Search Results (472)

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. Full article

Megafires are transforming western boreal forests, and many burned forests are salvage logged, removing more structure from landscapes and delaying forest regeneration. We studied forest-dwelling owls in a post-fire and salvage-logged landscape in central British Columbia, Canada, in 2018–2019 after the 2010 Meldrum Creek Fire and the 2017 Hanceville Fire. We examined owl habitat selection via call surveys compared to the habitats available in this landscape. Owl pellets were dissected to determine owl diets. We detected six owl species, of which Northern Saw-whet Owls (Aegolius acadicus) were the most common. Owls had weak and variable habitat selection within an 800 m radius of detections; all species used some burned area. Great Gray Owls (Strix nebulosa) and Great Horned Owls (Bubo virginanus) obtained more prey from mature forests (e.g., red-backed voles, Myodes gapperi, snowshoe hares, Lepus americanus) than other owls did, whereas other owls primarily consumed small mammals that were common in burned or salvaged areas. These results indicate a diverse community of owls can use landscapes within a decade after wildfire, potentially with some prey switching to take advantage of prey that use disturbed habitats. Despite that, owl numbers were low and some owls consumed prey that were not available in salvage-logged areas, suggesting that impacts on owls were more severe from the combination of fire and salvage logging than from fire alone. Full article

(1) Background: Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in Eurasia. Orthohantavirus puumalaense (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in this region. Despite ongoing efforts to develop effective drugs and vaccines against PUUV, this challenge remains. (2) Aim: In this study, we aimed to express a large quantity of the PUUV recombinant N (rN) protein using E. coli. We also sought to develop a protocol for extracting the rN protein from pellets, solubilizing, and refolding it to restore its native form. This protocol is crucial for producing a large quantity of rN protein to develop vaccines and diagnostic tools for HFRS. (3) Methods; PUUV S segment open reading frame (ORF) coding for N protein was synthesized and cloned into the plasmid vector pET-28 (A+). The ORF was transformed, expressed and induced in BL21(DE3) pLysS E. coli strain. Subsequently, rN protein was purified using immobilized metal affinity and ion chromatography. Immune reactivity of rN protein was tested by employing in house and commercial VektoHanta-IgG kit ELISA methods (both in vitro and in vivo). (4) Results: The best conditions for scaling up the expression of the PUUV rN protein were an incubation temperature of 20 °C during a 20 h incubation period, followed by induction with 0.5 mM IPTG. The most significant protein yield was achieved when the pellets were incubated in denaturing buffer with 8M urea. The highest yield of refolded proteins was attained using non-denaturing buffer (50 mM Tris-HCl) supplemented with arginine. A final 50 μL of PUUV rN protein solution with a concentration of 7 mg/mL was recovered from 1 L of culture. The rN protein elicited an antibody response in vivo and reacted with serum taken from patients with HFRS by ELISA in vitro. (5) Conclusion: Therefore, the orthohantavirus N protein’s ability to elicit immune response in vivo suggests that it can be used to develop vaccines against PUUV after conducting in vitro and in vivo studies to ascertain neutralising antibodies. Full article

Background/Objectives: Myogenesis, the process by which myoblasts differentiate into multinucleated muscle fibers, is tightly regulated by transcription factors, signaling pathways, and metabolic cues. Among these, fatty acids have emerged as key regulators beyond their traditional role as energy substrates. Oleic acid, a monounsaturated fatty acid, has been shown to modulate muscle differentiation, potentially influencing myogenic pathways. This study examines the role of oleic acid in promoting C2C12 myoblast differentiation and its associated molecular mechanisms, comparing it to standard horse serum (HS)-based differentiation protocols. Methods: C2C12 murine myoblasts were cultured under proliferative conditions and differentiated using DMEM supplemented with either 2% HS or oleic acid (C18:1, n-9). The molecular signaling pathway was evaluated by measuring the expression of p38 MAPK, β-catenin, GLUT4, and NDRG1. Results: Oleic acid promoted the differentiation of C2C12 cells, as evidenced by a progressively elongated morphology, as well as the induction of muscle-specific myogenin, myosin heavy chain (MHC), and MyoD. Moreover, oleic acid reduced the expression of Atrogin-1 and MuRF1 ubiquitin E3 ligase. BODIPY staining revealed the enhanced accumulation of lipid droplets in oleic acid-treated cells. The Western blot analysis demonstrated robust activation of p38 MAPK and β-catenin pathways in response to oleic acid, compared with HS. Additionally, oleic acid upregulated GLUT4 expression and increased the phosphorylation of insulin receptor and NDRG1, indicating an enhanced glucose uptake capacity. Conclusions: These findings demonstrate that oleic acid promotes C2C12 myoblast differentiation and improves glucose uptake via GLUT4. Oleic acid emerges as a promising metabolic regulator of myogenesis, offering potential therapeutic applications for muscle regeneration in muscle-related pathologies. Full article

This study elucidates the mechanisms underlying the positive effect of glyceryl monolaurate (GML) on fetal intrauterine development via maternal gut-microbiota modulating effects using a sow model. Addition of GML (1000 mg/kg) improved neonatal intestinal conditions (jejunal villus height, VH/CD ratio and tight junctions) and dorsal longissimus muscle (MyoD, MyoG and MSTN) development in the GML-treated group. Furthermore, GML improved maternal gut microbiota composition by enriching short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Akkermansia. Meanwhile, SCFA concentrations in sow feces and newborn plasma, as well as their receptors (GPR41/43) in intestine and muscle were upregulated with GML, corresponding with enhanced antioxidative and anti-inflammatory capacity. Further correlation analysis revealed Akkermansia and Lactobacillus positively correlated with SCFAs, antioxidative indicators, and anti-inflammatory capacity markers. Moreover, GML inhibited the activation of the MAPK/NF-κB inflammatory signaling pathway. In summary, GML enhanced fetal intrauterine development by modulating sow intestinal SCFA-producing bacteria. Full article

The polysaccharide of Millettia speciosa Champ. ex Benth (MSCP) has antioxidant properties, but its impact on chicken growth and development is not yet known. This study used chlortetracycline as a control to assess MCSP as a feed antibiotic substitute and its effects on Wenchang chicken production, slaughter performance, and meat quality. A total of 576 healthy 80-day-old Wenchang chickens were randomly allocated to six experimental groups. The control group (Control) received a basal diet, while the antibiotic group (CTC) was supplemented with 2 g/kg chlortetracycline (CTC). Four additional experimental groups were administered varying doses of MSCP: 400 mg/kg (MSCP₄₀₀), 800 mg/kg (MSCP₈₀₀), 1600 mg/kg (MSCP₁₆₀₀), and 3200 mg/kg (MSCP₃₂₀₀), respectively. The study discovered that incorporating MSCP and CTC into chicken diets significantly boosted the final body weight and average daily feed intake compared to the control group (p < 0.01), with MSCP notably enhancing average daily weight gain. With the addition of 800 mg/kg MSCP, chicken growth performance is comparable to that achieved with antibiotics in feed. However, it did not impact slaughtering performance (p > 0.05). In addition, MSCP significantly raised the pH after 24 h (p < 0.05) and decreased the yellowness (p < 0.01) of breast muscle. MSCP increased the essential amino acids (EAA) proportion in breast muscle (p < 0.05), EAA to nonessential amino acids (NEAA) ratio (p < 0.05), and diversity of fatty acids while decreasing C20:0 and increasing C18:2N6 and C22:1N9 content. Moreover, MSCP significantly reduced muscle fiber size (p < 0.01), increased fiber density (p < 0.01), boosted MYOD1 expression (p < 0.05), and decreased MSTN expression in breast muscle (p < 0.01). Overall, our study showed that supplementing the diet with MSCP, particularly at a dose of 800 mg/kg, enhanced growth, meat quality, muscle morphology, amino acid content, fatty acid composition, and gene expression related to muscle development in breast muscle. The results indicate that MSCP is a feed additive with the potential to replace antibiotics and improve meat quality, showing promising application potential. Full article

Skeletal muscle diseases often exhibit fiber-type-specific characteristics and pose substantial clinical challenges, necessitating innovative therapies. The extracellular matrix (ECM) plays a pivotal role in muscle physiology and regeneration, influencing cell differentiation. However, its specific role and mechanisms influencing muscle fiber type specification remain insufficiently understood. In this study, C2C12^GFP myoblasts were differentiated into myofibers on plates coated with fibronectin, Collagen I, and Geltrex™. Differentiation occurred successfully across all ECM substrates, resulting in myofiber formation. Quantitative polymerase chain reaction (qPCR) analysis confirmed myogenic marker expression patterns, indicating decreased Pax7 and increased Myog levels by day 7. Protein analysis through Western blot and immunofluorescence assays along with transcriptomic profiling through RNA sequencing consistently indicated that Collagen I promoted slow-type fibers development, as evidenced by increased slow myofiber protein expression and the upregulation of slow fiber-associated genes, potentially mediated by pathways involving calcineurin/NFAT, MEF2, MYOD, AMPK, PI3K/AKT, and ERK1. In contrast, fibronectin and Geltrex™ led to fast-type fiber development, with elevated fast-type fiber protein levels and upregulation of fast fiber-associated genes, possibly through activation of HIF1A, FOXO1, NFKB, and ERK2. These findings elucidate ECM-mediated muscle fiber type differentiation mechanisms, informing future targeted therapies for muscle regeneration. Full article

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast differentiation, and the introduction of the mechanomiR-200c antagomir restored the stretch effect. This suggests that stretch blocks differentiation, in part, through mechanomiR-200c. The gene encoding the transcription factor FoxO3 is a known direct target of mechanomiR-200c. Interestingly, MyoD binds to the mechanomiR-200c promoter in differentiating myoblasts, whereas stretch appears to reverse such binding. Our data further demonstrate that the levels of mechanomiR-200c are robustly elevated during the early stage of the muscle repair process in young mice, but not in the injured muscle of aged mice. Overall, we identified a novel pathway, MyoD/mechanomiR-200c/FoxO3a, and the potential mechanism by which stretch inhibits myoblast differentiation. Full article

Aeromonas hydrophila ST251 is a crucial pathogen responsible for the outbreaks of Motile Aeromonas Septicemia (MAS) in global aquaculture. To elucidate the genetic basis underlying its hypervirulence, we investigated strain D4, an ST251 isolate recovered from diseased blunt snout bream. Phenotypic assays revealed that, compared to the environmental strain ATCC 7966^T, D4 exhibited enhanced motility, hemolytic activity, and protease production. Average nucleotide identity (ANI) analysis demonstrated that D4 clustered within a distinct ST251 clade, with ANI values ≥ 99.74%. Comparative genomic analysis of D4, nine additional ST251 strains, and ATCC 7966^T identified multiple unique genomic islands in ST251 strains, including pathways for myo-inositol and L-fucose utilization and a pseudaminic acid biosynthesis gene cluster. These genetic elements are associated with nutrient acquisition and flagellar assembly, potentially enhancing colonization and environmental adaptability. In addition, distinct plasmids and prophages in ST251 strains may contribute to host adaptation and virulence by regulating stress responses and virulence-associated genes. These findings offer new insights into the molecular mechanisms driving the pathogenicity and adaptability of hypervirulent A. hydrophila ST251 strains. Full article

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors continually stabilize hypoxia-inducible factor-1α (HIF-1α). These inhibitors are effective in the clinical treatment of renal anemia. However, the effects of continued HIF-1α stabilization on skeletal muscle differentiation remain unclear. This study aimed to investigate the effects of continued HIF-1α stabilization on skeletal muscle differentiation using a HIF-PH inhibitor in both in vitro and in vivo models. We cultured mouse C2C12 myoblasts to differentiate into myotubes with or without FG-4592, a HIF-PH inhibitor. Additionally, we treated nine-week-old male C57BL/6 mice with either FG-4592 or vehicle via intraperitoneal injections three times a week for four weeks. In vitro, FG-4592 treatment stabilized HIF-1α continually. Morphological analysis revealed that 72 h FG-4592 treatment suppressed differentiation of C2C12 myoblasts into myotubes. This treatment decreased the gene and protein expression of MyoD and myogenin, reduced the protein expression of myosin heavy chain (MHC), and increased the gene and protein expression of myostatin. HIF-1α knockdown mitigated the decrease in MHC protein expression induced by FG-4592. In vivo, FG-4592 treatment increased HIF-1α protein expression and decreased MyoD, myogenin, and MHC protein expression in gastrocnemius muscle. These findings suggest that pharmacological HIF-PH inhibition suppresses myoblast differentiation through continued HIF-1α stabilization. Full article

A high-fat diet (HFD) can lead to obesity and skeletal muscle atrophy. Sleeve gastrectomy (SG) improves obesity and increases skeletal muscle mass. This study examined whether SG prevented skeletal muscle atrophy in a diet-induced rat obesity rat model. First, 8-week-old male Sprague-Dawley rats underwent surgical (sham-operated or SG) and dietary (standard, high-fat diet, or same pair feeding as SG [PF]) interventions without exercise. In the second experiment, treadmill exercise was added for 4 weeks post-SG (SG + Ex). In the third experiment, rats received an adiponectin receptor agonist (AdipoRon) injection. The HFD induced weight gain and decreased muscle fiber area. SG + Ex reversed these levels, followed by increases in adiponectin in the blood and skeletal muscle and myoblast determination protein 1 (MyoD) and decreased peri-muscular adipose tissue (PMAT) mass, but SG alone did not. No similar changes were observed in the PF group, with or without exercise. Injection of AdipoRon had a similar effect on skeletal muscle and PMAT as SG + Ex. The combination of SG and exercise, but not calorie restriction alone, had better impacts on skeletal muscle and PMAT than SG or exercise alone. Full article

In fibrotic skeletal muscles, excessive extracellular matrix (ECM) deposition is a result of increased activation and decreased apoptosis of myofibroblasts. The aim of this study is to investigate whether treatment with quercetin, kaempferol or capsaicin can reduce the transforming growth factor-beta 1 (TGF-β1)-induced myofibroblast differentiation and fibrotic ECM expression in differentiated C2C12 cells. Two-day-differentiated C2C12 cells were treated with TGF-β1 for 48 h to induce myofibroblast differentiation. Twenty-four hours before (pre-treatment) and for forty-eight hours with (co-treatment) TGF-β1 treatment, cells were exposed to quercetin (25, 50 µM), kaempferol (10, 25, 50 µM) or capsaicin (25, 50 µM). The immunofluorescence intensity of alpha smooth muscle actin (αSMA) and collagen type I/III gene expression were assessed as myofibroblast markers. MyoD immunofluorescence intensity was measured as a myogenic marker. Co-treatment of TGF-β1 with the phytochemicals was most effective, resulting in a decreased number of αSMA-positive cells (all three compounds), decreased collagen type I (kaempferol, capsaicin) and type III (kaempferol) gene expression, and increased MyoD (kaempferol, capsaicin) protein expression compared to TGF-β1 treatment. This study demonstrates that treatment with quercetin, kaempferol or capsaicin can reduce myofibroblast markers. This suggests a possible anti-fibrotic effect of the phytochemicals in skeletal muscle. Full article

DNA methylation plays a pivotal role in the epigenetic regulation of gene expression and holds promise for enhancing livestock meat production. In this study, we analyzed the DNA methylome and transcriptome of the longissimus dorsi muscle (LDM) in Duroc pigs with varying growth rates. Our results reveal that DNA methylation suppressed the expression of key muscle development markers (MYOD, MYOG, MHC1) and proliferation markers (PI67, PCNA), as well as the protein expression and phosphorylation of PI3K and AKT (p < 0.05). Dual-luciferase reporter assays and EMSA showed that SP1 overexpression enhanced the luciferase activity of the wild-type LPAR1 promoter, an effect amplified by the demethylating agent 5-AZA (p < 0.05). The EMSA further demonstrates the relationship between SP1 and the LPAR1 promoter region. Overexpression of SP1 upregulated LPAR1 expression at both the mRNA and protein levels (p < 0.05). Knockdown of LPAR1 reduced muscle marker gene expression and delayed myotube formation, while silencing SP1 disrupted the expression of LPAR1, MEF2C, and MHC1 (p < 0.05), and the demethylation induced by 5-AZA partially reversed these effects. These findings suggest that the DNA methylation/SP1/LPAR1 axis is critical for skeletal muscle growth and development, underscoring the regulatory role of DNA methylation in muscle formation. Full article

Polycystic ovary syndrome (PCOS) is the expression of a complex alteration of the reproductive system. It is characterised by the increase in androgens, causing symptoms such as hirsutism, as well as infertility in many. This paper reviews whether Clomiphene Citrate, Letrozole and Inositol function better as monotherapy or combined therapy for anovulatory infertile PCOS patients. Ovulation and pregnancy rate were used as primary outcomes. PubMed and Scopus were the search engines of choice. Papers were excluded if patients were undertaking other fertility interventions, overlapping populations and non-RCT papers. It was found that co-prescribing Letrozole or Clomiphene Citrate alongside Metformin should be considered, Inositol should be examined as an alternative insulin sensitiser to Metformin and studies should be undertaken to identify the ideal dose and duration of Inositol therapy. Further large, well-designed, multi-centre studies should be conducted to solidify the claims of this review. Full article