Search Results (2,532)

The influenza A virus (IAV) has been responsible for multiple seasonal epidemics and poses a pandemic threat, and the growing number of variant strains constitutes a persistent threat to humanity. This study aimed to identify anti-influenza compounds from a traditional Chinese medicine (TCM) monomer library using a machine learning approach, with calmodulin as a hypothesis-driven target. The antiviral efficacy of the compounds with the highest predicted binding scores from virtual screening was evaluated using integrated computational and experimental approaches. A pre-trained protein language model (ConPLex) was employed for virtual screening. Molecular docking was used to predict binding characteristics, and network pharmacology was applied to generate hypotheses on multi-target mechanisms. The cytotoxicity and anti-H1N1 activity of the selected compounds were assessed in vitro, followed by in vivo evaluation of survival, lung pathology, viral load, and inflammatory mediators in a lethal mouse infection model. Sodium deoxycholate (NaDC) and deoxycholic acid (DCA) were identified as promising lead compounds. Both exhibited dose-dependent inhibition of viral replication in vitro with low cytotoxicity. Treatment with NaDC and DCA significantly improved survival rates and reduced lung pathology in H1N1-infected mice. Treatment was associated with suppression of nuclear factor kappa-B (NF-κB) activation, reduced pro-inflammatory cytokines, and elevated interleukin-10 (IL-10) levels. Molecular docking predictions indicated that NaDC and DCA exhibit moderate binding affinity for calmodulin, with binding energies of −8.38 kcal/mol and −7.61 kcal/mol, respectively. Furthermore, network pharmacology analysis suggested that these compounds may modulate pathways related to viral infection, inflammation, and immune regulation. NaDC and DCA demonstrate anti-influenza activity both in vitro and in vivo, reducing viral replication and alleviating inflammatory lung injury. These findings position NaDC and DCA as promising lead compounds for anti-influenza drug development and provide a foundation for further mechanistic validation. Full article

Juvenile intestinal ischemia–reperfusion (JII/R) is a pediatric surgical emergency caused by mesenteric vessel occlusion and has a high mortality rate. Malrotation can cause intestinal ischemia in infants due to midgut volvulus. It affects not only the intestine itself but also other organs, such as cardiac tissue. Therefore, searching for more effective therapeutic solutions is an essential critical need. This directed our thoughts to evaluate the role of ambrisentan (AMB) in a rat model of induced JII/R by clamping the superior mesenteric artery. Forty juvenile male Wistar albino rats (3–4 weeks old) were randomly divided into four experimental groups: control (CON) group, JII/R group, and AMB-treated groups (30, 60 mg/kg) with JII/R. Induction of JII/R results in significant changes in cardiac enzymes, oxidative stress, inflammatory, and apoptotic parameters with high expression of endothelin receptor A (ERA). Also, histopathological changes revealed extensive mucosal damage, loss of intestinal villi, dysregulated and degenerated cardiac fibers with inflammatory cell infiltration, and tissue necrosis. In contrast, AMB administration significantly reduced the elevated levels of cardiac enzymes, malondialdehyde (MDA), nuclear factor kappa B (NF-κB), ERA, and caspase-3 expression. However, AMB treatment increased immune expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), Ki-67, and mammalian target of rapamycin (mTOR) and showed remarkable improvement in the histopathological changes. AMB could be considered as an adjuvant medical treatment for cases of JII/R. 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

Salmonella primarily affects the gastrointestinal tract, causing local and systemic symptoms. Fucoidan exhibits therapeutic potential against Salmonella-induced pathology; however, the influence of its molecular weight on efficacy remains poorly understood. In this study, low-molecular-weight fucoidan from Undaria pinnatifida (LUPF) was prepared and characterized, and its protective effects against Salmonella infection were evaluated in a mouse model. LUPF effectively mitigated Salmonella-induced multiple organ damage by preserving mucin secretion and tight junction protein expression. Metabolomics analysis further demonstrated that LUPF normalized Salmonella-induced metabolic disturbances, thereby reducing systemic dysfunction. Mechanistically, LUPF suppressed inflammation by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, while alleviating oxidative stress through activation of the Nrf2 pathway. In addition, LUPF restored gut microbiota homeostasis by reducing Proteobacteria levels, improving the Bacteroidota/Firmicutes ratio, enriching beneficial taxa, and enhancing short-chain fatty acid production. In vitro experiments further revealed that LUPF attenuated Salmonella-induced inflammation by modulating macrophage polarization. Collectively, these results suggest that LUPF has promising potential as a prebiotic candidate for reducing the risk of Salmonella-associated diseases. Full article

Associated with high morbidity and mortality, cisplatin-induced acute kidney injury (AKI) is a common clinical complication characterized by oxidative stress, inflammation, and mitochondria-associated signaling. Although multiple signaling pathways have been implicated in AKI progression, effective interventions targeting these complex mechanisms are still lacking. As a medicinal fungus with antioxidant and anti-inflammatory properties, Schizophyllum commune (SC) has shown potential biological activities; however, its renoprotective effects in cisplatin-induced AKI remain unclear. Therefore, this study aimed to investigate SC’s protective effects and underlying mechanisms in a cisplatin-induced AKI mouse model. SC treatment improved renal function and attenuated histopathological damage. It reduced oxidative stress and inflammatory responses, as evidenced by the modulation of malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), and pro-inflammatory cytokines. Mechanistically, SC regulated multiple signaling pathways, including mitogen-activated protein kinase (MAPK), toll-like receptor 4/nuclear factor kappa B (TLR4/ NF-κB), PI3K/AKT, nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1), and the calcium/calmodulin-dependent protein kinase kinase–AMP-activated protein kinase–sirtuin 1 (CaMKK–AMPK–Sirt1) axis. In addition, SC modulated apoptosis, autophagy, and PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy, suggesting improved mitochondrial homeostasis. These findings indicate that SC exerts renoprotective effects and may contribute to cisplatin-induced nephrotoxicity mitigation strategies. Full article

Food-derived bioactive peptides have become a research hotspot in diabetes nutritional intervention due to their high safety, wide availability, and multi-target activities. This review addresses this by proposing a systems biology integration framework that defines these peptides as pleiotropic regulators of the gut microbiota-immune inflammation-metabolic signaling network, offering a novel systems-level perspective beyond previous reviews focused on single enzymes or pathways. The framework consists of three synergistic tiers. Tier 1 inhibits α-amylase, α-glucosidase or dipeptidyl peptidase-IV (DPP-IV) to control postprandial blood glucose. Tier 2 corrects insulin resistance by modulating phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), activating nuclear factor erythroid 2-related factor 2 (Nrf2), and suppressing nuclear factor kappa-B (NF-κB). Tier 3 uses the gut as a hub to remotely coordinate metabolism via the gut–liver and gut–pancreas axes. The review also systematically summarizes the major sources and preparation methods of food-derived antidiabetic peptides, analyzes their advantages including multi-target network regulation, safety, and sustainability, as well as challenges such as oral bioavailability, insufficient clinical evidence, processing stability, and regulatory hurdles. Finally, it outlines future directions focusing on three actionable priorities: AI-assisted design, oral delivery systems, and high-quality clinical studies. This framework offers a new perspective for applying food-derived peptides in precision nutrition intervention for diabetes. Full article

Dendrobium officinale has attracted increasing attention as a functional food because of its diverse biological activities; however, the photoprotective potential of its protein-derived peptides remains poorly understood. In this study, D. officinale protein hydrolysates were fractionated by ultrafiltration according to molecular weight, and their protective effects against ultraviolet B (UVB)-induced photoaging were systematically evaluated in HaCaT keratinocytes. Among the tested fractions, low-molecular-weight peptide fractions exhibited relatively stronger antioxidant activity and effectively reduced intracellular reactive oxygen species (ROS) accumulation in UVB-irradiated cells. In addition, the peptide fractions alleviated UVB-induced inflammatory responses and decreased matrix metalloproteinase (MMP) expression, which was associated with modulation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Higher-molecular-weight fractions showed relatively stronger effects on maintaining skin barrier-related functions and were associated with regulation of transforming growth factor-β/Smad (TGF-β/Smad) signaling and collagen-related protein expression. Overall, these findings demonstrate functional differences among Dendrobium officinale peptide fractions and suggest their potential application as natural photoprotective ingredients in functional foods and cosmeceutical products. Full article

The CD40–CD154 receptor-ligand axis is a core costimulatory regulator of antiviral immunity in mammals, but its functional role in teleosts remains largely unknown. Here, we identified the CD40 and CD154 homologs (MsCD40 and MsCD154) from largemouth bass (Micropterus salmoides), a globally farmed perciform teleost. Bioinformatic analysis confirmed that MsCD40 and MsCD154 harbor the conserved domain architectures of tumor necrosis factor receptor superfamily and TNF superfamily, respectively, with a teleost-specific phylogenetic clustering pattern. Both genes were ubiquitously expressed in immune-relevant tissues, and their transcription was dynamically regulated in response to viral hemorrhagic septicemia virus (VHSV) and largemouth bass virus (LMBV) challenge in vivo. Co-immunoprecipitation and immunofluorescence co-localization assays verified that MsCD40 and MsCD154 physically interact at the plasma membrane, forming a functional receptor-ligand complex. Functional assays showed that overexpression of either MsCD40 or MsCD154 significantly suppressed VHSV and LMBV infection in vitro. Furthermore, MsCD40 and MsCD154 overexpression dose-dependently activated nuclear factor-κB (NF-κB) reporter activity, and markedly upregulated the transcription of NF-κB downstream effector genes, including IL-8, NLRP3 and P105, under both VHSV and LMBV infection. Collectively, our findings demonstrate that the teleost CD40–CD154 costimulatory axis restricts both RNA and DNA viral infection in largemouth bass through NF-κB-mediated immune activation, which provides promising molecular targets for the development of broad-spectrum antiviral strategies in largemouth bass aquaculture. Full article

Background: Metabolic-associated fatty liver disease (MAFLD) has a high prevalence of 30–40% in China and Asia, with a complex pathogenesis and no specific therapeutic drugs. Phytochemicals have become a research hotspot for MAFLD prevention, and ginsenosides, the core active components of Panax ginseng, show great potential in anti-MAFLD research. This review aims to comprehensively clarify the key mechanisms and targets of ginsenosides in preventing and treating MAFLD, to provide a theoretical basis for their application in metabolic diseases, and to promote the development of natural phytochemical resources. Method: The literature review method was adopted to sort out the regulatory effects and molecular targets of ginsenosides in multiple pathological processes of MAFLD from published studies. Results: Ginsenosides regulated MAFLD through multi-pathway and multi-target effects: antioxidant regulation occurred via Nuclear factor E2-related factor 2 (Nrf2)/Silent information regulator 1/6 (SIRT1/6) pathways, and anti-inflammatory regulation was achieved by inhibiting the Nuclear factor kappa-B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Additionally, the measures adopted improved insulin resistance and lipid metabolism disorder, suppressed hepatocyte apoptosis/pyroptosis, repaired autophagy, alleviated hepatocyte senescence, and reshaped gut microbiota to restore gut–liver axis homeostasis. Conclusions: Ginsenosides have good potential for MAFLD prevention and treatment, but there is a prominent lack of human clinical evidence as most existing studies are only based on in vitro cell and in vivo animal models, and the synergistic mechanisms among different ginsenoside components remain unclear. Future research needs multi-omics analysis, formulation optimization, and large-sample clinical trials, and ginsenosides have broad application prospects in MAFLD intervention. Full article

Gingivitis, periodontitis, and stomatitis are common oral inflammatory disease affecting a large proportion of the global population. Increasing attention has recently been given to the development of health functional materials aimed at maintaining oral health and preventing microbial-associated oral disease. This study evaluated the efficacy of the lipoteichoic acid (LTA) fraction derived from the probiotic Lactiplantibacillus plantarum K8 (pLF) in preventing oral inflammation and microbial infection using the oral epithelial cell line YD-38. The results confirmed that pLF enhances the expression of interleukin-1 receptor-associated kinase M (IRAK-M), a negative regulator of Toll-like receptor (TLR) signaling, and inhibits the expression of pro-inflammatory cytokines, including C-C motif ligand 2 (CCL2), interleukin-6 (IL-6), and interleukin-8 (IL-8), in YD-38 cells stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Furthermore, it was demonstrated that pLF induces IRAK-M expression in a TLR2-involved manner and inhibits nuclear factor-kappa B (NF-κB) signaling, thereby reducing the expression of pro-inflammatory cytokines. pLF also exhibits oral antimicrobial efficacy by increasing the expression of the antimicrobial peptide human β-defensin 1 (hBD1) and human β-defensin 2 (hBD2) in a TLR2-involved manner and effectively inhibiting the growth of Porphyromonas gingivalis and Staphylococcus aureus in the epithelial cell associated system. Therefore, the LTA fraction derived from L. plantarum K8 represents a promising postbiotic candidate for the regulation of oral immune and microbial responses. Full article

Oligodendrocytes (OLs) are specialized glial cells essential for the formation and maintenance of the myelin sheath within the central nervous system (CNS). Historically, OLs were considered a functionally homogeneous population. However, the advent and widespread application of single-cell and single-nucleus RNA sequencing (scRNA-seq/snRNA-seq) technologies since 2015 have revealed substantial transcriptional heterogeneity, varying according to developmental stage, anatomical region, and disease state. In this review, we synthesized current advances in the understanding of OL heterogeneity. Nine OL cell classes have been identified in the mouse somatosensory cortex and hippocampal CA1 region, later expanding to 13 distinct subpopulations across ten CNS regions. Furthermore, we characterized disease-associated oligodendrocytes (DAOs)/disease-associated oligodendrocyte lineages (DOLs), identified in various neurological diseases, including multiple sclerosis (MS), Alzheimer’s disease (AD), and spinal cord injury, focusing on their molecular markers, spatial distribution, and pathophysiological roles. We summarized key transcriptional regulatory networks underlying DAO induction, including the signal transducer and activator of transcription (STAT)/interferon regulatory factor (IRF) family, the Yin Yang 1 (YY1)/nuclear factor kappa B (NF-κB) axis, and the SOX9/SOX10 regulatory system. The utility of region-specific brain analyses using spatial transcriptomics (ST) in conjunction with these approaches was also discussed. Finally, we compiled the implications of patient stratification according to white matter glial response patterns derived from large-scale snRNA-seq analyses of patients with progressive MS. Our synthesis shows that oligodendrocytes consist of multiple distinct subtypes that vary across development, brain regions, and disease conditions. In pathological states, they adopt specific disease-associated programs that reflect context-dependent responses and may influence disease progression and repair. This work provides a framework for understanding how oligodendrocyte diversity contributes to neurological disease and may support the development of targeted remyelination therapies. Full article

Food and medicine homology (FMH) substances are increasingly utilized as nutritional and medicinal resources in sustainable livestock production. Their active ingredients include polysaccharides, flavonoids, and terpenes, which may positively affect livestock meat quality by maintaining gut microbiota homeostasis, enhancing intestinal barrier function, and facilitating nutrient absorption, as well as regulating key signaling pathways such as mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and nuclear factor-κB (NF-κB). Notably, the meat quality improvement can also be indirectly achieved via the gut–muscle axis. Gut microbiota metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and amino acid derivatives, modulate microbial homeostasis, intestinal barrier function, and nutrient absorption through the gut microbiota–metabolite axis, gut–immune axis, and nutrient absorption–signaling axis. These processes remotely regulate skeletal muscle metabolism, inflammation, and fiber type transformation, ultimately influencing meat tenderness, flavor, juiciness, and nutritional value. Despite their potential to reduce reliance on antibiotic growth promoters and enhance meat quality, multiple challenges persist, including complex component profiles, elusive mechanisms, undefined dose–effect relationships, inadequate standardization, insufficient safety evaluation and scarce direct trials on livestock meat quality endpoints. This review summarizes FMH substances that modulate the gut–muscle axis in meat quality regulation across different animal species and outlines their application prospects, aiming to facilitate antibiotic-free agriculture, the development of green functional feeds, and sustainable animal husbandry. Full article

Acute kidney injury (AKI) is a life-threatening event prevalent in hospitalized patients but also not rare among endurance sports athletes. Hypoxia, oxidative stress, and sterile inflammation are the key pathophysiological factors driving kidney damage in AKI. Zinc is an essential trace element required for the intact function of approximately 3000 proteins (~10% of the human proteome), including over 300 enzymes for which zinc serves as a cofactor. Cell biological tasks of zinc signaling include adaptive responses to hypoxia and oxidative stress, as well as anti-inflammatory effects. The underlying molecular pathways involve modulation of hypoxia-inducible factor signaling, suppression of reactive oxygen species (ROS) generation, and inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the latter being the major pro-inflammatory transcription factor. As a catalytic cofactor for the “classical” histone deacetylases, zinc is essential for epigenetic control of gene expression, thereby exerting further adaptive effects. Apart from the intracellular zinc signaling, extracellular zinc elicits cytoprotective and anti-inflammatory effects via the G Protein-Coupled Receptor 39 (GPR39). GPR39 activation by zinc binding may exert antioxidant and anti-inflammatory effects mediated by the zinc-finger protein A20 (TNFAIP3) and NF-κB suppression, followed by reduced production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), and IL-6. At the same time, GPR39 signaling may stimulates the release of the anti-inflammatory cytokine IL-10, thus shifting the kidney tissue towards an anti-inflammatory milieu, promoting renal recovery. The present review focuses on the role of zinc in AKI to identify potential therapeutic strategies targeting zinc signaling for renoprotection and biomarker-based risk stratification. Full article

Ultraviolet A (UVA) radiation disrupts the redox balance of melanocytes and may lead to the development of melanoma, highlighting the need for new skin protection strategies. This study assessed the effect of phytocannabinoids [cannabigerol (CBG), cannabidiol (CBD), and CBG + CBD] on redox homeostasis in control and UVA-exposed melanocytes and in melanoma cells (SK-Mel-5). UVA radiation increased the activity of prooxidant enzymes in both melanocytes and SK-Mel-5 cells and, consequently, the level of reactive oxygen species (ROS) (approx. 2-fold). It also activated nuclear factor erythroid 2 (Nrf2), as reflected by increased expression of heme oxygenase 1 (HO-1) (melanocytes approx. 2-fold; SK-Mel-5 approx. 7-fold). Concomitantly, antioxidant mechanisms were impaired, as demonstrated by reduced superoxide dismutase (SOD1/SOD2) activity and impaired glutathione and thioredoxin function. These changes were accompanied by increased levels of oxidative damage markers (isoprostanes, 4-hydroxynonenal-4-HNE, and 4-HNE-protein adducts) (43–100%) and increased inflammatory signaling, including increased expression of nuclear factor kappa B (NF-κB) subunits (melanocytes: p52 ~2-fold, p65 ~75%; SK-Mel-5: ~4–4.5-fold) and tumor necrosis factor alpha (TNF-α; ~30%). Phytocannabinoid treatment modulated these UVA-induced changes. In SK-Mel-5 cells, phytocannabinoids normalized the activity of prooxidant enzymes and consequently reduced ROS levels (~30%). They also reduced Nrf2 activation and HO-1 expression; however, CBG increased HO-1 level in melanocytes (~25–40%). Furthermore, phytocannabinoids enhanced antioxidant defense by increasing SOD activity, particularly in melanocytes (~10–40%), and restoring the glutathione and thioredoxin systems. Markers of oxidative damage were reduced by approximately 23–37% after treatment. Furthermore, phytocannabinoids attenuated NF-κB activation (p52 ~18–28%, p65 ~25–29% in melanocytes; ~20% in SK-Mel-5), while TNF-α levels remained unchanged. The effects in non-irradiated cells were modest (<15%). These results suggest that phytocannabinoid-mediated modulation of redox balance may stabilize melanocytes exposed to UVA radiation and potentially reduce the risk of neoplastic transformation. However, the observed protective effects in SK-Mel-5 cells require further investigation and detailed molecular analysis. Full article

Postbiotics are increasingly recognized as a predominant group of biotherapeutic agents sourced from the microbial secretome, offering functional benefits, while circumventing the safety concerns associated with the application of live microbial consortia. These microbial derivatives are emerging as promising approaches for tackling complex diseases, encompassing cancer, autoimmune diseases, and metabolic disorders, through modulation of host cell signalling pathways, including G protein-coupled receptors (GPCRs), the NF-κB (Nuclear Factor Kappa B) pathway, and epigenetic regulatory pathways. Besides systemic effects, postbiotics may also have localized effects, such as epithelial regeneration, modulation of fibroblast functions, and control of collagen remodelling. Eventually, the scale-up in the production of postbiotics has initiated new avenues in improving sustainable agriculture and environmental biotechnology. This comprehensive review attempts to integrate mechanistic insights and translational applications, highlighting the therapeutic potential of postbiotics across biomedical and ecological domains. These observations could pave the way to bridge the gap between microbiome regulation, precision medicine, and sustainable biotechnology, thereby positioning postbiotics as a versatile tool addressing some of the most pressing health and sustainability challenges of the 21st century. Full article