To investigate the mechanism of poricoic acid A (PAA) for alleviating dextran sulfate sodium (DSS)-induced colitis in mice. Eighteen C57BL/6 mice were randomly divided into control group, DSS-induced colitis model group, and PAA intervention (10 mg/kg) group. The changes in body weight, colon length, disease activity index (DAI), and histopathological scores of the mice were evaluated. In a DSS-induced Caco-2 cell model, the changes in expressions of ZO-1, claudin-1, Bcl-2, Bax, cleaved caspase-3, LC3-II/I, and P62 were detected. Molecular docking and Western blotting were used to analyze the mechanisms underlying the ameliorating effect of PAA on DSS-induced colitis. In the mouse models of DSS-induced colitis, PAA significantly ameliorated DSS-induced weight loss, colon shortening, and elevation of DAI scores while reducing colonic IL-1β and TNF-α levels. HE staining showed that PAA obviously alleviated colonic crypt damage, reduced inflammatory cell infiltration, and lowered histopathological scores of the colon. AB-PAS staining revealed significantly increased goblet cell counts in PAA-treated mice compared to those in DSS group. In DSS-induced Caco-2 cells, PAA treatment effectively inhibited DSS-induced downregulation of the tight junction proteins, reduced Bax and cleaved caspase-3 expressions, increased Bcl-2 expression and the LC3-II/I ratio, and decreased P62 expression. Mechanistic study suggested that PAA targeted the AMPK/mTOR pathway to activate autophagy and suppress cell apoptosis. PAA protects intestinal barrier function and alleviates DSS-induced colitis in mice by activating AMPK/mTOR-mediated autophagy and inhibiting intestinal epithelial cell apoptosis.

Alcohol-associated liver disease (ALD), characterized by gut barrier disruption and microbial dysbiosis, is associated with significant depletion of the genus Bifidobacterium in patients, as evidenced by our cohort of 127 subjects. Functional screening revealed B. pseudocatenulatum as a protective strain. In a murine ALD model established with a Lieber-DeCarli ethanol diet, oral administration of B. pseudocatenulatum for 8 weeks ameliorated hepatomegaly, steatosis, and serum transaminase levels. Probiotic intervention restored intestinal barrier function, as indicated by reduced lipopolysaccharide-binding proteins and upregulated tight junction protein expression. Microbiome analysis revealed a mitigation of dysbiosis, with a reduction in pathogenic Escherichia-Shigella and Parabacteroides and an enrichment of beneficial Bifidobacterium and Blautia, concomitant with shifts in lipid metabolism. Mechanistically, B. pseudocatenulatum-derived short-chain fatty acids downregulated the expression of hepatic lipogenic genes (Cd36, Fasn, Accα) and pro-inflammatory cytokines (Il-1β, Ccl2, Tnf-α). These results suggest that B. pseudocatenulatum is a promising probiotic candidate for ALD management.

The purpose of this research was to investigate how adding dietary guar gum to high‐lipid diets affected the fish growth and gut health of common carp (Cyprinus carpio). A normal‐lipid diet (5% crude lipid; control) and four high‐lipid diets (10% crude lipid) with 0% (high‐fat [HF]), 0.3% (GG0.3), 1% (GG1), and 3% (GG3) of guar gum were developed and fed to fish (4.53 g) for 8 weeks. The findings showed that HF induced impairment of intestinal morphology and mucosal barrier, oxidative stress, gut dysbiosis, and gut inflammation. Compared to the HF, guar gum‐containing diets substantially improved gut villus height, upregulated the expression levels of nuclear factor erythroid 2-related factor 2 and zonula occludens-1, and downregulated the expression levels of toll-like receptor 1 (tlr1), tlr5, myeloid differentiation factor 88, interleukin-1β (il-1β), il-6, and il-8. Moreover, the GG0.3 and GG1 diets dramatically increased catalase (cat) and occludin expression levels. Furthermore, the GG1 and GG3 diets improved the microbiota composition by increasing Fusobacteria and Cetobacterium abundance while lowering Proteobacteria, Acidovorax, Acinetobacter, Serratia, and Comamonas abundance. Correlation analysis revealed that guar gum improved gut health by modulating gut microbiota and tight junction proteins. The findings indicated that guar gum can ameliorate HF diet‐induced intestinal damage in fish.

Introduction Avian pathogenic Escherichia coli (APEC) poses a serious challenge to global poultry production, where it causes enteritis, septicemia, and high mortality, resulting in substantial economic losses. Although antibiotics have been traditionally used to control APEC, the rise of antimicrobial resistance and concerns over drug residues underscore the need for effective and sustainable alternatives. Probiotics have emerged as promising candidates because of their ability to modulate the intestinal microbiota, strengthen host immunity, and preserve epithelial barrier integrity. In this study, we investigated the protective role of Lactobacillus plantarum ZG-7 against APEC infection in Muscovy ducks. Methods 40 one-day-old ducks (equal numbers of males and females) were randomly allocated to five groups (n = 8 per group): control (CON), probiotic alone (LP), APEC-infected (EC), probiotic-pretreated APEC-infected (LPEC), and colistin sulfate-treated APEC-infected (CSEC), with the latter serving as a positive control and exhibiting expected protective effects. On day 7, ducks in the EC and LPEC groups received two oral doses of pathogenic E. coli O78 (3 × 10^9 CFU/mL, 0.2 mL) at an 8-hour interval, while ducks in the CON and LP groups received sterile saline. Serum and intestinal samples were collected on day 15. Results APEC infection significantly reduced average daily gain during days 9–15 and across the trial. Histopathological analysis showed epithelial disruption, crypt and gland loss, reduced goblet cells, diminished mucus secretion, and decreased expression of tight junction proteins (ZO-1, MUC2, Occludin). In contrast, L. plantarum ZG-7 treatment alleviated intestinal injury and restored growth performance. 16S rRNA sequencing further revealed that APEC challenge increased the abundance of unclassified Lachnospiraceae, Lachnoclostridium, norank RF39 group , and Paludicola ( P < 0.05), whereas L. plantarum ZG-7 treatment reduced these taxa. Moreover, probiotic supplementation alone significantly enriched Bacteroides ( P < 0.001). Discussion Taken together, these results demonstrate that L. plantarum ZG-7 helps maintain a beneficial microbial composition, protects epithelial barrier function, and mitigates the adverse effects of APEC infection in Muscovy ducks, highlighting its potential as a natural and sustainable alternative for improving poultry health.

Introduction Lactiplantibacillus plantarum ( L. plantarum ) has been reported to attenuate ulcerative colitis (UC) and restore intestinal barrier integrity. However, it remains unclear whether culture supernatant or extracellular vesicles (EVs) are more effective. Methods UC was induced in mice to compare the effects of L. plantarum 25 (LP25) supernatant and EVs on disease severity, survival, and tight junction protein expression. Gut microbiota and metabolism were analyzed by 16S rRNA sequencing and untargeted metabolomics. In vitro , LPS-stimulated Caco-2 cells and a Caco-2/RAW 264.7 co-culture model were used to evaluate barrier integrity, immune responses, and TLR4/NF-κB pathway activation. Results Compared with EVs, LP25 supernatant significantly improved survival, alleviated disease severity, preserved tight junction protein expression, modulated gut microbiota, enhanced intestinal functional protein expression, and inhibited macrophage TLR4/NF-κB activation. Discussion LP25 supernatant exerts superior protective effects compared with EVs in alleviating UC and maintaining intestinal barrier function, highlighting its potential as a functional component for dietary interventions targeting inflammatory bowel diseases.

To investigate the ameliorative effects of quercetin (QE) on spermatogenic function and elucidate the underlying molecular mechanisms in vivo. Thirty male C57BL/6 mice (6-8 weeks old) were randomly divided into 5 groups using a random number (n=6 per group): control, triptolide (TP) model (0.1 mg/kg per day), and different doses of quercetin (QE) treatment groups (25, 50, and 100 mg/kg per day, intragastrically). Except for controls, all mice received TP to induce spermatogenic impairment, with concurrent QE administration in treatment groups. The intervention lasted 35 days, covering 1 complete spermatogenic cycle, and mice were euthanized on day 38. Histopathological damage and apoptosis in spermatogenic cells were evaluated using hematoxylin and eosin (H&E) staining, TUNEL assay, and Western blot analysis for Bcl-2, Bax, and cleaved caspase-9. Blood-testis barrier (BTB) integrity was assessed by immunofluorescence and Western blot for tight junction proteins, including zonula occludens-1 (ZO-1) and junctional adhesion molecule A (JAMA). The PI3K/AKT signaling pathway was investigated through Western blot analysis of PI3K, AKT, and phosphorylated AKT (p-AKT). Network pharmacology and molecular docking simulations were performed to predict QE's molecular mechanisms, followed by experimental verification. QE treatment significantly ameliorated TP-induced testicular damage, increased spermatogenic epithelial thickness and spermatogonial tubule diameter, and decreased apoptosis of spermatogenic cells (P<0.05 or P<0.01). QE also improved the distribution and expression of key BTB proteins, including ZO-1 and JAMA (P<0.05 or P<0.01). Network pharmacology and molecular docking studies suggested that QE influences the PI3K-AKT signaling pathway, which was confirmed by increased AKT phosphorylation levels observed in Western blot results (P<0.05 or P<0.01). QE can mitigate TP-induced spermatogenic dysfunction, reduce apoptosis of spermatogenic cells, and preserve BTB structural integrity by upregulating the PI3K-AKT signaling pathway. QE may be a potential therapeutic agent for treating TP-induced spermatogenic disorders.

I3C protects IPEC-J2 cells by inhibiting ferroptosis through activation of the AhR-Nrf2-SLC7A11-GPX4 pathways.

Remdesivir alleviates inflammation and tissue damage in experimental colitis via AnxA5 Signaling.

Exogenous IL-33 mitigates inflammatory responses by suppressing the NF-Κb signaling pathway, promoting blood-spinal cord barrier repair and neural functional recovery.

Dietary inulin mediates the molecular mechanism of intestinal metabolites to alleviate high salt diet-induced chronic kidney disease in mice.

BACKGROUNDUlcerative colitis (UC) is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe. Cedrol (CE) is a bioactive natural product present in many traditional Chinese medicines. It is known for its suppression of inflammation and mitigation of oxidative stress. Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIMTo investigate the therapeutic potential and mechanisms of CE in UC.METHODSThe anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model. Network pharmacology was employed to predict potential targets and pathways. Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. The anti-inflammatory mechanisms were further verified using in vitro assays. Additionally, the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTSCE significantly alleviated colitis symptoms, mitigated histopathological damage, and suppressed inflammation. Moreover, CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins (zonula occludens 1, occludin, claudin-1). Mechanistically, CE stably bound to MD2, inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells. This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, downregulating the expression of tumor necrosis factor-alpha, interleukin-1β, and interleukin-6. Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSIONCE acted on MD2 to suppress proinflammatory cascades, promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.

Pediatric asthma, a chronic respiratory disorder characterized by airway inflammation and remodeling, is increasingly linked to epigenetic dysregulation of the airway epithelial barrier. This review explores how DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) impair epithelial integrity, amplify immune responses, and sustain chronic inflammation and tissue remodeling. Aberrant methylation of barrier-related genes (FLGs, CLDNs) disrupts tight junctions and enhances allergen penetration. Methylation abnormalities of immune regulators (IL-13, ALOX12) drive Th2-mediated inflammation, with environmental pollutants such as PM2.5 exacerbating these changes. Elevated H3K27me3 levels and histone deacetylase (HDAC) overactivation suppress immune tolerance genes (e.g., IL-4) and compromise junctional proteins (e.g., occludin), whereas HDAC inhibitors demonstrate preclinical efficacy in restoring barrier function. Dysregulated ncRNAs, such as miR-21 and miR-146, modulate inflammatory pathways, with miR-146a mimics reducing eosinophilic inflammation via NF-κB inhibition. Clinically, epigenetic biomarkers such as ALOX12 hypomethylation have diagnostic potential for asthma phenotypes. Emerging therapies, including DNA methyltransferase inhibitors (5-azacytidine) and HDAC inhibitors (vorinostat), show promise but face challenges such as limited clinical validation and discrepancies between animal models and human disease. Future priorities involve integrating multi-omics approaches to unravel the complexity of asthma, optimizing non-invasive biomarker detection, and developing personalized therapies tailored to epigenetic profiles. By bridging mechanistic insights with clinical innovations, epigenetic strategies may revolutionize precision medicine in pediatric asthma management.

Background and aim Hydrogen sulfide (H2S) is a common gas with an unpleasant odor similar to rotten eggs. The extent of injury from inhaled H2S depends on the gas concentration. Chronic exposure to H2S has been reported to cause immunotoxicity and inflammatory effects in the lung. However, the molecular mechanisms underlying lung injury induced by continuous, low-concentration H2S exposure remain unclear. Experimental approach Twenty male ICR mice, 6–7 weeks old, were randomly assigned to two groups. The control group was exposed to clean air (21.9% O2, 0 ppm H2S), while the H2S group was exposed to air containing H2S (21.9% O2, 5 ± 1 ppm H2S) for 21 days. Key findings and conclusions Inhaled H2S induced pulmonary injury and fibrosis, promoted the release of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and inhibited the anti-inflammatory cytokine IL-10. Additionally, H2S inhalation altered the expression of occludin, a tight junction–related protein. These findings enhance understanding of H2S-associated occupational health risks.

Bluetongue virus (BTV) infects various ruminant species, posing significant threats to animal health and causing substantial economic losses to the livestock industry. Ovine type II alveolar epithelial cells (OAECIIs) play crucial roles in maintaining pulmonary structural integrity and modulating immune responses. Their dysfunction is closely associated with lung disease pathogenesis, making them important therapeutic targets. However, OAECIIs’ immunoregulatory functions and early response mechanisms during BTV infection remain unclear. To address this, we analyzed transcriptomic changes in OAECIIs following BTV-1 infection. RNA-seq revealed 1047 and 852 differentially expressed genes (DEGs) at 8 and 12 h post-infection (hpi), respectively, compared to uninfected controls. Bioinformatics analysis showed significant upregulation of nucleic acid-sensing receptors, interferon-stimulating factors, inflammatory mediators, and cytokines during early infection, mediated primarily through type I interferon signaling, TNF signaling, and cytosolic DNA-sensing pathways. We identified MAD5, ZNFX1, cGAS, OAS, PKR and ZBP1 as key pattern recognition receptors in OAECIIs during BTV infection. The IFN-β, MX1/2, RSAD2 and PLSCR1 pathways mediated antiviral responses, while IL-15, CXCL10, CCL2 triggered inflammatory responses, collectively causing structural alterations through AQP1/9 and tight junction protein modulation. These findings provide critical insights into early antiviral mechanisms and cellular structural changes in OAECIIs during BTV infection, establishing a foundation for understanding pneumonia pathogenesis and developing targeted BTV therapies.

Peptide-based biomaterials have emerged as versatile tools for pharmaceutical drug delivery due to their biocompatibility and tunable sequences, yet a comprehensive overview of their categories, mechanisms, and optimization strategies remains lacking to guide clinical translation. This review systematically collates advances in peptide-based biomaterials, covering peptide excipients (cell penetrating peptides, tight junction modulating peptides, and peptide surfactants/stabilizers), self-assembling peptides (peptide-based nanospheres, cyclic peptide nanotubes, nanovesicles and micelles, peptide-based hydrogels and depots), and peptide linkers (for antibody drug-conjugates, peptide drug-conjugates, and prodrugs). We also dissect sequence-based optimization strategies, including rational design and biophysical optimization (cyclization, stapling, D-amino acid incorporation), functional motif integration, and combinatorial discovery with AI assistance, with examples spanning marketed drugs and research-stage candidates. The review reveals that cell-penetrating peptides enable efficient intracellular payload delivery via direct penetration or endocytosis; self-assembling peptides form diverse nanostructures for controlled release; and peptide linkers achieve site-specific drug release by responding to tumor-associated enzymes or pH cues, while sequence optimization enhances stability and targeting. Peptide-based biomaterials offer precise, biocompatible and tunable solutions for drug delivery, future advancements relying on AI-driven design and multi-functional modification will accelerate their transition from basic research to clinical application.

The objective of this study was to evaluate the effects of sodium butyrate and organic zinc supplementation, alone or combined, on performance, zinc metabolism, blood parameters, and gut health in Holstein calves highly challenged by heat and diarrhea during the pre-weaning and weaning periods. Forty-eight male calves were assigned to one of four treatments: control (CON), SB (3 g/kg of sodium butyrate in dry matter [DM]), OZn (262 mg/kg of organic zinc in DM), or SBOZn (3 g/kg of sodium butyrate and 262 mg/kg of organic zinc in DM). Calves were monitored from days 7 to 63 for feed intake, weight gain, body morphometry, fecal score, and blood parameters. Zinc balance was evaluated from days 45 to 49, and 24 calves were slaughtered on day 64 for jejunal sampling to assess tight junction gene expression. Diarrhea incidence was high (&gt;90%) across groups. Fecal scores varied over time but did not differ between treatments. The OZn and SBOZn groups had higher Zn intake, with greater absorption and retention of the mineral compared to the CON and SB groups. Additionally, the OZn group tended to have higher serum Zn concentrations. SB and OZn, separately or combined, had limited effects and did not consistently improve the performance or health of calves highly challenged during pre-weaning and weaning.

Combined histopathological, immunoenzymatic and transcriptomic analyses reveal the immune response mechanisms of silver pomfret infected by Vibrio parahaemolyticus.

Saccharomyces/pearl ferment lysate filtrate repairs UVB-induced skin barrier damage by regulating Nrf2/HO-1 and JNK/MAPK signaling pathways.

Traumatic brain injury (TBI) causes severe disruption of the blood-brain barrier (BBB), a key event that contributes to secondary neurological damage. Interleukin-25 (IL-25) has recently emerged as an important regulator of neuroinflammation, yet its role in BBB repair after TBI remains unclear. This study investigated the protective effects of IL-25 on BBB integrity and neurological function in mice following TBI and explored the underlying mechanisms. IL-25 expression in mouse serum and cortical tissue after TBI was quantified using enzyme-linked immunosorbent assays, and its cellular sources were identified via immunofluorescence staining. The impact of exogenous IL-25 on BBB integrity was evaluated by measuring, tight junction proteins (ZO-1, occludin, and claudin-5), Evans Blue extravasation, and cerebral edema on magnetic resonance imaging. Mechanistic, investigations using flow cytometry and in vitro oxygen glucose deprivation/reoxygenation models assessed whether IL-25 acted directly on brain microvascular endothelial cells (BMECs) or indirectly through immune pathways. Cytokine array and Western blot analyses were used to identify downstream mediators, and single-cell RNA sequencing was performed to characterize IL-25-induced transcriptional changes. Neurological function was assessed using the modified Neurological Severity Score, rotarod test, and Morris water maze. IL-25 levels increased significantly in the cortex and serum after TBI, peaking at day 3, with neurons and BMECs identified as the main sources. Exogenous IL-25 administration alleviated BBB dysfunction, restored tight junction protein expression, reduced Evans Blue leakage, and diminished cerebral edema. Mechanistically, IL-25 acted indirectly by activating brain-resident group 2 innate lymphoid cells to secrete interleukin-13 (IL-13), rather than acting directly on BMECs. IL-13 preserved BBB integrity by suppressing C-X-C motif chemokine ligand 10 (CXCL-10) expression and inhibiting endothelial pyroptosis. Single-cell RNA sequencing confirmed upregulation of BBB-protective genes such as Tiam1, Hsp90aa1, and Hes1, along with activation of tight junction and transforming growth factor-β signaling pathways. IL-25 treatment improved both motor coordination and cognitive performance after TBI. IL-25 promotes BBB repair and enhances neurological recovery following TBI by inducing ILC2-derived IL-13, which suppresses CXCL-10 and endothelial pyroptosis. These findings identify IL-25 as a potential therapeutic target for mitigating BBB damage and improving outcomes after TBI.

Egg yolk phosphatidylcholine (EYPC), the most vital functional lipid in egg yolk, has demonstrated neuroprotective, antibacterial, and cardioprotective effects. However, there is little information about its immunoregulation effect. Therefore, the aim of this study is to assess the effects and mechanisms of EYPC on intestinal immune homeostasis through an immunosuppressed mouse model induced by cyclophosphamide (CTX). The protective effect of intestinal immunity was evaluated on the basis of immune organ indices, intestinal tight junction (TJ) proteins, sIgA and cytokine secretion, nuclear transcription factor levels, and the equilibrium between Th1 and Th2 cells. It was shown that EYPC obviously inhibited thymus and spleen atrophy, enhanced the expression of TJ proteins, promoted the secretion of sIgA and cytokines, increased the levels of Th1 and Th2 cells, and also modulated the balance of Th1 and Th2 cells. The composition of the gut microbiota and metabolites were discussed to outline mechanisms. The results elucidated that EYPC could alleviate the gut microbiota dysbiosis caused by CTX via reducing the relative abundance of Akkermansia muciniphila and promoting the proliferation of Prevotella and Lactobacillus reuteri. Furthermore, EYPC improved the fecal metabolic profile, restoring the relative content of 13 metabolites and regulating bile secretion. Collectively, these findings suggested that EYPC may contribute to intestinal immune homeostasis through modulating gut microbiota and their metabolism, highlighting its potential as an immunomodulator.