Signaling In Muscle Research Articles

Investigation of Maximum Voluntary Contraction Activity during Robotic Gait

The purpose of this study is to investigate healthy people’s and patients’ lower extremity muscle activities during robotic gait using kinesiology analysis. Initially, muscle signals were taken from 6 paraplegic patients such as spinal cord injury (SCI) and stroke patients, 2 hemiplegic patients and 4 healthy persons. Then, signals were analyzed by using signal processing techniques such as filtering, rectifying, Root Mean Square (RMS) and also by calculating the Max Voluntary Contraction (MVC). As a result, it was seen that hip muscles such as the Gluteus Maximus (GMA), Gluteus Medius (GM) and Iliopsoas (ILP) had lower MVC values in the hemiplegic patients than those of the SCI patients and the healthy persons. Additionally, when the signals that were obtained were analyzed, it was found that the activity of the Medial Gastrocnemius (MG) muscle could be used in determination of movement path and movement intention. Moreover, the EMG results of gait motion may be helpful in applying accurate amplitude and frequency stimulation in epidural stimulation (ES) therapy.

Myofiber directs macrophages IL-10-Vav1-Rac1 efferocytosis pathway in inflamed muscle following CTX myoinjury by activating the intrinsic TGF-β signaling

BackgroundTo explore the role of skeletal muscle specific TGF-β signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection.MethodsCTX myoinjury was manipulated in TGF-βr2flox/flox (control) mice or transgenic mice with TGF-β receptor 2 (TGF-βr2) being specifically deleted in skeletal muscle (SM TGF-βr2−/−). Gene levels of TGF-β signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-β pathway molecules, myokines and embryonic myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation.ResultsIn control mice, TGF-β-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-β signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-β signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V−F4/80+Tunel+ macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67+ apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-β signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages.ConclusionsOur data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-β signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis.2-7di1wFqhyvGwQ3tfntcnVideo

Loss of NOR-1 represses muscle metabolism through mTORC1-mediated signaling and mitochondrial gene expression in C2C12 myotubes.

Gene expression of the NR4A nuclear orphan receptor NOR-1 is reduced in obesity and in human skeletal muscle during disuse. It has been well established that NOR-1 is highly responsive to both aerobic and resistance exercise and NOR-1 overexpression is coincident with a plethora of metabolic benefits. However, it is unclear whether loss of NOR-1 contributes to inappropriate metabolic signaling in skeletal muscle that could lead to insulin resistance. The purpose of this study was to elucidate the impact of NOR-1 deficiency on C2C12 metabolic signaling. Changes in gene expression after siRNA-mediated NOR-1 knockdown in C2C12 myotubes were determined by qPCR and bioinformatic analysis of RNA-Seq data. Our RNA-Seq data identified several metabolic targets regulated by NOR-1 and implicates NOR-1 as a modulator of mTORC1 signaling via Akt-independent mechanisms. Furthermore, pathway analysis revealed NOR-1 knockdown perturbs the insulin resistance and insulin sensitivity pathways. Taken together, these data suggest skeletal muscle NOR-1 deficiency may contribute to altered metabolic signaling that is consistent with metabolic disease. We postulate that strategies that improve NOR-1 may be important to offset the negative impact that inactivity, obesity, and type 2 diabetes have on mitochondria and muscle metabolism.

A Mango Leaf Extract (Zynamite®) Combined with Quercetin Has Exercise-Mimetic Properties in Human Skeletal Muscle

Zynamite PX®, a mango leaf extract combined with quercetin, enhances exercise performance by unknown molecular mechanisms. Twenty-five volunteers were assigned to a control (17 males) or supplementation group (8 males, receiving 140 mg of Zynamite® + 140 mg quercetin/8 h for 2 days). Then, they performed incremental exercise to exhaustion (IE) followed by occlusion of the circulation in one leg for 60 s. Afterwards, the cuff was released, and a 30 s sprint was performed, followed by 90 s circulatory occlusion (same leg). Vastus lateralis muscle biopsies were obtained at baseline, 20 s after IE (occluded leg) and 10 s after Wingate (occluded leg), and bilaterally at 90 s and 30 min post exercise. Compared to the controls, the Zynamite PX® group showed increased basal protein expression of Thr287-CaMKIIδD (2-fold, p = 0.007) and Ser9-GSK3β (1.3-fold, p = 0.005) and a non-significant increase of total NRF2 (1.7-fold, p = 0.099) and Ser40-NRF2 (1.2-fold, p = 0.061). In the controls, there was upregulation with exercise and recovery of total NRF2, catalase, glutathione reductase, and Thr287-CaMKIIδD (1.2–2.9-fold, all p < 0.05), which was not observed in the Zynamite PX® group. In conclusion, Zynamite PX® elicits muscle signaling changes in resting skeletal muscle resembling those described for exercise training and partly abrogates the stress kinases responses to exercise as observed in trained muscles.

1625-P: Osteoprotection by FNIP1 Signaling in Skeletal Muscle

Obesity is increasingly recognized to exert negative impact on bone mass. Skeletal muscle and bone are closely related throughout life, and muscle dysfunction can cause osteoporosis. Understanding of the crosstalk between muscle and bone could have implications for maintaining bone fitness in various disease states such as obesity. FNIP1 is emerging as key regulator of muscle metabolism acting via AMPK. However, the role of muscle FNIP1 in bone mass control is unknown. Using both gain- and loss-of function muscle-specific genetic models, we show that in addition to the known role in the regulation of mitochondrial function muscle fiber type, FNIP1 participates in muscle programs that govern bone homeostasis. FNIP1 KO mice showed a decrease in trabecular bone volume and bone mineral density, whereas muscle specific restoration of FNIP1 expression in KO mice (FNIP1Tg/KO) reversed the bone loss phenotypes. Femoral bending tests revealed a marked decrease in elastic modulus and maximum force in FNIP1 KO mice but increase in FNIP1 TgKO mice. Consistent with these findings, muscle cell-specific deletion of FNIP1 resulted in a pronounced bone structural and mechanical dysfunction. Using AMPKα1/α2 KO lines, we show that muscle FNIP1 exerts control actions upon bone homeostasis independently of AMPK. Through comprehensive RNA-seq and genomic analyses, we reveal that muscle FNIP1 deficiency induces IGF2 secretion, thereby driving an IGF2-depenent osteoclast program. Importantly, we also found that the muscle FNIP1-IGF2 regulatory circuit is associated with osteoporosis in humans. Thus, muscle FNIP1 is a critical safeguard of bone mass. These findings provide new therapeutic opportunities for enhancing muscle fitness to combat a variety of metabolic and musculoskeletal diseases. Disclosure M.Yan: None. Z.Xu: None. Y.Yin: None. T.Fu: None. Z.Zhou: None. L.Yang: None. Z.Gan: None.

Surface electromyography evaluation of selected manual and physical therapy interventions in women with temporomandibular joint pain and limited mobility. Randomized controlled trial (RCT)

Non-invasive approach is gaining an increasing recognition in the TMD patients management. It is therefore reasonable to conduct RCTs evaluating the effectiveness of both physical and manual physiotherapy interventions. The aim of this study was to evaluate the short-term efficacy of selected physiotherapeutic interventions and their effect on the bioelectrical function of the masseter muscle in patients with pain and limited TMJ mobility. The study was conducted on a group of 186 women (T) with the Ib disorder diagnosed in DC/TMD. The control group consisted of 104 women without diagnosed TMDs. Diagnostic procedures were performed in both groups. The G1 group was randomly divided into 7 therapeutic groups in which the therapy was carried out for 10 days: magnetostimulation (T1), magnetoledotherapy (T2), magnetolaserotherapy (T3), manual therapy- positional release and therapeutic exercises (T4), manual therapy – massage and therapeutic exercises (T5), manual therapy – PIR and therapeutic exercises (T6), self therapy - therapeutic exercises (T7). In the T4 and T5 groups, the treatments led to complete resolution of pain after the 10th day of therapy and to the largest minimal clinically significant difference in the MMO and LM parameter. GEE model for PC1 values using treatment method and time point showed that T4, T5 and T6 treatments had the strongest effect on the parameters studied. Therefore, it may be concluded that SEMG testing is a helpful indicator to assess the therapeutic effectiveness of physiotherapeutic interventions. BackgroundNon-invasive approach is gaining an increasing recognition in the TMD patients management. It is therefore reasonable to conduct RCTs evaluating the effectiveness of both physical and manual physiotherapy interventions in a qualitative and quantitative manner. However, there were numerous controversies reported regarding the use of surface electromyography (SEMG) in Orofacial Pain patients. Therefore, we wanted to assess the effectiveness of physiotherapy interventions in TMD patients using SEMG. PurposeEvaluation of the short-term efficacy of selected physiotherapeutic interventions and their effect on the bioelectrical function of the masseter muscle in patients with pain and limited TMJ mobility. Material and MethodsThe study was conducted on a group of 186 women (T) with the Ib disorder diagnosed in DC/TMD (Ib - myofascial pain with restricted mobility). The control group consisted of 104 women without diagnosed TMDs (normal reference values for TMJ ROM and masseter muscle SEMG bioelectric activity). Diagnostic procedures were performed in both groups (SEMG of the masseter muscles at baseline and during exercise, measurement of TMJ mobility, assessment of pain intensity - NRS scale). The G1 group was randomly divided into 7 therapeutic groups in which the therapy was carried out for 10 days: magnetostimulation (T1), magnetoledotherapy (T2), magnetolaserotherapy (T3), manual therapy- positional release and therapeutic exercises (T4), manual therapy – massage and therapeutic exercises (T5), manual therapy – PIR and therapeutic exercises (T6), self-therapy - therapeutic exercises (T7). Each time after therapy, the intensity of pain and TMJ mobility were assessed. Sealed, opaque envelopes were used for randomization. After 5 and 10 days of therapy, bilateral SEMG signals of the masseter muscles were acquired. PC1 factor analysis was performed. A score of 99% in the PC1 parameter, demonstrates the clinical relevance of electromyography (MVC). ResultsSynergism of physical factors will lead to a higher MID on the NRS scale. Evaluating the MID of the therapeutic interventions used showed a better therapeutic effect of manual interventions over physical and self-therapy. In the T4 and T5 groups, the treatments led to complete resolution of pain after the 10th day of therapy and to the largest minimal clinically significant difference in the MMO and LM parameter. GEE model for PC1 values using treatment method and time point showed that T4, T5 and T6 treatments had the strongest effect on the parameters studied. Conclusions1. Exercise SEMG testing is a helpful indicator to assess the therapeutic effectiveness of physiotherapy interventions. 2. Manual therapy treatments are superior to physical treatments in their relaxation and analgesic efficacy and should therefore be prescribed as a first line non-invasive intervention for TMD pain patients.

Vamorolone improves Becker muscular dystrophy and increases dystrophin protein in bmx model mice

There is no approved therapy for Becker muscular dystrophy (BMD), a genetic muscle disease caused by in-frame dystrophin deletions. We previously developed the dissociative corticosteroid vamorolone for treatment of the allelic, dystrophin-null disease Duchenne muscular dystrophy. We hypothesize vamorolone can treat BMD by safely reducing inflammatory signaling in muscle and through a novel mechanism of increasing dystrophin protein via suppression of dystrophin-targeting miRNAs. Here, we test this in the bmx mouse model of BMD. Daily oral treatment with vamorolone or prednisolone improves bmx grip strength and hang time phenotypes. Both drugs reduce myofiber size and decrease the percentage of centrally nucleated fibers. Vamorolone shows improved safety versus prednisolone by avoiding or reducing key side effects to behavior and growth. Intriguingly, vamorolone increases dystrophin protein in both heart and skeletal muscle. These data indicate that vamorolone, nearing approval for Duchenne, shows efficacy in bmx mice and therefore warrants clinical investigation in BMD.

Locomotor function of skeletal muscle is regulated by vitamin D via adenosine triphosphate metabolism

ObjectivesDuring musculoskeletal development, the vitamin D endocrine system is crucial, because vitamin D–dependent calcium absorption is a major regulator of bone growth. Because exercise regimens depend on bone mass, the direct action of active vitamin D (1,25-dihydroxyvitamin D3 [1,25(OH)2D3]) on musculoskeletal performance should be determined. MethodsTo evaluate the effect of 1,25(OH)2D3 on muscle tissue, the vitamin D receptor (Vdr) gene was genetically inactivated in mouse skeletal muscle and the role of 1,25(OH)2D3-VDR signaling on locomotor function was assessed. The direct action of 1,25(OH)2D3 on muscle development was determined using cultured C2C12 cells with myogenic differentiation. ResultsThe lack of Vdr activity in skeletal muscle decreased spontaneous locomotor activity, suggesting that the skeletal muscle performance depended on 1,25(OH)2D3-VDR signaling. Bone phenotypes, reduced femoral bone mineral density, and accelerated osteoclast bone resorption were confirmed in mice lacking skeletal muscle Vdr activity. In vitro study revealed that the treatment with 1,25(OH)2D3 decreased the cellular adenosine triphosphate (ATP)–to–adenosine monophosphate ratio without reducing ATP production. Remarkably, protein expressions of connexin 43, an ATP releaser to extracellular space, and ATP metabolizing enzyme ectonucleotide pyrophosphatase phosphodiesterase 1 were increased responding to 1,25(OH)2D3 treatment. Furthermore, the concentration of pyrophosphate in the culture medium, which inhibits tissue calcification, was increased with 1,25(OH)2D3 treatment. In the presence of 1,25(OH)2D3-VDR signaling, calcium accumulation was suppressed in both muscle samples isolated from mice and in cultured C2C12 cells. ConclusionsThis study dissected the physiological functions of 1,25(OH)2D3-VDR signaling in muscle and revealed that regulation of ATP dynamics is involved in sustaining locomotor function.

Efficient and Specific Generation of MSTN-Edited Hu Sheep Using C-CRISPR.

Hu sheep, an indigenous breed in China known for its high fecundity, are being studied to improve their growth and carcass traits. MSTN is a negative regulator of muscle development, and its inactivation results in muscularity. The C-CRISPR system, utilizing multiple neighboring sgRNAs targeting a key exon, has been successfully used to generate genes for complete knockout (KO) monkeys and mice in one step. In this study, the C-CRISPR system was used to generate MSTN-edited Hu sheep; 70 embryos injected with Cas9 mRNA and four sgRNAs targeting exon 3 of sheep MSTN were transferred to 13 recipients. Out of 10 lambs born from five recipients after full-term pregnancies, nine had complete MSTN KO with various mutations. No off-target effects were found. These MSTN-KO Hu sheep showed a double-muscled (DM) phenotype, characterized by a higher body weight at 3 and 4 months old, prominent muscular protrusion, clearly visible intermuscular groves, and muscle hypertrophy. The molecular analysis indicated enhanced AKT and suppressed ERK1/2 signaling in the gluteus muscle of the edited Hu sheep. In conclusion, MSTN complete KO Hu sheep with a DM phenotype were efficiently and specifically generated using C-CRISPR, and the C-CRISPR method is a promising tool for farm animal breeding.

Combined exercise and nutrition intervention for older women with spinal sarcopenia: an open-label single-arm trial

PurposeSpinal sarcopenia is a multifactorial disorder associated with atrophy and fatty changes in paraspinal muscles. Interventional studies for spinal sarcopenia are limited. We aimed to evaluate the effectiveness of a combined exercise and nutrition intervention for the treatment of spinal sarcopenia.Methods35 community-dwelling older women diagnosed with spinal sarcopenia in a previous cohort study were included. The 12-week combined intervention consisted of back extensor strengthening exercises and protein supplementation. The following outcomes were measured at baseline (week 0), after the intervention (week 12), and follow-up (week 24): conventional variables of sarcopenia (appendicular skeletal muscle mass, handgrip strength, 6-meter gait speed, and short physical performance battery); lumbar extensor muscle mass; lumbar extensor muscle volume and signal intensity; back extensor isokinetic strength; and back performance scale. We used the intention-to-treat analysis method, and repeated measures analysis of variance was used to analyze the data.ResultsOf the total 35 potential participants, 26 older women participated in the study (mean age 72.5 ± 4.0 years old). After 12 weeks of combined exercise and nutrition intervention, there were no changes in the appendicular skeletal muscle mass, lumbar extensor muscle mass, volume, or signal intensity. Handgrip strength and back extensor isokinetic strength did not change significantly. Short physical performance battery significantly increased (P = 0.042) from 11.46 ± 0.86 to 11.77 ± 0.53 at week 12 and 11.82 ± 0.40 at week 24. The back performance scale sum score also significantly improved (P = 0.034) from 2.68 ± 1.81 to 1.95 ± 1.21 at week 12 and 2.09 ± 1.34 at week 24.ConclusionThe combined exercise and nutrition intervention for community-dwelling older women with spinal sarcopenia could be feasible and helpful in improving the physical performance as well as back performance.

Concurrent and Continuous Prediction of Finger Kinetics and Kinematics via Motoneuron Activities.

Robust neural decoding of intended motor output is crucial to enable intuitive control of assistive devices, such as robotic hands, to perform daily tasks. Few existing neural decoders can predict kinetic and kinematic variables simultaneously. The current study developed a continuous neural decoding approach that can concurrently predict fingertip forces and joint angles of multiple fingers. We obtained motoneuron firing activities by decomposing high-density electromyogram (HD EMG) signals of the extrinsic finger muscles. The identified motoneurons were first grouped and then refined specific to each finger (index or middle) and task (finger force and dynamic movement) combination. The refined motoneuron groups (separate matrix) were then applied directly to new EMG data in real-time involving both finger force and dynamic movement tasks produced by both fingers. EMG-amplitude-based prediction was also performed as a comparison. We found that the newly developed decoding approach outperformed the EMG-amplitude method for both finger force and joint angle estimations with a lower prediction error (Force: 3.47±0.43 vs 6.64±0.69% MVC, Joint Angle: 5.40±0.50° vs 12.8±0.65°) and a higher correlation (Force: 0.75±0.02 vs 0.66±0.05, Joint Angle: 0.94±0.01 vs 0.5±0.05) between the estimated and recorded motor output. The performance was also consistent for both fingers. The developed neural decoding algorithm allowed us to accurately and concurrently predict finger forces and joint angles of multiple fingers in real-time. Our approach can enable intuitive interactions with assistive robotic hands, and allow the performance of dexterous hand skills involving both force control tasks and dynamic movement control tasks.

Effects of Resistance Exercise Training on Aged Skeletal Muscle: Potential Role of Muscle Stem Cells

PURPOSE: The prevalence of sarcopenia, which can lead to disability, hospitalization, and death, is increasing among older populations. Resistance exercise training (RT) is currently the most effective strategy for combating sarcopenia by stimulating hypertrophy and increasing strength. This review describes the underlying mechanisms of aging skeletal muscle and whether RT attenuates aging-related loss of muscle function and mass.METHODS: We reviewed and summarized previous research using PubMed, Science Direct, and Google Scholar databases.RESULTS: Load-induced muscle growth is a complex phenomenon that depends on various physiological systems and signaling pathways. Muscle growth occurs through signaling events arising from mechanical stress and consequent muscle protein turnover controlled by the balance between protein synthesis and degradation, which is negatively affected by aging. The authors used the myonuclear domains mediated by muscle satellite cells to explain the molecular machinery of exercise-induced muscle growth and recovery in aging muscles.CONCLUSIONS: Despite a blunted molecular response to an exercise bout, aging muscle cells demonstrated remarkable plasticity, with substantial improvements in myofibril size and strength during RT. More studies are necessary to elucidate the specific mechanisms by which RT activates muscle satellite cells and mitogenic and myogenic signaling in aged muscles.

Evaluation of surface electromyography of selected neck muscles during the whiplash mechanism in aware and unaware conditions due to safe punching in kickboxing

BackgroundKickboxing is considered as a combat sport in progress, in which injuries are frequent and significant, and close injury monitoring is highly recommended. Sports injuries to the head and neck are estimated to cause 70% deaths and 20% permanent disabilities although they are much less common than those to the limbs. Whiplash mechanism involves the rapid extension (opening) and flexion (bending) of neck. The purpose of the current study was to investigate the electromyographic activity of selected muscles in the whiplash mechanism in aware and unaware conditions of the safe punching in kickboxing so that we can design special exercises.MethodIn the present study, 24 male kickboxing athletes aged 18–40 years were selected based on a purposive sampling method. The surface electromyography (EMG) signals of muscles were recorded with and without awareness of safe punching by using a nine-channel wireless EMG device. Additionally, a nine-channel 3D inertial measurement unit (IMU, wireless,) was utilized to determine the acceleration, kinematics, and angular velocity of the subjects’ head. The statistical dependent t-test was applied to compare the EMG activity of each muscle, as well as its participation ratio.ResultsThe results of statistical analysis represented a significant increase in the EMG activity of sternocleidomastoid (p = 0.001), upper trapezius (p = 0.001) and cervical erector spinae muscles (p = 0.001), as well as the neck extension and flexion angles between the athletes aware (open eyes) and unaware (closed eyes) of the safe punching.ConclusionIn this study, the EMG activity of the sternocleidomastoid, upper trapezius, and cervical erector spine muscles in the aware condition was significantly different from the activity under unaware condition. In fact, the intended muscles exhibited significantly different behaviors in preventing extension and flexion in the two conditions.

Annona muricate Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle-Brain Connectivity in Diabetic Mice.

Type 2 diabetes mellitus (T2DM) is related with the incidence of sarcopenia and cognitive impairment that reduces quality of life in the elderly. Recent evidence has demonstrated that sarcopenia is associated with cognitive dysfunction, and muscle-derived endocrine factors might contribute to cognitive function by the skeletal muscle-brain endocrine loop. This study investigated the beneficial effects of Annona muricata (AM, graviola) on multi-organ energy metabolism with muscle-brain connectivity via brain function-related myokines in mice. Body composition, fasting blood glucose level, insulin, HbA1c%, histopathological changes, and the protein levels of insulin-signaling, energy metabolism, neuroprotection, inflammation, and protein-degradation pathways were measured. AM extract (AME) treatment selectively enhanced insulin signaling in the skeletal muscle and hippocampus of T2DM mice. Furthermore, AME treatment effectively increased muscle-derived fibroblast growth factor 21 (FGF21), cathepsin-B (CTSB), irisin, brain-derived neurotrophic factor (BDNF), and liver-derived FGF21 that contribute to whole-body energy homeostasis. In particular, AME increased the levels of circulating myokines (FGF21, BDNF, irisin, and CTSB), and these were accordance with the hippocampal neurotrophic factors (BDNF and CTSB) in T2DM mice. In conclusion, we suggest that AME would be a potential nutraceutical for improving the energy metabolism associated with muscle-brain connectivity via brain function-related myokines in T2DM.

At-home wireless sleep monitoring patches for the clinical assessment of sleep quality and sleep apnea

Although many people suffer from sleep disorders, most are undiagnosed, leading to impairments in health. The existing polysomnography method is not easily accessible; it's costly, burdensome to patients, and requires specialized facilities and personnel. Here, we report an at-home portable system that includes wireless sleep sensors and wearable electronics with embedded machine learning. We also show its application for assessing sleep quality and detecting sleep apnea with multiple patients. Unlike the conventional system using numerous bulky sensors, the soft, all-integrated wearable platform offers natural sleep wherever the user prefers. In a clinical study, the face-mounted patches that detect brain, eye, and muscle signals show comparable performance with polysomnography. When comparing healthy controls to sleep apnea patients, the wearable system can detect obstructive sleep apnea with an accuracy of 88.5%. Furthermore, deep learning offers automated sleep scoring, demonstrating portability, and point-of-care usability. At-home wearable electronics could ensure a promising future supporting portable sleep monitoring and home healthcare.

Β-GPA administration activates slow oxidative muscle signaling pathways and protects soleus muscle against the increased fatigue under 7-days of rat hindlimb suspension

Unloading of slow-twitch muscles results in increased muscle fatigue and the mechanisms of this effect are poorly studied. We aimed to analyze the role of high-energy phosphates accumulation during the first week of rat hindlimb suspension plays in a fiber-type phenotype shift towards fast-type fatigable muscle fibers. Male Wistar rats were divided into 3 groups (n = 8): C - vivarium control; 7HS - 7-day hindlimb suspension; 7HB - 7-day hindlimb suspension with intraperitoneal injection of beta-guanidine propionic acid (β-GPA, 400 mg/kg b w). β‐GPA is a competitive inhibitor of creatine kinase and it reduces concentrations of ATP and phosphocreatine. In the 7HB group, β-GPA treatment protected a slow-type signaling network in an unloaded soleus muscle, including MOTS-C, AMPK, PGC1 α and micro-RNA-499. These signaling effects resulted in a preserved soleus muscle fatigue resistance, slow-type muscle fibers percentage and mitochondrial DNA copy number under muscle unloading.

Glyphosate potentiates insulin resistance in skeletal muscle through the modulation of IRS-1/PI3K/Akt mediated mechanisms: An in vivo and in silico analysis

Herbicides have been linked to a higher risk of developing diabetes. Certain herbicides also operate as environmental toxins. Glyphosate is a popular and extremely effective herbicide for weed control in grain crops that inhibits the shikimate pathway. It has been shown to negatively influence endocrine function. Few studies have demonstrated that glyphosate exposure results in hyperglycemic and insulin resistance; but the molecular mechanism underlying the diabetogenic potential of glyphosate on skeletal muscle, a primary organ that includes insulin-mediated glucose disposal, is unknown. In this study, we aimed to evaluate the impact of glyphosate on the detrimental changes in the insulin metabolic signaling in the gastrocnemius muscle. In vivo results showed that glyphosate exposure caused hyperglycemia, dyslipidemia, increased glycosylated hemoglobin (HbA1c), liver function, kidney function profile, and oxidative stress markers in a dose-dependent fashion. Conversely, hemoglobin and antioxidant enzymes were significantly reduced in glyphosate-induced animals indicating its toxicity is linked to induce insulin resistance. The histopathology of the gastrocnemius muscle and RT-PCR analysis of insulin signaling molecules revealed glyphosate-induced alteration in the expression of IR, IRS-1, PI3K, Akt, β-arrestin-2, and GLUT4 mRNA. Lastly, molecular docking and dynamics simulations confirmed that glyphosate showed a high binding affinity with target molecules such as Akt, IRS-1, c-Src, β-arrestin-2, PI3K, and GLUT4. The current work provides experimental proof that glyphosate exposure has a deleterious effect on the IRS-1/PI3K/Akt signaling pathways, which in turn causes the skeletal muscle to become insulin resistant and eventually develop type 2 diabetes mellitus.

Estrogen-related Receptor Signaling in Skeletal Muscle Fitness.

Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors, and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On the other hand, conditions such as diabetes and muscular dystrophy suppress expression of ERRs in the skeletal muscle, likely contributing to disease progression. We highlight key functions of ERRs in the skeletal muscle including the regulation of fiber type, mitochondrial metabolism, vascularization, and regeneration. We also describe how ERRs are regulated in the skeletal muscle, and their interaction with important muscle regulators (e. g. AMPK and PGCs). Finally, we identify critical gaps in our understanding of ERR signaling in the skeletal muscle, and suggest future areas of investigation to advance ERRs as potential targets for function promoting therapeutics in muscle diseases.

Development of skeletal muscle fibrosis in a rodent model of cancer cachexia.

Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes. Female and male C57BL6/J mice were injected with phosphate-buffered saline or Lewis Lung Carcinoma (LLC) at 8-week of age, and tumors were allowed to develop for 1, 2, 3, or 4 weeks. 3wk and 4wk female tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. In vitro analyses were also performed on cocultured C2C12 and 3T3 cells exposed to LLC conditioned media. Immunohistochemistry and quantitative polymerase chain reaction (qPCR) analysis were used to investigate fibrosis and fibrosis-related signaling in skeletal muscle. Collagen deposition in skeletal muscle was increased in the 1wk, LT, and HT groups in female mice. However, collagen deposition was only increased in the 4wk group in male mice. In general, female mice displayed earlier alterations in extracellular matrix (ECM)-related genes beginning at 1wk post-LLC injection. Whereas this was not seen in males. While overall tumor burden is tightly correlated to cachexia development in both sexes, fibrotic development is not. Male mice did not exhibit early-stage alterations in ECM-related genes contrary to what was noted in female mice.

Enhancement of EEG–EMG coupling detection using corticomuscular coherence with spatial–temporal optimization

Objective. Corticomuscular coherence (CMC) is widely used to detect and quantify the coupling between motor cortex and effector muscles. It is promisingly used in human–machine interaction (HMI) supported rehabilitation training to promote the closed-loop motor control for stroke patients. However, suffering from weak coherence features and low accuracy in contingent neurofeedback, its application to HMI rehabilitation robots is currently limited. In this paper, we propose the concept of spatial–temporal CMC (STCMC), which is the coherence by refining CMC with delay compensation and spatial optimization. Approach. The proposed STCMC method measures the coherence between electroencephalogram (EEG) and electromyogram (EMG) in the multivariate spaces. Specifically, we combined delay compensation and spatial optimization to maximize the absolute value of the coherence. Then, we tested the reliability and effectiveness of STCMC on neurophysiological data of force tracking tasks. Main results. Compared with CMC, STCMC not only enhanced the coherence significantly between brain and muscle signals, but also produced higher classification accuracy. Further analysis showed that temporal and spatial parameters estimated by the STCMC reflected more detailed brain topographical patterns, which emphasized the different roles between the contralateral and ipsilateral hemisphere. Significance. This study integrates delay compensation and spatial optimization to give a new perspective for corticomuscular coupling analysis. It is also feasible to design robotic neurorehabilitation paradigms by the proposed method.