Aster glehni Extract, Including Caffeoylquinic Acids as the Main Constituents, Induces PPAR ß/δ-Dependent Muscle-Type Change and Myogenesis in Apolipoprotein E Knockout Mice.

To probe the functions of Aster glehni (AG) extract containing various caffeoylquinic acids on dyslipidemia, obesity, and skeletal muscle-related diseases focused on the roles of skeletal muscle, we measured the levels of biomarkers involved in oxidative phosphorylation and type change of skeletal muscle in C2C12 cells and skeletal muscle tissues from apolipoprotein E knockout (ApoE KO) mice. After AG extract treatment in cell and animal experiments, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to estimate the levels of proteins that participated in skeletal muscle type change and oxidative phosphorylation. AG extract elevated protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor beta/delta (PPARß/δ), myoblast determination protein 1 (MyoD), and myoglobin in skeletal muscle tissues. Furthermore, it elevated the ATP concentration. However, protein expression of myostatin was decreased by AG treatment. In C2C12 cells, increments of MyoD, myoglobin, myosin, ATP-producing pathway, and differentiation degree by AG were dependent on PPARß/δ and caffeoylquinic acids. AG extract can contribute to the amelioration of skeletal muscle inactivity and sarcopenia through myogenesis in skeletal muscle tissues from ApoE KO mice, and function of AG extract may be dependent on PPARß/δ, and the main functional constituents of AG are trans-5-O-caffeoylquinic acid and 3,5-O-dicaffeoylquinic acid. In addition, in skeletal muscle, AG has potent efficacies against dyslipidemia and obesity through the increase of the type 1 muscle fiber content to produce more ATP by oxidative phosphorylation in skeletal muscle tissues from ApoE KO mice.

GNE deficiency impairs Myogenesis in C2C12 cells and cannot be rescued by ManNAc supplementation.

GNE myopathy (GNEM) is a late-onset muscle atrophy, caused by mutations in the gene for the key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). With an incidence of one to nine cases per million it is an ultra-rare, so far untreatable, autosomal recessive disease. Several attempts have been made to treat GNEM patients by oral supplementation with sialic acid precursors (e.g. N-acetylmannosamine, ManNAc) to restore sarcolemmal sialylation and muscle strength. In most studies, however, no significant improvement was observed. The lack of a suitable mouse model makes it difficult to understand the exact pathomechanism of GNEM and many years of research have failed to identify the role of GNE in skeletal muscle due to the lack of appropriate tools. We established a CRISPR/Cas9-mediated Gne-knockout cell line using murine C2C12 cells to gain insight into the actual role of the GNE enzyme and sialylation in a muscular context. The main aspect of this study was to evaluate the therapeutic potential of ManNAc and N-acetylneuraminic acid (Neu5Ac). Treatment of Gne-deficient C2C12 cells with Neu5Ac, but not with ManNAc, showed a restoration of the sialylation level back to wild type levels-albeit only with long-term treatment, which could explain the rather low therapeutic potential. We furthermore highlight the importance of sialic acids on myogenesis, for C2C12 Gne-knockout myoblasts lack the ability to differentiate into mature myotubes.

Effect of Zinc Amino Acid Complexes on Growth Performance, Tissue Zinc Concentration, and Muscle Development of Broilers.

The present study aimed to evaluate the effects of zinc amino acid complexes on growth performance, tissue zinc concentration, and muscle development in broilers. A total of 504 day-old male arbor acres broilers were randomly divided into seven treatments (fed with a basal diet or a basal diet supplemented with 120 mg kg-1 Zn as ZnSO4, 30, 60, 90 or 120 mg kg-1 Zn as ZnN, or 30 mg kg-1 Zn as ZnA separately). Each group had six replicates, with 12 birds per replicate. The results showed that the addition of 60 mg kg-1 ZnN significantly increased (P < 0.05) the average daily gain (ADG) and breast muscle percentage of broilers. Zinc concentration of ZnN and ZnA added groups were higher than (P < 0.05) that in the Zn sulfate group under the same addition dose. Except for the 30 mg kg-1 ZnN group, the muscle fiber diameter and cross-sectional area (CSA) were significantly increased (P < 0.05) in the ZnN addition groups. Compared with the basal diet group, adding ZnN significantly increased (P < 0.05) the expression of MTOR, MYOD, and MYOG at day 21 and decreased (P < 0.05) the expression of Atrogin-1. The expression levels of AKT, MTOR, P70S6K, and MYOD were increased at day 42, while the expression levels of MuRF1 and Atrogin-1 were decreased. Adhesion, backbone regulation of actin, MAPK, mTOR, and AMPK were significantly enriched as indicated by KEGG pathway enrichment analysis. In conclusion, zinc amino acid complexes could improve growth performance, tissue zinc concentration, and regulate breast muscle development.

Protective effects of hachimijiogan (HJG), a Japanese Kampo medicine, on cancer cachectic muscle wasting in mice.

Myogenesis is required to generate skeletal muscle tissue and to maintain skeletal muscle mass. Decreased myogenesis under various pathogenic conditions results in muscular atrophy. Through a small screening of Japanese traditional (Kampo) medicines, hachimijiogan (HJG) was shown to promote the myogenic differentiation of C2C12 myoblasts through the upregulation of myogenin. In tumor-bearing cancer-cachectic mice, HJG was also found to have a protective effect against cancer-cachectic muscle wasting. This effect was significant when HJG was administered in combination with aerobic exercise by treadmill running. Moreover, HJG ameliorated the cellular atrophy of C2C12 myotubes induced by treatment with conditioned medium derived from a colon-26 cancer cell culture. In addition, HJG suppressed H2O2-dependent myotube atrophy, suggesting that HJG could reverse the atrophic phenotypes by eliminating reactive oxygen species.

Vitamin D3 decreases myoblast fusion during the growth and increases myogenic gene expression during the differentiation phase in muscle satellite cells from Korean native beef cattle.

The process of myogenesis, which involves the growth and differentiation of muscle cells, is a crucial determinant of meat yield and quality in beef cattle. Essential nutrients, such as vitamins D and A, play vital roles in the development and maintenance of various tissues, including muscle. However, limited knowledge exists regarding the specific effects of vitamins A and D in bovine muscle. Therefore, the aim of this study was to investigate the impact of vitamins A and D treatment on myogenic fusion and differentiation in bovine satellite cells (BSC). BSC were isolated from Korean native beef cattle, specifically from four female cows approximately 30 mo old. These individual cows were used as biological replicates (n = 3 or 4), and we examined the effects of varying concentrations of vitamins A (All-trans retinoic acid; 100 nM) and D (1,25-dihydroxy-vitamin D3; 1 nM, 10 nM, and 100 nM), both individually and in combination, on myoblast fusion and myogenic differentiation during the growth phase (48 h) or differentiation phase (6 d). The results were statistically analyzed using GLM procedure of SAS with Tukey's test and t-tests or one-way ANOVA where appropriate. The findings revealed that vitamin A enhanced the myoblast fusion index, while vitamin D treatment decreased the myoblast fusion index during the growth phase. Furthermore, vitamin A treatment during the differentiation phase promoted terminal differentiation by regulating the expression of myogenic regulatory factors (Myf5, MyoD, MyoG, and Myf6) and inducing myotube hypertrophy compared to the control satellite cells (P < 0.01). In contrast, vitamin D treatment during the differentiation phase enhanced myogenic differentiation by increasing the mRNA expression of MyoG and Myf6 (P < 0.01). Moreover, the combined treatment of vitamins A and D during the growth phase increased myoblast fusion and further promoted myogenic differentiation and hypertrophy of myotubes during the differentiation phase (P < 0.01). These results suggest that vitamin A and D supplementation may have differential effects on muscle development in Korean native beef cattle during the feeding process.

The study investigated the effects of vitamins A and D on the growth and differentiation phases of bovine satellite cells and found that both vitamins have a positive impact on muscle development. Vitamin A promoted myoblast fusion during the growth phase, leading to increased myotube formation, while vitamin D suppressed myoblast fusion during this phase. However, during the differentiation phase, both vitamins enhanced terminal differentiation and hypertrophy. Vitamin A promoted the activation of satellite cells, while vitamin D promoted the expression of genes that enhance myogenesis. The combination treatment of vitamins A and D during the growth phase complemented each other to increase myogenic cell fusion, and during differentiation, promoted terminal differentiation and hypertrophy. These findings suggest that supplementing cattle feed with both vitamins A and D has the potential to enhance muscle development, which would be advantageous for the meat industry.

Supplemental Clostridium butyricum modulates skeletal muscle development and meat quality by shaping the gut microbiota of lambs.

This study evaluated the contributions of Clostridium butyricum on skeletal muscle development, gastrointestinal flora and meat quality of lambs. Eighteen Dorper (♂) × Small Tailed Han sheep (♀) crossed ewe lambs of similar weight (27.43 ± 1.94 kg; age, 88 ± 5 days) were divided into two dietary treatments. The control group was fed the basal diet (C group), and the probiotic group was supplemented with C. butyricum on the basis of the C group (2.5 × 108 cfu/g, 5 g/day/lamb; P group) for 90 d. The results showed that dietary C. butyricum elevated growth performance, muscle mass, muscle fiber diameter and cross-sectional area, and decreased the shear force value of meat (P < 0.05). Moreover, C. butyricum supplementation accelerated protein synthesis by regulating the gene expression of IGF-1/Akt/mTOR pathway. We identified 54 differentially expressed proteins that regulated skeletal muscle development through different mechanisms by quantitative proteomics. These proteins were associated with ubiquitin-protease, apoptosis, muscle structure, energy metabolism, heat shock, and oxidative stress. The metagenomics sequencing results showed that Petrimonas at the genus level and Prevotella brevis at the species level in the rumen, while Lachnoclostridium, Alloprevotella and Prevotella at the genus level in the feces, were significantly enriched in the P group. Also, butyric acid and valeric acid levels were elevated in both rumen and feces of the P group. Overall, our results support the idea that C. butyricum could change gastrointestinal flora, and affect skeletal muscle development and meat quality of lambs by modulating gut-muscle axis.

Protective effects of chlorogenic acid on growth, intestinal inflammation, hepatic antioxidant capacity, muscle development and skin color in channel catfish Ictalurus punctatus fed an oxidized fish oil diet.

Under oxidative stress condition, the protective effects of dietary chlorogenic acid (CGA) supplementation on liver antioxidant capacity, intestinal inflammation and barrier function, muscle development and skin coloration in channel catfish Ictalurus punctatus were explored in the current study. With that purpose, I. punctatus were fed five experimental diets containing 2% fresh fish oil (FFO, 9.2 meqO2/kg) or 2% oxidized fish oil (OFO, 897.4 meqO2/kg) without or with CGA supplementation (0.02%, 0.04% and 0.08%) for 8 weeks. Upon comparative analysis, the oxidized fish oil consumption significantly lowered weight gain rate, decreased intestinal villi length and muscular thickness values and the tight junction proteins mRNA abundance, augmented the intestinal proinflammatory factors, attenuated hepatic antioxidant enzymes activities and related genes mRNA expression levels, influenced the myogenic regulatory factors expression profile and impacted the myocyte density, myocyte area values as well as the skin pigments contents compared to the FFO treatment. Collectively, long-term feeding of the oxidized fish oil diet suppressed the growth performance, destroyed intestinal structural integrity, caused intestinal inflammation and hepatic oxidative stress, impacted the skeletal development and skin color of I. punctatus. Whereas CGA supplementation in oxidized fish oil diets partially counteracted the negative effects of the oxidized fish oil on I. punctatus in terms of increasing the growth performance, improving the intestinal mucosal structure, alleviating hepatic oxidative stress and intestinal inflammation, recompiling the myogenic regulatory factors expression and improving skin color. In conclusion, CGA has great potential to be an aquatic feed additive.

Myogenesis and Analysis of Antimicrobial Potential of Silver Nanoparticles (AgNPs) against Pathogenic Bacteria.

The widespread and indiscriminate use of broad-spectrum antibiotics leads to microbial resistance, which causes major problems in the treatment of infectious diseases. However, advances in nanotechnology have opened up new domains for the synthesis and use of nanoparticles against multidrug-resistant pathogens. The traditional approaches for nanoparticle synthesis are not only expensive, laborious, and hazardous but also have various limitations. Therefore, new biological approaches are being designed to synthesize economical and environmentally friendly nanoparticles with enhanced antimicrobial activity. The current study focuses on the isolation, identification, and screening of metallotolerant fungal strains for the production of silver nanoparticles, using antimicrobial activity analysis and the characterization of biologically synthesized silver nanoparticles by X-ray diffraction (XRD) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM). In total, 11 fungal isolates were isolated and screened for the synthesis of AgNPs, while the Penicillium notatum (K1) strain was found to be the most potent, demonstrating biosynthetic ability. The biologically synthesized silver nanoparticles showed excellent antibacterial activity against the bacteria Escherichia coli (ATCC10536), Bacillus subtilis, Staphylococcus aureus (ATCC9144), Pseudomonas aeruginosa (ATCC10145), Enterococcus faecalis, and Listeria innocua (ATCC13932). Furthermore, three major diffraction peaks in the XRD characterization, located at the 2θ values of 28.4, 34.8, 38.2, 44, 64, and 77°, confirmed the presence of AgNPs, while elemental composition analysis via EDX and spherical surface topology with a scanning electron microscope indicated that its pure crystalline nature was entirely composed of silver. Thus, the current study indicates the enhanced antibacterial capability of mycologically synthesized AgNPs, which could be used to counter multidrug-resistant pathogens.

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy.

To find inhibitors against skeletal muscle loss, we isolated a lignan compound ((-)-(2R,3R-1,4-O-diferuloylsecoisolarciresinol, DFS) from the stem of Alnus japonica. C2C12 myoblasts were treated with DFS during differentiation. To induce an in vitro atrophic condition, differentiated myotubes were treated with dexamethasone (a synthetic glucocorticoid). DFS (10 nM) increased expression levels of myogenic factors and the number of multi-nucleated myotubes expressing myosin heavy chain (MHC). The myogenic potential of DFS could be attributed to p38 MAPK activation. DFS also protected against dexamethasone-induced damage, showing increased expression of MHC and mammalian target of rapamycin (mTOR), a major anabolic factor. Under atrophic condition, the anti-myopathy effect of DFS was associated with inactivation of NF-κB signaling pathway and the subsequent suppression of muscle degradative E3 ligases and myostatin. DFS treatment also restored fast muscle fiber (type II a, II b, and II x), known to be susceptible to dexamethasone. These results indicate that DFS isolated from A. japonica can stimulate myogenesis via p38 MAPK activation and alleviate muscle atrophy by modulating the expression of genes associated with muscle protein anabolism/catabolism. Thus, we propose that DFS can be used as a pharmacological and nutraceutical agent for increasing muscle strength or protecting muscle loss.

Hyperpigmentation Inhibits Early Skeletal Muscle Development in Tengchong Snow Chicken Breed.

Tengchong snow, which has white feathers and black meat, is one of the most important black-bone chicken breeds and a genetic treasure of black food in China. Although the black meat traits are dominant, there are some chickens with white meat traits born in the process of folk selection and breeding. The purpose of this study was to compare the differences in skeletal muscle development between Tengchong snow black meat chickens (BS) and white meat chickens (WS), as well as whether excessive melanin deposition has an effect on skeletal muscle development. The BS and WS groups were selected to determine their muscle development difference at stages of 1, 7, 14, 21, and 42 days, using histological stain methods to analyze the development and composing type of breast and leg muscle fibers, as well as the count of melanin in BS muscle fibers. Finally, we were validated key candidate genes associated with muscle development and melanin synthesis. The results showed that BS breast muscle development was inhibited at 7, 14, and 21 days, while the leg muscle was inhibited at 7, 14, 21, and 42 days, compared to WS. Melanin deposition was present in a temporal migration pattern and was greater in the leg muscles than in the breast muscles, and it focused around blood vessels, as well as the epithelium, perimysium, endomysium, and connective tissue. Additionally, melanin produced an inhibitory effect similar to MSTN during skeletal muscle fiber development, and the inhibition was strongest at the stage of melanin entry between muscle fibers, but the precise mechanisms need to be confirmed. This study revealed that melanin has an inhibitory effect on the early development of skeletal muscle, which will provide new insights into the role of melanin in the black-boned chicken and theoretical references for the future conservation and utilization of black-boned chicken.

Effects of Vitamin D on Satellite Cells: A Systematic Review of In Vivo Studies.

The non-classical role of vitamin D has been investigated in recent decades. One of which is related to its role in skeletal muscle. Satellite cells are skeletal muscle stem cells that play a pivotal role in skeletal muscle growth and regeneration. This systematic review aims to investigate the effect of vitamin D on satellite cells. A systematic search was performed in Scopus, MEDLINE, and Google Scholar. In vivo studies assessing the effect of vitamin D on satellite cells, published in English in the last ten years were included. Thirteen in vivo studies were analyzed in this review. Vitamin D increases the proliferation of satellite cells in the early life period. In acute muscle injury, vitamin D deficiency reduces satellite cells differentiation. However, administering high doses of vitamin D impairs skeletal muscle regeneration. Vitamin D may maintain satellite cell quiescence and prevent spontaneous differentiation in aging. Supplementation of vitamin D ameliorates decreased satellite cells' function in chronic disease. Overall, evidence suggests that vitamin D affects satellite cells' function in maintaining skeletal muscle homeostasis. Further research is needed to determine the most appropriate dose of vitamin D supplementation in a specific condition for the optimum satellite cells' function.

Transcriptome analysis reveals the molecular regulatory network of muscle development and meat quality in Sunit lamb supplemented with dietary probiotic.

Supplementing animal feed with probiotic additives can promote muscle production and improve meat quality. The study aimed to explore the effects of dietary probiotics supplementation on the performance, meat quality and muscle transcriptome profile in Sunit lamb. Overall, feeding probiotics significantly increased the body length, LT area, pH24h and intramuscular fat (IMF) content, but decreased cooking loss and meat shear force compared to the control group (P < .05). A total of 651 differentially expressed genes (DEGs) were found in probiotic supplemented lambs. Pathway analysis revealed that DEGs were involved in multiple pathways related to muscle development and fat deposition, such as the ECM-receptor interactions, the MAPK signaling pathway and the FoxO signaling pathway. Therefore, dietary probiotic supplementation can improve muscle development and final meat quality in Sunit lambs by altering gene expression profiles associated with key pathways, providing unique insights into the molecular mechanisms by which dietary probiotics regulate muscle development in the lamb industry.

Identification and Evaluation of Traditional Chinese Medicine Natural Compounds as Potential Myostatin Inhibitors: An In Silico Approach.

Myostatin (MSTN), a negative regulator of muscle mass, is reported to be increased in conditions linked with muscle atrophy, sarcopenia, and other muscle-related diseases. Most pharmacologic approaches that treat muscle disorders are ineffective, emphasizing the emergence of MSTN inhibition. In this study, we used computational screening to uncover natural small bioactive inhibitors from the Traditional Chinese Medicine database (~38,000 compounds) for the MSTN protein. Potential ligands were screened, based on binding affinity (150), physicochemical (53) and ADMET properties (17). We found two hits (ZINC85592908 and ZINC85511481) with high binding affinity and specificity, and their binding patterns with MSTN protein. In addition, molecular dynamic simulations were run on each complex to better understand the interaction mechanism of MSTN with the control (curcumin) and the hit compounds (ZINC85592908 and ZINC85511481). We determined that the hits bind to the active pocket site (Helix region) and trigger conformational changes in the MSTN protein. Since the stability of the ZINC85592908 compound was greater than the MSTN control, we believe that ZINC85592908 has therapeutic potential against the MSTN protein and may hinder downstream singling by inhibiting the MSTN protein and increasing myogenesis in the skeletal muscle tissues.

Effects of in ovo injection of nicotinamide riboside on high-yield broiler myogenesis.

The objective of this study was to determine the effects of in ovo injection of high-yield broiler embryos with nicotinamide riboside (NR) on pectoralis major muscle (PMM) development, growth, and gene expression. Fertilized Cobb 700 broiler eggs were randomly assigned to one of four treatments within a 2 × 2 factorial design. Factor 1 consisted of NR dose (DOS) with eggs receiving 0 or 2.5 mM NR. Factor 2 consisted of injection location (LOC), with treatments injected into either the yolk sac or albumen. At day 10 of incubation, 100 µL of the assigned NR dose was injected into the yolk sac of the developing embryo and chicks were euthanized within 24 h of hatching. Chick PMM and individual fiber morphometrics, and expression of genes associated with cell cycle progression were analyzed. There were DOS × LOC interactions for hatched chick PM weight and length (P < 0.04). When NR was injected into the albumen, PMM weight decreased (P < 0.05); when NR was injected into the yolk, PMM weight increased (P < 0.05). Pectoralis major length was not affected (P > 0.05) when NR was injected into the albumen but was increased (P < 0.05) when NR was injected into the yolk. There was a DOS × LOC interaction (P = 0.04) for muscle fiber density and tended to be a DOS × LOC interaction (P = 0.07) for muscle fiber CSA. Pectoralis major muscle fiber density was not affected when NR was injected into the albumen (P > 0.05), but density increased when NR was injected into the yolk (P < 0.05). There were DOS × LOC interactions for hatched chick COXII, cyclin D, and SIRT1 expression (P ≤ 0.04), which may indicate NR improves skeletal muscle development and growth by enhancing myoblast proliferation during embryonic development.

Broiler chicken weight gain is a result of genetics and nutrition, with increased muscle mass attributed to accelerated embryonic myogenesis and posthatch muscle growth. During the avian incubation period, in ovo injection may be used as a strategy to deliver exogenous supplements into growing embryos for improving skeletal muscle development and growth. Nicotinamide riboside (NR), a vitamin B3 analog, is a human performance supplement used to stimulate mitochondria biogenesis and elevate tissue NAD+ levels. Research showed injecting NR into the chick embryonic yolk sac increased breast muscle weight and muscle satellite cell numbers and proliferation rate. Therefore, our objective was to determine the effects of in ovo injection of high-yield broilers with NR on broiler breast muscle development and growth. Our study showed in ovo injection of NR into the yolk sac increased hatched chick breast muscle morphometrics, which coincided with an increase in muscle fiber density and tended to decrease fiber cross-sectional area. Increased Sirtuin1 and cyclin D mRNA expression of hatched chicks from eggs injected with 2.5 mM NR into yolk sac indicate a potential NR regulated Sirtuin1/cyclin D molecular mechanism mediating chicken muscle early development.

Vitamin C Promotes Muscle Development Mediated by the Interaction of CSRP3 with MyoD and MyoG.

Previous studies have reported that vitamin C (VC), an essential nutrient, exerts beneficial effects on muscle health. However, the molecular mechanism involved in the VC-mediated regulation of muscle development is still unclear. The roles of VC in muscle development and the underlying molecular mechanisms were examined using cell and molecular biology, transcriptomics, proteomics, and animal experiments in this study. VC upregulated the expression of sodium-dependent vitamin C transporter 2 (SVCT2) and cysteine rich protein 3 (CSRP3). Additionally, VC promoted the differentiation of C2C12 cells and the repair of mouse muscle injury by upregulating the nuclear translocation of CSRP3, which subsequently interacted with MyoD and MyoG. This study provided a theoretical basis for elucidating the mechanism underlying the VC-mediated regulation of muscle development, as well as for developing animal nutritional supplements and therapeutic drugs for muscle diseases.

Decapeptide from Potato Hydrolysate Induces Myogenic Differentiation and Ameliorates High Glucose-Associated Modulations in Protein Synthesis and Mitochondrial Biogenesis in C2C12 Cells.

Sarcopenia is characterized as an age-related loss of muscle mass that results in negative health consequences such as decreased strength, insulin resistance, slowed metabolism, increased body fat mass, and a substantially diminished quality of life. Additionally, conditions such as high blood sugar are known to further exacerbate muscle degeneration. Skeletal muscle development and regeneration following injury or disease are based on myoblast differentiation. Bioactive peptides are biologically active peptides found in foods that could have pharmacological functions. The aim of this paper was to investigate the effect of decapeptide DI-10 from the potato alcalase hydrolysate on myoblast differentiation, muscle protein synthesis, and mitochondrial biogenesis in vitro. The treatment of C2C12 myoblasts with DI-10 (10 µg/mL) did not induce cell death. DI-10 treatment in C2C12 myoblast cells accelerates the phosphorylation of promyogenic kinases such as ERK, Akt and mTOR proteins in a dose-dependent manner. DI-10 improves myotubes differentiation and upregulates the expression of myosin heavy chain (MyHC) protein in myoblast cells under differentiation medium with high glucose. DI-10 effectively increased the phosphorylation of promyogenic kinases Akt, mTOR, and mitochondrial-related transcription factors AMPK and PGC1α expression under hyperglycemic conditions. Further, decapeptide DI-10 decreased the expression of Murf1 and MAFbx proteins, which are involved in protein degradation and muscle atrophy. Our reports support that decapeptide DI-10 could be potentially used as a therapeutic candidate for preventing muscle degeneration in sarcopenia.

Effects of photobiomodulation therapy on regulation of myogenic regulatory factor mRNA expression in vivo: A systematic review.

Non-invasive promotion of myogenic regulatory factors (MRFs), through photobiomodulation therapy (PBMT), may be a viable method of facilitating skeletal muscle regeneration post-injury, given the importance of MRF in skeletal muscle regeneration. The aim of this systematic review was to collate current evidence, identifying key themes and changes in expression of MRF in in vivo models. Web of Science, PubMed, Scopus and Cochrane databases were systematically searched and identified 1459 studies, of which 10 met the inclusion criteria. Myogenic determination factor was most consistently regulated in response to PBMT treatment, and the expression of remaining MRFs was heterogenous. All studies exhibited a high risk of bias, primarily due to lack of blinding in PBMT application and MRF analysis. Our review suggests that the current evidence base for MRF expression from PBMT is highly variable. Future research should focus on developing a robust methodology for determining the effect of laser therapy on MRF expression, as well as long-term assessment of skeletal muscle regeneration.

RGD-pectin microfiber patches for guiding muscle tissue regeneration.

Opportunely arranged microscaled fibers offer an attractive 3D architecture for tissue regeneration as they may enhance and stimulate specific tissue regrowth. Among different scaffolding options, encapsulating cells in degradable hydrogel microfibers appears as particularly attractive strategy. Hydrogel patches, in fact, offer a highly hydrated environment, allow easy incorporation of biologically active molecules, and can easily adapt to implantation site. In addition, microfiber architecture is intrinsically porous and can improve mass transport, vascularization, and cell survival after grafting. Anionic polysaccharides, as pectin or the more popular alginate, represent a particularly promising choice for the fabrication of cell-laden patches, due to their extremely mild gelation in the presence of divalent ions and widely accepted biocompatibility. In this study, to combine the favorable properties of hydrogel and fibrous architecture, a simple coaxial flow wet-spinning system was used to prepare cell-laden, 3D fibrous patches using RGD-modified pectin. Rapid fabrication of coherent self-standing patches, with diameter in the range of 100-200 µm and high cell density, was possible by accurate choice of pectin and calcium ions concentrations. Cells were homogeneously dispersed throughout the microfibers and remained highly viable for up to 2 weeks, when the initial stage of myotubes formation was observed. Modified-pectin microfibers appear as promising scaffold to support muscle tissue regeneration, due to their inherent porosity, the favorable cell-material interaction, and the possibility to guide cell alignment toward a functional tissue.

Dietary lysine supplementation improves growth performance and skeletal muscle development in rabbits fed a low protein diet.

The purpose of this study was to investigate the effects on growth of Lysine (Lys) supplementation in a low protein diet. We also investigated the gene or protein expression related to skeletal muscle development and intestinal amino acid transporters, and determined the major signalling associated with Lys-regulating skeletal muscle development. 1000 healthy, weights averaging 938.6 ± 6.54 g weaned rabbits were randomly divided into five groups (five replicates in each group and 40 rabbits in each replicate). These groups consisted of the normal protein group (NP group, consuming a diet containing 16.27% protein), the low protein group (LP group, 14.15%-14.19% protein) and the LP group with an addition of 0.15%, 0.3% or 0.45% Lys. The trial included 7 d of pre-feeding and 28 d of exposure to the treatment. Compared with NP diet and LP diet, LP+0.3% Lys group improved growth performance (p < 0.05), full-bore weight and half-bore weight of rabbits (p < 0.05). The LP+0.3% Lys group also resulted in a decrease in the excretion of faecal nitrogen and urinary nitrogen (FN; UN; p < 0.05), and an increase in nitrogen utilisation rate (NUR; p < 0.05). LP diet increased the mRNA expression of MSTN and WWP1, and decreased the mRNA expression of IGF1 (p < 0.05). LP diet decreased the protein expression of P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group attenuated the effects of LP diet on the expression of MSTN, WWP1, IGF1, P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group resulted in an increase in mRNA expression of MyoD and protein expression of P-mTOR relative to the NP and LP groups (p < 0.05). In summary, the addition of Lys to a LP diet provides a theoretical basis for the popularisation and application of Lys in rabbit production.

Effects of ferulic acid on muscle development and intestinal microbiota of zebrafish.

Ferulic acid (FA) is one of a common ingredients in Chinese herbal medicine. FA has the interesting property of promoting growth and improving meat quality in livestock, but the mechanism is not understood. This study evaluated both safety and mechanism of efficacy in zebrafish model. At 15 µg/mL or above, FA led to pericardial oedema and delayed growth in zebrafish embryos. Dietary FA promoted growth and feed assimilation in male adult zebrafish. Genes related to myogenic development (myod1, myog and myf5) were significantly upregulated by FA and muscle fibre width in skeletal muscle was increased. At 20 µg/g, FA significantly increased number of goblet cells in zebrafish intestinal tissue, and gut microbiota composition also changed. Based on 16s rRNA gene sequences, 20 µg/g FA decreased Firmicutes and increased Bacteroides. 20 µg/g FA also stimulated the expression of PPAR-α, a gene associated with fat metabolism, and decreased the expression of PPAR-ß and PPAR-γ. These gene expression changes were beneficial to fatty acid synthesis and metabolism and decreased fat deposition. Our overall results indicated that FA can be a safe growth promotor in fish particularly in skeletal muscles.