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Background: Muscle disuse and offloading in microgravity are likely the primary factors mediating spaceflight-induced muscle atrophy, for which there is currently no effective treatment other than exercise. Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) possess anti-inflammatory and antioxidant properties, offering a potential strategy for combating weightless muscular atrophy. Methods: In this study, human BMSCs-EVs (hBMSC-EVs) were isolated using super-centrifugation and characterized. C2C12 myotube nutrition-deprivation and mice tail suspension models were established. Subsequently, the diameter of C2C12 myotubes, Soleus mass, cross-sectional area (CSA) of muscle fibers, and grip strength in mice were assessed to investigate the impact of hBMSC-EVs on muscle atrophy. Immunostaining, transmission electron microscopy observation, and western blot analysis were employed to assess the impact of hBMSC-EVs on muscle fiber types, ROS levels, inflammation, ubiquitin–proteasome system activity, and autophagy lysosome pathway activation in skeletal muscle atrophy. Results: The active hBMSC-EVs can be internalized by C2C12 myotubes and skeletal muscle. hBMSC-EVs can effectively reduce C2C12 myotube atrophy caused by nutritional deprivation, with a concentration of 10 × 108 particles/mL showing the best effect (P < 0.001). Additionally, hBMSC-EVs can down-regulate the protein levels associated with UPS and oxidative stress. Moreover, intravenous administration of hBMSC-EVs at a concentration of 1 × 1010 particles/mL can effectively reverse the reduction in soleus mass (P < 0.001), CSA (P < 0.01), and grip strength (P < 0.001) in mice caused by weightlessness. They demonstrate the ability to inhibit protein degradation mediated by UPS and autophagy lysosome pathway, along with the suppression of oxidative stress and inflammatory responses. Furthermore, hBMSC-EVs impede the transition of slow muscle fibers to fast muscle fibers via upregulation of Sirt1 and PGC-1α protein levels. Conclusions: Our findings indicate that hBMSC-EVs are capable of inhibiting excessive activation of the UPS and autophagy lysosome pathway, suppressing oxidative stress and inflammatory response, reversing muscle fiber type transformation, effectively delaying hindlimb unloading-induced muscle atrophy and enhancing muscle function. Our study has further advanced the understanding of the molecular mechanism underlying muscle atrophy in weightlessness and has demonstrated the protective effect of hBMSC-EVs on muscle atrophy. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Sarcopenia is the age-related loss of muscle and fiber number and decreased regenerative capacity with increased abundance of reactive oxygen species levels and electron transport chain abnormalities. The aim of this study was to investigate the antisarcopenia effect of MFG-E8 in alleviating skeletal muscle dysfunction induced by D-galactose, and reveal the mechanism promoting myoblast cell proliferation and mediating the cell cycle. This in vivo experiment showed that MFG-E8 can improve the antioxidant status and increase soleus muscle mass (35.61%) and fiber diameter (39.72%) in the aging rats. The western blot assay preliminarily proved that increased ERK phosphorylation determines the repairment of injured skeletal muscle, but not JNK and p38. In vitro experiments further verified that MFG-E8 can increase the number of mitochondria, cell vitality, cell density, and reduce apoptosis rate. Flow cytometry and quantitative real-time PCR proved that MFG-E8 promoted cell proliferation by upregulating mRNA expression of cyclin D1, cyclin E1, CDK, and downregulating mRNA expression of p21 and p27, thereby increasing the S and G 2 /M phase and decreasing the G 0 /G 1 phase. Molecular level further proved that MFG-E8 mediated cell cycle and promoted cell proliferation by activating the MAPK/ERK signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Motor dysfunction and muscle atrophy are typical symptoms of patients with spinal cord injury (SCI). Exercise training is a conventional physical therapy after SCI, but exercise intervention alone may have limited efficacy in reducing secondary injury and promoting nerve regeneration and functional remodeling. Our previous research found that intramedullary pressure after SCI is one of the key factors affecting functional prognosis. It has been reported that GsMTx-4, a specific blocker of the mechanosensitive ion channels Piezo1, can protect the integrity of the neuromuscular junction and promote nerve regeneration, and thus has the potential as a therapeutic agent for SCI. In this study, we observed the combined and separate therapeutic effect of GsMTx-4 and exercise on the structure of the soleus muscle and motor function in rats with SCI. At 42 days post-injury, compared with SCI rats, the Basso–Beattie–Bresnahan score (P = 0.0007) and Gait Symmetry (P = 0.0002) were significantly improved after combination therapy. On histology of rat soleus muscle, compared with SCI rats, the combined treatment significantly increased the wet weight ratio, muscle fiber cross-sectional area and acetylcholinesterase (all P<0.0001). On histology of rat spinal tissue, compared with SCI rats, the combined treatment significantly increased neuron counts and BDNF levels, and significantly reduced the percentage of TUNEL-positive cells (all P<0.0001). On physiology of rat soleus muscle, compared with SCI rats, the combined treatment increased the succinate dehydrogenase expression (P<0.0001), while the expression of α-glycerophosphate dehydrogenase (P<0.0001) and GDF8 protein (P = 0.0008) decreased. Results indicate the combination therapy effectively improves histopathology of spinal cord and soleus muscle in SCI rats, enhancing motor function. This study was conducted on animal models, it offers insights for SCI treatment, advancing understanding of lower limb muscle pathology post-SCI. Further research is needed for clinical validation in the future. [ABSTRACT FROM AUTHOR]

During skeletal muscle unloading, phosphoinositide 3-kinase (PI3K), and especially PI3K gamma (PI3Kγ), can be activated by changes in membrane potential. Activated IP3 can increase the ability of Ca2+ to enter the nucleus through IP3 receptors. This may contribute to the activation of transcription factors that initiate muscle atrophy processes. LY294002 inhibitor was used to study the role of PI3K in the ATP-dependent regulation of skeletal muscle signaling during three days of unloading. Inhibition of PI3K during soleus muscle unloading slows down the atrophic processes and prevents the accumulation of ATP and the expression of the E3 ubiquitin ligase MuRF1 and ubiquitin. It also prevents the increase in the expression of IP3 receptors and regulates the activity of Ca2+-dependent signaling pathways by reducing the mRNA expression of the Ca2+-dependent marker calcineurin (CaN) and decreasing the phosphorylation of CaMKII. It also affects the regulation of markers of anabolic signaling in unloaded muscles: IRS1 and 4E-BP. PI3K is an important mediator of skeletal muscle atrophy during unloading. Developing strategies for the localized skeletal muscle release of PI3K inhibitors might be one of the future treatments for inactivity and disease-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue that lacks effective treatment. Hindlimb unloading is a commonly used model of muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particularly from the perspective of the myocyte proteome and metabolism. We first used mass spectrometry for proteomic sequencing and untargeted metabolomics to analyze soleus muscle changes in rats with hindlimb unloading. The study found 1052 proteins and 377 metabolites (with the MS2 name) that were differentially expressed between the hindlimb unloading group and the control group. Proteins like ACTN3, MYH4, MYBPC2, and MYOZ1, typically found in fast-twitch muscles, were upregulated, along with metabolism-related proteins GLUL, GSTM4, and NDUFS4. Metabolites arachidylcarnitine and 7,8-dihydrobiopterin, as well as pathways like histidine, taurine, and hypotaurine metabolism, were linked to muscle atrophy. Protein and metabolism joint analyses revealed that some pathways, such as glutathione metabolism, ferroptosis, and lysosome pathways, were likely to be involved in soleus atrophy. In this study, we have applied integrated deep proteomic and metabolomic analyses. The upregulation of proteins that are expressed in fast-twitch fibers indicates the conversion of slow-twitch fibers to fast-twitch fibers under hindlimb unloading. In addition, some differentially abundant metabolites and pathways revealed the important role of metabolism in muscle atrophy of the soleus. As shown in the graphical abstract, our study provides insights into the pathogenesis and treatment of muscle atrophy that results from unloading by integrating proteomics and metabolomics of the soleus muscles. [ABSTRACT FROM AUTHOR]

The virtual movement of an augmented body, perceived as part of oneself, forms the basis of kinesthetic perception induced by visual stimulation (KINVIS). KINVIS is a visually induced virtual kinesthetic perception that clinically suppresses spasticity. The present study hypothesized that central neural network activity during KINVIS affects subcortical neural circuits. The present study aimed to elucidate whether reciprocal and presynaptic inhibition occurs during KINVIS. Seventeen healthy participants were recruited (mean age: 27.9 ± 3.6 yr), and their soleus Hoffmann-reflexes (H-reflexes) were recorded by peripheral nerve stimulation while perceiving the dorsiflexion kinesthetic illusion in the right-side foot (seated in a comfortable chair). Two control conditions were set to observe the same foot video without the kinesthetic illusion while focusing on the static foot image. Unconditioned H-reflex and two types of conditioned H-reflexes were measured: Ia (reciprocal inhibition) and D1 (presynaptic inhibition). Reciprocal Ia and D1 inhibition of the soleus muscle was significantly enhanced during the kinesthetic illusion compared with the condition without kinesthetic illusion (a post hoc analysis using the Bonferroni test: Ia inhibition, P = 0.002; D1 inhibition, P = 0.049). This study indicates that kinesthetic illusion elicits an inhibitory effect on the monosynaptic reflex loop of Ia afferents, potentially inhibiting the hyperexcitability of the stretch reflex. These findings demonstrate that brain activity associated with visually induced kinesthetic illusions acts on spinal inhibition circuits. These insights may be valuable in clinical rehabilitation practice, specifically for the treatment of spasticity. NEW & NOTEWORTHY: Neural effects in visual-induced kinesthetic illusion expand into the spinal reflex. Kinesthetic illusion inhibits the monosynaptic reflex in an antagonistic muscle via reciprocal and presynaptic inhibition. Visually induced kinesthetic illusion is a suitable treatment for spasticity in patients with stroke. [ABSTRACT FROM AUTHOR]

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• Anoxia associated with sensorimotor restriction reproduces motor phenotype similar to CP. • The combination of insults increases damage to muscle tissue, especially in the soleus. • Microglial activation is high in the experimental model of cerebral palsy. • Neuronal proliferation is not affected by anoxia associated with sensorimotor restriction. Several experimental cerebral palsy models have been created to investigate cellular and molecular mechanisms involved in this condition and develop new therapeutic strategies. The model that has come closest to a motor phenotype similar to cerebral palsy is the one that combines perinatal anoxia with hindlimb sensorimotor restriction, as it induces visible changes at the peripheral and central levels. This systematic review with meta-analysis presents the impact of the cerebral palsy model that associates perinatal anoxia with hindlimb sensorimotor restriction on the nervous, muscular and skeletal systems. Studies with perinatal anoxia associated with sensorimotor restriction and which evaluated outcomes related to skeletal, muscle, or nervous tissue were recovered from the databases: Embase, PubMed, Scopus, and Web of Science. The methodological and quantitative assessment was performed after eligibility screening (PROSPERO - ID: CRD42023477770). After screening of 4,641 articles, 21 studies with a moderate quality of evidence were chosen to be included in this review and 11 articles were included in the meta-analysis. The results of the meta-analysis reported a significant reduction in the media area of the soleus muscle fibers, increased number of glia cells and glia/neuron index in the somatosensory cortex, increased microglial activation in the hippocampus, and no changes in the corpus callosum thickness or neuron cells. The combination of perinatal anoxia and sensorimotor restriction entails muscle deficits and excessive activation of glial cells in brain areas. These results contribute to a methodological refinement of cerebral palsy models and favor new studies proposed for methodological elucidation in animal experimentation. [ABSTRACT FROM AUTHOR]

Background and Clinical Significance: Sarcopenia, characterized by muscle loss and fat infiltration, poses a significant health burden for aging populations. Quantitative Color 2D and 3D radiodensitometry provides a powerful tool to monitor muscle quality and quantity through CT imaging. This study assessed the impact of a ten-year-long home-bed gym exercise intervention on muscle quality in an elderly subject using CT-derived radiodensitometric analysis. The study involved two comparative analyses: Study A, which compared knee-to-ankle CT scans of the subject between 2013 and 2023; and Study B, which compared the subject's 2023 thigh CT scan with a cohort of 2500 elderly Icelandic individuals from the AGES-Reykjavik study. Case Presentation: A 70-year-old male began a home-based Full-Body In-Bed Gym exercise program in 2013. Quantitative muscle volume and radiodensity measurements were performed using CT at baseline and after ten years. Results: Study A shows significant improvements in muscle volume observed in the knee-to-ankle region, while a slower decline in radiodensity was noted, indicating substantial preservation of muscle quality despite the expected decay of ten-year aging. For instance, muscle volume increased by 15% in the left Soleus muscle and by 6% in the right Soleus muscle, while the average radiodensity decreased by 12–17 HU. The subject's thigh muscle quality at 80-years-old is above the AGES-Reykjavik's cohort average, with reduced fat infiltration. Conclusions: Long-term home Full-Body In-Bed Gym, a low-impact exercise, can mitigate aging sarcopenia, as evidenced by improved tissue radiodensity and muscle mass substantial preservation. This suggests potential applications in personalized healthcare strategies to enhance muscle preservation among aging populations. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle resident fibro-adipogenic progenitor cells (FAPs) control skeletal muscle regeneration providing a supportive role for muscle stem cells. Altered FAPs characteristics have been shown for a number of pathological conditions, but the influence of temporary functional unloading of healthy skeletal muscle on FAPs remains poorly studied. This work is aimed to investigate how skeletal muscle disuse affects the functionality and metabolism of FAPs. Methods: Hindlimb suspension (HS) rat model employed to investigate muscle response to decreased usage. FAPs were purified from m. soleus functioning muscle (Contr) and after functional unloading for 7 and 14 days (HS7 and HS14). FAPs were expanded in vitro, and tested for: immunophenotype; in vitro expansion rate, and migration activity; ability to differentiate into adipocytes in vitro; metabolic changes. Crosstalk between FAPs and muscle stem cells was estimated by influence of medium conditioned by FAP's on migration and myogenesis of C2C12 myoblasts. To reveal the molecular mechanisms behind unloading-induced alterations in FAP's functionality transcriptome analysis was performed. Results: FAPs isolated from Contr and HS muscles exhibited phenotype of MSC cells. FAPs in vitro expansion rate and migration were altered by functional unloading conditions. All samples of FAPs demonstrated the ability to adipogenic differentiation in vitro, however, HS FAPs formed fat droplets of smaller volume and transcriptome analysis showed fatty acids metabolism and PPAR signaling suppression. Skeletal muscle unloading resulted in metabolic reprogramming of FAPs: decreased spare respiratory capacity, decreased OCR/ECAR ratio detected in both HS7 and HS14 samples point to reduced oxygen consumption, decreased potential for substrate oxidation and a shift to glycolytic metabolism. Furthermore, C2C12 cultures treated with medium conditioned by FAPs showed diverse alterations: while the HS7 FAPs-derived paracrine factors supported the myoblasts fusion, the HS14-derived medium stimulated proliferation of C2C12 myoblasts; these observations were supported by increased expression of cytokines detected by transcriptome analysis. Conclusion: the results obtained in this work show that the skeletal muscle functional unloading affects properties of FAPs in time-dependent manner: in atrophying skeletal muscle FAPs act as the sensors for the regulatory signals that may stimulate the metabolic and transcriptional reprogramming to preserve FAPs properties associated with maintenance of skeletal muscle homeostasis during unloading and in course of rehabilitation. [ABSTRACT FROM AUTHOR]

Introduction: MyotonPRO technology is a clinically accessible tool for objectively monitoring the biomechanical and viscoelastic properties of musculoskeletal tissues. This study aimed to identify the level of accuracy needed for recording from specified measurement sites on the soleus muscle and plantar fascia (PF), which are important for postural control and gait. Methods: In 20 healthy adults, MyotonPRO measurements were taken 1 cm above and below a standardized point on the soleus and PF. Ultrasound scans were also taken at each site to measure subcutaneous tissue thickness to aid interpretation of MyotonPRO findings. Results: Biomechanical and viscoelastic properties of the soleus and PF, measured using the MyotonPRO, were not affected by the change in the recording site. Subcutaneous tissue thickness above the PF changed significantly (p < 0.001) by 0.61 cm when moving distally by 2 cm, whilst above the soleus, these did not differ significantly (p = 0.175) when moving distally by 2 cm. Conclusion: Changing the recording site 1 cm above or below the standardized site did not affect either the MyotonPRO results (soleus and PF) or ultrasound results for soleus, whilst this same distance affected ultrasound measurements of subcutaneous tissue thickness above the PF significantly. Moving away from the musculoskeletal junction reduces the need for precision in relocating the recording site for measuring soleus. These findings allow for quicker and easier measurement of soleus or PF using the MyotonPRO. [ABSTRACT FROM AUTHOR]

Activation of the transcription factors FoxO3a and NF-κB is necessary for muscle atrophy, which occurs during cancer cachexia and detraining. It is not known how high-intensity interval training (HIIT) and detraining affect activation of these pathways. Two-month-old male Sprague-Dawley rats were assigned to sedentary control (SC) (n = 6) and HIIT (HIIT) (n = 18) groups. The HIIT group was divided into three subgroups: HIIT (n = 6), HIIT + 7-day detraining (n = 6), and HIIT + 14-day detraining (n = 6). The expression of FoxO3a, NF-κB, MuRF1, and PGC-1α in the soleus muscle was examined by RT-PCR using CYBR Green. The 2-Ct, Livak method was used to calculate the changes in data expression. The soleus muscle mass increased after HIIT (35.10%) and decreased after 7- and 14-day of detraining (15 and 21%, respectively). The mRNA expression levels of NF-κB, MuRF1, and PGC1α in the soleus muscle were upregulated, and FoxO3a levels were significantly lower in the HIIT group compare to the SC group (p = 0.001). Taken together, the activity of the FoxO3a/MuRF1 pathway, but not NF-κB /MuRF1, can promote atrophy due to detraining, and MuRF1 is not always a good marker of atrophy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cannabis (THC) and ethanol (EtOH) are widely used for their anti-inflammatory and analgesic properties. Whether both drugs have deleterious effects on skeletal muscle needs further investigations, particularly looking at mitochondria, the energy producers of the cells. We determined the effects of EtOH, alone and associated with THC, on skeletal muscle mitochondrial respiration, on predominantly glycolytic gastrocnemius muscles (less mitochondria) and oxidative soleus (many mitochondria) muscles in young and middle-aged rats (12 and 49 weeks). Considering the gastrocnemius, EtOH impaired mitochondrial respiration in a similar manner in young- and middle-aged muscles (−34.97 ± 2.97% vs. −37.50 ± 6.03%). Interestingly, concomitant THC aggravated EtOH-related mitochondrial impairment in young gastrocnemius muscles (−49.92 ± 1.69%, vs. −34.97 ± 2.97). Concerning the soleus, EtOH alone mainly decreased young muscle mitochondrial respiration (−42.39 ± 2.42% vs. −17.09 ± 7.61%, at 12 and 49 weeks). The soleus was less impaired at 12 weeks by THC and EtOH association than the gastrocnemius. In conclusion, EtOH, alone and associated with THC, significantly impairs skeletal muscle mitochondrial respiration and THC aggravates EtOH-induced alterations in young glycolytic muscle. Caution is therefore warranted if using THC or EtOH alone, and even more caution is needed if both drugs are concomitantly used. The anti-inflammatory and analgesic properties of cannabis might be useful to treat muscle diseases, including those linked or not to alcohol. Nevertheless, delta 9 tetrahydrocannabinol (THC) and ethanol (EtOH), often used concomitantly, can have deleterious effects on cardiac mitochondria. We therefore determined whether EtOH, alone and associated with THC, impairs skeletal muscle mitochondrial respiration. Further, we investigated potential modulation by metabolic phenotype and age by analyzing predominantly glycolytic gastrocnemius and oxidative soleus muscles in young and middle-aged rats (12 and 49 weeks). Considering the gastrocnemius, EtOH impaired mitochondrial respiration in a similar manner in young- and middle-aged muscles (−34.97 ± 2.97% vs. −37.50 ± 6.03% at 2.1 × 10−5 M; p < 0.05). Interestingly, concomitant THC aggravated EtOH-related mitochondrial impairment in young gastrocnemius (−49.92 ± 1.69%, vs. −34.97 ± 2.97 p < 0.05). Concerning the soleus, EtOH alone mainly decreased young muscle mitochondrial respiration (−42.39 ± 2.42% vs. −17.09 ± 7.61% at 2.1 × 10−5 M, p < 0.001, at 12 and 49 weeks). The soleus was less impaired at 12 weeks by THC and EtOH association than the gastrocnemius (−49.92 ±1.69 vs. −27.22 ± 8.96% in gastrocnemius and soleus, respectively, p < 0.05). In conclusion, EtOH, alone and associated with THC, significantly impairs skeletal muscle mitochondrial respiration and THC aggravates EtOH-induced effects on young glycolytic muscle. Age and metabolic phenotypes modulate these deleterious effects, with the glycolytic muscles of young rats being more prone to impairments than oxidative muscles. [ABSTRACT FROM AUTHOR]

Background/Objectives: Acute ruptures of the Achilles Tendon (AT) are common injuries in the active population, in particular among men aged 30 to 50. Full functional recovery after this kind of injury is long and challenging and nowadays there is no universal "gold standard" strategy when dealing with them. Methods: When it comes to surgical treatment, various techniques have been described: in case of a typical lesion at the midportion of the tendon (which is the most common type), the basic principle of surgical repair is the end-to-end suture of the tendon stumps. The AT ("calcaneal tendon" according to the International Anatomical Terminology) is the strongest tendon of the human body, it is the conjunct tendon of the two Gastrocnemii Muscles and the Soleus Muscle and has a well-recognizable twisted structure: the subtendon from the Medial Head of the Gastrocnemius attaches postero-laterally on the calcaneal tendon footprint, the subtendon from the Lateral Head of the Gastrocnemius attaches antero-laterally and the subtendon from the Soleus attaches medially, therefore creating a 90° twist of the tendon structure. Results: the twisted structure of the human AT is of central importance to its biomechanics, since it gives the tendon a higher resistance to deformation and concurs in supination of the subtalar joint during gait. Conclusions: given the abovementioned anatomical and biomechanical premises, we believe that the restoration of the subtendons anatomy can lead to a better functional recovery of the Triceps Surae—Achilles Tendon complex, therefore we recently decided to adopt for open surgical repair the Direct Anatomical Reconstruction of the Achilles Tendon, which we describe in the present article. [ABSTRACT FROM AUTHOR]

Chronic neuromuscular inactivity induces capillary regression within skeletal muscle. The objective of this study was to investigate the potential effects of dietary nucleic acids in counteracting the capillary reduction linked to chronic neuromuscular inactivity in the soleus muscle. The study utilized four distinct groups of female Wistar rats: a control group (CON), a hindlimb-unloading group (HU), an HU group supplemented with DNA (HU + DNA), and an HU group supplemented with RNA (HU + RNA). For a duration of two weeks, rats in the HU + DNA and HU + RNA groups were administered 1500 mg/kg of DNA or RNA orally on a daily basis. Two weeks of hindlimb unloading was concomitant with a reduction in the absolute weight of the soleus muscle and the capillary-to-fiber (C/F) ratio. This was associated with changes due to disuse, including increased accumulation of reactive oxygen species (ROS) and reduced levels of superoxide dismutase (SOD-2), along with elevated levels of thrombospondin-1 (TSP-1), an anti-angiogenic factor. Administering DNA at a medium concentration in the diet did not effectively prevent the reduction in the ratio between capillaries and fibers. In contrast, the equivalent concentration of RNA successfully averted the regression of capillaries during the unloading phase. Additionally, reactive oxygen species (ROS), superoxide dismutase-2 (SOD-2), and thrombospondin-1 (TSP-1) protein were kept at the same levels as in the control. The aforementioned findings reveal that RNA is more effective than DNA in preventing capillary regression triggered by muscle atrophy. [ABSTRACT FROM AUTHOR]

Purpose: Reduced capillary number in skeletal muscle due to disuse can hinder the delivery of insulin and amino acid delivery to muscle cells, diminishing insulin activity and muscle protein synthesis, ultimately contributing to anabolic resistance. However, it remains unknown whether mitigating capillary regression during inactivity improves anabolic resistance. This study aimed to investigate the effect of increasing capillary number through the administration of prazosin, which can increase blood flow and prevent capillary regression, on anabolic resistance in skeletal muscle induced by disuse. Methods: Male Sprague Dawley rats were divided into control and hindlimb unloading (HU) groups, with half of each group receiving prazosin (50 mg/L) in their drinking water for 2 weeks. Histological analysis of the soleus muscles was conducted to measure the capillary-to-fiber (C/F) ratio, while western blotting was performed to measure the activation of the Akt/mTORC1 muscle protein synthesis pathway before and after insulin stimulation. Results: The C/F ratios were significantly lower in the HU and HU + Prz groups than in the control group but were significantly higher in the HU + Prz group than in the HU group. Following insulin stimulation, the phosphorylation levels of Akt, p70S6K, and S6RP increased in all groups, with a significantly greater increase observed in the HU + Prz group compared to the HU group, indicating improved molecular signaling related to muscle protein synthesis. Conclusion: Administration of prazosin during hindlimb unloading mitigated capillary regression and enhanced insulin-stimulated muscle protein synthesis response. These findings suggest that enhancing capillary number may reduce the anabolic resistance caused by muscle disuse. [ABSTRACT FROM AUTHOR]

Clonus is characterized by involuntary, rhythmic, oscillatory muscle contractions, typically triggered by rapid muscle stretching and is frequently associated with spastic equinovarus foot (SEVF), where it may increase risk of falls and cause discomfort, pain, and sleep disorders. We hypothesize that selective diagnostic nerve block (DNB) of the tibial nerve motor branches can help identify which muscle is primarily responsible for clonus in patients with SEVF and provide useful information for botulinum neurotoxin type A (BoNT-A) treatment. This retrospective study explored which calf muscles contributed to clonus in 91 patients with SEFV after stroke (n = 31), multiple sclerosis (n = 21), and cerebral palsy (n = 39), using selective DNB. We found that SEVF-associated clonus was most commonly driven by the soleus muscle, followed by the gastrocnemius lateralis and medialis, tibialis posterior, and flexor digitorum longus, and that frequency differed according to SEVF etiology. Our data suggest that identifying the muscles involved in SEVF-associated clonus may aid clinicians in personalizing BoNT-A treatment to single patients. Also, the findings of this study suggest that applying a 'stroke model' to treating spasticity secondary to other etiologies may not always be appropriate. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dexamethasone and hindlimb suspension are commonly used methods for modeling sarcopenia in animal experiments due to their short modeling time, ease of operation, and low cost. OBJECTIVE: To compare the differences in muscle mass, strength and functional phenotypes and molecular mechanisms between two mouse sarcopenia models induced by dexamethasone and hindlimb suspension. METHODS: Thirty male C57BL/6 mice were randomly divided into three groups (n=10 per group). The normal control group received no intervention. The dexamethasone group received daily intraperitoneal injections of 1 mg/kg/d dexamethasone sodium phosphate solution for 6 continuous days to establish sarcopenia models in mice, while mice in the hindlimb suspension group were suspended by tail harness for 16 hours, once per day, to establish sarcopenia models. Within 6 weeks after modeling, changes in body mass were monitored. After 6 weeks of modeling, mice were tested for limb grip strength, mobility (swimming test), skeletal muscle wet mass, and skeletal muscle pathological morphology. Expressions of skeletal muscle protein synthesis and catabolism indexes as well as the AMPK/FoXO3α signaling pathway were detected by RT-PCR and western blot. RESULTS AND CONCLUSION: (1) Two weeks after modeling, both dexamethasone and hindlimb suspension groups showed a significant decrease in body mass compared with the normal control group (P < 0.001). After 6 weeks of modeling, grip strength of mice in both dexamethasone and hindlimb suspension groups was lower than that in the normal control group (P < 0.001). The wet mass of gastrocnemius and extensor digitorum longus muscles and the crosssectional area of gastrocnemius and soleus muscles in the dexamethasone group were lower than those in the normal control group (P < 0.05). Compared with the hindlimb suspension group, the cross-sectional area of gastrocnemius muscle was significantly smaller in the dexamethasone group (P < 0.05), while the cross-sectional area of soleus muscle was larger in the dexamethasone group (P < 0.05). Mice in the dexamethasone group had reduced mobility when compared with those in the normal control group and the hindlimb suspension group (P < 0.05). (3) Compared with the normal control group, PI3K, mTOR, AMPK, and PGC-1α mRNA expression and P-AMPK/AMPK protein were decreased in the two modeling groups (P < 0.05), and FoXO3α mRNA expression and PGC-1α and FoXO3 protein expression were elevated (P < 0.05); in the dexamethasone group, Akt1 mRNA expression was decreased (P < 0.05), while Atrogin-1 and MuRF-1 mRNA expression was elevated (P < 0.05); in the hindlimb suspension group, Akt1 mRNA expression was elevated (P < 0.05). (4) Compared with the dexamethasone group, mTOR, Akt1, and FoXO3α mRNA expression was elevated in the hindlimb suspension group (P < 0.05), while Atrogin-1 and MuRF-1 mRNA expression was decreased (P < 0.05). To conclude, both modeling methods could decrease the levels of mitochondrial energy metabolism in skeletal muscle, with the dexamethasone group mediating atrophy of skeletal muscle through the dual action of ubiquitin proteasome and energy metabolism pathways, and the hindlimb suspension group inducing atrophy of skeletal muscle by mediating the energy metabolism pathway through the AMPK/FoXO3α signaling pathway, subsequently causing a reduction in mass, strength, and function of skeletal muscle. [ABSTRACT FROM AUTHOR]

Electromyographic (EMG) recordings indicate that both the flexor digitorum brevis and soleus muscles contribute significantly to the control of standing balance, However, less is known about the adjustments in EMG activity of these two muscles across different postures. The purpose of our study was to use deep-learning models to distinguish between the EMG activity of the flexor digitorum brevis and soleus muscles across four standing postures. Deep convolutional neural networks were employed to classify standing postures based on the temporal and spatial features embedded in high-density surface EMG signals. The EMG recordings were obtained with grid electrodes placed over the flexor digitorum brevis and soleus muscles of healthy young men during four standing tasks: bipedal, tandem, one-leg, and tip-toe. Two-way repeated-measures analysis of variance demonstrated that the model achieved significantly greater classification accuracy, particularly during tandem stance, using EMG data from flexor digitorum brevis compared with soleus muscle. Average classification accuracy was 84.6 % for flexor digitorum brevis and 79.1 % for soleus. The classification accuracy of both muscles varied across the four postures. There were significant differences in classification accuracy for flexor digitorum brevis between bipedal and tandem stances compared with one-leg and tip-toe stances. In contrast, the EMG data for soleus were only significantly different between bipedal stance and one-leg stance. These findings indicate that flexor digitorum brevis exhibited more distinct adjustments than soleus in the temporo-spatial features of EMG activity across the four postures. • High-density EMG recordings were obtained from flexor digitorum brevis and soleus during four standing postures. • Deep-learning models identified significant differences in EMG activity between the two muscles. • Adjustments in EMG activity were more distinct across the four postures for flexor digitorum brevis than for the soleus. [ABSTRACT FROM AUTHOR]

Abstract The high incidence of deep vein thrombosis (DVT) in evacuees has been recognized since the 2004 Niigata-Chuetsu Earthquake in Japan. We hypothesized that the number and location of communicating branches of the soleal veins might influence thrombus development and that the median septum of the soleus muscle influences the venous network of the soleal veins. This study aimed to investigate how the network of soleal veins varies with the shape and thickness of the median septum and to elucidate factors predisposing soleal veins to DVT. The lower legs of 30 sides from 15 formalin-preserved cadavers were observed. The central soleal vein, the predilection site for thrombus among the six veins within the soleus muscle, divides into three branches: medial, central, and lateral. The soleus muscle has a unique architecture with converging muscle fibers on the anterior surface of the median septum. We examined the positional relationship between the central soleal vein and the median septum. The median septum morphology was either straight (14 sides, 46.7%) or curved (16 sides, 53.3%). The number of communicating branches was significantly higher in the curved type. The curved type also had a communicating vein penetrating the median septum, with the central branch passing deeper than in the straight type. The median septum could restrict the enlargement of communicating branches, causing thrombosis through disturbance of venous blood flow. Future research will clarify the median septum’s influence on the soleal vein, potentially identifying soleus muscles at high risk of developing DVT.

In most mammals, postural soleus muscles are involved in the maintenance of the stability of the body in the gravitational field of Earth. It is well established that immediately after a laboratory rat is exposed to conditions of weightlessness (parabolic flight) or simulated microgravity (hindlimb suspension/unloading), a sharp decrease in soleus muscle electrical activity occurs. However, starting from the 3rd day of mechanical unloading, soleus muscle electrical activity begins to increase and reaches baseline levels approximately by the 14th day of hindlimb suspension. This phenomenon, observed in the course of rat hindlimb suspension, was named the "spontaneous electrical activity of postural muscle". The present review discusses spinal mechanisms underlying the development of such spontaneous activity of rat soleus muscle and the effect of this activity on intracellular signaling in rat soleus muscle during mechanical unloading. [ABSTRACT FROM AUTHOR]

Traumatic skeletal muscle injury is a complex pathology caused by high-energy trauma to muscle tissue. Previously, a positive effect was established when C60 fullerene was administered against the background of muscle ischemia, mechanical muscle injury, and other muscle dysfunctions, which probably protected the muscle tissue from damage caused by oxidative stress. Using tensiometry and biochemical analysis, the biomechanical parameters of skeletal muscle contraction and biochemical indices of the blood of rats 15 days after traumatic injury of the soleus muscle caused by myocyte destruction by compression were studied. The intraperitoneal administration of C60 fullerene aqueous solution (C60FAS) in a daily dose of 1 mg/kg improved its contractile function by 28–40 ± 2% and the values of the investigated biochemical indices of the animals' blood by 15–34 ± 2% relative to the trauma group. The obtained results indicate the potential ability of C60 fullerenes, as powerful antioxidants, to reduce the development of post-traumatic dysfunction of the soleus muscle. [ABSTRACT FROM AUTHOR]

Patients with myotonia congenita suffer from slowed muscle relaxation caused by hyperexcitability. The diaphragm is only mildly affected in myotonia congenita; discovery of the mechanism underlying its resistance to myotonia could identify novel therapeutic targets. Intracellular recordings from two mouse models of myotonia congenita revealed the diaphragm had less myotonia than either the extensor digitorum longus (EDL) or the soleus muscles. A mechanism contributing to resistance of the diaphragm to myotonia was reduced depolarization of the interspike membrane potential during repetitive firing of action potentials, a process driven by build‐up of K+ in small invaginations of muscle membrane known as t‐tubules. We explored differences between diaphragm and EDL that might underlie reduction of K+ build‐up in diaphragm t‐tubules. Smaller size of diaphragm fibres, which promotes diffusion of K+ out of t‐tubules, was identified as a contributor. Intracellular recording revealed slower repolarization of action potentials in diaphragm suggesting reduced Kv conductance. Higher resting membrane conductance was identified suggesting increased Kir conductance. Computer simulation found that a reduction of Kv conductance had little effect on K+ build‐up whereas increased Kir conductance lessened build‐up, although the effect was modest. Our data and computer simulation suggest opening of K+ channels during action potentials has little effect on K+ build‐up whereas opening of K+ channels during the interspike interval slightly lessens K+ build‐up. We conclude that activation of K+ channels may lessen myotonia by opposing depolarization to action potential threshold without worsening K+ build‐up in t‐tubules. Key points: In mouse models of the muscle disease myotonia congenita, the diaphragm has much less myotonia (muscle stiffness) than the extensor digitorum longus or soleus muscles.Identifying why the diaphragm is resistant to myotonia may help in developing novel therapy.We found the reason the diaphragm has less myotonia is that it is less prone to depolarization caused by K+ build‐up in t‐tubules during repetitive firing of action potentials.Smaller fibre size contributes to resistance to K+ build‐up with differences in K+ currents playing little role.Our data suggest drugs that open K+ channels may be effective in treating myotonia as they may lessen excitability without worsening K+ build‐up in t‐tubules. [ABSTRACT FROM AUTHOR]

The high incidence of deep vein thrombosis (DVT) in evacuees has been recognized since the 2004 Niigata-Chuetsu Earthquake in Japan. We hypothesized that the number and location of communicating branches of the soleal veins might influence thrombus development and that the median septum of the soleus muscle influences the venous network of the soleal veins. This study aimed to investigate how the network of soleal veins varies with the shape and thickness of the median septum and to elucidate factors predisposing soleal veins to DVT. The lower legs of 30 sides from 15 formalin-preserved cadavers were observed. The central soleal vein, the predilection site for thrombus among the six veins within the soleus muscle, divides into three branches: medial, central, and lateral. The soleus muscle has a unique architecture with converging muscle fibers on the anterior surface of the median septum. We examined the positional relationship between the central soleal vein and the median septum. The median septum morphology was either straight (14 sides, 46.7%) or curved (16 sides, 53.3%). The number of communicating branches was significantly higher in the curved type. The curved type also had a communicating vein penetrating the median septum, with the central branch passing deeper than in the straight type. The median septum could restrict the enlargement of communicating branches, causing thrombosis through disturbance of venous blood flow. Future research will clarify the median septum's influence on the soleal vein, potentially identifying soleus muscles at high risk of developing DVT. [ABSTRACT FROM AUTHOR]

After the first day of muscle disuse (unloading) mitochondria-derived ROS accumulate in the postural-tonic soleus muscle. It is known that excess of ROS can lead to the accumulation of intramitochondrial calcium and overload of mitochondria with calcium, can negatively affect mitochondrial function and fatigue resistance of soleus muscle. We assumed that the use of mitochondrial ROS scavenger mito-TEMPO will be able to prevent the unloading-induced disruption of mitochondrial functions and will help maintain soleus muscle fatigue resistance. To test this hypothesis, male rats were divided into 3 groups (n = 16 in each): vivarium control with placebo (C), 7-day hindlimb suspension with placebo (7HS) and 7-day hindlimb suspension with intraperitoneal administration of the mimetic superoxide dismutase mito-TEMPO at a dose of 1 mg/kg (7HSM). In the 7HS group, increased fatigue of the soleus muscle was found in the ex vivo test, accompanied with increased activity of ETC complex I and "leak" respiration, as well as a twofold increased content of oxidized tropomyosin (a marker of ROS level in tissues) and increase in intramitochondrial calcium compared to C. In 7HSM, the activity of ETC complex I and "leak" respiration had no significant differences from the control group, and the increase in intramitochondrial calcium and the content of oxidized tropomyosin was partially prevented, however, muscle fatigue was also significantly higher than in the control group. Thus, mitochondrial ROS under 7-day muscle unloading contribute to the accumulation of intramitochondrial calcium and oxidation of tropomyosin, but do not have a significant effect on soleus muscle function. [Display omitted] • ROS accumulate in unloaded muscle. • Calcium accumulates in mitochondria during soleus muscle 7-day unloading. • ROS scavenger mito-TEMPO treatment partially prevented mitochondrial calcium accumulation. • It did not prevent unloaded soleus muscle weakness, but attenuated atrophy and electron transport chain Complex I overactivation. [ABSTRACT FROM AUTHOR]

The role of stress granules (SGs) in pulmonary arterial hypertension (PAH) is unknown. We hypothesized that SG formation contributes to abnormal vascular phenotypes, and cardiac and skeletal muscle dysfunction in PAH. Using the rat Sugen/hypoxia (SU/Hx) model of PAH, we demonstrate the formation of SG puncta and increased expression of SG proteins compared to control animals in lungs, right ventricles, and soleus muscles. Acetazolamide (ACTZ) treatment ameliorated the disease and reduced SG formation in all of these tissues. Primary pulmonary artery smooth muscle cells (PASMCs) from diseased animals had increased SG protein expression and SG number after acute oxidative stress and this was ameliorated by ACTZ. Pharmacologic inhibition of SG formation or genetic ablation of the SG assembly protein (G3BP1) altered the SU/Hx-PASMC phenotype by decreasing proliferation, increasing apoptosis and modulating synthetic and contractile marker expression. In human PAH lungs, we found increased SG puncta in pulmonary arteries compared to control lungs and in human PAH-PASMCs we found increased SGs after acute oxidative stress compared to healthy PASMCs. Genetic ablation of G3BP1 in human PAH-PASMCs resulted in a phenotypic switch to a less synthetic and more contractile phenotype. We conclude that increased SG formation in PASMCs and other tissues may contribute to PAH pathogenesis. [ABSTRACT FROM AUTHOR]

Background and Purpose: The balance between antioxidant and oxidative systems in skeletal muscle is crucial for maintaining both health and sports performance. Cold water immersion (CWI) as a recovery method may help in improving the performance of these systems and reduce the damage caused by oxidative stress. This study aimed to investigate the effect of cold water immersion after eccentric exercise (ECC) on antioxidant and oxidant indices in the skeletal muscle of rats. Materials and Methods: Twenty-five male Wistar rats (12 weeks old; weight, 230±5 g) were randomly divided into control, Eccentric + PR (passive recovery), Eccentric + CWI, Eccentric + NWI (normal water immersion), and Eccentric + AR (active recovery) groups. The Eccentric exercise consisted of 90 min of downhill running on a treadmill with a speed of 16 m/min and -16° incline. For an active recovery, after eccentric exercise, rats ran on a treadmill for 10 min at a speed of 12 m/min on a flat surface. For the normal water immersion and cold water immersion protocols, after eccentric exercise the entire body of rats (excluding the head of animals) was immersed in plastic containers containing normal water at 25°C or cold water at 10°C for 10 minutes. One day after eccentric exercise, the animals were euthanized by peritoneal injection of ketamine + xylazine (10+100mg/kg) and their soleus muscles were removed under sterile conditions and transferred into a -70 °C freezer. Results: Eccentric + Passive recovery significantly (p<0.05) reduced antioxidant indices including total antioxidant capacity (TAC), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH) compared to the control group. It also caused a significant (p<0.05) increase in oxidant indices including total oxidant status (TOS), oxidative stress index (OSI), and oxidized glutathione (GSSG). There was no significant differences between recovery methods after eccentric exercise (cold water immersion, normal water immersion, active recovery) in terms of antioxidant levels (GPX, glutathione S -transferase (GST), and GR) and oxidant levels (GSSG and glutathione ratio reduced to oxidized (GSH/GSSG)) compared to passive recovery (p>0.05). Despite this, cold water immersion significantly (p<0.05) increased antioxidant indices (GSH and TAC) and decreased oxidant indices (TOS and OSI) compared to passive recovery. Conclusion: The results of this study demonstrated that eccentric exercise has a significant negative impact on the antioxidant and oxidative status of skeletal muscle and cold water immersion reduced oxidative stress and improved antioxidant status after eccentric exercise. [ABSTRACT FROM AUTHOR]

Background and Aims: Gait initiation (GI) in individuals with chronic ankle instability (CAI) has shown differences in the center of pressure (COP) and muscular measures compared to healthy controls. Some studies reported that these alterations appeared when GI was with the affected leg, while others indicated that they occurred when GI was with the non‐affected leg. This systematic review aimed to understand kinetic and muscular differences between individuals with CAI, healthy controls, and the affected and non‐affected legs of individuals with CAI. Methods: PubMed, Science Direct, Web of Science, Google Scholar, and Scopus databases (1990–2023) were searched using the Population, Exposure, Comparator, and Outcome measure. The PRISMA guidelines were followed. The outcome measures were the peak and rate of COP displacement in the medial‐lateral and anterior‐posterior directions, and resultant plane during phases 1, 2, and 3 of COP trace during GI and the duration of each phase. The other measures included the onset time of the tibialis anterior and soleus muscle activity between individuals with CAI, healthy controls, and the affected and non‐affected legs of the individuals with CAI. The studies' quality assessment was conducted based on the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Results: Five studies were included in the final evaluation. The results of included studies showed, individuals with CAI spent less time during phases 1 and 2, as well as a shorter peak of COP displacement in the lateral direction during phase 1 compared to healthy controls, regardless of whether the GI was with the affected or non‐affected leg. Conclusion: Individuals with CAI have probably adopted a strategy involving adjusting the peak of COP displacement to manage internal sway while in a single‐leg stance. Overall, there was no comprehensive conclusion about differences between the two legs in individuals with CAI. [ABSTRACT FROM AUTHOR]

The hormone ghrelin serves a protective role in cancer-related anorexia-cachexia syndrome (CACS)—a condition in which plasma levels of ghrelin rise, its administration lessens CACS severity, and experimentally reduced signaling by its receptor (GHSR) worsens fat loss and anorexia and accelerates death. Yet, actions for the related hormone liver-expressed antimicrobial peptide-2 (LEAP2), which is an endogenous GHSR antagonist, are unexplored in CACS. Here, we found that plasma LEAP2 and LEAP2/ghrelin ratio were lower in Lewis lung carcinoma (LLC) and RM-9 prostate cancer CACS mouse models. Ghrelin deletion exaggerated losses of tumor-free body weight and fat mass, reduced food intake, reduced soleus muscle weight, and/or lowered grip strength in LLC or RM-9 tumor-bearing mice. LEAP2 deletion lessened reductions in tumor-free body weight and fat mass and increased food intake in LLC or RM-9 tumor-bearing mice. In a 55-subject cohort of patients with CACS or weight-stable cancer, the plasma LEAP2/total ghrelin ratio was negatively correlated with 6-month weight change preceding blood collection. These data demonstrate that ghrelin deletion exacerbates CACS in the LLC and RM-9 tumor-bearing mouse models while contrastingly, LEAP2 deletion reduces measures of CACS in these tumor-bearing mouse models. Further, they suggest that lower plasma LEAP2/ghrelin ratio protects against worsened CACS. [ABSTRACT FROM AUTHOR]

Limited ankle dorsiflexion range of motion is one of the most important risk factors for lower limb injury, which changes the biomechanics and the neuromuscular control of the lower limb muscles. This study aims to test the effectiveness of a comprehensive corrective exercise program (CCEP) on the range of motion, proprioception, dynamic balance, and muscle activation in female athletes with limited weight-bearing lunge ankle dorsiflexion range of motion. 30 female athletes aged 15 to 25 years with dorsiflexion under 34° were randomized to two groups. The intervention group (n = 15) received eight weeks of CCEP including soft tissue mobilization, joint mobilization, stretching, and strengthening, and the control (n = 15) group did not receive any intervention. range of motion, proprioception, dynamic balance, and muscle activation were assessed before and after the intervention. The training group showed clinically acceptable and statistically significant changes in ankle dorsiflexion range of motion (ES = 0.714), balance (ES = 0.423), and proprioception (ES = 0.253; P < 0.05). There were significant changes in the activity of the tibialis anterior and soleus muscles in the dynamic overhead squat test (descending and ascending phases) and the activity of the medial gastrocnemius in the descending phase decreased significantly (P < 0.05). No significant change was observed in the activity of the peroneus longus muscle (P > 0.05). The findings show that CCEP appears to be beneficial in increasing dorsiflexion range of motion, proprioception, balance, and decreasing ankle muscle activity among individuals with limited ankle dorsiflexion. Improving the dorsiflexion range of motion may be promising for reducing ankle sprain injury. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscles possess unique abilities known as adaptation or plasticity. When exposed to external stimuli, such as mechanical loading, both myofiber size and myonuclear number increase. Muscle stem cells, also known as muscle satellite cells (MuSCs), play vital roles in these changes. HeyL, a direct target of Notch signaling, is crucial for efficient muscle hypertrophy because it ensures MuSC proliferation in surgically overloaded muscles by inhibiting the premature differentiation. However, it remains unclear whether HeyL is essential for MuSC expansion in physiologically exercised muscles. Additionally, the influence of myofiber type on the requirement for HeyL in MuSCs within exercised muscles remains unclear. Methods: We used a voluntary wheel running model and HeyL-knockout mice to investigate the impact of HeyL deficiency on MuSC-derived myonuclei, MuSC behavior, muscle weight, myofiber size, and myofiber type in the running mice. Results: The number of new MuSC-derived myonuclei was significantly lower in both slow-twitch soleus and fast-twitch plantaris muscles from exercised HeyL-knockout mice than in control mice. However, expect for the frequency of Type IIb myofiber in plantaris muscle, exercised HeyL-knockout mice exhibited similar responses to control mice regarding myofiber size and type. Conclusions: HeyL expression is crucial for MuSC expansion during physiological exercise in both slow and fast muscles. The frequency of Type IIb myofiber in plantaris muscle of HeyL-knockout mice was not significantly reduced compared to that of control mice. However, the absence of HeyL did not affect the increased size and frequency of Type IIa myofiber in plantaris muscles. In this model, no detectable changes in myofiber size or type were observed in the soleus muscles of either control or HeyL-knockout mice. These findings imply that the requirement for MuSCs in the wheel-running model is difficult to observe due to the relatively low degree of hypertrophy compared to surgically overloaded models. [ABSTRACT FROM AUTHOR]

Muscle wasting is a serious complication in heart failure patients. Oxidative stress and inflammation are implicated in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE), which covalently bind with proteins and DNA and activate atrophic pathways. Whether the formation of lipid peroxidation products and metabolic pathways that remove these toxic products are affected during heart failure-associated skeletal muscle wasting has never been studied. Male C57BL/6J mice were subjected to sham and transverse aortic constriction (TAC) surgeries for 4, 8 or 14 weeks. Different skeletal muscle beds were weighed, and the total cross-sectional area of the gastrocnemius muscle was measured via immunohistochemistry. Muscle function and muscle stiffness were measured by a grip strength meter and atomic force microscope, respectively. Atrophic and inflammatory marker levels were measured via qRT‒PCR. The levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, the histidyl dipeptide-synthesizing enzyme carnosine synthase (CARNS), and amino acid transporters in the gastrocnemius muscle were measured via Western blotting and qRT‒PCR. Histidyl dipeptides and histidyl dipeptide aldehyde conjugates in the Gastrocnemius and soleus muscles were analyzed by LC/MS–MS. Body weight, gastrocnemius muscle and soleus muscle weights and the total cross-sectional area of the gastrocnemius muscle were decreased after 14 weeks of TAC. Heart weight, cardiac function, grip strength and muscle stiffness were decreased in the TAC-operated mice. Expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, was increased ~ 1.5–2fold in the gastrocnemius muscle after 14 weeks of TAC (p < 0.05 and p = 0.004 vs sham). The formation of HNE and acrolein protein adducts was increased, and the expression of the aldehyde-removing enzyme aldehyde dehydrogenase (ALDH2) was decreased in the gastrocnemius muscle of TAC mice. Carnosine (sham: 5.76 ± 1.3 vs TAC: 4.72 ± 0.7 nmol/mg tissue, p = 0.04) and total histidyl dipeptide levels (carnosine and anserine; sham: 11.97 ± 1.5 vs TAC: 10.13 ± 1.4 nmol/mg tissue, p < 0.05) were decreased in the gastrocnemius muscle of TAC mice. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, CARNS and TAUT protein expression were decreased in the atrophic gastrocnemius muscle. Our data reveals that reduced expression of ALDH2 and depletion of histidyl dipeptides in the gastrocnemius muscle during heart failure leads to the accumulation of toxic aldehydes and might contribute to muscle wasting. [ABSTRACT FROM AUTHOR]

Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) are noninvasive techniques used to induce muscle contraction, aiding motor function restoration in individuals with neurological disorders. Understanding sensory inputs from PNS and MPS is crucial for facilitating neuroplasticity and restoring impaired motor function. Although previous studies suggest that MPS could induce Ia-sensory inputs less than PNS, experimental evidence supporting this claim is insufficient. Here, we implemented a conditioning paradigm combining transcutaneous spinal cord stimulation (tSCS) with PNS or MPS to investigate their Ia-sensory inputs. This paradigm induces postactivation depression of spinal reflexes associated with transient decreases in neurotransmitter release from Ia-afferent terminals, allowing us to examine the Ia-sensory input amount from PNS and MPS based on the depression degree. We hypothesized that MPS would induce less postactivation depression than PNS. Thirteen individuals underwent MPS and PNS on the soleus muscle as conditioning stimuli, with tSCS applied to the skin between the spinous processes (L1–L2) as test stimuli. PNS- and MPS-conditioned spinal reflexes were recorded at five interstimulus intervals (ISIs) and four intensities. Results revealed that all PNS conditioning showed significant decreases in spinal reflex amplitudes, indicating postactivation depression. Furthermore, PNS conditioning exhibited greater depression for shorter ISIs and higher conditioning intensities. In contrast, MPS conditioning demonstrated intensity-dependent depression, but without all-conditioning depression and clear ISI dependency as seen in PNS conditioning. In addition, PNS induced significantly greater depression than MPS across most conditions. Our findings provide experimental evidence supporting the conclusion that MPS activates Ia-sensory nerves less than PNS. NEW & NOTEWORTHY: Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) induce neuroplasticity, but differences in their effects on Ia-sensory inputs are unclear. We investigated their Ia-sensory inputs using a conditioning paradigm with spinal reflexes. Results showed that PNS conditioning significantly inhibited spinal reflexes than MPS conditioning, indicating greater postactivation depression due to Ia-sensory nerve activation. These findings provide experimental evidence that MPS activates Ia-sensory nerves to a lesser extent than PNS, enhancing our understanding of neuroplasticity. [ABSTRACT FROM AUTHOR]

Introduction: This study investigates the impact of dry needling on myofascial trigger points in the soleus muscles among soccer players with medial tibial stress syndrome (MTSS). Materials and Methods: Soccer players diagnosed with MTSS were enlisted and randomly divided into two groups (11 participants in the experimental group [Group 1] and 11 participants in the control group [Group 2]). Pre-intervention measurements included repeated shuttle sprint ability, MTSS score, and pain pressure threshold (PPT) for both groups. In the experimental group, dry needling was performed on the soleus muscle, followed by active stretching and cryotherapy. The control group underwent active stretching of the soleus muscle and cryotherapy exclusively. Post-intervention measurements of repeated shuttle sprint ability, MTSS score, and PPT were taken for both groups after 2 days. Results: The experimental group exhibited a statistically significant improvement in PPT, MTSS score, and repeated shuttle sprint ability. Conversely, within the control group, statistically significant changes were observed only in PPT values through paired t-test assessment. Between-group analysis using an independent t-test revealed significant enhancement in PPT (P=0.000) and MTSS score (P=0.01) within the experimental group compared to the control group. Conclusion: Addressing myofascial trigger points in the soleus muscle through dry needling offers a more effective approach to treating MTSS than relying solely on muscle stretching. [ABSTRACT FROM AUTHOR]

Using produced polyclonal antibodies specific to the N-terminal sequence (residues 61-298) of rat obscurin, we investigated the isoform composition of this protein in 4 striated muscles: myocardium of the left ventricle, diaphragm, skeletal m. gastrocnemius (containing mainly fast fibers), and m. soleus (containing mainly slow fibers). The m. gastrocnemius, m. soleus, and diaphragm were found to have 2 giant isoforms of obscurin: a smaller A-isoform and a larger B-isoform. Their molecular weights were ~870 and ~1150 kDa in the diaphragm and m. gastrocnemius and ~880 and ~1130 kDa in m. soleus, respectively. The B-isoform to A-isoform ratio was 1:3 in the diaphragm and m. soleus and 1:4 in the m. gastrocnemius. In the left-ventricular myocardium, A-isoform of obscurin with a molecular weight of ~880 kDa was found. No other obscurin isoforms or their fragments within the molecular weight range of 10 up to ~800 kDa were revealed in the investigated rat striated muscles. The antibodies produced are recommended for research into qualitative and quantitative changes of giant obscurin isoforms in rat striated muscles in the norm and during the development of pathological processes. [ABSTRACT FROM AUTHOR]

This study aimed to investigate changes in protein signaling associated with muscle regeneration in aged rats with obesity and diabetes following high-intensity interval training (HIIT) and SP supplementation. Forty male Wistar rats weighting 280-325 g were used in this study. Obesity was induced by eight weeks of a high-fat diet, and diabetes was induced by intraperitoneal injection of 40 mg/kg streptozocin. Rats were randomly divided into control (CON), sham, SP, HIIT, and HIIT+SP groups. HIIT was performed five times per week during the 8-week period. SP dose was 50 mg/kg. Real-time PCR was used to evaluate the expression of myogenin, MyoD1, and Pax7. The decreases in body mass in the HIIT, HIIT+SP and SP groups were significantly higher than those in the sham and CON groups (p=0.0001). The soleus muscle mass increased significantly only in the HIIT and HIIT+SP groups (p<0.01). HIIT+SP improved fasting blood glucose and insulin levels more than HIIT alone and SP (p<0.05), while HIIT increased the expression levels of myogenic factors more than other groups (p=0.0001). In conclusion HIIT alone had a significant impact on myogenic factors, whereas Spirulina had an effect only when combined with HIIT. [ABSTRACT FROM AUTHOR]

Versican is increased with inflammation and fibrosis, and is upregulated in Duchenne muscular dystrophy. In fibrotic diaphragm muscles from dystrophic mdx mice, genetic reduction of versican attenuated macrophage infiltration and improved contractile function. Versican is also implicated in myogenesis. Here, we investigated whether versican modulated mdx hindlimb muscle pathology, where inflammation and regeneration are increased but fibrosis is minimal. Immunohistochemistry and qRT-PCR were used to assess how fiber type and glucocorticoids (α-methylprednisolone) modify versican expression. To genetically reduce versican, female mdx and male versican haploinsufficient (hdf) mice were bred resulting in male mdx-hdf and mdx (control) pups. Versican expression, contractile function, and pathology were evaluated in hindlimb muscles. Versican immunoreactivity was greater in slow versus fast hindlimb muscles. Versican mRNA transcripts were reduced by α-methylprednisolone in soleus, but not in fast extensor digitorum longus, muscles. In juvenile (6-wk-old) mdx-hdf mice, versican expression was most robustly decreased in soleus muscles leading to improved force output and a modest reduction in fatiguability. These functional benefits were not accompanied by decreased inflammation. Muscle architecture, regeneration markers, and fiber type also did not differ between mdx-hdf mice and mdx littermates. Improvements in soleus contractile function were not retained in adult (20-wk-old) mdx-hdf mice. In conclusion, soleus muscles from juvenile mdx mice were most responsive to pharmacological or genetic approaches targeting versican; however, the benefits of versican reduction were limited due to low fibrosis. Preclinical matrix research in dystrophy should account for muscle phenotype (including age) and the interdependence between inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

The study of drugs of natural origin that increase endurance and/or accelerate recovery is an integral part of sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) and two ammonium salts—chloride (ACL) and carbonate (ACR)—were tested individually and in combination with GTE as stimulants of physical performance in a forced swimming rat experimental model. The determined parameters can be divided into seven blocks: functional (swimming duration); biochemistry of blood plasma; biochemistry of erythrocytes; hematology; immunology; gene expression of slow- and fast-twitch muscles (m. soleus, SOL, and m. extensor digitorum longus, EDL, respectively); and morphometric indicators of slow- and fast-twitch muscles. Regarding the negative control (intact animals), the maximum number of changes in all blocks of indicators was recorded in the GTE + ACR group, whose animals showed the maximum functional result and minimum lactate values on the last day of the experiment. Next, in terms of the number of changes, were the groups ACR, ACL, GTE + ACL, GTE and NaCl (positive control). In general, the number of identified adaptive changes was proportional to the functional state of the animals of the corresponding groups, in terms of the duration of the swimming load in the last four days of the experiment. However, not only the total number but also the qualitative composition of the identified changes is of interest. The results of a comparative analysis suggest that, in the model of forced swimming we developed, GTE promotes restoration of the body and moderate mobilization of the immune system, while small doses of ammonium salts, especially ammonium carbonate, contribute to an increase in physical performance, which is associated with satisfactory restoration of skeletal muscles and the entire body. The combined use of GTE with ammonium salts does not give a clearly positive effect. [ABSTRACT FROM AUTHOR]

After an initial increase, isovelocity elongation of a muscle fiber can lead to diminishing (referred to as Give in the literature) and subsequently increasing force. How the stretch velocity affects this behavior in slow-twitch fibers remains largely unexplored. Here, we stretched fully activated individual rat soleus muscle fibers from 0.85 to 1.3 optimal fiber length at stretch velocities of 0.01, 0.1, and 1 maximum shortening velocity, vmax, and compared the results with those of rat EDL fast-twitch fibers obtained in similar experimental conditions. In soleus muscle fibers, Give was 7%, 18%, and 44% of maximum isometric force for 0.01, 0.1, and 1 vmax, respectively. As in EDL fibers, the force increased nearly linearly in the second half of the stretch, although the number of crossbridges decreased, and its slope increased with stretch velocity. Our findings are consistent with the concept of a forceful detachment and subsequent crossbridge reattachment in the stretch's first phase and a strong viscoelastic titin contribution to fiber force in the second phase of the stretch. Interestingly, we found interaction effects of stretch velocity and fiber type on force parameters in both stretch phases, hinting at fiber type-specific differences in crossbridge and titin contributions to eccentric force. Whether fiber type-specific combined XB and non-XB models can explain these effects or if they hint at some not fully understood properties of muscle contraction remains to be shown. These results may stimulate new optimization perspectives in sports training and provide a better understanding of structure–function relations of muscle proteins. [ABSTRACT FROM AUTHOR]

Background: Individuals with subacute severe hemiplegia often undergo alternate gait training to overcome challenges in achieving walking independence. However, the ankle joint setting in a knee–ankle–foot orthosis (KAFO) depends on trunk function or paralysis stage for alternate gait training with a KAFO. The optimal degree of ankle joint freedom in a KAFO and the specific ankle joint conditions for effective rehabilitation remain unclear. Therefore, this study aimed to investigate the effects of different degrees of freedom of the ankle joint on center-of-pressure (CoP) parameters and muscle activity on the paretic side using a KAFO and to investigate the recommended setting of ankle joint angle in a KAFO depending on physical function. Methods: This study included 14 participants with subacute stroke (67.4 ± 13.3 years). The CoP parameters and muscle activity of the gastrocnemius lateralis (GCL) and soleus muscles were compared using a linear mixed model (LMM) under two ankle joint conditions in the KAFO: fixed at 0° and free ankle dorsiflexion. We confirmed the relationship between changes in CoP parameters or muscle activity under different conditions and physical functional characteristics such as the Fugl–Meyer Assessment of Lower Extremity Synergy Score (FMAs) and Trunk Impairment Scale (TIS) using LMM. Results: Anterior–posterior displacement of CoP (AP_CoP) (p = 0.011) and muscle activity of the GCL (p = 0.043) increased in the free condition of ankle dorsiflexion compared with that in the fixed condition. The FMAs (p = 0.004) and TIS (p = 0.008) demonstrated a positive relationship with AP_CoP. A positive relationship was also found between TIS and the percentage of medial forefoot loading time in the CoP (p < 0.001). Conclusions: For individuals with severe subacute hemiplegia, the ankle dorsiflexion induction in the KAFO, which did not impede the forward tilt of the shank, promotes anterior movement in the CoP and muscle activity of the GCL. This study suggests that adjusting the dorsiflexion mobility of the ankle joint in the KAFO according to improvement in physical function promotes loading of the CoP to the medial forefoot. [ABSTRACT FROM AUTHOR]

Membrane IP3 receptors (IP3Rs) abound in the sarcoplasmic reticulum, nucleus and mitochondria of muscle fibers. We hypothesized that IP3R activation during muscle unloading may elicit a weak Ca2+ release signal, both cytosolic and nucleoplasmic, which promotes (perhaps in cooperation with other signaling cascades) the activation of transcription factors and thus leads to the expression or repression of genes associated with muscle phenotypes. Here, we tested this hypothesis by blocking IP3Rs with 2-APB (2-aminoethoxydiphenyl borate, 10 mg/kg in 5% DMSO i.p. daily) in a rat 7-day hindlimb suspension model of soleus muscle unloading. The blocking of IP3Rs prevented a decrease in the cross-sectional area of both slow and fast soleus muscle fibers and thus slowed down the development of atrophic processes in this postural muscle during 7-day hindlimb suspension. Such an effect of blocking IP3Rs during rat soleus muscle unloading may be due to preventing a decrease in ribosomal biogenesis and an increase in the expression of autophagy markers ULK-1 and IL-6. [ABSTRACT FROM AUTHOR]

Hypoxic preconditioning is known to protect against various functional disorders, including skeletal muscle dysfunction. Na,K-ATPase, which plays an important role in adaptation to hypoxia, is critical for maintaining the performance of skeletal muscles, which co-express the α1 and α2 isozymes of the enzyme. Persistent dysfunction of α2 Na,K-ATPase isozyme is characteristic of the motor inactivity of skeletal muscles. In this study, we tested our hypothesis that mild hypoxia is able to improve Na,K-ATPase in disused soleus muscle. Rats were subjected to simulated high-altitude (3000 m above sea level) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber. Then, 18 h after control or HH conditions, rats were subjected to 6 h of hindlimb suspension (HS), a model of skeletal muscle disuse. Isolated soleus muscles were tested. HH itself stably increased the α2 Na,K-ATPase isozyme membrane abundance and its electrogenic activity. These effects were accompanied by a decrease in serum level of circulating endogenous ouabain, a specific ligand for Na,K-ATPase. HS itself caused loss of electrogenic activity of α2 Na,K-ATPase, but pretreatment with HH protected against this impairment. This protective effect was accompanied by an increase in the α2 Na,K-ATPase membrane abundance without a change in total protein content, suggesting an increase in the α2 Na,K-ATPase traffic from the intracellular pool to the sarcolemma; serum ouabain level was significantly increased. We suggest that these findings open a new field for further studies and may have therapeutic implications for disuse-induced skeletal muscle pathology. [ABSTRACT FROM AUTHOR]

Muscle hyperemia in exercise is usually the combined result of increased cardiac output and local muscle vasodilation, with the latter reflecting muscle's capacity for increased blood perfusion to support exercise. In this study, we aim to quantify muscle's vasodilation capability with dynamic BOLD imaging. A deoxyhemoglobin-kinetics model is proposed to analyze dynamic BOLD signals acquired during exercise recovery, deriving a hyperemia index (HI) for a muscle group of interest. We demonstrated the method's validity with calf muscles of healthy subjects who performed plantar flexion for muscle stimulation. In a test with exercise load incrementally increasing from 0 to 16 lbs., gastrocnemius HI showed considerable variance among the 4 subjects, but with a consistent trend, i.e. low at light load (e.g. 0–6 lbs) and linearly increasing at heavy load. The high variability among different subjects was confirmed with the other 10 subjects who exercised with a same moderate load of 8 lbs., with coefficient of variance among subjects' medial gastrocnemius 87.8%, lateral gastrocnemius 111.8% and soleus 132.3%. These findings align with the fact that intensive exercise induces high muscle hyperemia, but a comparison among different subjects is hard to make, presumably due to the subjects' different rate of oxygen utilization. For the same 10 subjects who exercised with load of 8 lbs., we also performed dynamic contrast enhanced (DCE) MRI to measure muscle perfusion (F). With a moderate correlation of 0.654, HI and F displayed three distinctive responses of calf muscles: soleus of all the subjects were in the cluster of low F and low HI, and gastrocnemius of most subjects had high F and either low or high HI. This finding suggests that parameter F encapsulates blood flow through vessels of all sizes, but BOLD-derived HI focuses on capillary flow and therefore is a more specific indicator of muscle vasodilation. In conclusion, the proposed hyperemia index has the potential of quantitatively assessing muscle vasodilation induced with exercise. [ABSTRACT FROM AUTHOR]

Background and aims: Exercise training is employed as a practical method to combat muscle atrophy. The purpose of this study was to investigate the effects of high-intensity interval training (HIIT) conducted before and after hindlimb suspension (HLS) on the gene expression of MSTN and ActRIIB in the skeletal muscle of male Wistar rats. Methods: Thirty-two male rats, aged four to six months, were randomly divided into four groups (N=8 each): (1) control, (2) training-suspension-retraining, (3) non-training-suspension-retraining, and (4) training-suspension-non-training. The HIIT duration was five weeks, while the HLS lasted for two weeks. Gene expression levels were assessed using RT-PCR. Results: A significant decrease in the expression of MSTN and ActRIIB was observed in the soleus muscle of the group (2) compared to the other groups (p<0.05). There was also a notable reduction in MSTN expression in the extensor digitorum longus (EDL) muscle among the experimental groups relative to the control group (p<0.05), with the group (2) showing a greater effect than the others. Additionally, a significant decline in ActRIIB expression in the EDL muscle of the group (2) was noted compared to the other groups (p<0.05). The group (3) also exhibited a significant decrease in ActRIIB expression in the EDL muscle compared to the control group (p<0.05). Conclusion: The findings of this study suggest that the training-retraining approach (with HIIT) is particularly effective in mitigating muscle atrophy induced by HLS. These results highlight the HIIT training model as a highly efficient treatment method for preventing and reducing atrophy in rodent skeletal muscle. [ABSTRACT FROM AUTHOR]

We investigated the shuttling of Homer protein isoforms identified in soluble (cytosolic) vs. insoluble (membrane–cytoskeletal) fraction and Homer protein–protein interaction/activation in the deep postural calf soleus (SOL) and non-postural gastrocnemius (GAS) muscles of het−/− mice, i.e., mice with an autosomal recessive variant responsible for a vestibular disorder, in order to further elucidate a) the underlying mechanisms of disrupted vestibular system-derived modulation on skeletal muscle, and b) molecular signaling at respective neuromuscular synapses. Heterozygote mice muscles served as the control (CTR). An increase in Homer cross-linking capacity was present in the SOL muscle of het−/− mice as a compensatory mechanism for the altered vestibule system function. Indeed, in both fractions, different Homer immunoreactive bands were detectable, as were Homer monomers (~43–48 kDa), Homer dimers (~100 kDa), and several other Homer multimer bands (>150 kDA). The het−/− GAS particulate fraction showed no Homer dimers vs. SOL. The het−/− SOL soluble fraction showed a twofold increase (+117%, p ≤ 0.0004) in Homer dimers and multimers. Homer monomers were completely absent from the SOL independent of the animals studied, suggesting muscle-specific changes in Homer monomer vs. dimer expression in the postural SOL vs. the non-postural GAS muscles. A morphological assessment showed an increase (+14%, p ≤ 0.0001) in slow/type-I myofiber cross-sectional area in the SOL of het−/− vs. CTR mice. Homer subcellular immuno-localization at the neuromuscular junction (NMJ) showed an altered expression in the SOL of het−/−mice, whereas only not-significant changes were found for all Homer isoforms, as judged by RT-qPCR analysis. Thus, muscle-specific changes, myofiber properties, and neuromuscular signaling mechanisms share causal relationships, as highlighted by the variable subcellular Homer isoform expression at the instable NMJs of vestibular lesioned het−/− mice. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the influence of combined intermittent fasting (IF) and high‐intensity interval training (HIIT) on morphology, caspase‐independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty‐day‐old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high‐intensity‐interval training (T), and high‐intensity‐interval training and intermittent fasting (T‐IF). The C and T groups received ad libitum chow daily; IF and T‐IF received the same standard chow every other day. Animals from T and T‐IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro‐apoptotic proteins apoptosis‐inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved‐to‐non‐cleaved PARP‐1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved‐to‐total PARP‐1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross‐sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved‐to‐non‐cleaved PARP‐1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase‐independent apoptosis signaling. [ABSTRACT FROM AUTHOR]

The elimination of ground reaction force (support withdrawal) vastly affects slow postural muscles in terms of their regulation and structure. One of the effects of support withdrawal in this study was an immediate postural muscle inactivation, followed by the daily gradual development of spontaneous activity of the slow postural soleus muscle in response to rat hindlimb suspension to mimic space flight. The origin of this activity is somewhat akin to muscle spasticity after spinal cord injuries and is the result of KCC2 content decline in the spinal cord's motor neurons. However, the physiological consequences of unloading-induced spontaneous activity remain unexplored. We have conducted an experiment with the administration of a highly specific KCC2 activator during 7-day unloading. For this experiment, 32 male Wistar rats were divided into 4 groups: C+placebo, C+CLP-290 (100 mg/kg b w), 7HS+placebo, and 7HS+CLP—hindlimb-suspended group with CLP-290 administration (100 mg/kg b w). The soleus muscles of the animals were dissected and analyzed for several proteostasis- and metabolism-related parameters. CLP-290 administration to the unloaded animals led to the upregulation of AMPK downstream (p-ACC) and mTOR targets (p-p70S6k and p-4E-BP) and an enhanced PGC1alpha decrease vs. the 7HS group, but neither prevented nor enhanced atrophy of the soleus muscle or myofiber CSA. [ABSTRACT FROM AUTHOR]

Background and Objectives: Bedridden patients are at a high risk of venous thromboembolism (VTE). Passive devices such as elastic compression stockings and intermittent pneumatic compression are common. Leg exercise apparatus (LEX) is an active device designed to prevent VTE by effectively contracting the soleus muscle and is therefore expected to be effective in preventing disuse of the lower limbs. However, few studies have been conducted on the kinematic properties of LEX. Therefore, this study aimed to compare the exercise characteristics of LEX with those of an ergometer, which is commonly used as a lower-limb exercise device, and examine its effect on the two domains of muscle activity and circulatory dynamics. Materials and Methods: This study used a crossover design in which each participant performed both exercises to evaluate the exercise characteristics of each device. Fifteen healthy adults performed exercises with LEX and an ergometer (Terasu Erugo, SDG Co., Ltd., Tokyo, Japan) for 5 min each and rested for 10 min after each exercise. Muscle activity was measured using surface electromyography (Clinical DTS, Noraxon, Scottsdale, AZ, USA), and circulatory dynamics were recorded using a non-invasive impedance cardiac output meter (Physioflow Enduro, Manatec Biomedical, Paris, France). The primary outcome was the mean percentage of maximum voluntary contraction (%MVC) of the soleus muscle during exercise. Results: The mean %MVC of the soleus muscle was significantly higher in the LEX group, whereas no significant differences were observed across the periods and sequences. Heart rate, stroke volume, and cardiac output increased during exercise and decreased thereafter; however, the differences between the devices were not significant. Conclusions: LEX may not only have a higher thromboprophylaxis effect, but also a higher effect on preventing muscle atrophy as a lower-extremity exercise device. Additionally, LEX could potentially be used safely in patients who need to be monitored for changes in circulatory dynamics. [ABSTRACT FROM AUTHOR]