Antioxidant Activity of Valeriana fauriei Protects against Dexamethasone-Induced Muscle Atrophy

Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.

circTAF8 Regulates Myoblast Development and Associated Carcass Traits in Chicken

Recent studies have shown that circular RNAs (circRNAs) play important roles in skeletal muscle development. CircRNA biogenesis is dependent on the genetic context. Single-nucleotide polymorphisms in the introns flanking circRNAs may be intermediate-inducible factors between circRNA expression and phenotypic traits. Our previous study showed that circTAF8 is an abundantly and differentially expressed circRNA in leg muscle during chicken embryonic development. Here, we aimed to investigate circTAF8 function in muscle development and the association of the SNPs in the circTAF8 flanking introns with carcass traits. In this study, we observed that overexpression of circTAF8 could promote the proliferation of chicken primary myoblasts and inhibit their differentiation. In addition, the SNPs in the introns flanking the circTAF8 locus and those associated with chicken carcass traits were analyzed in 335 partridge chickens. A total of eight SNPs were found associated with carcass traits such as leg muscle weight, live weight, and half and full-bore weight. The association analysis results of haplotype combinations were consistent with the association analysis of a single SNP. These results suggest that circTAF8 plays a regulatory role in muscle development. These identified SNPs were found correlated with traits to muscle development and carcass muscle weight in chickens.

Fermented Antler Recovers Stamina, Muscle Strength and Muscle Mass in Middle-Aged Mice

In a previous study, we found that Lactobacillus curvatus HY7602-fermented antler (FA) improved exercise endurance by increasement of muscle mass and strength in a young mouse model. In this study, we investigated the effect of FA on recovery of muscle mass and strength in aging-induced muscle loss. We have used a middle-aged model in which muscle decline begins in many mammalian species. All mice performed treadmill exercise and forced swimming, and measured muscle grip strength. Then, calf muscle weight and histological analysis, blood biomarker and gene expression in soleus muscle tissue were measured. Muscle strength and forced swimming time were significantly increased in the FA-intake groups compared to controls. The levels of muscle and liver damage-related indicators (ATL, ALP, LDH and CK) and muscle endurance, fatigue and exercise performance-related indicators (lactate and creatinine) were significantly improved by FA supplementation. In addition, FA regulates genes related to muscle protein degradation (Atrogin-1 and MuRF1) and muscle fiber synthesis (MyoD and Myf5), resulting in increased muscle mass, and fiber diameter and area values. The Bax/Bcl-2 ratio, related to apoptosis in skeletal muscle was significantly decreased. These results demonstrate that FA improves exercise performance with ameliorating blood biomarkers and also increases muscle mass and muscle strength by inhibiting muscle proteolysis and promoting muscle synthesis in a middle-aged mouse.

Large-Scale Whole Genome Sequencing Study Reveals Genetic Architecture and Key Variants for Breast Muscle Weight in Native Chickens

Breast muscle weight (BrW) is one of the most important economic traits in chicken, and directional breeding for that results in both phenotypic and genetic changes. The Jingxing yellow chicken, including an original (without human-driven selection) line and a selected line (based on selection for increased intramuscular fat content), were used to dissect the genetic architecture and key variants associated with BrW. We detected 1069 high-impact single nucleotide polymorphisms (SNPs) with high conserved score and significant frequency difference between two lines. Based on the annotation result, the ECM-receptor interaction and fatty acid biosynthesis were enriched, and muscle-related genes, including MYOD1, were detected. By performing genome-wide association study for the BrW trait, we defined a major haplotype and two conserved SNPs that affected BrW. By integrated genomic and transcriptomic analysis, IGF2BP1 was identified as the crucial gene associated with BrW. In conclusion, these results offer a new insight into chicken directional selection and provide target genetic markers by which to improve chicken BrW.

Nerve recovery from treatment with a vascularized nerve graft compared to an autologous non-vascularized nerve graft in animal models: A systematic review and meta-analysis

Background Treatment of nerve injuries proves to be a worldwide clinical challenge. Vascularized nerve grafts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous non-vascularized nerve graft. However, there is no adequate clinical evidence for the beneficial effect of vascularized nerve grafts and they are still disputed in clinical practice. Objective To systematically review whether vascularized nerve grafts give a superior nerve recovery compared to non-vascularized nerve autografts regarding histological and electrophysiological outcomes in animal models. Material and methods PubMed and Embase were systematically searched. The inclusion criteria were as follows: 1) the study was an original full paper which presented unique data; 2) a clear comparison between a vascularized and a non-vascularized autologous nerve transfer was made; 3) the population study were animals of all genders and ages. A standardized mean difference and 95% confidence intervals for each comparison was calculated to estimate the overall effect. Subgroup analyses were conducted on graft length, species and time frames. Results Fourteen articles were included in this review and all were included in the meta-analyses. A vascularized nerve graft resulted in a significantly larger diameter, higher nerve conduction velocity and axonal count compared to an autologous non-vascularized nerve graft. However, during sensitivity analysis the effect on axonal count disappeared. No significant difference was observed in muscle weight. Conclusion Treating a nerve gap with a vascularized graft results in superior nerve recovery compared to non-vascularized nerve autografts in terms of axon count, diameter and nerve conduction velocity. No difference in muscle weight was seen. However, this conclusion needs to be taken with some caution due to the inherent limitations of this meta-analysis. We recommend future studies to be performed under conditions more closely resembling human circumstances and to use long nerve defects.

Systemic Supplementation of Collagen VI by Neonatal Transplantation of iPSC-Derived MSCs Improves Histological Phenotype and Function of Col6-Deficient Model Mice

Collagen VI is distributed in the interstitium and is secreted mainly by mesenchymal stromal cells (MSCs) in skeletal muscle. Mutations in COL6A1-3 genes cause a spectrum of COL6-related myopathies. In this study, we performed a systemic transplantation study of human-induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) into neonatal immunodeficient COL6-related myopathy model (Col6a1KO/NSG) mice to validate the therapeutic potential. Engraftment of the donor cells and the resulting rescued collagen VI were observed at the quadriceps and diaphragm after intraperitoneal iMSC transplantation. Transplanted mice showed improvement in pathophysiological characteristics compared with untreated Col6a1KO/NSG mice. In detail, higher muscle regeneration in the transplanted mice resulted in increased muscle weight and enlarged myofibers. Eight-week-old mice showed increased muscle force and performed better in the grip and rotarod tests. Overall, these findings support the concept that systemic iMSC transplantation can be a therapeutic option for COL6-related myopathies.

Indole-3-Propionic Acid, a Functional Metabolite of Clostridium sporogenes, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation

Clostridium sporogenes (C. sporogenes), as a potential probiotic, metabolizes tryptophan and produces an anti-inflammatory metabolite, indole-3-propionic acid (IPA). Herein, we studied the effects of C. sporogenes and its bioactive metabolite, IPA, on skeletal muscle development and chronic inflammation in mice. In the in vivo study, the muscle tissues and serum samples of mice with C. sporogenes supplementation were used to analyze the effects of C. sporogenes on muscle metabolism; the IPA content was determined by metabonomics and ELISA. In an in vitro study, C2C12 cells were exposed to lipopolysaccharide (LPS) alone or LPS + IPA to verify the effect of IPA on muscle cell inflammation by transcriptome, and the involved mechanism was revealed by different functional assays. We observed that C. sporogenes colonization significantly increased the body weight and muscle weight gain, as well as the myogenic regulatory factors’ (MRFs) expression. In addition, C. sporogenes significantly improved host IPA content and decreased pro-inflammatory cytokine levels in the muscle tissue of mice. Subsequently, we confirmed that IPA promoted C2C12 cells’ proliferation by activating MRF signaling. IPA also effectively protected against LPS-induced C2C12 cells inflammation by activating Pregnane X Receptor and restoring the inhibited miR-26a-2-3p expression. miR-26a-2-3p serves as a novel muscle inflammation regulatory factor that could directly bind to the 3′-UTR of IL-1β, a key initiator factor in inflammation. The results suggested that C. sporogenes with its functional metabolite IPA not only helps muscle growth development, but also protects against inflammation, partly by the IPA/ miR-26a-2-3p /IL-1β cascade.

Ameliorating Effects of Coriander on Gastrocnemius Muscles Undergoing Precachexia in a Rat Model of Rheumatoid Arthritis: A Proteomics Analysis

Coriander is a commonly used vegetable, spice, and folk medicine, possessing both nutritional and medicinal properties. Up to two-thirds of patients with rheumatoid arthritis (RA) exhibit loss of body mass, predominately skeletal muscle mass, a process called rheumatoid cachexia, and this has major effects of the quality of life of patients. Owing to a lack of effective treatments, the initial stage of cachexia has been proposed as an important period for prevention and decreasing pathogenesis. In the current study, we found that cachexia-like molecular disorders and muscle weight loss were in progress in gastrocnemius muscle after only 5 days of RA induction in rats, although rheumatoid cachexia symptoms have been reported occurring approximately 45 days after RA induction. Oral administration of coriander slightly restored muscle loss. Moreover, iTRAQ-based quantitative proteomics revealed that coriander treatment could partially restore the molecular derangements induced by RA, including impaired carbon metabolism, deteriorated mitochondrial function (tricarboxylic acid cycle and oxidative phosphorylation), and myofiber-type alterations. Therefore, coriander could be a promising functional food and/or complementary therapy for patients with RA against cachexia.

Carbon-nanotube yarns induce axonal regeneration in peripheral nerve defect

Carbon nanotubes (CNTs) are cylindrical nanostructures and have unique properties, including flexibility, electrical conductivity, and biocompatibility. We focused on CNTs fabricated with the carbon nanotube yarns (cYarn) as a possible substrate promoting peripheral nerve regeneration with these properties. We bridged a 15 mm rat sciatic nerve defect with five different densities of cYarn. Eight weeks after the surgery, the regenerated axons crossing the CNTs, electromyographical findings, and muscle weight ratio of the lower leg showed recovery of the nerve function by interfacing with cYarn. Furthermore, the sciatic nerve functional index (SFI) at 16 weeks showed improvement in gait function. A 2% CNT density tended to be the most effective for nerve regeneration as measured by both histological axonal regeneration and motor function. We confirmed that CNT yarn promotes peripheral nerve regeneration by using it as a scaffold for repairing nerve defects. Our results support the future clinical application of CNTs for bridging nerve defects as an off-the-shelf material.