Search Results (13,770)

Herpes simplex virus type 1 (HSV-1) remains a significant pathogen, particularly in immunocompromised patients. The emergence of drug-resistant strains necessitates alternative therapeutic agents. Lentinula edodes (LE), Hypsizygus marmoreus, and Pleurotus eryngii are edible mushrooms with recognized medicinal properties. However, their effects on drug-resistant HSV-1 remain unclear. This study characterized metabolites from high-temperature/high-pressure (121 °C) water extracts of fresh and dried fruiting bodies and evaluated anti-HSV-1 activities using in vitro and in silico approaches. Metabolic profiles were analyzed by electrospray ionization–quadrupole time-of-flight mass spectrometry. Antiviral activity against HSV-1 KOS (wild-type) and HSV-1 dxpiii (drug-resistant) strains was assessed by plaque assays and qPCR. Molecular docking and network pharmacology were performed on candidate compounds. LE extract from dried mushroom tended to show the highest levels of selected major bioactive constituents, along with greater antioxidant activities. All extracts significantly inhibited viral infection and gene expression in both strains. LE extract from dried mushroom modulated the expression of NFKB1 and IL6. Molecular docking analysis revealed that eritanidine showed a predicted binding affinity to HSV-1 DNA polymerase (−7.95 kcal/mol). Additionally, eritanidine, 5′-methylthioadenosine, and 3-indoleacrylic acid were predicted to interact with TNF and MAPK1. Several compounds also demonstrated favorable drug-likeness properties. Overall, these mushroom extracts are promising natural sources of antiviral agents against HSV-1, including drug-resistant variants. Full article

Spermatogenesis is a highly coordinated biological process in which diploid spermatogonia undergo mitotic expansion, meiotic division, and terminal differentiation into haploid spermatozoa. This process is tightly regulated by intrinsic germ cell programs and extrinsic signals from Sertoli cells within the seminiferous epithelium. Among the signaling pathways governing male germ cell development, all-trans retinoic acid (RA), a bioactive metabolite of vitamin A, has emerged as a master regulator of meiotic initiation and spermatogonial differentiation in mammals. RA functions through nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which regulate transcriptional networks essential for germ cell progression, including the activation of Stimulated by Retinoic Acid 8 (STRA8), a key determinant of meiotic entry. Intratesticular RA homeostasis is maintained by a balance between synthesis via aldehyde dehydrogenase (ALDH) enzymes and degradation by cytochrome P450 family 26 (CYP26) enzymes, ensuring precise temporal and spatial control of germ cell development. While rodent models have defined core mechanisms of RA signaling, the canine testis provides a valuable comparative and translational system due to its physiological similarity to human spermatogenesis and relevance to reproductive management. Recent studies highlight conserved RA signaling pathways in dogs, including receptor-mediated transcriptional regulation, feedback control of RA metabolism, and post-transcriptional modulation via microRNAs. Importantly, pharmacological manipulation of RA signaling can reversibly disrupt spermatogenesis, supporting its potential applications in non-hormonal male contraception. This review integrates molecular, developmental, pharmacological, and comparative evidence and presents RA signaling as a central regulatory axis of spermatogenesis with important translational applications. Full article

Chemical analysis of the marine-derived Saccharopolyspora sp. PG10 led to the isolation of a novel macrolactam, cebulactam A₃ (1), along with four known congeners, cebulactams A₁ and A₂ (2 and 3) and shengliangmycins B and D (4 and 5). The structure of 1 was established by high-resolution mass spectrometry (HRMS) and comprehensive nuclear magnetic resonance (NMR) analyses, and its absolute configuration was determined using Mosher’s method. Genome analysis identified a putative biosynthetic gene cluster consistent with a hybrid polyketide pathway. Antimicrobial evaluation revealed that shengliangmycin B exhibited the strongest activity, whereas cebulactam analogs exhibited weaker effects. These findings expand the structural diversity of cebulactam-type macrolactams and provide insights into their stereochemical variation. Full article

Agaricus bisporus (A. bisporus) is susceptible to rapid postharvest deterioration. Although elevated CO₂ (6%) delays senescence, the metabolic mechanisms remain unclear. In this study, untargeted and targeted metabolomic analyses were employed to explore these pathways in A. bisporus. The results revealed that elevated CO₂ treatment promoted glycolysis by upregulating Hexokinase (HK), Phosphofructokinase (PFK), and Pyruvate Kinase (PK), accumulating Glucose-6-phosphate (G-6-P) and Fructose-6-phosphate (F-6-P). Concurrently, elevated CO₂ treatment upregulated the expression of genes associated with the tricarboxylic acid (TCA) cycle and increased the enzymatic activities of Malate Dehydrogenase (MDH) and Fumarate hydratase (FUM). These changes led to the rapid consumption of key intermediate metabolites (Fumarate (Fum), Malate (Mal), and α-Ketoglutarate (α-KG)), collectively enhancing the efficiency of the TCA cycle. Furthermore, elevated CO₂ treatment significantly suppressed the activities of Glutamine Synthetase (GS) and Xanthine Oxidase (XOD), inhibiting the synthesis of Glutamine (Gln) and Pyroglutamate (pGlu) while promoting the accumulation of Hypoxanthine (Hx). This coordinated reprogramming of amino acid metabolism and purine metabolism contributed to improved energy efficiency and enhanced cellular integrity in postharvest A. bisporus. This study elucidates the specific mechanism by which elevated CO₂ levels regulate the postharvest energy metabolism of A. bisporus from a metabolomics perspective, providing a theoretical basis for developing strategies to control its postharvest quality. Full article

The present investigation evaluated the therapeutic potential of ethanol-derived extracts from Kadsura coccinea root (KCR) against alcohol-induced liver injury (ALI) utilizing a murine experimental system. Male Balb/c mice were administered alcohol intragastrically in a stepwise manner over 8 weeks to establish the ALI model. Experimental outcomes demonstrated that KCR administration substantially improved hepatic functional status, evidenced by marked reductions in circulating hepatic enzymes, specifically aspartate aminotransferase (AST) and alanine aminotransferase (ALT). KCR also increased glutathione (GSH) activity, reduced malondialdehyde (MDA) levels in the liver, and exerted antioxidant effects by boosting the expression of enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase 4 (GPX4). Additionally, metabolomic and transcriptomic analyses identified metabolites and pathways closely linked to oxidative stress, including Glutathione metabolism and the MAPK signaling pathway. Further mechanistic studies revealed that KCR could decrease the phosphorylation of p38, JNK, and ERK, while increasing the expression of Nrf2, HO-1, and NQO1. In conclusion, KCR alleviates ALI by modulating the MAPK/Nrf2 pathway, restoring redox homeostasis, enhancing antioxidant defenses, and improving metabolic disorders. Full article

Salt stress is a major abiotic stress that threatens citrus yield and quality. To elucidate the molecular mechanisms underlying differential salt tolerance in citrus rootstocks, we performed an integrative transcriptomic and metabolomic analysis of salt-sensitive trifoliate orange (Poncirus trifoliata) and salt-tolerant Goutoucheng (Citrus aurantium) under 60 mM NaCl treatment for 12 h and 24 h. Physiological observations confirmed that Goutoucheng exhibited less growth inhibition and leaf damage than trifoliate orange. Transcriptome sequencing identified 2081 and 1588 differentially expressed genes (DEGs) in trifoliate orange at 12 h and 24 h, respectively, compared with 1166 and 997 DEGs in Goutoucheng. Metabolome profiling revealed 217 and 173 differentially accumulated metabolites (DAMs) in trifoliate orange versus 162 and 239 DAMs in Goutoucheng at the two time points. KEGG pathway analysis showed that DEGs were mainly enriched in the Mitogen-activated protein kinase (MAPK) signaling pathway—plant, plant hormone signal transduction, and flavonoid biosynthesis—and DAMs were mainly enriched in flavonoid biosynthesis, starch and sucrose metabolism, and glutathione metabolism. Integrative nine-quadrant and two-way orthogonal partial least squares analyses further pinpointed flavonoid biosynthesis as a central hub in salt response. Notably, quercetin derivatives accumulated preferentially in the salt-tolerant rootstock Goutoucheng. Several transcription factor families—including HSF, MYB, NAC, HB-HD-ZIP, C2H2, bHLH, AP2/ERF, and Trihelix—may enhance antioxidant capacity under salt stress by regulating flavonoid accumulation. Collectively, these results indicated that coordinated regulation of flavonoids contributed critically to salt stress adaptation in citrus rootstocks. The identified DEGs, DAMs, and transcription factors provide candidate targets for genetic improvement of salt tolerance in citrus. Full article

Circaea lutetiana (Onagraceae) is a perennial medicinal species widely distributed across temperate forest ecosystems of Europe, Asia, and North America. This mini-review integrates current knowledge on the botanical characteristics, ecological distribution, phytochemical composition, and biological properties of Circaea lutetiana, with particular emphasis on its dominant polyphenolic constituents. Available studies demonstrate that the species is rich in flavonoids, phenolic acids, ellagic acid derivatives, and ellagitannins, among which oenothein B represents a characteristic and major constituent. Beyond polyphenols, structurally characterized glycosides, lipophilic metabolites, phytosterols, triterpenoids, fatty acids, tocopherols, and mineral elements contribute to the chemical complexity of the species. The reported biological activities of Circaea lutetiana, including antioxidant, anti-inflammatory, antihypertensive, and antimicrobial effects, are discussed in relation to the phytochemical profile of the plant and the biological significance of its major constituents. Recent research in green nanotechnology has additionally highlighted the potential of Circaea lutetiana extracts, particularly in the biosynthesis of silver nanoparticles, where plant metabolites act as reducing and stabilizing agents and may contribute to improved antimicrobial performance. Full article

Chronic low-grade inflammation is a hallmark of aging and a major driver of metabolic and degenerative diseases. While systemic immune dysfunction has been widely investigated, the contribution of barrier tissues to persistent inflammatory signaling remains incompletely defined. The oral mucosa represents a uniquely exposed barrier, continuously challenged by microbial, mechanical, and metabolic stressors and characterized by a specialized immune architecture. Here, we synthesize current evidence supporting the oral barrier as an active immunometabolic interface linking local immune activation to systemic inflammatory tone. Spatially organized epithelial, neutrophil, and antigen-presenting cell (APC) compartments coordinate immune responses tightly coupled to metabolic reprogramming, including hypoxia-inducible factor-1α (HIF-1α)-dependent glycolysis and mitochondrial reactive oxygen species (mtROS) production. In parallel, the oral microbiota provides ligands and metabolites such as lipopolysaccharide (LPS), short-chain fatty acids (SCFAs), and succinate, which activate pattern-recognition receptors (PRRs), including toll-like receptors (TLRs) and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, thereby sustaining nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-mediated inflammatory signaling. Barrier disruption and dysbiosis promote microbial translocation and persistent innate immune activation, while saliva and gingival crevicular fluid facilitate systemic dissemination of inflammatory mediators. Overall, sustained immunometabolic engagement at the oral barrier emerges as a key driver of chronic low-grade systemic inflammation and a potential therapeutic target in inflammaging. Full article

Smilacis Glabrae Rhizoma is a traditional Chinese medicine commonly used for hyperuricemia. Engeletin, one of its major flavonoids, exhibits various pharmacological activities, but its in vivo uric acid-lowering activity and metabolic processes remain unclear. This study aims to elucidate the in vivo existence forms of engeletin and the pharmacological basis underlying its uric acid-lowering effects. The in vivo metabolites of engeletin were identified by using UHPLC-Q-TOF-MS. The xanthine oxidase inhibitory activity was investigated using in vitro enzymatic assays. The in vivo uric acid-lowering effect was evaluated in hyperuricemic mice. A total of 11, 34, 7, 6, and 5 compounds were detected in urine, feces, serum, liver, and kidney samples, respectively. After removing duplicates, 52 compounds were preliminarily identified as in vivo existence forms of engeletin. The main metabolic reaction types were glucuronidation, sulfation, and hydrolysis. Engeletin exhibited no xanthine oxidase inhibitory activity in vitro but possessed uric acid-lowering activity in vivo. Neoisoastilbin and naringenin were metabolites with both xanthine oxidase inhibitory activity and uric acid-lowering activity. The in vivo uric acid-lowering activity of engeletin may be attributable to its two metabolites rather than itself. This study elucidated the pharmacological basis of engeletin and laid the foundation for developing potential therapeutics for hyperuricemia. Full article

Botrytis cinerea is a major phytopathogenic fungus responsible for substantial economic losses in horticultural crops, underscoring the need for sustainable alternatives to synthetic fungicides. This study investigated the influence of physical, chemical and biological culture parameters on the antifungal activity of culture filtrates produced by Trichoderma harzianum BOL-12QD. Culture conditions were sequentially optimised by evaluating light-filter exposure, carbon and nitrogen source composition, potato ecotype selection, co-cultivation with Botrytis cinerea, and volatile-mediated interactions. Antifungal activity was assessed using mycelial growth inhibition assays against Botrytis cinerea. Among the individual factors, violet-filter illumination, a medium containing 5 g L⁻¹ glucose and 250 g L⁻¹ potato extract, the Leke Pek’e potato ecotype, ammonium nitrate as nitrogen source, and co-cultivation with Botrytis cinerea at 10⁴ conidia mL⁻¹ produced the highest inhibitory effects. Sequential integration of these optimised conditions resulted in enhanced antifungal activity, reaching up to 62% inhibition. Volatile organic compounds produced by Trichoderma harzianum BOL-12QD exhibited only minimal antifungal activity under the conditions tested, suggesting that volatile-mediated antagonism plays a limited role in this system. In contrast, culture-dependent modulation of extracellular metabolite profiles was evidenced by comparative ¹H NMR fingerprinting, which revealed condition-specific spectral differences, with the optimised treatment displaying a distinct metabolic signature relative to all other conditions. Cytotoxicity assays in murine peritoneal macrophages showed no significant reduction in cell viability at concentrations up to 200 μg mL⁻¹. In vivo exposure to the optimised culture filtrate (250 mg kg⁻¹ d⁻¹ for 10 days) induced transient treatment-related clinical observations without mortality, indicating a need for further detailed toxicological characterisation. Overall, these findings demonstrate that the antifungal activity of Trichoderma harzianum BOL-12QD is strongly modulated by interacting environmental, nutritional and biological culture parameters. The results support the potential of optimised culture filtrates as a source of bioactive metabolites for biocontrol applications, while highlighting the importance of integrated biochemical and toxicological evaluation. Full article

The gut–vagina axis has emerged as a growing area of interest in female health due to its potential role in mediating physiological processes via interactions between distinct microbiomes, including microbial migration, hormonal and immune regulation, and metabolite exchange. Recent advances in microbiome research suggest bidirectional communication between gut and vaginal communities, with potential effects on microbial composition, immune responses, hormonal balance, and metabolic activity in both sites. In this review, we outline the most promising features of the gut–vaginal relationship, emphasize the significance of their plausible bidirectional communication, and discuss how these interactions may affect local and systemic health. Full article

Melittin, the principal active peptide of bee venom, exhibits potent cytotoxicity against cancer cells. However, its lipid-level mechanisms remain unclear. Here, we present the first untargeted lipidomic dataset that reveals melittin-induced lipid remodeling in triple-negative breast cancer (TNBC) cells (MDA-MB-231). Cells were exposed to 4 μg/mL of melittin for 15 min, and lipid extracts were analyzed by employing high-resolution LC–MS/MS in both ion modes. Data were processed with XCMS and metaX for peak extraction, normalization, and metabolite annotation, followed by multivariate and KEGG pathway analyses. The results highlight significant alterations in phospholipids, sphingolipids, and acylglycerols, indicative of melittin-mediated disruption of membrane integrity and lipid metabolism. All raw and processed data are publicly accessible at NGDC (accession number PRJCA048975). This dataset not only serves as a comprehensive resource for investigating lipid-based mechanisms underlying melittin’s anticancer effects but also supports its potential in lipid-targeted therapeutic strategies for TNBC. Full article

Breast cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide. The growing interest in natural bioactive compounds has highlighted plant-derived phytochemicals as promising agents for cancer prevention and adjunctive therapy due to their pleiotropic biological activities and relatively low toxicity. In parallel, increasing attention has been directed toward agro-industrial by-products generated during food processing, which represent abundant and sustainable sources of valuable phytochemicals. This review provides a comprehensive overview of recent advances in the identification, extraction, and biological evaluation of phytochemicals derived from plants and agro-industrial residues, using pomegranate (Punica granatum) peels, onion (Allium cepa) skins, and citrus by-products as representative examples of phytochemical-rich agro-industrial residues. These by-products are rich in polyphenols, flavonoids, and other secondary metabolites—including punicalagins, ellagic acid, quercetin, hesperidin, and naringin—that have demonstrated significant antioxidant, anti-inflammatory, and anticancer properties. Recent in vitro and in vivo studies indicate that these compounds can modulate key molecular pathways involved in breast cancer initiation and progression, such as oxidative stress regulation, apoptosis induction, inhibition of cell proliferation, and suppression of signaling cascades including PI3K/Akt, NF-κB, and MAPK pathways. Furthermore, the valorization of agro-industrial waste offers a sustainable strategy to recover high-value bioactive compounds while reducing environmental impact. Overall, phytochemicals obtained from plant materials and food processing by-products represent promising functional agents for breast cancer prevention and therapy, although further studies are required to improve bioavailability, elucidate mechanisms of action, and validate their clinical potential. Full article

Seasonal variation in aroma quality is critical for commercial grading of Xinyang Maojian (XYMJ) green tea, and how seasonal changes shape its volatile composition and aroma profile remains unclear. This study investigated the volatile profiles of XYMJ harvested in spring, summer, and autumn using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and odor activity value (OAV) analysis. A total of 93 volatile compounds were identified, with alkenes, alcohols, and esters being the most numerous chemical classes. Total volatile content decreased significantly seasonally (p < 0.05), being highest in spring (1716.68 μg/kg), followed by summer (1566.72 μg/kg) and autumn (1378.21 μg/kg). PCA and PLS-DA clearly distinguished seasons. Using a dual-filtering strategy (variable importance in the projection > 1.0 and p < 0.01), 14 differential volatile metabolites were identified as core seasonal markers. Geraniol, cis-jasmone, and indole were identified as key drivers of the premium floral fragrance in spring XYMJ, while cis-3-hexenyl hexanoate and linalool peaked in the summer harvest. OAV results and cross-modal sensory interaction principles suggest that the superior flavor of spring XYMJ arises from both higher aromatic intensity and an optimized aroma-taste balance. These findings provide useful insights into the seasonal variations in the metabolic and chemical profiles of XYMJ, enhancing our understanding of the biochemical markers associated with its production timeline. Full article

Plant-based symbiotic systems are often limited by poor storage stability and inconsistent biofunctional performance. This study evaluated the stability and functionality of a fermented blend based on sacha inchi (Plukenetia volubilis) oil press cake (SIC) and yacon (Smallanthus sonchifolius) flour (YF) as sources of protein and fructooligosaccharides (FOS), respectively, using two processing strategies: fermentation with Lactobacillus rhamnosus (T1) and combined enzymatic hydrolysis with Alcalase and fermentation with Lactobacillus plantarum (T2). Both treatments maintained viable cell counts (VCC) above probiotic thresholds (>10⁶ CFU mL⁻¹) during 28 days of storage at 4 °C, confirming their suitability as probiotic carriers. Notably, T2 significantly enhanced metabolic activity, as evidenced by higher organic acid production and increased soluble protein content due to Alcalase-mediated hydrolysis, which promoted the generation of bioactive peptides associated with improved antioxidant and antihypertensive activities. Biofunctional properties, including total phenolic content, antioxidant capacity (AC), and angiotensin-converting enzyme (ACE) inhibitory activity, remained stable throughout storage, while FOS degradation was minimal, confirming preservation of prebiotic functionality. LC–MS/MS Q-TOF analysis revealed a complex phenolic profile that was differentially modulated by lactic acid fermentation, with L. plantarum (T2) promoting extensive phenolic biotransformation and increased metabolite diversity, whereas L. rhamnosus (T1) largely preserved the original phenolic profile. These findings demonstrate that the synergistic interaction between enzymatic hydrolysis and L. plantarum fermentation promoted peptide release, intensified microbial metabolism, and enhanced phenolic biotransformation, thereby contributing to the superior functional properties observed in T2, while maintaining stable biofunctional characteristics throughout refrigerated storage in both treatments. Full article