Search Results (1,995)

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe hepatic steatosis, lobular inflammation, and fibrosis. Although hesperidin, a citrus-derived flavanone, has been reported to exert metabolic and anti-inflammatory effects, its role in severe inflammatory and fibrotic conditions such as MASH remains incompletely understood. This study aimed to evaluate the effects of hesperidin in MASH using integrated in silico and in vivo approaches. Methods: Potential targets of hesperidin were identified using network pharmacology and molecular docking. For in vivo validation, C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for five weeks, with oral administration of hesperidin (150 or 300 mg/kg/day) starting from week two. The MCD model induces severe hepatic inflammation and fibrosis but does not fully reflect metabolic features such as obesity and insulin resistance. Hepatic histology, serum transaminases, immune cell populations, and hypothalamic neuroinflammatory markers were assessed. Results: In silico analyses suggested that hesperidin interacts with key regulators associated with MASH, including PPARG, TGFB1, and TNF. In the in vivo MCD-induced model, hesperidin treatment reduced hepatic lipid accumulation and collagen deposition, accompanied by significant decreases in serum ALT and AST levels (by approximately 30–34% and 42–53%, respectively, depending on dose). These effects were associated with downregulation of pro-inflammatory and pro-fibrogenic gene expression and increased expression of antioxidant markers. In addition, hesperidin decreased circulating Ly6C^high monocytes and hepatic Kupffer cells, along with reduced hypothalamic microglial and astrocyte activation. Conclusions: Hesperidin attenuated key pathological features of MASH, including steatosis, inflammation, and fibrosis, and was associated with modulation of peripheral immune responses and central neuroinflammatory markers. These findings suggest that hesperidin may influence the liver–immune–brain axis and warrant further investigation in models that more closely reflect human metabolic conditions. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive stage of metabolic dysfunction-associated steatotic liver disease characterized by lipid dysregulation, oxidative stress, inflammation, and fibrosis. Because these processes occur simultaneously, compounds targeting multiple pathways may offer therapeutic benefit. Naringin, a citrus-derived flavonoid, has reported antioxidant and anti-inflammatory properties, but its integrated effects in MASH remain unclear. In this study, the effects of naringin were evaluated using combined in silico analysis and in vivo experiments. Network pharmacology and molecular docking predicted targets related to lipid metabolism, oxidative stress, inflammation, and fibrosis, which were validated in a methionine- and choline-deficient diet-induced mouse model. Naringin reduced hepatic lipid accumulation and improved serum AST and ALT levels. It modulated oxidative stress-related genes, attenuated inflammatory responses, and reduced fibrogenic markers. Naringin also decreased Ly6Chigh inflammatory monocytes and Kupffer cell activation, and reduced hypothalamic microglial activation. These findings suggest that naringin exerts multi-target effects across hepatic, systemic, and central pathways, supporting its potential as a therapeutic candidate for MASH. Full article

Phelipanche aegyptiaca is a root parasitic weed that causes severe yield losses in tomato production. Current control methods are constrained by limited efficacy and environmental concerns. Although biocontrol microbes and amino acids have each been reported to suppress broomrape parasitism individually, their synergistic effects and underlying molecular mechanisms remain largely unexplored. This study evaluated the biocontrol performance of Bacillus velezensis strain N35, applied alone or in combination with five amino acids (methionine, isoleucine, valine, histidine, and proline), against P. aegyptiaca parasitism in tomato using pot experiments coupled with transcriptomic profiling of host roots. Both individual and combined treatments significantly reduced the number and fresh weight of P. aegyptiaca parasitic tubercles. Notably, the combinations of methionine + N35 and isoleucine + N35 achieved near-complete suppression of parasitism. Transcriptomic analysis revealed extensive reprogramming of gene expression in tomato roots, with significant enrichment in pathways associated with plant hormone signal transduction, MAPK signaling, phenylpropanoid biosynthesis, and carotenoid biosynthesis. The synergistic treatments coordinately activated ethylene, jasmonic acid, and salicylic acid-mediated signaling, while suppressing auxin and abscisic acid signaling. Moreover, key strigolactone biosynthesis genes (CCD7 and CCD8) were strongly downregulated, and specific genes involved in the biosynthesis of defense-related secondary metabolites were selectively upregulated. Collectively, these findings demonstrate a pronounced synergy between B. velezensis N35 and specific amino acids in suppressing P. aegyptiaca parasitism. This enhanced host resistance is achieved through the coordinated reprogramming of hormonal and metabolic networks, particularly via interference with strigolactone-mediated germination signal secretion. This study provides a theoretical basis for the development of microbe–metabolite synergistic strategies as sustainable and environmentally benign alternatives for broomrape management. Full article

Viruses are key regulators of marine microbial communities, yet their temporal dynamics in tropical intertidal sediments remain poorly characterized. We conducted a year-long metagenomic survey of sandy intertidal sediments in Sanya Bay (60 monthly samples from five sites) to examine viral taxonomy, community structure, lytic proteins, and auxiliary metabolic genes (AMGs). Within the classifiable fraction, the assemblages were consistently dominated by Assiduviridae. However, NMDS analysis revealed a significant overall seasonal shift, with October–December samples separating from the rest of the year. Co-occurrence network analysis identified five co-occurrence modules with distinct temporal patterns, alongside a concurrent decline in module abundance and lytic proteins in October. Functional annotation showed that cysteine and methionine metabolism, primarily driven by DNA methyltransferases, was identified as a highly represented AMG category among the annotated functions, while other pathways displayed seasonal variability. Collectively, these findings suggest that although characterized by a classifiable fraction dominated by Assiduviridae, the highly complex tropical intertidal viral communities undergo substantial seasonal reorganization in structure and functional potential. Full article

The secretome of ESKAPE pathogens, including Klebsiella pneumoniae, comprises a diverse array of bioactive molecules that govern virulence, antibiotic resistance, and the establishment of an immunosuppressive microenvironment. However, the high chemical complexity of the secretome impedes the identification of key metabolites mediating pathogenesis. In this study, we profiled the metabolite composition of cell-free K. pneumoniae supernatant using a combined approach of chromatographic fractionation and Raman spectroscopy. Chromatographic separation enabled the resolution of the complex secretome and revealed fractions with distinct biochemical signatures. A key finding was the identification of Fraction 3, characterized by a unique metabolic profile: it was enriched in nucleic acid fragments, peptides containing tyrosine and methionine, polysaccharides, and stress-response metabolites (e.g., citrate), while notably lacking markers of tryptophan and sterol-like lipids. These spectral signatures suggest a potential role for Fraction 3 metabolites in intercellular communication, biofilm formation, and protection against oxidative stress. The remaining fractions also exhibited distinct biochemical profiles, defined by unique profiles of lipids, nucleotides, and amino acids. Collectively, these data underscore the critical role of specific K. pneumoniae secreted metabolites to pathogen survival and host immune modulation. The combined approach effectively resolves functionally relevant secretome fractions, offering new avenues for identifying diagnostic and therapeutic targets for multidrug-resistant infections. Full article

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a major chronic liver disorder that progresses through inflammation and fibrosis to cirrhosis, yet no effective pharmacological therapy is available. Extracellular vesicles (EVs), which are key mediators of intercellular communication, have recently been reported to exert preventative and therapeutic effects in disease models. This study evaluated the oral efficacy of EVs derived from the microalga Chlorella vulgaris (CEVs) in an MASLD mouse model. Male C57BL/6J mice were assigned to a control group (normal diet), an MASLD group (choline- and methionine-deficient high-fat diet; CDHF), or CEV group (CDHF + CEVs). Twelve-week CEV administration did not alter the CDHF-induced reduction in circulating lipid levels or produce an increase in hepatic lipid content. However, CEV treatment significantly suppressed CDHF-induced fibrosis with collagen accumulation and reduced the mRNA expression of fibrosis-related genes, including Col1a1, Acta2, Mmp2, and Timp1. CEVs also significantly downregulated the expression of macrophage-derived inflammatory mediators—Ccl2, Ccr2, Il6 and Il1b—and reduced lobular inflammatory foci. These findings suggest that CEVs attenuate hepatic fibrosis by modulating early inflammation associated with steatosis and inhibiting hepatic stellate cell activation. This study supports the potential of CEVs as a novel oral intervention for slowing MASLD progression. Full article

Betaine-homocysteine methyltransferase (BHMT) is an enzyme involved in one-carbon metabolism and plays a crucial role in maintaining liver health. In this study, we investigated the impact of liver-specific deletion of BHMT on liver dysfunction using a mouse model. We generated BHMT floxed mice and bred them with albumin Cre to generate liver-specific BHMT knockout (BHMT LKO) mice. Liver tissues harvested from six-month-old chow-fed BHMT floxed and LKO mice were characterized through histological, biochemical, and molecular analyses. BHMT LKO mice displayed a complete loss of hepatic expression of BHMT mRNA, protein and enzyme activity. Histopathological analysis revealed the development of hepatic steatosis in BHMT LKO mice compared to the floxed mice. These morphological changes were supported by biochemical analysis showing elevated levels of hepatic triglycerides in conjunction with a profound decrease in the methylation potential (i.e., reduced S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio), which was mainly driven by a six- to sevenfold increase in SAH levels. BHMT LKO mice also exhibited increased lipid peroxidation and lysosomal dysfunction compared to floxed mice. Early signs of inflammation were seen in the livers of BHMT LKO mice of both sexes, as evident from significant increase in CD68-positive cells and interleukin 1β levels. Additionally, there was a moderate increase in fibrosis, as evidenced by the upregulated expression of α-smooth muscle actin and collagen II levels and the histological assessment of picrosirius red-stained liver sections of BHMT LKO mice of both sexes compared to their respective counterparts. These findings demonstrate that hepatic BHMT deficiency promotes lipid accumulation, lysosomal/proteasomal dysfunction, and early inflammatory and fibrotic changes in the liver by reducing the methylation potential. Collectively, our results underscore BHMT as a critical regulator of liver homeostasis and a potential therapeutic target in liver-related disorders. Full article

Background/Objectives: DNA methylation is a key epigenetic modification involved in regulating many cellular processes, including gene expression and the maintenance of genome stability. Ultraviolet (UV) radiation induces DNA damage in the form of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] and cyclobutane pyrimidine dimers (CPDs), which can lead to mutations if not efficiently repaired. While cytosine methylation has been implicated in influencing UV-induced DNA damage formation, the effect of DNA methylation modulators such as S-adenosyl-L-methionine (SAM) and RG108 on UV damage formation and repair remains unclear. Methods: Here, using immunoslot blot assays, we investigated the effects of SAM and RG108 on UV-induced DNA damage formation and repair in human lymphoblastoid cells. Results: We found that SAM, but not RG108, rapidly suppresses the formation of both (6-4)PP and CPD, with detectable effects within minutes of exposure. Although SAM pretreatment was associated with modestly accelerated early (6-4)PP repair, this effect was accompanied by substantially lower initial damage levels. When cells were treated with SAM or RG108 immediately after UV irradiation to ensure equivalent initial damage burden, no significant differences in repair were observed for either lesion type, demonstrating that the accelerated early (6-4)PP repair reflects reduced lesion burden rather than increased intrinsic nucleotide excision repair (NER). Global 5-methylcytosine (5mC) levels remained stable following SAM or RG108 treatment and during UV damage repair, suggesting that these effects occur independently of global alterations in DNA methylation. Conclusions: Together, our findings reveal that SAM modulates UV damage susceptibility at the level of lesion formation without altering repair, highlighting a previously unrecognized role for DNA methylation modulators in regulating genome stability. Full article

This study evaluated the effects of DL-methionine (DL-Met) and hydroxy–methionine (OH-Met) on the performance and meat quality of finishing pigs raised under intermittent hot environmental conditions. A total of 120 pigs (PIC337 × Camborough; 63.26 ± 4.49 kg initial body weight) were assigned to two dietary treatments in a randomized block design. Growth performance, carcass traits, and physicochemical meat parameters were assessed during the finishing period. Overall performance and carcass characteristics did not differ between treatments (p > 0.05). However, during finishing phase II (141–168 days), pigs fed OH-Met showed higher average daily gain (ADG; 1.027 vs. 0.957 kg/day; p < 0.05) and improved feed conversion ratio (FCR; 2.862 vs. 3.028; p < 0.05) compared with DL-Met. Meat from pigs receiving OH-Met presented a higher pH at 24 h postmortem (5.78 vs. 5.63; p = 0.022) and reduced water loss by pressure (26.14% vs. 28.78%; p = 0.047). No differences were detected for backfat thickness, longissimus dorsi depth, lean percentage, color parameters, or lipid oxidation (TBARS) (p > 0.05). In conclusion, under intermittent heat stress conditions during the late-finishing phase, diets formulated with OH-Met resulted in improved growth efficiency and reduced meat water loss compared with DL-Met diets. Full article

Background: Acute rejection remains a major complication following liver transplantation, yet reliable noninvasive biomarkers for its early prediction and diagnosis remain unidentified. This exploratory study characterized bile and serum metabolites associated with acute rejection in living donor liver transplantation using comprehensive metabolomic profiling combined with machine learning. Methods: Non-targeted metabolomics were performed on bile samples collected on post-operative day (POD) 1 (n = 38) and serum on POD 14 (n = 45) from liver transplant recipients. Partial least squares discriminant analysis-based variable selection was followed by logistic regression and least absolute shrinkage and selection operator models, which were evaluated via cross-validation in the discovery cohort to explore potential biomarkers for acute rejection. Results: A three-variable, bile-based model for predicting acute rejection achieved a mean cross-validated AUC of 0.872 (95% confidence interval: 0.814–0.930). Glycohyocholic acid and sulfolithocholylglycine were the main contributors. A nine-variable serum model for the Rejection Activity Index, including the change in γ-glutamyl transferase, showed a mean cross-validated R² of 0.728 (95% confidence interval: 0.609–0.846), with methionine, creatine, and oxidized fatty acids contributing prominently. Conclusions: These findings suggest that metabolomic profiling combined with machine learning may provide candidate biomarkers for acute rejection after liver transplantation. However, given the exploratory nature of the study and the lack of external validation, the clinical utility of these metabolite signatures remains to be determined. Therefore, external validation in larger, independent cohorts will be required. Full article

This study aimed to evaluate the compensatory effects of amino acid (AA) supplementation on laying hens fed a low-protein diet, focusing on production performance, egg quality, blood immunity, total tract retention, and intestinal health. A total of 180 Hy-Line Brown laying hens (35 weeks old) were randomly allocated to three dietary treatments with 12 replicates (5 hens/replicate): (1) control diet (15.90% crude protein, CON), (2) reduced-protein diet (15.20% crude protein, NG), and (3) reduced-protein diet supplemented with 400 g/t methionine, 400 g/t lysine, and 300 g/t threonine (15.20% crude protein, LAA). Over the 12-week experimental period, production parameters were monitored weekly. The results showed that compared to the NG group, AA supplementation significantly increased laying rates during weeks 1–4 (p < 0.05) and reduced the feed-to-egg ratio during weeks 9–12 (p < 0.05), with a 3.10% decrease in feed conversion ratio (FCR). By week 12, the NG group exhibited lower Haugh unit values than both the CON and LAA groups (p < 0.05), indicating improved egg quality with AA supplementation. Serum analysis revealed elevated immunoglobulin Y levels and upregulated expression of the anti-inflammatory cytokine IL-10 in the LAA group (p < 0.05). Total tract retention of crude protein (CP) and phosphorus (P) was significantly enhanced in the LAA group compared to CON and NG groups (p < 0.05). However, in terms of cecal microbiota, no significant differences were observed among the experimental groups. These findings demonstrate that AA supplementation alleviates the adverse effects of low-protein diets by enhancing nutrient utilization and immune modulation, thereby improving productive performance, egg quality, and total tract retention in laying hens. Full article

While the detrimental effects of high temperature stress on fish growth and disease resistance have been widely reported, its impact on muscle quality has received limited attention. In this study, largemouth bass Micropterus salmoides with an initial body weight of 45.73 g were subjected to a 60-day growth trial (~25 °C), followed by a 5-day acute warming phase and a subsequent 30-day chronic high temperature exposure (32 °C). Through integrated analyses of morphological parameters, texture characteristics, TUNEL assay, gene expression analysis, and metabolomics in muscle, the effects of high temperature stress on the meat quality of largemouth bass were systematically examined. The results showed that high temperature stress significantly upregulated key genes in the ubiquitin-proteasome pathway (trim13, foxo1α) and key genes in the autophagy-lysosome pathways (lc3α, lc3β, bcl2l1, ctsl2), induced apoptosis in muscle cells, and led to significant reductions in myofiber diameter and density. In terms of textural properties, high temperature stress significantly decreased parameters such as springiness, adhesiveness, and cohesiveness, as well as water holding capacity. Metabolomic analysis further revealed that high temperature induced remodeling of energy metabolism and significant reprogramming of purine and amino acid metabolic pathways, resulting in decreased levels of key flavor compounds, including IMP, GMP, flavor amino acids (glutamic acid, alanine, methionine, arginine, proline), and peptides (glu-glu-lys and glu-cys-gly), thereby adversely affecting muscle flavor quality. The findings of this study provide a theoretical basis for understanding the impact of thermal stress on the eating quality of farmed fish. Full article

Background: Rett Syndrome (RTT) is a progressive neurodevelopmental disorder caused by MECP2 gene mutations. MeCP2 protein binding to methylated DNA is involved in normal brain development and function. T158M is a common RTT-associated mutation, where a threonine is replaced with a methionine, affecting protein function and stability. RTT has recently been identified as a neurometabolic disorder, with metformin emerging as a potential candidate drug. Metformin is a safe and accessible drug, commonly used for Type 2 diabetes. Our team previously studied the regulatory role of metformin on the expression of RTT-related genes/proteins using in vitro and in vivo approaches. However, the phenotypical and behavioral impact of metformin in transgenic mice carrying the common T158M mutation was not explored. Methods: Wild type (WT) and mutant Mecp2^T158M (Mecp2^tm4.1Bird) male mice were subjected to daily intraperitoneal injection of metformin for 20 days. The control mice received a daily intraperitoneal injection of the solvent. The main RTT-like phenotypical criteria were assessed daily. Behavioral tests included the open field test and elevated plus maze. Results: Behavioral tests indicated no significant effect of metformin on the anxiety levels, locomotion, and exploratory behaviors in the hemizygous male Mecp2^T158M mice, despite our observation of increased anxiety levels in the WT counterparts. In hemizygous male Mecp2^T158M mice, metformin treatment showed beneficial effects on RTT-like phenotypes, including breathing irregularities, gait abnormalities, hindlimb clasping, and overall total score. The positive effect of metformin was also observed on the body weight in the hemizygous male Mecp2^T158M mice. Conclusions: Our findings provide evidence for potential therapeutic effects of metformin for MeCP2-associated neurological disorders. Full article

Peptide deformylase (PDF) belongs to a conserved enzyme family critical for N-terminal methionine excision (NME), an essential protein maturation process in prokaryotes and eukaryotic organelles (chloroplasts, mitochondria). To explore the potential functions of OsPDFs in Oryza sativa, this study employed bioinformatics approaches and experimental validation to systematically identify and analyze the OsPDF gene family. Three OsPDF genes (OsPDF1A, OsPDF1B, OsPDF1B2) were identified in rice. These genes are exclusively distributed on chromosome 1. The biophysical properties of these proteins showed that OsPDF1A and OsPDF1B are alkaline proteins, while OsPDF1B2 is acidic, and all are hydrophilic with moderate thermostability potential. Synteny analysis revealed closer evolutionary relationships between Oryza sativa and the monocot Triticum aestivum than with dicots, reflecting conserved PDF function in gramineous plants. Analysis of cis-acting elements in the 2000 bp upstream region of OsPDF gene promoters revealed numerous elements associated with abiotic stress response and hormone regulation. Furthermore, quantitative real-time PCR (qRT-PCR) data supported these findings, indicating that OsPDF1A and OsPDF1B were upregulated under low-temperature stress, and all three OsPDF genes were transcriptionally activated by heat, salt and UV-B stresses, indicating their active involvement in rice growth, development, and abiotic stress tolerance. In summary, OsPDFs exhibit significant functions in rice’s stress adaptation, growth, and development. This study not only enhances our understanding of the OsPDF gene family’s genomic, evolutionary, and functional characteristics, but also provides new perspectives and foundational data for further exploring their regulatory mechanisms in protein maturation and abiotic stress responses, as well as their potential applications in rice stress tolerance breeding. Full article

Pyropia haitanensis, an economically significant cultivated seaweed in China, exhibits substantial geographical variations in nutritional and sensory qualities that influence its market value. The nutritional quality of the samples, including total sugar, total protein, and amino acid content, as well as color quality, assessed through phycobiliprotein and chlorophyll content, and sensory quality evaluated using an electronic nose and electronic tongue, were determined. To elucidate these quality variations, this study employed an integrated metabolomics and chemometrics approach to analyze samples from five major cultivation regions. Principal component analysis (PCA) effectively differentiated the samples; orthogonal partial least squares discriminant analysis (OPLS-DA) validated this classification with robust model parameters (R²X = 0.791, R²Y = 0.995, Q² = 0.984) and identified key discriminatory metabolites. Weighted gene co-expression network analysis (WGCNA) identified origin-specific metabolic modules correlated with quality traits, revealing that pathways such as cysteine and methionine metabolism underpin the observed differences in flavor profiles across cultivation regions. Furthermore, mediation analysis quantitatively confirmed that inorganic nitrogen primarily influences key flavor attributes by regulating sulfur-containing amino acid and nucleotide metabolism. This study systematically elucidates the metabolic mechanisms governing quality formation in P. haitanensis, providing a scientific foundation for quality control and geographical origin traceability. Full article