Search Results (382)

The decline in differentiation capacity during skeletal muscle (SkM) aging contributes to the deterioration of skeletal muscle function and impairs regenerative ability. Epicatechin gallate (ECG), a major functional component of catechins found in tea, has an unclear role in aging-related sarcopenia. In vivo experiments in 54-week-old C57BL/6J mice showed that ECG treatment improved exercise performance, muscle mass, and fiber morphology and downregulated the expression of the testosterone metabolic enzyme gene UGT2A3 in aged mice. In vitro experiments with Leydig cells (TM3) demonstrated that ECG upregulated the mRNA and protein expression levels of testosterone synthase genes, including StAR, P450scc, 3β-HSD, CYP17a1, and 17β-HSD. Network pharmacology analysis further suggested that ECG can influence testosterone secretion through the regulation of cytokines, thereby promoting skeletal muscle differentiation. These findings indicate that ECG enhances the differentiation of skeletal muscle cells by modulating testosterone levels, which helps alleviate age-related muscle function decline. Full article

Sclerotinia sclerotiorum, known as a typical necrotrophic pathogenic fungus, exhibits a complex pathogenic mechanism. Research on S. sclerotiorum has primarily focused on oxalic acid, pathogenicity-related enzymes, and secreted proteins. In this study, we identified a transcription factor, SsSR (S. sclerotiorum Sterol-Related transcription factor), which regulates S. sclerotiorum infection by modulating virulence through ergosterol biosynthesis. We characterized the transcriptional activity of SsSR and its downstream target gene, SsCYP51. SsSR undergoes phosphorylation induced by the host plant, subsequently regulating the expression of SsCYP51. The deletion of SsSR or SsCYP51 does not affect the growth or acid production of S. sclerotiorum, but it leads to a reduction in ergosterol, significantly diminishing virulence and impairing the stress tolerance of the hyphae. In summary, this study identifies a transcription factor, SsSR, that specifically regulates the virulence of S. sclerotiorum. SsSR upregulates the expression of SsCYP51 through phosphorylation during the infection phase, leading to the synthesis of ergosterol, which enhances hyphal stress tolerance and thereby promotes infection. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease worldwide, driven by the global epidemics of obesity, type 2 diabetes, and metabolic syndrome. In this evolving nosological landscape, alcohol consumption—traditionally excluded from the diagnostic criteria of non-alcoholic fatty liver disease (NAFLD)—has regained central clinical importance. The recently defined MetALD phenotype acknowledges the co-existence of metabolic dysfunction and a significant alcohol intake, highlighting the synergistic nature of their pathogenic interactions. This narrative review provides a comprehensive analysis of the biochemical, mitochondrial, immunometabolic, and nutritional mechanisms through which alcohol exacerbates liver injury in MASLD. Central to this interaction is cytochrome P450 2E1 (CYP2E1), whose induction by both ethanol and insulin resistance enhances oxidative stress, lipid peroxidation, and fibrogenesis. Alcohol also promotes mitochondrial dysfunction, intestinal barrier disruption, and micronutrient depletion, thereby aggravating metabolic and inflammatory derangements. Furthermore, alcohol contributes to sarcopenia and insulin resistance, establishing a bidirectional link between hepatic and muscular impairment. While some observational studies have suggested a cardiometabolic benefit of a moderate alcohol intake, emerging evidence challenges the safety of any threshold in patients with MASLD. Accordingly, current international guidelines recommend alcohol restriction or abstinence in all individuals with steatotic liver disease and metabolic risk. The review concludes by proposing an integrative clinical model and a visual cascade framework for the assessment and management of alcohol consumption in MASLD, integrating counseling, non-invasive fibrosis screening, and personalized lifestyle interventions. Future research should aim to define safe thresholds, validate MetALD-specific biomarkers, and explore the efficacy of multidisciplinary interventions targeting both metabolic and alcohol-related liver injury. Full article

Plant hormones are critical regulators of graft union healing, yet the specific role of exogenous naphthylacetic acid (NAA) in graft union healing efficiency and grafted seedling growth remains unexplored. In this study, we investigated the effects of exogenous NAA treatment (40 mg·L⁻¹) on graft union healing and grafted seedling quality in oriental melon scion grafted onto squash rootstock. Our results demonstrated that exogenous NAA application significantly accelerated vascular bundle reconnection, a key indicator of successful graft union formation. The exogenous NAA treatment enhanced indole-3-acetic acid (IAA) biosynthesis by upregulating key enzymes (TDC, PDC, FMO, NIT, and TAA) and gene expression (CmYUCCA10, CmCYP450, CmoCYP450, and CmoTAA1). The exogenous NAA treatment also upregulated critical graft healing-related genes (CmoWIND1, CmoWOX4, CmoCDKB1;2, CmTMO6, CmoTMO6, CmVND7, and CmoVND7). The exogenous NAA-treated seedlings exhibited better growth. These findings reveal the potential molecular and physiological mechanisms by which exogenous NAA promotes graft union healing of melon grafted onto squash. While the results highlight the potential of exogenous NAA as a grafting enhancer under controlled conditions, further field studies are also needed to validate its practical applicability in commercial production. Full article

Background: Prolactin (PRL) is a key reproductive hormone that regulates follicular development through endocrine and paracrine mechanisms. However, its specific role in porcine follicular development remains unclear. Methods: In the in vivo experiments, follicular fluid and tissue cells were obtained from small (1–2 mm), medium (3–4 mm), and large (5–6 mm) porcine follicles. PRL levels in follicular fluid were measured by ELISA. The expression levels of genes and proteins related to follicular development were assessed using quantitative real-time PCR (RT-qPCR) and Western blotting (WB). In the in vitro experiments, CCK-8, RT-qPCR, and WB were used to detect the effects of different concentrations (0, 30, and 300 ng/mL) of recombinant porcine prolactin (prPRL) on granulosa cell (GC) proliferation, steroid hormone synthesis, and angiogenesis, and transcriptome sequencing was performed. Results: The PRL concentration was significantly higher in large follicles compared to small and medium follicles. During follicular development, expression levels of PRL, PRL receptor (PRLR), proteolytic enzymes (CTSD, MMP2, MMP14, and BMP-1), and angiogenic factors (VEGFA and FGF-2) increased and then decreased. Moreover, prPRL promoted GC proliferation, increased the expression of PCNA and cyclin D1, upregulated steroidogenesis-related genes CYP11A1 and 3β-HSD, and significantly enhanced the expression of key angiogenic factors VEGFA and FGF-2. RNA-seq analysis identified 226 differentially expressed genes (DEGs), which were mainly enriched in signaling pathways such as the Hippo, JAK/STAT, and Rap1 pathways. Conclusions: PRL may regulate porcine follicle development by affecting cell proliferation and angiogenesis in GCs through the Hippo, JAK/STAT and Rap1 signaling pathways. Full article

Tan sheep outperform Dorper sheep in meat-quality traits, including muscle fiber characteristics and fatty acid composition, while Dorper sheep excel in carcass weight. However, the molecular mechanisms underlying these breed-specific traits, especially gut microbiota–bile acid (BA) interactions, remain poorly understood. As host–microbiota co-metabolites, BAs are converted by colonic microbiota via bile salt hydrolase (BSH) and dehydroxylases into secondary BAs, which activate BA receptors to regulate host lipid and glucose metabolism. This study analyzed colonic BA profiles in 8-month-old Tan and Dorper sheep, integrating microbiome and longissimus dorsi muscle transcriptome data to investigate the gut–muscle axis in meat-quality and carcass trait regulation. Results showed that Tan sheep had 1.6-fold higher secondary BA deoxycholic acid (DHCA) levels than Dorper sheep (p < 0.05), whereas Dorper sheep accumulated conjugated primary BAs glycocholic acid (GCA) and tauro-α-muricholic acid (p < 0.05). Tan sheep exhibited downregulated hepatic BA synthesis genes, including cholesterol 7α-hydroxylase (CYP7A1) and 27-hydroxylase (CYP27A1), alongside upregulated transport genes such as bile salt export pump (BSEP), sodium taurocholate cotransporting polypeptide (NTCP), and ATP-binding cassette subfamily B member 4 (ABCB4), with elevated gut BSH activity (p < 0.05). DHCA was strongly correlated with g_Ruminococcaceae_UCG-014, ENSOARG00000001393, and ENSOARG00000016726, muscle fiber density, diameter, and linoleic acid (C18:2n6t) (|r| > 0.5, p < 0.05). In contrast, GCA was significantly associated with g_Lachnoclostridium_10, g_Rikenellaceae_RC9_gut_group, ENSOARG0000001232, carcass weight, and net meat weight (|r| > 0.5, p < 0.05). In conclusion, breed-specific colonic BA profiles were shaped by host–microbiota interactions, with DHCA potentially promoting meat quality in Tan sheep via regulation of muscle fiber development and fatty acid deposition, and GCA influencing carcass traits in Dorper sheep. This study provides novel insights into the gut microbiota–bile acid axis in modulating ruminant phenotypic traits. Full article

Background/Objectives: Recent global trends highlight a concerning rise in youth-onset type 2 diabetes (YOT2D), with a marked female preponderance. We aim to explore the crosstalk between gestational diabetes mellitus (GDM) and YOT2D in female offspring. Methods: In vivo, GDM mice were induced by Western diet (WD), and their female offspring were fed normal diet or WD within 3 to 8 weeks. We continuously detected the glucose metabolism disorders, serum estradiol level (ELISA), and the process of ovarian maturation. Meanwhile, the dynamic changes in ERα and insulin signal in liver were monitored (qPCR, Western blot). In vitro, LO2 cells were treated with estradiol or ER antagonist BHPI to further explore the mechanism. Results: More than 85% of pregnant mice induced by WD were GDM models. The serum estradiol level in GDM offspring mice was decreased during sexual maturation, accompanied by marked oral glucose intolerance, insulin resistance, and even diabetes. The advance of sexual maturation and the decrease in serum estradiol in GDM offspring were mainly due to the downregulation of CYP19A1 in the ovaries, the reduced area of secondary follicles, and the increased number of atresia follicles, which could be greatly worsened by WD. Furthermore, GDM suppressed the protein levels of ERα, p-IRS-1, and p-Akt in liver tissue, that is, estrogen signals and insulin signaling were simultaneously weakened. WD further exacerbated the above changes. In vitro, estradiol upregulated the protein levels of ERα, p-IRS-1, and p-Akt in LO2 cells, while BHPI inhibited these changes. Conclusions: Maternal GDM promotes a high incidence of YOT2D in female offspring by affecting ovarian maturation, and a high-calorie diet exacerbates this process. Full article

The sterol demethylation inhibitors (DMIs) are among the most widely used fungicides for controlling black Sigatoka (Mycosphaerella fijiensis) and yellow Sigatoka (Mycosphaerella musicola) in banana plantations in Brazil. Black Sigatoka is considered more important due to causing yield losses of up to 100% in commercial banana crops under predisposing conditions. In contrast, yellow Sigatoka is important due to its widespread occurrence in the country. This study aimed to determine the current sensitivity levels of Mf and Mm populations to DMI fungicides belonging to the chemical group of triazoles. Populations of both species were sampled from commercial banana plantations in Registro, Vale do Ribeira, São Paulo (SP), Ilha Solteira, Northwestern SP, and Janaúba, Northern Minas Gerais, and were further characterized phenotypically. Additionally, allelic variation in the CYP51 gene was analyzed in populations of these pathogens to identify and characterize major mutations and/or mechanisms potentially associated with resistance. Sensitivity to the triazoles propiconazole and tebuconazole was determined by calculating the 50% inhibitory concentration of mycelial growth (EC₅₀) based on dose–response curves ranging from 0 to 5 µg mL⁻¹. Variation in sensitivity to fungicides was evident with all nine Mf isolates showing moderate resistance levels to both propiconazole or tebuconazole, while 11 out of 42 Mm strains tested showed low to moderate levels of resistance to these triazoles. Mutations leading to CYP51 substitutions Y136F, Y461N/H, and Y463D in Mm and Y461D, G462D, and Y463D in Mf were associated with low or moderate levels of resistance to the triazoles. Interestingly, Y461H have not been reported before in Mm or Mf populations, and this alteration was found in combination with V106D and A446S. More complex CYP51 variants and CYP51 promoter inserts associated with upregulation of the target protein were not detected and can explain the absence of highly DMI-resistant strains in Brazil. Disease management programs that minimize reliance on fungicide sprays containing triazoles will be needed to slow down the further evolution and spread of novel CYP51 variants in Mf and Mm populations in Brazil. Full article

Long non-coding (lnc) RNAs exhibit tissue-specific expression characteristics and have been shown to be involved in the regulation of various biological processes. The testis is one of the organs with the most abundant lncRNAs. However, the functions of many testis-specific or -enriched lncRNAs in male fertility remain undisclosed. In this study, we screened lncRNA 1700009J07Rik (07Rik) to investigate its roles in spermatogenesis and male fertility using knockout (KO) mice. We found that 07Rik mainly acted as an intact lncRNA rather than a small protein, being highly expressed in various spermatogenic cells, which suggests its potential involvement in spermatogenesis. Unexpectedly, the deletion of 07Rik did not impact spermatogenesis or sperm functions. Intriguingly, two-thirds of the male KO were infertile, which was ascribed to the lack of sexual behaviors rather than abnormalities in spermatogenesis or sperm functions. Further results reveal that, compared with wild-type mice, free testosterone content in serum was significantly reduced in the KO infertile (KO-I) mice, whereas it was remarkably elevated in the testes. Correspondingly, Hsd3b2, a key gene that promotes testosterone synthesis, was dramatically upregulated. Cyp19a1 and Cyp11b1, which are responsible for testosterone metabolism, were downregulated in the testes. In addition, the expression of sex hormone-binding globulin was observably elevated in the testes of 07Rik KO-I mice, which might partially explain the decrease in testosterone in the serum. These results suggest that disruptions in testosterone synthesis and metabolism might contribute to the loss of libido in 07Rik KO-I mice. Our findings expand the understanding of lncRNA function and provide novel insights into the role of lncRNAs in male fertility, particularly in relation to hormonal turnover disorders that mediate sexual behavior defects. Full article

Modified biochar can effectively improve the quality and environment of coastal saline–alkali soil, but its effects on the growth and development of halophytes and its mechanism are still unclear. This study systematically evaluated the growth-promoting effects and preliminary mechanisms of H₃PO₄-modified biochar (HBC) and H₃PO₄–kaolinite–biochar composite (HBCK) on the economically important halophyte Kosteletzkya virginica. The results demonstrated that the application of HBC/HBCK significantly enhanced plant growth, resulting in increases of over 55% in plant height and greater than 100% in biomass relative to the control. Multidimensional mechanistic analysis revealed the following: (1) accumulation of nitrogen (N), phosphorus (P), and potassium (K) increased by at least 40%, significantly enhancing nutrient uptake; (2) increases in the activities of superoxide dismutase (SOD) and peroxidase (POD) by over 100% and 70%, respectively, markedly boosting antioxidant capacity and effectively alleviating oxidative stress; (3) molecular regulation via the activation of transcription factor networks (HSP, MYB, TCP, AP2/ERF, bZIP, and NLP) and modulation of key genes in ABA, BR, and JA signaling pathways (CYP707A, CYP90, and OPR2), establishing a multi-layered stress adaptation and growth promotion system. Beyond assessing the growth-promoting effects of modified biochars, this study provides novel insights into the regulatory transcription factor networks and phytohormone signaling pathways, offering theoretical foundations for the molecular design of biochars for saline–alkali soil remediation. Full article

Environmental pollutants like PM2.5 contribute to chronic rhinosinusitis (CRS). The aryl hydrocarbon receptor (AhR), a contaminant sensor linked to tryptophan metabolites, is regulated by IL4I. However, how PM2.5 stimulation via IL4I1 influences AhR activation and CRS pathogenesis remains unclear. This study explored the IL4I1-AhR pathway in CRS using patient tissues, HNEpCs, and murine models. Methods included IHC, qRT-PCR, and WB under PM2.5 exposure, with further investigation into downstream effects on CYP1B1 and epithelial–mesenchymal transition (EMT). Significant upregulation of IL4I1, AhR, and CYP1B1 was observed in CRS tissues, with higher expression levels in CRS patients. Exposure to PM2.5 activated the IL4I1-AhR pathway, leading to decreased E-cadherin, increased N-cadherin and vimentin, and impaired nasal mucosal barrier function. In vitro experiments demonstrated that PM2.5-induced EMT in HNEpCs was mediated by IL4I1-dependent AhR activation. CH223191 reduced cell migration and EMT, while IL4I1 knockdown attenuated AhR activation and EMT marker expression. Murine models further confirmed that PM2.5 exacerbated nasal polyp formation and tissue remodeling via the IL4I1-AhR pathway. This study underscores the critical role of the IL4I1-AhR signaling pathway in PM2.5-induced nasal mucosal barrier dysfunction and EMT in CRS. IL4I1, as an upstream regulator of AhR, promotes EMT and nasal mucosal barrier disruption. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) has become the leading cause of hepatocellular carcinoma and liver disorders globally. Nevertheless, only one expensive drug, resmetirom (Res), has been approved by the FDA for MASH treatment to date. However, its high price has imposed a heavy financial burden on patients. Methods: In this study, half-dose Res and low-dose metformin (Met) (referred to as RM) were administered in combination to treat MASH models in vitro and in vivo. We utilized transcriptome and lipidomics sequencing to assess the efficacy of RM in improving MASH. Our goal was to systemically compare the therapeutic effects of RM, Met, and Res on MASH and elucidate the underlying mechanisms. Results: Our results demonstrated that RM was comparable to Res and superior to Met in reducing lipid production in vitro, attenuating lipid accumulation, inhibiting inflammation, and improving fibrosis in vivo. Transcriptome and lipidome analyses further revealed that RM regulated the expression of genes and lipids in a manner similar to Res, particularly in pathways related to cholesterol metabolism and inflammation. Further validation showed that RM facilitated cholesterol transformation by robustly promoting the expression of CYP7A1, thereby mitigating MASH. Conclusions: Collectively, our findings highlight that a combination of half-dose Res and Met is equivalent to Res alone in terms of MASH treatment efficacy. This study provides a novel therapeutic strategy that is not only effective for MASH treatment but also reduces the economic burden on patients. Full article

Background/Objectives: This study evaluated the potential of a polysaccharide (PCS) extracted from the brown alga Cystoseira spinosa as an antioxidant and anti-inflammatory agent. Collected off the coast of Alkhoms, Libya, PCS was investigated for its wound-healing and pro-angiogenic properties, addressing the need for natural bioactive compounds in therapeutic applications. Methods: The monosaccharide composition of PCS was analyzed using HPLC-RID, identifying glucuronic acid and xylose as major components. In vitro tests assessed antioxidant activity, while in vivo experiments on 24 rats evaluated wound healing. Rats were divided into four groups: control (saline), standard drug (CYTOL CENTELLA cream), glycerol, and glycerol+PCS. Wound healing was analyzed macroscopically, histologically, and biochemically. The chick chorioallantoic membrane (CAM) model assessed pro-angiogenic effects, and computational analyses explored COX-2 and VEGF pathways. Pharmacokinetic properties were also evaluated. Results: PCS demonstrated significant antioxidant activity and accelerated wound healing after 16 days, with improved wound appearance scores and increased collagen content. Histological analysis confirmed PCS outperformed the standard drug. The CAM model showed PCS increased blood vessel density, length, and junctions while reducing lacunarity. Computational analyses supported involvement of COX-2 and VEGF pathways. Pharmacokinetic assessments indicated good bioavailability, non-inhibition of CYP enzymes, and favorable skin permeability. Conclusions: PCS shows promise as a natural bioactive polymer for wound healing and tissue regeneration. Its antioxidant, anti-inflammatory, and pro-angiogenic properties, combined with favorable pharmacokinetics, highlight its therapeutic potential. This study provides new insights into the mechanisms of C. spinosa polysaccharides and their application in promoting tissue repair. Full article

Deficiencies in immune function increase susceptibility to infections and chronic diseases by impairing immune surveillance and tolerance mechanisms, especially in children with immature immune systems. Chronic inflammation associated with immune dysfunction can impair childhood by suppressing the GH–IGF-1. HT042 is composed of Astragalus mongholicus, Eleutherococcus senticosus, and Phlomis umbrosa, which are medicinal herbs that are traditionally utilized in East Asia to promote growth and enhance immune function; thus, HT042 itself holds potential as an immunomodulator. We evaluated the immunomodulatory effects of HT042 in a cyclophosphamide (CYP)-induced immunosuppressed mouse model, as well as in ex vivo primary splenocytes and RAW 264.7 macrophages. HT042 demonstrated remarkable immune-enhancing effects, including the restoration of weight loss and hematological parameters, as well as enhancing NK cell activity. Primary splenocytes treated with HT042 showed increased expression of CD3, CD4, and CD8, along with Th subset transcription factors (T-bet, GATA3, RORγt, Foxp3) and corresponding cytokines (IFN-γ, IL-4, IL-17, IL-10). In RAW 264.7 macrophages, HT042 increased nitric oxide production and upregulated NOS2, COX-2, and inflammatory cytokines (IL-6, IL-1β, TNF-α). It is noteworthy that HT042 enhances both innate and adaptive immune pathways, particularly via T cell modulation and macrophage activation, as this study is among the first to demonstrate such effects in the context of CYP-induced immunosuppression. Full article

Tea plants (Camellia sinensis) are among the world’s most significant economic tree species. Tissue culture serves as a crucial method in commercial breeding by facilitating the rapid propagation of valuable genotypes and the generation of disease-free clones. However, callus browning represents a prevalent challenge in tea plant tissue culture, and may adversely affect explant growth and development. Our research demonstrates that although anti-browning agents can effectively suppress browning, they induce distinct color changes in the callus. These color variations could significantly influence callus induction and subsequent growth patterns. In this study, callus tissues from C. sinensis var. Assamica cv. Mengku were employed as experimental materials and treated with three commonly used anti-browning agents: ascorbic acid (VC), activated carbon (AC), and polyvinylpyrrolidone (PVP). The results demonstrated that while these three reagents effectively inhibited browning, they also induced distinct color changes in the explants, which appeared red, green, and white, respectively. Furthermore, this study investigated the molecular mechanisms underlying callus color changes using transcriptomic and metabolomic approaches. Based on transcriptome analysis, it was revealed that photosynthesis and flavonoid biosynthesis pathways were significantly enriched. Metabolome analysis identified 14 phenolic acids, which exhibited significant variation in accumulation across calluses of different colors. The differential expression of genes involved in flavonoid biosynthesis pathways, coupled with the distinct accumulation patterns of metabolites, can effectively alleviate photooxidative damage and enhance the resistance of callus to browning. AC activates the photosynthesis of callus by regulating carbon source allocation and upregulating the expression of key genes in the psa, psb, and pet families within the photosynthetic system. This process promotes chlorophyll biosynthesis, thereby enabling the callus to grow green, while VC activates the expression of key genes such as CHS, F3H, C4H, CYP75B1, and ANR in the flavonoid pathway, which are involved in the regulation of pigment synthesis in red callus. This study elucidated the molecular mechanisms underlying the effects of anti-browning agents on color variations in C. sinensis callus, thereby providing a robust theoretical foundation for optimization, the establishment of tea plant tissue culture systems, and enhancing cultivar quality. Full article