Search Results (722)

Tumour necrosis factor-alpha (TNF-α) disrupts bioenergetic homeostasis in skeletal muscle cells through the suppression of ion-dependent ATPase activities, mitochondrial depolarisation, and impairment of antioxidant defences. Carvacrol, a phenolic monoterpenoid constituent of thyme and oregano essential oil, has been shown to exert cytoprotective effects in TNF-α-challenged L6 rat myoblasts. The mechanistic basis of these effects, specifically the relationship between membrane-associated ATPase function, mitochondrial polarisation status, and transcriptional regulation of metabolic stress-response genes, has not been formally characterised. L6 rat myoblasts were exposed to TNF-α (10 ng/mL, 1 h), then treated with carvacrol (6.25 µg/mL, 24 h) in a post-inflammatory rescue paradigm. Cell viability (MTT), membrane integrity (LDH), ion-dependent ATPase activities (Na⁺/K⁺, Ca²⁺, Mg²⁺), antioxidant enzyme activities (catalase, SOD), mitochondrial membrane potential (Muse™ MitoPotential flow cytometry), and SIRT1/AMPK mRNA expression were quantified. TNF-α significantly suppressed Na⁺/K⁺, Ca²⁺, and Mg²⁺-dependent ATPase activities (all p < 0.001), consistent with impaired membrane-associated bioenergetic function. Post-TNF-α carvacrol treatment partially restored all three ATPase activities (p < 0.05) and reduced the proportion of mitochondrially depolarised cells from 31.65 ± 4.25% to 19.0 ± 2.6% (p < 0.05). LDH release, catalase activity, and SOD activity were also significantly modulated. At the transcriptional level, carvacrol increased SIRT1 mRNA by 1.6-fold and AMPK mRNA by 2.0-fold relative to TNF-α-treated cells. An integrative bioenergetic model is proposed in which carvacrol’s membrane-intercalating properties restore the phospholipid environment required for ATPase conformational cycling, attenuating the Ca²⁺ overload that drives mitochondrial permeability transition, and thereby partially preserving Δψm. Transcriptional upregulation of SIRT1 and AMPKα may represent an adaptive response to residual energetic stress. The mechanistic relationships among these endpoints and the causal contribution of SIRT1 and AMPK to observed bioenergetic changes require protein-level and pathway-specific experimental validation. Full article

Economic traits in livestock and poultry arise from the intricate interplay between genetic inheritance and environmental factors, mediated largely by epigenetic regulation. Histone modifications, particularly methylation and acetylation, serve as fundamental epigenetic mechanisms that dynamically remodel chromatin architecture and regulate gene expression in response to developmental and environmental cues. By bridging the gap between static DNA sequences and complex phenotypes, these dynamic marks offer a novel perspective for elucidating trait formation. This review examines the regulatory roles of histone modifications in shaping key economic traits, focusing on skeletal muscle development, fat deposition, and reproductive performance. Furthermore, we highlight two prospective strategies for integrating histone modification data into modern breeding programs: utilizing comprehensive epigenomic maps as novel biomarkers for precision selection, and implementing targeted nutritional regimens to program early phenotypic development. Despite substantial mechanistic advances, critical challenges persist, including high detection costs, inherent tissue specificity, and the necessity to validate transgenerational stability. Looking forward, the integration of multi-omics approaches is anticipated to propel animal breeding beyond traditional genomic selection toward an era of precise epigenomic design. Full article

Metabolic syndrome (MetS) drives cardiac remodeling and fibrosis, contributing to diastolic dysfunction and heart failure with preserved ejection fraction, but chamber-specific mechanisms remain poorly defined. New Zealand White rabbits were fed a high-fat/high-sucrose diet for 28 weeks to induce experimental MetS. Systemic phenotype, cardiac structure (echocardiography), myocardial fibrosis (Picrosirius red histology), myosin/collagen gene expression (qRT-PCR), and chamber-specific proteomics were assessed across left/right atria and ventricles. The model reproduced central obesity, glucose intolerance, dyslipidemia, and mild hypertension, with concentric left ventricular hypertrophy and selective ventricular fibrosis, as follows: increased collagen in left ventricle (LV) and right ventricle (RV), unchanged in atria. Ventricular α-myosin heavy-chain gene expression was upregulated, while collagen I and α-smooth muscle actin transcripts showed ventricular-specific downregulation. Proteomics revealed atrial metabolic and cytoskeletal adaptations with minimal extracellular matrix involvement; ventricles displayed early profibrotic cues (galectin-3 in LV), metabolic inefficiency (impaired glycolysis/ATP production in LV; lipid oxidation shift in RV), and diminished provisional matrix support. Conclusions: concentric LV hypertrophy and great vessel enlargement occurred without systolic/diastolic dysfunction; ventricular-selective fibrosis, α-myosin heavy-chain upregulation, type I collagen/α-smooth muscle actin downregulation, and chamber-specific proteomic changes showed atrial adaptation versus ventricular early profibrotic/metabolic inefficiency. Full article

The skeletal muscle (SkM) secretome has been widely studied since the establishment of its endocrine function. Extracellular vesicles (EVs) are the most recently identified elements of the SkM secretome. These nano-sized lipid-bound vesicles carry molecular cargo and function as a means of intercellular communication. The effect of exercise on SkM EV micro-RNA cargo (miRNAs) remains a challenge to elucidate. Electrical pulse stimulation (EPS) was applied to C2C12 myotubes at high (30 Hz) and low (2 Hz) frequencies. EVs released during 10 h of stimulation were isolated and characterized and used to treat myoblasts. Their miRNA cargo was sequenced. EVs were used to treat myoblasts (2.19 × 10⁸ EVs per mL) to determine the effects on myoblast migration and differentiation. Sequencing revealed over 300 known miRNAs packaged into myotube EVs. Many were differentially expressed after EPS, either positively or negatively. Muscle-important miRNAs were present (miR-206 was 4.8-fold more prevalent than any other miRNA). EV treatments improved myoblast migration and differentiation without a frequency-specific influence. Gene Ontology analysis based on differentially expressed miRNAs between control and EPS-EVs indicates an effect of EPS frequency on muscle EV signaling. Full article

Overcoming fishmeal dependence is crucial for the sustainable development of Penaeus vannamei aquaculture, yet the molecular mechanisms underlying the efficient utilization of plant-based diets remain poorly understood. In this study, residual feed intake (RFI) was used as an indicator to investigate these mechanisms. Transcriptome sequencing of the intestine, hepatopancreas, and muscle was performed on shrimp fed a plant-based diet, followed by weighted gene co-expression network analysis (WGCNA) and validation in an independent population. Phenotypic analysis revealed extensive variation in growth performance and RFI among individuals fed the plant-based diet. WGCNA identified four tissue-specific modules significantly associated with RFI, from which 20 hub genes were screened. Independent validation confirmed that seven genes were significantly differentially expressed between high- and low-feed-efficiency groups (q < 0.1): five in the intestine (LOC113811628, LOC113811631, LOC113824170, LOC113817752, LOC113811632) and two in the hepatopancreas (LOC113809216, LOC113820990). These genes are involved in mitochondrial function, energy metabolism, intracellular pH homeostasis, and nucleic acid metabolism, suggesting potential coordination between the intestine and hepatopancreas in response to plant-based diets. Collectively, these findings provide insights into the genetic basis of shrimp adaptation to plant-based diets and offer candidate molecular targets that may inform selective breeding efforts aimed at improving feed efficiency in P. vannamei. Full article

White Striping (WS) is a macroscopic defect of the pectoralis major muscle, characterized by distinct white striations that impair meat acceptability and commercial value. It is a phenotype with polygenic inheritance, controlled by several QTLs and genes associated with muscle repair and metabolism. Beyond genetic factors, phenotypic manifestation is strongly modulated by the environment. This review integrates research on genetic predispositions and modulating factors to provide a holistic overview of WS in broilers. The defect predominantly affects heavier birds with high breast yield and elevated ultimate breast pH. LRSAM1 gene, on chromosome GGA17, is identified as a putative candidate gene as its expression co-localizes with the phenotypic QTL. Chromosome GGA5 has recently been identified as the primary genomic region of interest hosting a cluster of specific markers. Research on dietary strategies has extensively explored the manipulation of feed formulations, especially of amino acids. While results for some nutrients like methionine remain conflicting, restricting lysine during the growth phase could be an effective dietary intervention for reducing WS severity. Management offers the most practical short-term solutions, whereas selective breeding enables meaningful and permanent progress across generations, given the moderate heritability of many quality-related traits. Effective mitigation requires an integrated approach combining welfare, environmental control, and precision feeding throughout the production cycle, while acknowledging trade-offs with productivity. To meet evolving consumer expectations, the industry must embrace practices that are simultaneously scientifically rigorous, ethically responsible, and environmentally sustainable. Full article

This study evaluates how titanium and polymethyl methacrylate (PMMA) Boston Keratoprosthesis backplate substrates influence human corneal fibroblast proliferation, cytotoxicity, morphology, activation phenotype, and mechanotransductive signaling. Human corneal fibroblasts were cultured on titanium and PMMA, with tissue culture plastic or glass as controls. Proliferation was assessed over 7 days using metabolic assays, and cytotoxicity was measured by lactate dehydrogenase release. Cell morphology and surface coverage were examined by scanning electron microscopy, while immunofluorescence quantified fibroblast-specific protein 1 (FSP-1) and α-smooth muscle actin (α-SMA). Gene expression of α-SMA, collagen I, FSP-1, and focal adhesion kinase (FAK) was analyzed by quantitative PCR. Cells cultured on both substrates maintained stable viability with modest increases in estimated cell numbers and comparable proliferation curves, indicating preserved metabolic activity without growth suppression. Cytotoxicity remained low and similar between groups. SEM demonstrated broader and more continuous cell spreading on titanium, whereas cells on PMMA were more sparsely distributed. Immunofluorescence showed higher FSP-1 expression on titanium and increased α-SMA on PMMA. Gene expression analysis revealed higher FAK transcripts on PMMA, with no significant differences in α-SMA, FSP-1, or collagen I. These results confirm the cytocompatibility of both titanium and PMMA backplates with human corneal fibroblasts and support their use with the Boston Keratoprosthesis. Full article

The present work was designed to investigate the impacts of tartary buckwheat flavonoids (TBF) on the growth performance and physiological metabolism of Liangshan Yanying chickens. A total of 144 healthy 4-week-old Liangshan Yanying chickens of uniform body weight were randomly divided into four groups. Each group consisted of six replicates with six chickens per replicate. The control group was fed a basal diet, whereas the treatment groups received the same basal formulation supplemented with TBF at concentrations of 20, 40, and 60 mg/kg, respectively. The entire feeding trial lasted for 10 consecutive weeks. Growth performance, serum parameters, bone quality, slaughter traits, and hepatic lipid metabolism were determined and statistically analyzed. Results showed that dietary TBF supplementation had no significant impact on the overall growth performance (p > 0.05); however, final body weight and average daily weight gain displayed a positive linear trend in response to increasing TBF levels (0.05 < p < 0.1). For serum parameters, TBF supplementation significantly increased total antioxidant capacity (p < 0.05) and decreased malondialdehyde content (p < 0.05) in a linear manner. Specifically, compared with the control group, the 60 mg/kg TBF group increased T-AOC by approximately 64.6% and reduced MDA by approximately 67.9%, demonstrating a robust antioxidant effect. A linear increase in high-density lipoprotein cholesterol levels approaching significance (p = 0.055) was also observed. A significant quadratic regulatory effect of TBF was observed on serum glucose concentrations (p < 0.05), whereby the 60 mg/kg TBF dose reduced serum glucose by 15.6% relative to the control (p < 0.05), reflecting a robust hypoglycemic effect. Regarding bone quality, supplementation with 20 and 60 mg/kg TBF significantly elevated tibial phosphorus content relative to the 0 mg/kg TBF group (p < 0.05). Regression analysis showed that increasing dietary TBF levels linearly elevated tibial calcium content (p < 0.05) and resulted in linear increasing trends in tibial ash content, tibial phosphorus content, femur ash content, and femur calcium content (0.05 < p < 0.1). Concerning slaughter performance, dietary TBF inclusion resulted in a significant linear rise in breast muscle percentage (p < 0.05). At the molecular level, TBF upregulated the mRNA expression of hepatic AMPKα1 and CPT1, while concurrently downregulating the expression of FAS and ACC (p < 0.05). Collectively, dietary TBF supplementation in Liangshan Yanying chickens effectively improved antioxidant capacity, promoted tibial calcium and phosphorus deposition, regulated hepatic fatty acid oxidation and synthesis via AMPK-related genes, and enhanced lean meat deposition, with no adverse effects on growth performance under the experimental conditions. Full article

In northwestern China, there is an abundance of saline-alkali water resources, but their high alkalinity severely restricts the development of inland saline-alkali water aquaculture. As an important aquaculture species, the whiteleg shrimp, Litopenaeus vannamei, shows an unclear physiological adaptation mechanism under high-alkaline stress. In this study, multi-omics and physiological methods were used to systematically reveal the effects of high-alkaline stress on the molt, antioxidation response, and immune defense in L. vannamei. The results showed that high-alkaline stress caused damage to the intestinal tissues of the shrimp and weakened the mucous barrier function, which was accompanied by a significant decrease in the activities of antioxidant enzymes (SOD, CAT, and GPx) and non-specific immune indicators (PO and LZM) (p < 0.05). The transcriptome results showed that the expression of genes related to chitin metabolism and calcium ion binding was upregulated, whereas that of genes related to muscle contraction and cell skeleton construction was downregulated. The structure of the intestinal microbiota changed significantly, with a decrease in microbiota diversity, whereas the abundance of potential pathogenic species (e.g., Photobacterium) increased. These results provide a theoretical basis for clarifying the molting response and antioxidant defense mechanism of L. vannamei in high-alkaline environments, with significance for saline-alkali water aquaculture practices. Full article

Background: Circadian disruption exacerbates type 2 diabetes mellitus (T2DM). Time-restricted feeding (TRF) and exercise (EX) improve metabolic health, but their combinatory effect remains unclear. This study investigated whether combined TRF and EX additively ameliorates metabolism via circadian reprogramming in db/db mice. Methods: Eight-week-old male db/db mice were assigned to control (Con), diabetic model (DM), TRF (8 h feeding window), EX (treadmill, 60 min/day, 5 days/week), or combined TRF + EX groups for 8 weeks (n = 8/group). Body weight, glucose/insulin tolerance, and 24 h energy metabolism (CLAMS) were assessed. Mitochondrial function, oxidative stress, inflammation, and expression of mitophagy (Pink1, Park2, Bnip3, Fundc1) and thermogenic (Ucp1, Pgc1a, Prdm16, Cidea) genes were measured. Results: Compared with the con group, DM mice showed obesity, hyperglycemia and blunted circadian metabolic rhythm. The TRF and EX groups improved these defects. Specifically, combined TRF + EX reduced fasting blood glucose from 25.3 ± 3.1 mmol/L (DM) to 13.2 ± 1.8 mmol/L (p < 0.05), body weight from 49.8 ± 2.5 g to 39.5 ± 1.7 g (p < 0.05), and body fat percentage from 45.6 ± 3.2% to 32.1 ± 2.2% (p < 0.05). GTT area under the curve (AUC) decreased from 3711.0 ± 186.5 (DM) to 2118.0 ± 112.4 (p < 0.05), and ITT AUC decreased from 2617.5 ± 135.8 to 1260.0 ± 68.9 (p < 0.05). Notably, the combination of TRF + EX produced greater effects than either intervention alone: body weight, fasting blood glucose, and glucose/insulin tolerance were greatly improved (p < 0.05). In addition, compared with the DM group, the diurnal metabolic amplitude and phase were improved in the TRF or EX group; the combination group showed further improvements in these parameters. Furthermore, TRF and EX each resulted in significantly higher expression of key thermogenic genes (Ucp1, Pgc1a, Prdm16, Cidea) in white adipose tissue (WAT) and brown adipose tissue (BAT) (p < 0.05), and the TRF + EX group showed the highest expression levels. Combined intervention also restored skeletal muscle SOD activity (31.2 ± 2.9 U/mg prot vs. DM 20.1 ± 2.5 U/mg prot, p < 0.05) and reduced serum TNF-α (28.5 ± 4.5 pg/mL vs. DM 65.8 ± 8.5 pg/mL, p < 0.05) and IL-6 (21.6 ± 3.8 pg/mL vs. DM 50.3 ± 7.1 pg/mL, p < 0.05). Conclusions: TRF + EX additively restores metabolic homeostasis in diabetes by re-entraining circadian energy rhythms, improving mitochondrial quality, and activating adipose thermogenesis, supporting further investigation of integrated lifestyle timing as a potential therapeutic strategy. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1α, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes. Full article

A high-fat (HF) diet disrupts metabolic homeostasis and impairs peripheral circadian rhythms in key metabolic tissues. β-Hydroxybutyrate (BHB), a major circulating ketone body, functions not only as an energy substrate but also as a signaling metabolite regulating nutrient-sensing and inflammatory pathways. However, its role in modulating metabolic–circadian interactions under conditions of nutrient excess remains unclear. In this study, we investigated whether BHB supplementation influences metabolic signaling and circadian clock oscillations in liver, skeletal muscle and adipose tissue under chow and HF conditions. Male C57BL/6 mice were fed chow or HF with or without BHB supplementation (500 mg/kg body weight in the diet) for 7 weeks. Metabolic parameters were assessed by indirect calorimetry, and tissues were collected every 4 h across the circadian cycle. HF feeding increased body weight and adiposity (p < 0.01), reduced AMPK activation, enhanced AKT/mTOR signaling, elevated NF-κB levels and dampened clock gene rhythmicity. BHB supplementation significantly decreased food intake in HF-fed mice (p < 0.01) and partially reversed several molecular alterations in a tissue-specific manner. In skeletal muscle and adipose tissue, BHB increased AMPK activation and reduced mTOR and NF-κB signaling (p < 0.05), whereas hepatic effects were more modest. Notably, BHB modulated circadian gene expression, restoring aspects of rhythmic amplitude and/or phase, particularly in adipose tissue. These findings may indicate that BHB supplementation modulates nutrient-sensing pathways and partially restores peripheral circadian rhythms under HF conditions. While some effects may be influenced by reduced energy intake, BHB may serve as a metabolic signal linking nutrient status to circadian regulation. Full article

Bronchial thermoplasty (BT) is a non-pharmacological treatment for severe asthma. The working mechanism and response determinants of BT remain partly unknown. This study aims to investigate whether a systemic transcriptomic response to BT can be detected and contextualized against a control cohort. Whole blood was collected at baseline and six months after BT from severe asthma patients (n = 31) and a control cohort (n = 126). RNA was isolated and sequenced. The following comparisons were made: before and after BT, responders and non-responders, and severe asthma (at baseline) versus controls. Differentially expressed genes were identified across 179 samples using DESeq2. Pathway enrichment was investigated using gene set enrichment and overrepresentation analyses. Following BT, pathways related to nervous system development, ion channel activity, muscle tissue development, and cilia function were downregulated. In responders specifically, gene sets involved in nervous system and muscle development were downregulated. Compared with the control cohort, pathways related to nervous system development and ion channel activity were upregulated in the severe asthma cohort at baseline. In conclusion, systemic blood-derived transcriptomic changes can be detected in severe asthma patients six months after BT and may provide insight into BT mechanisms and its responder profile. Full article

Both breed and plumage color are considered potential genetic factors influencing meat quality in pigeons, yet their independent effects remain poorly distinguished. This study aimed to disentangle the regulatory roles of breed and plumage color on meat quality, nutritional composition, and flavor-related metabolites in meat pigeons. White-feathered (SQB) and grey-feathered (SQH) Shiqi pigeons were compared with European Mimas white pigeons (MMS) under identical rearing conditions. Slaughter performance, meat quality traits, and flavor profiles were assessed, followed by untargeted metabolomics and transcriptomics sequencing of pectoral muscle tissues. The results demonstrated that breed exerted a significant influence on carcass traits, water-holding capacity, collagen content, as well as the composition of fatty acids and free amino acids. In contrast, no notable disparity in meat quality was observed between the white- and gray-feathered varieties within the same Shiqi pigeon breed. A total of 114 and 205 differentially expressed metabolites (DEMs), and 11 and 327 differentially expressed genes (DEGs) were identified in plumage color and breed comparisons, respectively. Key flavor-associated metabolites, including glutathione, L-histidine, L-carnosine, and cytidine-5′-monophosphate, were identified as candidate biomarkers for breed-specific flavor differentiation. Breed is the dominant genetic factor determining meat quality and flavor in meat pigeons, while plumage color variation within breed has a limited impact. The identified pathways and regulatory networks provide actionable targets for the precision breeding and flavor enhancement of local pigeon breeds. Full article

Carcass growth and development are crucial evaluation indicators influencing the economic efficiency of goats (Capra hircus). This study aimed to screen the nucleotide variation sites (SNPs) of the APOE gene in Guizhou white goats and explore the correlation between APOE gene variations and body size traits, as APOE had been identified as a key candidate gene regulating growth and development in this breed through transcriptome sequencing screening. A total of 324 Guizhou white goats were used in this study for SNP detection, population genetic analysis, real-time fluorescence quantitative PCR (RT-qPCR) and association analysis. The results showed that one nucleotide mutation site (g.353 A > G) was detected in the APOE gene, which yielded two alleles (A and G) and three genotypes (AA, AG and GG). The site exhibited moderate polymorphism and conformed to Hardy–Weinberg equilibrium. The mRNA expression level of APOE in longissimus dorsi muscle was significantly higher in males than in females. Association analysis revealed a sex-specific effect of this locus on body size traits. The A allele and AA genotype were significantly associated with increased body weight and heart girth in females, whereas no significant effect was detected in males. Therefore, the identified APOE gene mutation site can serve as a candidate molecular marker for the early selection of growth traits in Guizhou white goats. Full article