Search Results (2,862)

Diarrhea is a common gastrointestinal disorder in animals, often worsened by antibiotic use. Pulsatilla chinensis (PC) is traditionally used for gastrointestinal issues, but its bioactive constituents and mechanisms remain unclear. This study investigated the preventive effects of PC in a canine model of antibiotic-associated diarrhea using an integrated multi-omics approach. LC–MS identified key constituents of PC, including anemoside B4, berberine, stigmasterol, and quercetin. In silico analyses predicted that stigmasterol and quercetin target EGFR and AKT1, modulating inflammation and epithelial repair via PI3K–Akt and IL-17 signaling pathways. In vivo, treatment with PC significantly reduced serum pro-inflammatory cytokines such as TNF-α and IL-6 and elevated immune markers including IgG and IgA compared to the control group. Furthermore, 16S rRNA analysis revealed that PC restored gut microbial diversity, reflected by increased Sobs and Chao1 indices, enriched beneficial Lactobacillus, and decreased the abundance of inflammation-associated taxa such as Proteobacteria, Desulfobacterota, and Escherichia-Shigella. These findings suggest that PC suppresses inflammation and remodels the gut microbiome, providing a mechanistic basis for its use as an herbal alternative to antibiotics. Future studies should include fecal microbiota transplantation and targeted metabolomics to establish causality and optimize therapeutic strategies. Full article

This study compared intestinal polyamine metabolism and barrier function between Ningxiang (NX) and Duroc × Landrace × Yorkshire (DLY) piglets under baseline conditions and following ETEC challenge. Experiment 1 (baseline, n = 12/breed) assessed colonic barrier integrity, immune status, polyamines, and microbiota. Experiment 2 (ETEC challenge, n = 8/group/breed) evaluated responses to oral ETEC (10⁹ CFU) over 3 days. Under baseline conditions, NX piglets showed superior barrier integrity, higher goblet cell numbers and mucin 2 (MUC2) protein expression, and lower plasma levels of intestinal permeability markers—diamine oxidase (DAO), D-lactate (DLA), and endotoxin (ET)—compared with DLY piglets. NX piglets also exhibited reduced colonic pro-inflammatory cytokine levels (IL-6 and IL-1β) and higher expression of immune-related markers (CD3, CD68, and IgA) versus DLY piglets. In contrast, DLY piglets displayed more active microbial polyamine metabolism in the colon, with higher concentrations of putrescine, spermidine, and spermine, as well as increased ornithine decarboxylase (ODC) expression. 16S rRNA sequencing revealed greater microbial diversity and enrichment of taxa (Muribaculaceae_unclassified, Prevotella) in NX piglets, whereas DLY piglets showed enrichment of polyamine-associated genera (Collinsella, Veillonella). Following the ETEC challenge, DLY piglets displayed pronounced polyamine upregulation, including elevated polyamine levels and ODC1 expression. Conversely, NX piglets maintained more stable polyamine metabolism, higher expression of tight junction proteins (ZO-1 and occludin), lower plasma permeability markers, reduced pro-inflammatory cytokine expression (IL-6, IL-1β, IL-22), and increased anti-inflammatory IL-10 expression. Collectively, these findings demonstrate that NX piglets possess superior intestinal barrier integrity and immune maturity, while DLY piglets exhibit a more active but stress-responsive polyamine metabolic phenotype. The divergent metabolic and immune responses to ETEC challenge underscore the distinct strategies employed by these two breeds in maintaining gut homeostasis. These findings provide preliminary insights that may inform future breeding strategies aimed at enhancing intestinal health and disease resistance in pigs, pending validation in broader genetic backgrounds and mechanistic studies. Full article

Hepatocellular carcinoma (HCC) is the most common type of liver cancer that is mostly preceded by cirrhosis, with a high mortality rate. Therefore, diagnosis is critical in the early stages. In this study, we explored the liver expression of metabotropic glutamate receptor 3 (mGluR3), a group II mGluR, during the progression from fibrosis to cirrhosis and, ultimately, to HCC induced by diethylnitrosamine (DEN) in rats. We found that mRNA expression of mGluR3 (Grm3) was upregulated in HCC, while the protein level was significantly increased from the cirrhosis stage, and even more in HCC. Grm3 correlated with interleukin-6 (Il6) and transforming growth factor-β (Tgfb) mRNA expression. Furthermore, serum and intrahepatic glutamate concentrations were augmented in HCC. Immunohistochemical analysis revealed that mGluR3 is expressed in hepatocytes and non-parenchymal cells (endothelial cells and macrophages), and we observed a positive signal in the cytoplasmic membrane, cytoplasm, and nuclei of tumor and non-tumor cells. We confirmed that normal hepatocytes (C9 cell line) express low levels of mGluR3 protein and HCC-derived cells (HepG2) express high levels of this receptor. Using HepG2 cells, we observed that mGluR3 activation by glutamate and the group II-selective agonist LY354740 treatments were functional, as both inhibited cAMP generation induced by forskolin and increased cellular viability with no effect on dead cells. These results showed that mGluR3 is differentially expressed throughout the progression of liver pathologies, is associated with the inflammatory environment, and plays a role in HCC cell survival, with potential utility as an early biomarker and therapeutic target. Full article

Postprandial variability in glucose and protein levels is one of the elements of insulin resistance (IR) and prediabetes, which is an area precursor to type 2 diabetes mellitus (DM). The objective of the study was a comprehensive proteomic analysis according to glucose tolerance in the general population who did not self-report DM or other diseases. We used Olink^® Reveal, a novel, high-throughput platform by Olink Proteomics based on their Proximity Extension Assay (PEA), to identify levels of 1034 circulating proteins in small volumes (4 µL) of plasma samples. The study enrolled 508 participants (mean age 52 ± 10.5 years, 47.2% men) from the population-based study, Bialystok PLUS Polish Longitudinal University Study. The study population was categorized according to glucose metabolism in comparison to impaired fasting blood glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed DM. Analysis of variance (ANOVA) adjusted for age, weight, fat mass, lean mass, and body mass index (BMI), identified 19 proteins significantly associated with categories of glucose tolerance. Of the five markers with the greatest ability to distinguish newly diagnosed diabetes from non-diabetic participants, paralemmin 2 performed best (AUC = 0.81; 77% sensitivity, 75% specificity), whereas furin was the most accurate for detecting any abnormal glucose regulation (AUC = 0.69). A linear regression model adjusted for the same confounding factors showed statistically significant associations between Hb_A1c levels and 37 proteins. Our findings highlight multiple proteins with significantly different levels across categories of glucose tolerance, especially between the healthy controls and the group with newly diagnosed DM. The consistent patterns of protein level differences, independent of body composition, suggest potential involvement in the progression of glucose metabolism disturbances and provide unique insights into pathomechanisms. These findings identify PALM2, FURIN, PDZK1, ACAA1, and IL18R1 as potential biomarkers of early dysglycemia. Full article

Background: Inflammatory bowel disease (IBD) is frequently complicated by secondary bone loss driven by chronic inflammation and gut–bone axis dysregulation. Although dried ginger has pharmacological activities relevant to intestinal inflammation, the effects of dried ginger milk extract (DGME), a lipophilic constituent-enriched preparation, on IBD-associated bone loss (IBD-BL) remain unknown. This study evaluated the preventive and therapeutic effects of DGME on IBD-BL and explored the underlying mechanisms. Methods: Mice with DSS-induced IBD-BL were treated with DGME (250, 125, or 62.5 mg/kg) or sulfasalazine. Colitis severity, bone microarchitecture, osteoclast activity and Th17 cells were assessed by histology, micro-computed tomography, histomorphometry and flow cytometric analysis. UHPLC-Q-TOF MS, network pharmacology, 16S rRNA sequencing, fecal metabolomics, and in vitro assays were used for mechanistic investigation. Results: DGME ameliorated colitis, improved trabecular bone microarchitecture, and reduced osteoclast-related bone destruction. These effects were associated with selective suppression of pathogenic bone marrow TNF-α⁺ Th17 cells and downregulation of Il17a, Rorc, Tnfα, Ccr2, Ccr6, Cxcr4, Csf1, and Tnfsf11. Compared with aqueous extract, DGME was enriched in 19 lipophilic constituents. Multi-omics analyses showed that DGME remodeled gut microbiota and metabolite profiles, characterized by enrichment of Lactobacillus, Anaerotruncus, vanillin, and spermidine. Both vanillin and spermidine suppressed Th17 effector genes and inhibited MEK/ERK signaling in vitro. Conclusions: DGME alleviated IBD-BL by suppressing pathogenic TNF-α⁺ Th17 responses and remodeling the gut microbiota–metabolite axis. This study not only extends the therapeutic application of dried ginger from intestinal inflammation to IBD-BL, but also identifies vanillin and spermidine as candidate functional mediators linked to MEK/ERK inhibition. Full article

Background and Objectives: The pathogenesis of liver steatosis is associated with obesity and systemic inflammation, particularly in subjects with body mass index (BMI) above 40 kg/m² and altered serum levels of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). Recent evidence suggests that disruption of the blood–brain barrier (BBB) may be associated with the development of steatosis, although limited data are available in humans. Thus, we assessed serum levels of neuron-specific enolase (NSE), transglutaminase 2 (TGM2), and glial fibrillary acidic protein (GFAP) as indirect markers of BBB dysfunction and examined their associations with steatosis severity, TNF-α and IL-10 in patients with morbid obesity. Materials and Methods: We biopsied the liver during bariatric surgery to assess steatosis by histology and serum markers by ELISA. Results: Most study subjects were women aged 38.7 ± 9.9 years with an average BMI of 42.3 ± 7.9 kg/m² and a steatosis prevalence of 78.9%. After grading steatosis as none (n = 8), mild (n = 17), moderate (n = 8), or severe (n = 5), we found no differences in sex, age, BMI, comorbidities, or laboratory variables, including liver enzymes. One-way ANOVA showed that serum IL-10 was 4-fold less in severe steatosis than in mild steatosis (p = 0.038), whereas TNF-α levels increased twice in severe steatosis compared to no steatosis (p = 0.029). NSE and GFAP serum levels, but not TGM2, increased proportionally to steatosis stage, showing differences between severe steatosis and no steatosis (p = 0.012 and p = 0.0002, respectively). Pearson correlation coefficients showed that NSE and GFAP were significantly associated with TNF-α (r = 0.600 and r = 0.402, respectively), but not with IL-10. Conclusions: Steatosis severity is significantly associated with markers of BBB disruption and systemic inflammation in patients with morbid obesity, suggesting a link between the BBB and liver steatosis. Full article

The transformation of university libraries into learning commons has highlighted the importance of informal learning spaces (ILSs). However, the mechanisms through which spatial elements influence learning experiences remain underexplored, particularly in western China. Drawing on person-environment fit theory and a multi-coupling framework, this study develops a four-dimensional analytical model comprising spatial layout, facility configuration, environmental quality, and cultural perception. A mixed-methods approach was employed, including 532 valid questionnaires, behavioral observations, and comprehensive environmental measurements (illuminance, noise, CO₂, PM2.5, TVOC, thermal conditions) across three university libraries in Lanzhou, China. Structural equation modeling (SEM) and coupling coordination degree modeling were used for analysis. Spatial layout (β = 0.324, p < 0.001), facility configuration (β = 0.287, p < 0.001), environmental quality (β = 0.196, p < 0.01), and cultural perception (β = 0.158, p < 0.05) all significantly predicted learning satisfaction, jointly explaining 67.3% of the variance. Learning satisfaction partially mediated the relationship between spatial elements and learning outcomes (indirect effect 31.2%). Coupling coordination degrees ranged from 0.578 to 0.634, revealing a “high coupling, low coordination” pattern, with cultural perception as the common shortfall. Environmental measurements showed CO₂ concentrations ranging from 823 to 946 ppm in quiet zones and up to 1085 ppm in lounge areas, correlating negatively with satisfaction (r = –0.41, p < 0.05). Spatial elements influence learning outcomes primarily through satisfaction enhancement. An integrated optimization framework is proposed, offering actionable strategies for ILS design in similar contexts. Full article

Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden vision loss, yet no effective therapy exists to preserve retinal ganglion cells (RGCs) after ischemic injury. Nostoc commune (NC), an edible cyanobacterium with established antioxidant and anti-inflammatory activities, has emerged as a potential functional bioresource with relevance to ocular health. Here, we investigated the therapeutic effects of a crude aqueous extract of NC using a rodent model of anterior ischemic optic neuropathy (rAION). NC treatment significantly improved RGC survival, reduced apoptosis, attenuated macrophage and microglial activation (ED-1, Iba1), suppressed proinflammatory cytokine expression (IL-6), enhanced the reparative marker Ym1+2, and preserved optic-nerve myelination. Functionally, NC administration restored visual signaling as demonstrated by improved Flash Visual Evoked Potential amplitudes. Immunoblot analysis showed increased phosphorylation of PI3K/AKT/mTOR/p70S6K signaling components in retinal tissue following NC treatment. Proteomic profiling further demonstrated that NC extract comprises a coordinated repertoire of phycobiliproteins, antioxidant enzymes, and stress-response proteins that may collectively contribute to its biological effects. Together, these findings suggest that Nostoc commune extract may serve as a promising functional food-derived candidate for protecting RGCs and preserving visual function following ischemic optic neuropathy. Further studies are required to identify its active constituents, optimize formulation strategies, and evaluate its translational potential. Full article

Prophylactic antibiotic use in intensive aquaculture promotes antimicrobial resistance, necessitating the development of microbial-based interventions. This study evaluated the individual, complementary, and synergistic effects of Bacillus subtilis natto (BSN) and Lactobacillus plantarum (LP) on the physiological performance and intestinal microecology of juvenile Japanese flounder (Paralichthys olivaceus). Over a 60-day trial, juveniles (initial weight: 5.81 ± 0.03 g) received a basal diet (CON) or a diet supplemented with 10⁷ CFU/g of BSN, LP, or both (BSN+LP). The BSN+LP consortium elicited complementary improvements in final body weight (21.39 ± 0.75 g vs. 18.66 ± 0.44 g in CON) and feed conversion efficiency (p < 0.05). Transcriptomic analysis revealed synergistic upregulation of digestive proteases (trypsin, chymotrypsin). Notably, an in pro-inflammatory markers (IL-1β, TNF-α) was counterbalanced by substantial upregulation of anti-inflammatory cytokines (IL-10, 5.65-fold; TGF-β1, 4.48-fold), suggesting the induction of mucosal tolerance rather than pathological enteritis. High-throughput 16S rRNA sequencing showed that the control cohort had a potential baseline microbial, characterized by a high relative abundance of Proteobacteria. BSN+LP administration significantly altered this microbial community into a fermentative eubiosis enriched in Firmicutes and Bacteroidota. Correlation network analyses confirmed negative interaction dynamics: increased abundance of Lactobacillus, Bacteroides, and Muribaculaceae was negatively correlated with baseline pathobiont abundance. These findings indicate that co-administration of BSN and LP hypothetically enhances metabolic energy harvest via short-chain fatty acid-producing taxa, strengthens the gut–immune axis, and competitively mitigates opportunistic pathogens. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease linked to epidermal barrier dysfunction, Th2-skewed immune polarization, and disrupted gut microbiota homeostasis. While probiotic interventions show promise in managing AD, the mechanisms governing strain-specific efficacy—particularly systemic modulation via the “gut–skin axis”—remaining to be fully elucidated. Methods: This study systematically compared the oral therapeutic effects of three Lacticaseibacillus rhamnosus strains (MG-A047, MG-A054, and LGG) in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Results: By integrating behavioral, histopathological, and serological assessments with 16S rRNA-based gut microbiota profiling and in vitro functional assays, this study offers a multidimensional evaluation of the strain-specific advantages and potential therapeutic mechanisms of three L. rhamnosus strains. The results demonstrate that MG-A054 most effectively alleviated cutaneous inflammation and pruritus, significantly reduced serum IgE and IL-4 levels, and attenuated epidermal hyperplasia and inflammatory cell infiltration (including mast cells and eosinophils). Mechanistically, this strain may directly inhibit hyaluronidase activity and mast cell degranulation, and specifically remodel the gut microbiota structure, thereby promoting a shift toward a healthier functional profile. Conclusions: These findings suggest that the superior efficacy of MG-A054 may be achieved through coordinated modulation of the gut–skin axis and related pathways. This study offers new mechanistic clues for understanding the strain-specific actions of probiotics and lays a preclinical foundation for the further development of MG-A054 as a potential targeted microecological therapy for AD. Full article

The gut microbiota serves as a critical interface for host immunity, making it a promising target for probiotic intervention. In this study, we investigated the immunomodulatory potential of the strain Bifidobacterium breve (B. breve) MN15965 and the underlying role of gut bacterial communities in this process. We first assessed its in vitro immunomodulatory activity by measuring nitric oxide and cytokine secretion in THP-1 macrophages. Subsequently, an immunosuppressed mouse model was established by treating BALB/c mice with cyclophosphamide (CTX), a chemotherapeutic agent known to cause immune dysfunction and mucosal damage. In this model, we performed a series of analyses, including H&E staining, measurement of hematological parameters and serum cytokines/immunoglobulins, quantification of fecal short-chain fatty acids (SCFAs) by gas chromatography, and profiling of gut microbiota composition via 16S rRNA gene amplicon sequencing. The results showed that MN15965 supernatant enhanced TNF-α, IL-1β, and GM-CSF secretion in THP-1 cells, promoting M1 macrophage activation in vitro. In the in vivo model, MN15965 administration restored spleen and thymus tissue integrity and improved physiological indices, hematological parameters, and immunoglobulin levels. Furthermore, MN15965 increased fecal SCFAs, particularly butyric and valeric acid, increased gut bacterial diversity, and enriched potentially beneficial SCFA-producing taxa, including Lachnospiraceae and Eubacterium. These findings demonstrate that B. breve MN15965 alleviated CTX-induced immunosuppression by activating immune responses, regulating gut bacterial communities, and boosting SCFA production. Full article

Background/Objectives: The growing prevalence of obesity necessitates innovative gut-targeted material strategies to modulate diet-associated metabolic dysfunction. This study investigates a spray-dried konjac glucomannan–montmorillonite (KGM-MMT) hybrid designed to integrate fermentable polysaccharide properties with luminal lipid-adsorptive clay functions within a single micro-engineered formulation. Methods: In HFD-fed mice treated for 42 days with 2% w/w KGM-MMT, cumulative body weight gain was attenuated by 7.6%, with an AUC of 5094 ± 52.95, compared to 5513 ± 81.35 in HFD controls (p < 0.0001). Results: Serum IL-6 concentrations were reduced by 97% (p = 0.0002), while blood glucose decreased by 46% (p < 0.0001); these effects were greater than those observed with MMT (24%, p = 0.0271) and KGM (16%, ns). Gut microbiota profiling demonstrated a significant 6.2-log₂-fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log₂-fold increase in Enterococcaceae (p = 0.015) following KGM-MMT treatment. Functional shifts inferred from 16S rRNA gene-based prediction indicated a 1.9-fold increase in short-chain fatty acid-related pathways and a 5.4-fold increase in bile acid deconjugation pathways. Conclusions: Although the KGM-MMT hybrid did not consistently outperform its individual components across all endpoints, it consolidated complementary KGM- and MMT-associated effects within a single dosage form. These findings support spray-dried KGM-MMT as a gut-targeted biomaterial strategy that integrates multiple luminal and microbiota-associated functions within a single formulation. Future studies should define dose–response relationships, validate microbiota-derived functional predictions using higher-resolution approaches, and assess durability and safety under longer-term exposure. Full article

Background/Objectives: Ustekinumab has been approved for the treatment of moderate to severe ulcerative colitis. Real-world data regarding its efficacy and the discovery of predictive factors of response need to be studied further. We aimed to evaluate the efficacy and identify predictors of response to induction treatment with ustekinumab in patients with ulcerative colitis. Methods: This is a multicenter, prospective cohort study. Clinical response (CR) at week 16 was the primary endpoint, and steroid-free clinical remission (SFCRem) and endoscopic response were the secondary endpoints. Baseline histology, mucosal gene expression, and pharmacokinetics were studied for their effect on response to treatment. Results: We included 123 patients (mean age = 50.3 years). CR was recorded in 70.8% (75/106), SFCRem in 48% (59/123), endoscopic improvement in 71.4% (40/56), and mucosal healing in 28.6% (16/56). Higher PRO-stool frequency (OR = 0.49, p = 0.027), concomitant use of 5-ASA (OR = 3.69, p = 0.021), platelet number of ≥284 × 10⁹/L (OR = 6.52, p = 0.001) at baseline, and a drop in the total count of platelets by 10⁸/L (OR = 1.23, p = 0.022) at week 8 were independently associated with CR. Elevated trough levels of ustekinumab at week 16 were associated with a higher probability of endoscopic improvement (median difference = 3784 ng/mL, p = 0.013), with an optimal cut-off value of 3500 ng/mL (AUC = 0.82, 95% CI: 0.66–0.96). Increased mucosal mRNA expression for IL-23 (p = 0.007) and IL-23R (p = 0.031) at baseline was associated with increased probability of CR. Higher continuous Geboes scores at baseline were associated with a lower probability of CR (OR = 0.80, p = 0.045), with an optimal cut-off value of 14 (AUC = 0.75, 95% CI: 0.57–0.93). Conclusions: Clinical, laboratory, and molecular markers may identify patients with ulcerative colitis who are more likely to respond to ustekinumab. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune dysregulation that leads to widespread inflammation and damage across multiple organs. B lymphocytes play a vital role in SLE, with abnormal development and activation leading to autoreactive antibody production and immune complex formation, which damages tissues. Methods: The PPARα agonist WY14643 has anti-inflammatory effects in various inflammatory conditions, including CNS diseases. We investigated whether WY14643 decreases inflammatory mediator production in CD45R⁺ cells in the MRL/lpr mouse model of SLE. Flow cytometry was used to evaluate WY14643’s impact on the expression of IFN-γ, IL-6, iNOS, MCP-1, IL-1α, IL-2, Notch-1, Notch-3, GITR, and NF-κB p65 in splenic CD45R⁺ B cells. Additionally, we assessed the effect of WY14643 on the mRNA levels of these markers in the kidney using RT-PCR. Results: WY14643 decreased inflammatory markers such as CD45R⁺IFN-γ⁺, CD45R⁺IL-6⁺, CD45R⁺iNOS⁺, CD45R⁺MCP-1⁺, CD45R⁺IL-1α⁺, CD45R⁺IL-2⁺, CD45R⁺Notch1⁺, CD45R⁺Notch3⁺, CD45R⁺GITR⁺, and CD45R⁺NF-κB p65⁺ in splenic cells from MRL/lpr mice. Furthermore, WY14643 also lowered mRNA expression of IFN-γ, IL-6, iNOS, MCP-1, IL-2, IL-1α, Notch-1, Notch-3, GITR, and NF-κB p65 in the kidney. Conclusions: This study shows that WY14643 inhibits the production of inflammatory mediators and significantly reduces autoimmune features, including kidney inflammation, in MRL/lpr mice. Our results indicate that WY14643, a PPAR-α agonist, could be a potential therapy for lupus nephritis. Full article