Search Results (2,572)

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal barrier disruption and dysregulated immune responses. While Intravenous Immunoglobulin (IVIG) is widely used for its immunomodulatory effects in various autoimmune conditions, its specific therapeutic mechanisms and molecular targets in colitis remain to be fully elucidated. Objective: To elucidate the therapeutic mechanisms of IVIG in dextran sodium sulfate (DSS)-induced colitis, with a focus on pyroptosis regulation via the NOD-like receptor (NLR) signaling pathway. Methods: Colitis was induced in mice via DSS administration. IVIG was administered intravenously during disease progression. Colon tissues underwent proteomic profiling, and key targets (GBP5, NLRP3, Pro-Caspase-1, GSDMD) were validated by Western blotting (WB), while interleukin (IL)-1β and IL-18 levels were quantified via ELISA. Results: IVIG significantly attenuated weight loss, Disease Activity Index (DAI) scores, colon shortening, and histopathological damage. Proteomics analysis identified 172 differentially expressed proteins between DSS and DSS + IVIG groups, with pronounced downregulation of GBP5 and NLR pathway components. IVIG suppressed GBP5/NLRP3/CASP1 activation, reduced GSDMD cleavage, and significantly decreased IL-1β production (while showing a decreasing trend for IL-18). Conclusions: IVIG ameliorates colitis by inhibiting the GBP5/NLRP3/CASP1-mediated pyroptosis pathway, highlighting its potential as a targeted therapy for ulcerative colitis. Full article

High-dimensional covariance estimation remains a fundamental challenge when the number of variables (p) substantially exceeds the sample size (n). In such settings, the sample covariance matrix is unstable, singular, and heavily contaminated by estimation noise. Although shrinkage estimators improve stability and thresholding methods promote sparsity, each approach alone may introduce bias or lose structural information. This study proposes a Noise-Adjusted Shrinkage Covariance (NASC) framework as a post-processing enhancement strategy for shrinkage-based covariance estimators. The framework first stabilizes the covariance structure through shrinkage toward a structured target, then suppresses noise-induced small covariance entries via thresholding, and finally applies a stabilization step to ensure positive definiteness of the resulting estimator. Sensitivity analyses were conducted to investigate the effects of the shrinkage and thresholding parameters, and the Monte Carlo simulations were subsequently performed using the best-performing parameter configuration. The simulation results showed that shrinkage alone may not sufficiently suppress entrywise noise, whereas NASC-adjusted estimators improved upon their corresponding shrinkage baselines in many scenarios, with the strongest gains observed for sparse covariance structures and for shrinkage estimators that do not explicitly suppress entrywise estimation noise. Improvements were more limited for highly optimized shrinkage estimators. Real-data analyses were conducted on the SRBCT and colon cancer benchmark datasets. On the SRBCT dataset, numerical stability and positive-definiteness properties were examined, while LOOCV-LDA classification performance without prior feature selection or dimensionality reduction was evaluated on the colon cancer dataset. The results suggest that NASC provides a computationally simple and numerically stable extension to classical shrinkage covariance estimation methods for high-dimensions. Full article

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by a complex and dynamic interplay between immune dysregulation and epidermal barrier dysfunction. Emerging evidence supports an integrated pathogenic model in which immune activation and barrier impairment form a bidirectional and self-reinforcing axis rather than representing separate processes. This review synthesizes current knowledge on the role of IL-4/IL-13-dependent signaling in regulating keratinocyte lipid metabolism and its impact on epidermal barrier integrity. IL-4/IL-13 signaling via the JAK-STAT pathway, particularly STAT6, contributes to keratinocyte dysfunction, resulting in impaired differentiation and coordinated alterations in lipid metabolism, including fatty acid elongation and ceramide synthesis. These cytokine-driven processes disrupt the organization of the stratum corneum lipid matrix, resulting in increased transepidermal water loss, enhanced skin permeability, and susceptibility to microbial colonization, thereby promoting chronic inflammation. Collectively, these findings support the concept that IL-4/IL-13-mediated dysregulation of keratinocyte lipid metabolism may represent an important immunometabolic mechanism linking type 2 inflammation with secondary barrier dysfunction in atopic dermatitis, thereby contributing to disease persistence. Targeting both immune pathways and epidermal lipid homeostasis may represent an effective strategy to restore barrier function and improve clinical outcomes. Full article

Chronic sleep deprivation (SD) disrupts gut–brain axis (GBA) homeostasis and is closely associated with gut microbiota dysbiosis, neuroinflammation, and depression-like behaviors. This study investigated whether fermentation enhances the antidepressant-like effects of Dendrobium officinale by comparing fermented Dendrobium officinale (FDO) with unfermented Dendrobium officinale (DO) in a chronic SD mouse model. FDO significantly ameliorated anxiety and depressive-like behaviors in SD mice. It reshaped gut microbial structures, enriched beneficial bacteria taxa such as Dubosiella, [Eubacterium]_coprostanoligenes_group, and Allobaculum, and increased SCFA levels. FDO also enhanced colonic ZO-1 and Occludin expression and reduced serum levels of LPS and the pro-inflammatory cytokines. At the central nervous system level, FDO inhibited the activation of hippocampal microglia and astrocytes; alleviated neuroinflammation; restored hippocampal TPH2, 5-hydroxytryptamine (5-HT), and 5-HIAA levels; and modulated the 5-HT_1A/5-HT_2A receptor balance. In addition, FDO upregulated BDNF, PSD-95, and SYN expression and reduced corticosterone (CORT) levels. Compared with DO, FDO showed more pronounced regulatory effects. Correlation analysis suggested that 5-HT may link gut microbial metabolites, inflammation, and synaptic plasticity. In summary, these findings support FDO as a potential GBA-targeted functional food for SD-related depressive-like behaviors. Full article

The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively retrieve and screen eligible studies from multiple mainstream databases according to standardized inclusion and exclusion criteria, and systematically summarize current research progress on plant-derived bioactive compounds targeting the gut–bone axis for skeletal health regulation. This review systematically explores the underlying mechanisms of the gut–bone axis and critically evaluates the regulatory effects and therapeutic potential of plant-derived bioactive compounds. Particular attention is given to targeted interventions involving prebiotics, probiotics, synbiotics, and plant-rich diets or functional foods. Among these interventions, synbiotics represent the most successful strategy and show the most prominent therapeutic possibilities in bone-related disorders. Different from single prebiotics (only nourish endogenous intestinal microbes), individual probiotics (easy to be degraded in gastrointestinal tract with poor colonization) and ordinary plant-rich diets (unfixed effective dosage and weak targeting property), synbiotics combine prebiotic carriers and viable probiotic strains to produce complementary advantages, which is the core reason for its outstanding therapeutic prospect against bone diseases. Synbiotics exert synergistic effects on gut microecology, mineral absorption, and immune regulation, leading to more robust and consistent improvements in bone health than single prebiotics, probiotics, or general plant-rich diets. They have been verified in preclinical and clinical studies to ameliorate osteoporosis and related skeletal diseases via the gut–bone axis. These strategies offer novel insights into the prevention and treatment of bone metabolic disorders, such as osteoporosis, by targeting the gut–bone axis with phytochemicals. Key outcomes of this review include that synbiotics, soy isoflavones, naringin, curcumin, and resveratrol effectively improve bone mineral density, restore gut microbiota balance, and inhibit pathological bone resorption via the gut–bone axis. Collectively, the above bioactive substances realize bone protection mainly by reshaping gut flora, elevating mineral uptake and suppressing excessive osteoclast activity. Representative cases include soy isoflavones mitigating estrogen-deficient bone loss in OVX models, naringin improving the trabecular microarchitecture, and probiotic BL-11 promoting longitudinal bone growth in children. Future directions will focus on clarifying dose–response relationships, developing standardized synbiotic formulations, constructing microbiome-guided precision diets, and conducting large-sample randomized controlled trials to translate plant-derived compounds into clinical therapies. Full article

Background: Colorectal neuroendocrine carcinomas (NECs), including small cell (SCNEC) and large cell (LCNEC) subtypes, are rare but aggressive malignancies with limited population-level data. Moreover, prior studies have limited stratification by histologic subtype and anatomic location, despite evidence of disease heterogeneity in colorectal malignancies. This study aimed to characterize the clinical characteristics, treatment patterns, and outcomes of colorectal NEC by histologic subtype and tumor location, and to compare them with neuroendocrine tumors (NETs) and adenocarcinomas (ACs). Methods: A retrospective cohort review was conducted utilizing the SEER database from 2000 to 2022 to identify patients with colorectal SCNEC, LCNEC, NET, and AC. Demographic, clinical, therapeutic and survival data were analyzed and compared using Kaplan–Meier methods, log-rank tests, and Cox proportional hazards regression. Results: A total of 790 SCNEC, 498 LCNEC, 31,200 NET, and 638,898 AC cases were identified. SCNEC and LCNEC were associated with advanced stage at diagnosis (66% and 55% stage IV, respectively) and inferior survival outcomes compared to NET and AC (median OS (mOS) of 7 and 8 months for SCNEC and LCNEC, respectively, p = 0.0002). Stratified by location, colonic SCNEC had the poorest survival (mOS 5 months), worse than rectal SCNEC (mOS 9 months); this pattern was not observed in LCNEC. Surgical resection was associated with improved OS in both NEC subtypes (HR range 0.25–0.56, all p < 0.012). Radiation therapy was associated with improved survival in NEC overall (SCNEC HR 0.58; LCNEC HR 0.71, both p < 0.05), with the observed benefit appearing greatest in rectal NEC. Demographic factors were associated with survival in NET and AC but had no significant impact in NEC. Conclusions: Colorectal SCNEC and LCNEC are highly aggressive malignancies with poor outcomes, with SCNEC demonstrating modestly inferior outcomes compared to LCNEC. This study demonstrates that both histologic subtype and anatomic site of disease are important determinants of prognosis and treatment response. This supports the concept that colorectal NEC represents a biologically heterogeneous disease, with colonic SCNEC showing the worst outcomes and rectal NEC associated with a potential enhanced response to radiation. These findings support the need for further prospective and molecular studies to better define treatment approaches and targeted therapies for these rare malignancies. Full article

Cytolysin-positive Enterococcus faecalis is a key pathogen in severe alcoholic hepatitis, yet the mechanisms through which it worsens disease and possible therapeutic strategies remain poorly understood. This study aimed to clarify the pathogenic effects of E. faecalis in acute alcohol-associated liver disease (ALD) and to assess the protective potential of Akkermansia muciniphila (Akk11) against this pathogen. Using a mouse model of acute ethanol gavage, animals received E. faecalis and/or Akk11 under prophylactic or therapeutic regimens. Assessments included liver injury markers, histopathology, lipid profiles, inflammatory cytokines, gut barrier integrity, and gut microbiota composition. E. faecalis exacerbated ethanol-induced hepatic steatosis and injury, showing a paradoxical effect: it increased histological damage while lowering circulating LPS and transaminases. This was linked to upregulated hepatic autophagy (increased Atg7) and reduced cholesterol, yet it promoted neutral lipid accumulation. Importantly, E. faecalis aggravated gut dysbiosis by markedly enriching the pro-inflammatory pathobiont Helicobacter typhlonius and impairing colonic barrier function. Intervention with Akk11 alleviated liver injury, reduced lipid accumulation and oxidative stress, and restored cytokine balance. Akk11 also strengthened gut barrier integrity, lowered serum endotoxin, and beneficially reshaped the microbiota. Prophylactic administration was particularly effective, normalizing the Firmicutes/Bacteroidota ratio, suppressing H. typhlonius, and enriching beneficial Bacteroides sartorii. This study confirms the pathogenic role of E. faecalis in acute ALD and establishes A. muciniphila (Akk11) as a promising microbiota-targeted therapy, which protects against liver injury by reinforcing the gut barrier, selectively modulating microbiota, and reducing inflammation, with prophylactic administration showing superior efficacy. Full article

Background: Brain metastasis is associated with poor prognosis in lung adenocarcinoma (LUAD). Anoikis resistance may contribute to tumor cell survival during metastatic dissemination and brain colonization; however, robust biomarkers for prognostic stratification and brain metastasis-associated classification remain limited. This study aimed to investigate anoikis-related molecular features in LUAD brain metastasis and develop a machine learning-based signature for prognostic assessment and exploratory classification of primary and brain-metastatic LUAD samples. Methods: We integrated single-cell and multi-cohort bulk transcriptomic data. Single-cell analysis was performed to characterize anoikis-related cellular states and intercellular communication in primary and brain-metastatic LUAD samples. In the bulk transcriptomic analysis, TCGA-LUAD was used for prognostic feature selection and risk-model construction, and GSE26939 was used for external prognostic validation. The classification performance of the fixed signature for distinguishing primary LUAD from brain-metastatic LUAD samples was further evaluated in GSE161116 and GSE271259. Immune microenvironment features were assessed, and an LLM-assisted exploratory drug-screening strategy combined with molecular docking was used to prioritize candidate compounds. Results: Single-cell analysis suggested that metastatic epithelial cells exhibited enhanced anoikis-related activity, accompanied by macrophage-associated SPP1-CD44 and MIF-(CD74+CXCR4) communication patterns. Machine learning-based feature selection identified an eight-gene signature consisting of BIRC3, CCL20, CLEC7A, CTSL, GOLM1, ICAM3, MTUS1, and SERPINH1. The signature showed prognostic value in TCGA-LUAD and GSE26939 and demonstrated exploratory classification performance in distinguishing primary LUAD from brain-metastatic LUAD samples. High-risk patients exhibited immune microenvironment alterations and enrichment of tumor progression-related pathways. LLM-assisted compound prioritization and molecular docking highlighted resveratrol and SB431542 as hypothesis-generating candidates with predicted interactions with core targets. Conclusions: This study identified an anoikis-related eight-gene signature for LUAD prognostic stratification and exploratory brain metastasis-associated classification. The findings suggest the potential involvement of anoikis-related tumor–microenvironment interactions in LUAD brain metastasis and provide candidate genes and compounds for further experimental validation. Full article

Mitochondrial dysfunction in colonic smooth muscle cells (SMCs) is closely associated with impaired gut motility in functional constipation (FC), but the underlying molecular mechanisms remain incompletely understood. The mitochondrial unfolded protein response (UPR^mt) is a critical pathway for maintaining mitochondrial proteostasis, and heat shock factor 1 (HSF1) acts as an important upstream regulator of this response. In the present study, we employed a loperamide-induced FC mouse model, combined with single-cell transcriptomic, molecular, and functional analyses to characterize the HSF1-UPR^mt pathway in colonic SMCs and to investigate its role in FC. Single-cell transcriptomic analysis of colon tissue from FC mice revealed marked downregulation of UPR^mt-associated genes in colonic SMCs. Immunofluorescence, Western blotting, and RT-qPCR analyses of colonic tissue confirmed that HSF1 expression was reduced in colonic SMCs, along with the downregulation of the UPR^mt components, including HSP60, mtHSP70, and LONP1. These molecular changes were accompanied by mitochondrial structural damage, seen by transmission electron microscopy, and by functional impairments, including reduced mitochondrial membrane potential, elevated mtROS production, decreased ATP levels, and diminished activities of respiratory chain complexes I–V. AAV9-mediated overexpression of HSF1 reactivated the UPR^mt pathway, improved mitochondrial function, and ameliorated constipation, whereas shRNA-mediated knockdown of HSF1 further suppressed UPR^mt activity and aggravated mitochondrial damage, indicating that HSF1 bidirectionally regulates this pathway. Complementary experiments in primary colonic SMCs confirmed that this regulatory mechanism operates in a cell-autonomous manner, as modulation of HSF1 expression produced corresponding changes in the UPR^mt pathway, in the expression of mitochondrial respiratory chain complex subunits (ATP5A, NDUFA9, COX1, SDHA, UQCRC1), and in ATP production, mirroring the in vivo findings. Collectively, these results demonstrate that HSF1 plays a pivotal role in maintaining mitochondrial homeostasis in colonic SMCs through regulation of the UPR^mt pathway and that HSF1 dysfunction is closely associated with slowed gut motility in FC. These findings offer a new mechanistic perspective on FC and point to the HSF1–UPR^mt axis as a potential therapeutic target. Full article

Background: The incidence of inflammatory bowel disease (IBD) is growing in the population. At present, the etiology of inflammatory bowel disease remains unclear, and there is no effective and low-toxic therapeutic drug. This study aimed to investigate the role of Lobenzarit (Lbz) in the treatment of colitis in mice as well as the underlying mechanism. Methods: In this experiment, colitis was induced in mice with dextran sulphate sodium (Dss). Subsequently, the role of Lbz in colitis and its underlying mechanisms were examined using H&E staining, TEM, ELISA, PCR, and other assays. Results: Lbz significantly attenuated the related symptoms of Dss-induced colitis in mice. In addition, Lbz suppressed neutrophil infiltration and restored macrophage polarization towards an anti-inflammatory state. Lbz also inhibited (p < 0.05) the activation of signaling pathways TLR4 and MAPK (51.61% decrease for TLR4 and 56.94% decrease for MAPK), reduced the release of inflammatory factors as it significantly decreased (p < 0.05) colonic IL-1β, TNF-α, IFN-γ, COX2, and VEGF (47.63, 42.49, 53.42, 58.74, and 61.28% decreases respectively) thereby attenuating the inflammatory response in mice. Lbz administration also restored the permeability of the intestinal barrier by increasing (p < 0.05) tight junction-associated proteins (claudin-1, occludin, and ZO-1 with a 5.36- and 2.26-fold increase for claudin-1 and ZO-1, respectively) and decreasing (p < 0.05) MALK levels by 53.51%. In addition, Lbz upregulated colonic Cytochrome C oxidase II, PDH, and ATP synthase levels and upregulated CD163, CD206, c-Maf, and PPAR-γ levels as compared to the DSS-treated group. Conclusions: Lbz has a repairing effect on Dss-induced colitis and may alleviate Dss-induced colitis by targeting the TLR4 pathway and promoting intestinal stem cell proliferation. Full article

Background:/ Over the past decade, increasing evidence has shifted attention from the brain to the gut microbiota (MB) as a source and site of systemic dissemination of amyloid-β (Aβ), an APP derivative responsible for plaque formation in the brains of Alzheimer’s disease (AD) patients. Furthermore, AD patients and APP/PS1 mice, a transgenic model of AD, exhibit dysbiosis. Objectives: Using APP/PS1 mice treated from 2 to 8 months of age, we studied ileal and colonic epithelial integrity, intestinal barrier (IB) integrity assessed through tight junction (TJ) protein expression, local immune system, the presence/increase in Aβ expression in enterocytes, and the protective effects of synbiotic treatment. Methods: The tissue was stained with Periodic Acid-Schiff and Alcian Blue to evaluate epithelial morphology and mucus production, and immunohistochemistry was performed to assess TJs, immune markers, and Aβ expression. Results: Our results demonstrate that colonic and ileal epithelium of 8-month-old APP/PS1 mice displays IB impairment in term of alterations of goblet cells staining and TJ protein expression and signs of immune involvement. The ileum was more severely affected, showing a reduced epithelial surface area, decreased lysozyme production, and fewer tuft cells. Long-term synbiotic treatment largely prevented APP/PS1 mouse changes and caused a significant increase in Aβ expression in all treated mice. Conclusions: These findings support the belief in early intestinal involvement in AD and highlight the potential of the microbiota as a target for early intervention aimed at modifying the progression to neurodegeneration. Increased epithelial Aβ labeling after treatment raises the possibility of intestinal management of Aβ, which requires further validation. Full article

Background: Dental caries is a chronic disease mediated by biofilm, which is caused by Streptococcus mutans, and enamel genetics modulates susceptibility. The variants of ENAM might alter the adhesion of enamel and bacteria. One important anti-viral target is sortase A (SrtA), which restricts colonization but does not have an impact on bacterial survival. Aim: The aim of this study was to find out the relationship between ENAM rs3796704 and dental caries vulnerability among adult Iraqi Arab females and to assess the antibiofilm capacity of eugenol and cinnamic acid against S. mutans SrtA using molecular docking, ADMET prediction, and molecular dynamics modeling. Methods: A case–control study was done on 240 women (aged 25–30 years; 120 caries, 120 controls). HRM real-time PCR was done to genotype ENAM rs3796704. An analysis of allelic and genotypic distributions was done using chi-square tests and odds ratios (p < 0.05). An in silico docking analysis aimed at SrtA (PDB: 4TQX) was performed in AutoDock Vina, and this was followed by ADMET profiling and a 50 ns molecular dynamics simulation (OPLS4/TIP3P, NPT 300 K/1 atm). Results: The level of the G allele was found to be lower in the cases than in the controls (60% vs. 70; OR = 0.6429; p = 0.02), but the level of the A allele was found to be higher in the cases (40% vs. 30; OR = 1.5556; p = 0.02). Docking showed a minor difference in binding affinities with eugenol (−4.961 kcal/mol) and cinnamic acid (−4.939 kcal/mol) as compared with chlorhexidine (−4.692 kcal/mol). Both compounds showed stable binding for more than 50 ns as well as desirable predicted pharmacokinetics. Conclusions: The caries vulnerability in this sample was associated with ENAM rs3796704. Eugenol and cinnamic acid undergo stable dissociative interactions with SrtA and were found to have favorable safety profiles in silico. Therefore, they may be considered as adjunctive anti-virulence agents in the prevention of caries. Full article

Dormancy is an important factor influencing colorectal cancer (CRC) metastasis through diverse metabolic pathways and cell types. To elucidate its molecular mechanisms, bulk transcriptomic pathway scoring was integrated with single-cell RNA sequencing of epithelial, cancer stem, and immune cells to identify CRC dormancy-associated genes (CDAGs). Twenty-three CDAGs were identified. These genes were found to play a regulatory role in dormancy by participating in metabolic processes affecting energy supply or substance synthesis. In two independent CRC cohorts (GSE41258, GSE41568), machine learning models using these genes distinguished metastatic samples with area under the curve (AUC) of 0.79–0.87. High CDAG expression was associated with better recurrence-free survival in GSE41258 (p = 0.005), which remained significant after adjusting for age, sex, and adjuvant chemotherapy (p = 0.037). The prognostic value was validated in The Cancer Genome Atlas (TCGA) Colon and Rectal Cancer for progression-free survival (p = 0.004). Moreover, 20 CRC dormancy-associated drugs were identified, 12 of which were reported to be associated with CRC, two with experimental evidence of inhibiting CRC metastasis or recurrence. This study provided metabolic-oriented genes for characterizing CRC dormancy, which could distinguish metastatic samples and had independent prognostic value, and offered a foundation for further development of targeted therapeutic strategies. Full article

Background/Objectives: Listeria monocytogenes is a critical foodborne pathogen, with poultry products serving as a potential reservoir. Its ability to form biofilms may aid in its persistence on processing equipment and food-contact surfaces, while antibiotic resistance complicates efforts to control and treat infections. This study aimed to characterize, in parallel, the biofilm-forming capacity and antibiotic susceptibility of a large collection of poultry-derived L. monocytogenes isolates (n = 93) to better understand their potential for persistence and to clarify how the biofilm phenotype may relate to the bacterial antibiotic response and to inform risk assessment and targeted control strategies along poultry processing and supply chains. Methods: Biofilms were evaluated on polystyrene microtiter plates at 12 and 30 °C in a nutrient-rich laboratory medium. Susceptibility to eight clinically and food-relevant antibiotics was tested using disk diffusion and interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints when available. Results: At 30 °C for 48 h, 69.9% of isolates were classified as weak biofilm formers and 30.1% as non-biofilm formers, whereas at 12 °C for 120 h, 55.9% were weak, 16.1% moderate, and 28.0% non-biofilm formers, with no strong biofilm producers identified under either condition. Overall, the isolates remained largely susceptible to ampicillin, penicillin G, vancomycin, tetracycline, and chloramphenicol, with 87.3% of inhibition zones across all drugs falling within the 20–29 mm and 30–39 mm categories, while small subpopulations showed reduced susceptibility or resistance to trimethoprim–sulphamethoxazole (TMP-SMX) and, particularly, erythromycin and streptomycin. No consistent correlation was found between biofilm-forming ability and antibiotic susceptibility, indicating that these phenotypic traits are largely independent in this collection. Conclusions: These findings reveal that poultry-derived L. monocytogenes isolates can form weak to moderate biofilms under the tested monoculture conditions while generally maintaining susceptibility to first-line antibiotics. However, the development of macrolide- and aminoglycoside-resistant subpopulations, along with the potential for increased colonization within complex multispecies biofilms in real processing environments, emphasizes the importance of ongoing integrated surveillance across animal food systems. Full article

Tetrastigma hemsleyanum polysaccharide (TH-P) exhibited anti-inflammatory and intestinal protective activities, but its mechanism against ulcerative colitis (UC) remained unclear. This study used a multi-omics approach to elucidate the effects of TH-P in protecting against dextran sulfate sodium (DSS)-induced UC mice and the underlying mechanisms. In vitro, TH-P dose-dependently suppressed LPS-induced ROS production and pro-inflammatory cytokine release in RAW264.7 cells. In vivo, TH-P alleviated DSS-induced weight loss, disease activity index, colon shortening, edema, and mucosal damage. Transcriptomic analysis and Western blotting revealed that TH-P significantly reversed DSS-induced gene expression alterations, with particular enrichment of the PI3K/AKT signaling pathway. Serum metabolomics showed that TH-P restored metabolic disturbances in glycerophospholipid and arachidonic acid metabolism. The results of 16S rRNA sequencing indicated that TH-P increased microbial diversity, enriched beneficial Bacteroidota, and reduced opportunistic Actinomycetota and Pseudomonadota. Untargeted metabolomics further demonstrated elevated acetate, propionate, and butyrate levels. Collectively, TH-P alleviated UC through a multi-target mechanism involving antioxidant and anti-inflammatory activities, gut microbiota modulation, enhanced SCFA production, and activation of the PI3K/AKT signaling pathway. Full article