI, and BMD were calculated according quintiles of dietary magnesium, correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women respectively of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFM_BMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and have relevance for population prevention strategies for sarcopenia, osteoporosis and fractures.

Limb girdle muscular dystrophies (LGMD), caused by mutations in 29 different genes, are the fourth most prevalent group of genetic muscle diseases, leading to progressive weakness and atrophy of the skeletal muscles. Although the link between LGMD and their genetic origins has been determined, LGMD still represent an unmet medical need. In this paper, we describe a platform for modeling LGMD based on the use of human induced pluripotent stem cells (hiPSC). Thanks to the self-renewing and pluripotency properties of hiPSC, this platform provides an alternative and renewable source of skeletal muscle cells (skMC) to primary, immortalized or overexpressing cells. We report that skMC derived from hiPSC express the majority of the genes and proteins causing LGMD. As a proof of concept, we demonstrate the importance of this cellular model for studying LGMDR9 by evaluating disease-specific phenotypes in skMC derived from hiPSC obtained from four patients.

: This article was not intended to be a complete report of a standard clinical trial. It is a report of the outcomes of preliminary data for validation of the CMECD procedure (Coletti Method of EMG ChemoDenervation) protocol for the treatment of chronic pain resulting from chronic muscle spasm. Methods are here detailed on how to approach the patient with chronic pain, identify the presence of chronic muscle spasm, undertake the treatment protocol and how to perform the follow up process to confirm that chronic pain secondary to chronic muscle spasm was the accurate diagnosis. Furthermore, this article presents the results of a cohort of more than 90 patients treated by the CMECD procedure regarding location and duration of prior pain, prior treatment strategies, degree of success in resolving pain and duration of relief. Outcome data consisting of patient and staff reporting of specific situations in which the chronic pain treatment was successful has been included to help establish the “believability” of outcome successes and to elucidate the potential life altering effects of successful treatment of chronic pain secondary to chronic muscle spasm. This article will hopefully increase the interest in this treatment protocol and increase the chance that a classical international clinical trial will be undertaken.

Parascaris sp. is the only ascarid parasitic nematode in equids and one of the most threatening infectious organisms in horses. Only a limited number of compounds are available for treatment of horse helminthiasis and Parascaris sp. worms have developed resistance to the three major anthelmintic families. In order to overcome the appearance of resistance, there is an urgent need for new therapeutic strategies. The active ingredients of herbal essential oils are potentially effective antiparasitic drugs. Carvacrol is one of the principal chemicals of essential oil from Origanum, Thymus, Coridothymus, Thymbra, Satureja and Lippia herbs. However, the antiparasitic mode of action of carvacrol is poorly understood so far. Here, the objective of the work was to characterize the activity of carvacrol on Parascaris sp. nicotinic acetylcholine receptors (nAChRs) function both in vivo with the use of worm neuro-muscular flap preparations and in vitro with two-electrode voltage-clamp electrophysiology on nAChRs expressed in Xenopus oocytes. We have developed a neuromuscular contraction assay on Parascaris body flaps and obtained acetylcholine concentration-dependent contraction responses. Strikingly, we observed that 300 µM carvacrol fully and irreversibly abolished Parascaris sp. muscle contractions elicited by acetylcholine. Conversely, carvacrol antagonized acetylcholine-induced currents from both the nicotine-sensitive AChR and the morantel-sensitive AChR subtypes. Thus, we show for the first time that the body muscle flap preparation is a tractable approach to investigate the pharmacology of Parascaris sp. neuro-muscular system. Our results suggest an intriguing mode of action for carvacrol being a potent antagonist of muscle nAChRs of Parascaris sp. worms which may account for its antiparasitic potency.

The use of whole-body vibration (WBV) for therapeutic purposes is far from being standardized and only very recently an empirical foundation for reporting guidelines for human WBV studies has been published. Controversies about safety and therapeutic dosage stll exist. The present study aimed to investigate the metabolic and mechanical effects of low-intensity WBV in according to the ISO 2631 norm on subjects with obesity. 41 obese subjects (BMI≥ 35 kg/mˆ2) were recruited to participate in a 3-week multidisciplinary inpatient rehabilitation program including fitness training and WBV training. During WBV the posture was monitored with an optoelectronic system with 6 infrared cameras (Vicon, Vicon Motion System, Oxford, UK). The primary endpoints were: variation in body composition, factors of the metabolic syndrome, functional activity (sit-to-stand and 6-min walking test), muscle strength, and quality of life. Secondary endpoints were: modification of irisin, testosterone, growth hormone, IGF1 levels. We observed significant changes in salivary irisin levels, Group 2 (p&lt;0.01) as compared to the control group, while muscle strength, function, and other metabolic and hormonal factors did not change after a 3-week low-intensity WBV training respect control group. Future studies are needed to deeper investigate the potential metabolic effect of low-intensity WBV in managing weight.