Search Results (1,165)

Quercetagetin (QG), a principal flavonol from marigold (Tagetes erecta L.), is recognized for its potent antioxidant properties. However, its efficacy in mitigating intestinal injury under heat stress (HS) conditions remains unclear. We investigated the protective effects of QG using a mouse model of HS (41 °C, 70% humidity). Mice received oral QG (100 mg/kg/day) or saline for seven consecutive days before and during HS exposure. We assessed jejunal histopathology, oxidative stress markers, inflammatory cytokines, gene expression, and gut microbiota composition via 16S rRNA sequencing. QG supplementation significantly ameliorated HS-induced jejunal damage. It enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) while reducing malondialdehyde (MDA) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). QG downregulated the mRNA expression of heat shock proteins (Hsp70, Hsp90) and upregulated antioxidant-related genes (SOD1, GPX4, CAT, NQO1, Nrf2). Furthermore, QG preserved intestinal barrier integrity by upregulating tight junction proteins (Occludin, Zo-1, Claudin). 16S rRNA analysis revealed that QG significantly reshaped the gut microbiota, marked by an increased relative abundance of Lactobacillus and a decrease in potentially harmful taxa such as Allobaculum, Oscillibacter, and Colidextribacter. QG effectively alleviates HS-induced intestinal injury by enhancing antioxidant capacity, suppressing inflammation, and modulating the gut microbiota. These findings provide a scientific basis for the potential application of QG as a functional feed additive to improve animal health under heat stress conditions. Full article

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications. Full article

Organic acid supplementation in aquafeed plays a crucial role in enhancing fish health and performance, contributing to sustainable aquaculture practices amid growing global demand for protein sources. In a feeding trial lasting 8 weeks, 360 juvenile fish (43.5 ± 0.23 g) were randomly assigned to four groups (three replicates per group; 30 fish per replicate), following one of four dietary regimens: the control (CON), or the control diet supplemented with 0.3% citric acid, 0.3% fumaric acid, or 0.3% malic acid. The supplementation of diets with the three organic acids significantly promoted weight gain (WG) and specific growth rate (SGR). Additionally, a significant increase in the activities of serum antioxidant enzymes (SOD, CAT, AKP) was recorded, with concomitant decreases observed in hepatic parameters (TG, GLU, ALT, AST) and the serum lipid peroxidation product MDA. Similarly, the organic acids supplementation also enhanced the hepatic antioxidant capacity (CAT, T-AOC, GSH-PX) and their gene expression levels, and decreased hepatic lipid and glycogen levels. Additionally, dietary organic acid supplementation significantly enhanced the activities of both digestive and antioxidant enzymes in the intestine. Furthermore, it improved intestinal morphology, as evidenced by increases in villus height, villus width, and muscular thickness. Moreover, supplementation with organic acids improved intestinal permeability, mediated through the suppression of serum DAO activity and LPS levels, accompanied by upregulated intestinal expression of junction complex components (Claudin-1, ZO-1, Occludin-1) and downregulated pro-inflammatory mediators (tnf-α, il-1β). The 16S rRNA sequencing demonstrated that CA induced a significant shift in the intestinal microbiota composition, marked by an elevated relative abundance of Firmicutes (including Streptococcus) and Acinetobacter, along with a decreased abundance of Aeromonas. These findings demonstrate that organic acids may enhance fish growth performance and intestinal health through their modulating effects on gut microbiota, intestinal development, immune responses, and antioxidant capacity. Notably, the dietary CA supplementation exhibited the most pronounced efficacy. Full article

In rheumatoid arthritis (RA), activated synovial tissue-derived mesenchymal stem cells (MSC) acquire a pathogenic phenotype and produce pro-inflammatory cytokines, chemokines, metalloproteinases, pro-osteoclastic and pro-angiogenic factors. The acquisition of this aggressive phenotype might be due to modified expression of micro-RNAs. We aimed to clarify the role of specific micro-RNAs (miR-146a-5p, miR-221-3p, miR-34a-3p, miR-150, miR-203a-3p and miR-155-3p) in an in vitro model of RA. Methods: Micro-RNA expression was determined in RA patient plasma and in commercial human synovial tissue-derived MSC-like cells stimulated with a panel of pro-inflammatory mediators (poly I:C, TNF-α, IL-1β, IFN-γ) to mimic the rheumatoid arthritis pathogenic setting. Next, unstimulated cells or TNF-α stimulated cells were transfected with miR-146a-5p mimic or miR-221-3p mimic. Protein and/or mRNA expressions of chemokines, cytokines, VEGF, MMPs and RANKL were determined by ELISA or qRT-PCR. MiR-34a-3p, miR-146a-5p, miR-150, miR-221-3p and miR-203a-5p were upregulated in RA patient plasma versus healthy controls. Moreover, synovial tissue-derived MSC-like cells expressed miR-146a-5p and miR-221-3p in response to pro-inflammatory mediators. Overexpression of miR-146a-5p increased CCL2 and CXCL8 expression and miR-221-3p increased IL-1β and IL-6 expression in synovial tissue-derived MSC-like cells stimulated with TNF-α. Conclusion: Overexpression of miR-146a-5p and miR-221-3p might favour inflammation and participate in rheumatoid arthritis pathogenesis. Full article

Objective: The purpose of this study was to determine the biological association between host-derived HSP47 and fungal-derived HSP90 in the context of vulvovaginal candidiasis (VVC) and to examine their relationships with clinical, inflammatory, and metabolic phenotypes in infected and healthy women. Methods: This study followed a six-month case–control design (February–July 2025) and was conducted at the University of Tabuk Hospital in Tabuk, Saudi Arabia. A total of 84 women aged 18–45 years were recruited, of which 42 were VVC-infected, and 42 were healthy controls. ELISA kits were used to test vaginal swabs for HSP47 and HSP90. Clinical, hematological, cytokine, and metabolic markers were also evaluated. Mann–Whitney U, Spearman correlation, and multiple linear regression tests were performed to analyze the data. Results: The levels of HSP47 and HSP90 were significantly higher among infected patients (2.29 ng/mL and 3341 ng/mL, respectively) when compared with controls (0.58 ng/mL and 1025.7 ng/mL; p < 0.001). Women who were infected were older (p = 0.02), but there were no significant differences in terms of BMI (p = 0.29). The levels of vitamin D and adiponectin were significantly decreased (p < 0.001), while pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, TGF-β, and IL-8) and WBC counts were higher compared to the control group. The hematology results were characterized by inflammation-related anemia and disturbed protein metabolism. The ROC analysis demonstrated good diagnostic performance, with an AUC of 1.0 in the case of HSP47 and 0.905 in the case of HSP90. In the case of the infected patients, the regression models were found to be weak (HSP90 R² = 0.154; HSP47 R² = 0.273), although HSP47 retained significant connections with IL-8 (p = 0.005) and IFN-γ (p = 0.028). Conclusions: High levels of HSP47 and HSP90 are observed in VVC, reflecting an epithelial stress response and fungal persistence. These HSPs have high diagnostic accuracy, which justifies their potential as biomarkers for the timely detection of VVC; they also have further implications as early biomarkers for prognostic and treatment monitoring support, despite the poor predictive models. This study has some limitations that must be addressed; in particular, the regression analyses failed to provide statistically significant predictive models, likely due to the limited sample size. In addition, the specificity of HSP90 and HSP47 for VVC in comparison with other vaginal infections was not evaluated. Full article

Background/Objectives: Sporotrichosis is an emerging zoonotic subcutaneous fungal infection with limited therapeutic options, highlighting the need for improved immunomodulatory strategies. CTLA-4 is an inhibitory immune checkpoint that negatively regulates T-cell activation. In this study, we evaluated whether a CTLA-4 antisense oligonucleotide (CTLA-4 ASO) is associated with enhanced immune responses to an adjuvanted recombinant Sporothrix sp. enolase antigen (rSsEno) formulation. Methods: CTLA-4 ASO uptake, cytotoxicity, and gene-silencing activity were assessed in murine splenocytes in vitro. BALB/c mice were immunized with rSsEno formulated with Montanide Gel 01, either alone or in combination with 5 µg CTLA-4 ASO. Antigen-specific serum antibody responses were quantified by ELISA. Splenocytes from immunized mice were restimulated with enolase, and cytokine production (IFN-γ, IL-2, IL-17, and TNF-α) was measured using Cytometric Bead Array (CBA). Results: CTLA-4 ASO was efficiently internalized by splenocytes and was associated with reduced expression of CTLA-4 without detectable cytotoxicity in vitro. Mice receiving the ASO-supplemented formulation developed significantly higher anti-enolase antibody titers compared to those immunized with adjuvant alone. Upon antigen restimulation, splenocytes from ASO-treated mice produced higher levels of IFN-γ, IL-2, TNF-α, and IL-17, consistent with an enhanced recall response characterized by a mixed Th1/Th17 cytokine profile. Conclusions: CTLA-4 ASO was associated with an enhanced recall response characterized by a mixed Th1/Th17 cytokine profile. These findings suggest a potential immunomodulatory effect of CTLA-4 targeting. Further studies incorporating dose optimization, infection challenge models, and appropriate sequence controls are required to determine the specificity and relevance of these effects for protective immunity against sporotrichosis. Full article

Background: Mycoplasma pneumoniae (MP) is a major cause of respiratory tract infections in children and adolescents. Currently, there is no licensed vaccine, underscoring the urgent need for the development of safe and effective vaccines. Objective: The aim of this study is to develop a recombinant subunit vaccine candidate incorporating three antigens: the P1 protein, the P40/90 complex, and a detoxified mutant of community-acquired respiratory distress syndrome toxin. The protective efficacy of this vaccine candidate was also evaluated. Methods: Target genes were codon-optimized for expression in E. coli, and the recombinant proteins were successfully expressed and purified. The low-toxicity CARDS toxin mutant was screened based on TNF-α secretion levels in stimulated RAW264.7 cells. A three-component vaccine composed of P1, P40/90, and the mutant CARDS toxin was formulated and adjuvanted with either Al(OH)₃ alone or in combination with CpG. Mice were immunized, and immunogenicity was assessed by measuring antigen-specific IgG antibody titers. Protective efficacy was evaluated following challenge by analyzing lung histopathology, bacterial load, and inflammatory cytokine levels. Results: Seven high-purity recombinant proteins were successfully produced, including P1, the P40/90 complex, wild-type CARDS toxin, and four CARDS toxin mutants (E132A, E132Q, H36A, R10A). The E132A mutant was selected due to its significantly reduced toxicity while retaining immunogenicity. The three-component vaccine effectively elicited antibody responses against each of the included antigens. After three immunizations, IgG antibody titers in all groups reached approximately 10⁴. Immunized mice showed markedly reduced pulmonary pathology scores (control group: 2 or 2.67; immunized groups: 1.67, 1.33, and 0) and significantly decreased bacterial loads in lung tissue (control: 30.11 ± 10.40 cp/μL; immunized groups: 20.72 ± 4.37 cp/μL and 8.51 ± 8.32 cp/μL). Furthermore, the group receiving the alum + CpG adjuvant exhibited approximately a 10-fold higher antibody response compared with the alum-only group, indicating enhanced protective efficacy. Conclusions: The three-component candidate vaccine, MPtriV, adjuvanted with Al(OH)₃ + CpG, demonstrates promising immunogenicity, safety, and protective efficacy against Mycoplasma pneumoniae infection, providing a viable strategy and experimental foundation for the development of MP subunit vaccines. Full article

Background/Objectives: Ulcerative colitis (UC) involves inflammatory response, oxidative stress, changes in metabolites, and the gut microbiota. Jingangteng capsule (JGTC) has been utilized clinically for the treatment of inflammatory diseases for many years. However, the efficacy of JGTC in ameliorating UC remains unclear, and the underlying mechanisms have not yet been elucidated. This study aims to investigate the effect and mechanism of JGTC on UC. Methods: The chemical compositions of JGTC were examined using ultra-high-performance liquid chromatography with quadrupole time-of-fight mass spectrometry. The anti-UC effect of JGTC was evaluated by assessing the disease activity index (DAI), colon length, intestinal barrier recovery, and inflammatory factors in a dextran sulfate sodium (DSS)-induced colitis model. Mechanisms were investigated through fecal 16S rDNA sequencing, metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), Western blotting, and network pharmacology analysis. Results: JGTC significantly reduced the DAI scores in UC mice, increased their body weight and colon length (p < 0.001), repairing damaged intestinal tissue. It decreased the levels of inflammatory cytokines TNF-α, IL-6, IL-1β, and LPS (p < 0.01, p < 0.001), alleviating intestinal inflammation. It also raised the expression of tight junction proteins ZO-1, Claudin-1, and Occludin (p < 0.05, p < 0.001), thereby enhancing intestinal barrier function. Fecal metabolomic analysis revealed that the favorable alterations in amino acid and lipid metabolites were more pronounced. Heat maps showed strong correlations between pharmacological indicators and gut microbiota, as well as between the main differential metabolites and gut microbial communities. UPLC-QTOF-MS detection yielded 33 components of JGTC, and network pharmacology analysis based on these components predicted pathways of action of JGTC in UC. Functional pathways closely associated with significantly differential metabolites and metabolic pathways were also investigated. The PI3K-AKT-mTOR pathway was one of them, which is consistent with the conclusions drawn from network pharmacology. JGTC significantly modulated key factors in this pathway, inhibiting the expression of PI3K, Akt, PDK1, and mTOR, while augmenting the expression of PTEN (p < 0.05, p < 0.01, p < 0.001). It also mitigated the levels of related oxidative stress factors MDA, MPO, and D-LA, and raised SOD levels (p < 0.01, p < 0.001). Conclusions: JGTC improved the excessive inflammatory response in UC by regulating intestinal flora and metabolic disorders, affecting the PI3K-AKT-mTOR signaling pathway, restoring intestinal tissue damage and intestinal barrier, and inhibiting inflammatory and oxidative stress factors. Full article

Polyethylene terephthalate microplastics (PET-MPs) are emerging environmental pollutants, but the molecular mechanisms underlying their hepatotoxicity remain poorly understood. Here, we combined network toxicology with experimental validation to investigate how PET-MPs induce liver injury. In silico, we investigated the PET-repeating unit as the molecular basis for target interactions. We identified 59 overlapping genes between 157 putative PET-MPs targets and 1693 liver injury-associated genes. Protein–protein interaction analysis revealed six hub genes (AKT1, PIK3CA, PIK3CB, PIK3CD, PIK3R1, and SRC), all components of the PI3K/AKT signaling pathway. Gene ontology analysis showed that PET-MPs affect cellular stress responses and kinase activities, while pathway enrichment analysis identified PI3K-Akt, Ras, and reactive oxygen species pathways as primary targets. Molecular docking demonstrated strong binding affinity between PET-MPs and these core targets (binding free energies <−5 kcal/mol). In vitro, PET-MPs induced mitochondrial depolarization, oxidative stress, upregulation of TNF-α and IL-6, and decreased p-AKT/AKT ratio, accompanied by increased apoptosis; the apoptotic effect was reversed by the AKT agonist SC79. In vivo experiments confirmed that AKT activation reduced PET-MP-induced liver injury, evidenced by decreased inflammation, lower serum transaminases, and restored oxidative balance. These protective effects were abolished by PI3K/AKT pathway inhibitors. Our study identifies potential therapeutic targets and strategies for PET-MP-induced liver injury. Full article

Leucine-rich-repeat kinase 2 (LRRK2) is a multidomain protein highly expressed in immune cells and implicated in the regulation of immune functions including immune signaling, cytokine release and autophagy. LRRK2 is one of the therapeutic targets in Parkinson’s Disease (PD). Aberrant activation of LRRK2 can also contribute to intestinal inflammation, mainly in inflammatory bowel disease (IBD). Hence the modulation of LRRK2 may influence gut inflammation providing an improvement in disease outcomes. Over the years, microRNAs (miRNAs) have acquired much attention thanks to their potential as therapeutic targets in several pathological conditions, including inflammatory disorders. In this study, we aimed to examine the ability of miR-369-3p in the modulation of autophagy targeting LRRK2 expression. Bioinformatics analysis revealed that Lrrk2 is a target gene of miR-369-3p, and LRRK2 expression was increased in ulcerative colitis patients compared with that in a healthy control. In in vitro analysis, we validated that mimic transfection with miR-369-3p in Raw264.7 significantly reduced the expression of LRRK2 both in basal and inflammatory conditions. Moreover, the inhibition of LRRK2 limited the nuclear translocation of Nuclear factor kappa B (NF-κB) induced by lipopolysaccharide (LPS) stimulation. In turn, we found that, in inflammatory conditions, the intracellular increase in miR-369-3p precluded the inhibition of autophagy by LRRK2 by restoring autophagy marker light chain 3 (LC3)II/I ratio, BECLIN-1 and decreasing p62 expression. Furthermore, we detected that the upregulation of miR-369-3p decreased the release of pro-inflammatory mediators Tumor necrosis factor (TNF), C-C motif ligand 2/Monocyte chemoattractant protein-1 (CCL2/MCP-1), C-C motif ligand 3/Macrophage inflammatory protein-1 alpha (CCL3/MIP-1α) and C-C motif ligand 5/Regulated on activation, normal T-cell expressed and secreted (CCL5/RANTES) and increased the anti-inflammatory cytokine interleukin 10 (IL-10) in response to LPS. This study supports the anti-inflammatory potential of miR-369-3p in immune cells and suggests the potential of miR-369-3p as a therapeutic agent in the treatment of acute intestinal inflammatory conditions such as ulcerative colitis. Full article

Background/Objectives: Immunosuppression is a serious side effect of chemotherapeutic agents such as cyclophosphamide (CTX) and significantly increases the risk of infection in patients. Porcupine (Hystrix brachyura) bezoar (PB), a traditional medicine derived from the Hystrix brachyura species of porcupine, is renowned for its antioxidant and anti-inflammatory properties. However, its immunomodulatory potential has not been adequately investigated. This study aimed to systematically evaluate the protective effects of PB against CTX-induced immunosuppression and the underlying mechanisms in a rat model. Methods: An immunosuppression model was established in rats through the injection of CTX. The effects of PB on immune function were evaluated through the measurement of serum immunoglobulin (IgA and IgG) and pro-inflammatory cytokine (IL-6 and TNF-α) levels, as well as through a histopathological examination of immune organs. The mechanisms were further elucidated by analysing changes in serum metabolites and gut microbiota composition using integrated metabolomics and 16S rRNA sequencing. Results: Treatment with PB significantly alleviated CTX-induced immunosuppression, as demonstrated by elevated serum levels of IgA and IgG and reduced concentrations of IL-6 and TNF-α. PB also improved the architecture of spleen and thymus tissues. Metabolomic analysis revealed that PB regulated glycerophospholipid metabolism and steroid hormone biosynthesis, thereby reducing pro-inflammatory metabolites such as prostaglandin F2α. Furthermore, PB modulated the gut microbiota, increasing the abundance of beneficial bacteria (e.g., Bacteroidota and Lachnospiraceae) and decreasing that of harmful bacteria (e.g., Romboutsia and Clostridium sensu stricto). Conclusions: This study demonstrates that PB can effectively counteract CTX-induced immunosuppression in rats. This immunomodulatory effect is linked to changes in the gut microbiota and the regulation of specific metabolic pathways. These findings provide a scientific basis for the potential use of PB as an immunoadjuvant therapy, offering new insights into the mechanisms of traditional medicines. Full article

Background: Muscle atrophy is a major feature of Limb Girdle Muscular Dystrophy R1 (LGMDR1) patients, but its underlying molecular mechanisms have not been fully explored. While the ubiquitin–proteasome system (UPS) is known to be involved in muscle protein degradation, inflammation commonly observed in LGMDR1 patients may further activate the UPS. This study aimed to explore the role of inflammation in the muscle atrophy of LGMDR1 patients. Methods: Muscle biopsies from six confirmed LGMDR1 patients (with CAPN3 variants and reduced calpain-3 protein expression) were analyzed for atrophy-related markers, MuRF1 and Atrogin-1, using qRT-PCR and Western blotting. The expression of cytokines, TNF-α, IL-1β, and IL-6 was analyzed by qRT-PCR from muscle biopsies and by ELISA from serum samples. The NFκB, FOXO1, and FOXO3 gene expression was analyzed using qRT-PCR and Western blotting from muscle biopsies. Results: Elevated TNF-α levels were associated with increased UPS activity, reflected by upregulated NFκB, FOXO1, MuRF1, and Atrogin-1 expression in LGMDR1. Conclusion: Our findings indicate that increased TNF-α expression is associated with muscle wasting in LGMDR1 patients by targeting UPS pathway mediators that activate ubiquitin ligases—MuRF1 and Atrogin-1. These findings suggest that targeting TNF-α signaling and its downstream factors may help develop therapeutic interventions to prevent muscle atrophy in LGMDR1 patients. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden, yet effective therapeutic options remain limited. This study investigated the protective mechanisms of Astragalus membranous extract (AM) against high-fat diet (HFD)-induced MAFLD in mice using an integrated strategy combining network pharmacology, hepatic metabolomics, and 16S rRNA sequencing. UPLC–Q-Orbitrap–MS/MS identified 37 major constituents in AM, mainly phenolic acids and flavonoids. Iristectorin A, isorhamnetin, ononin, and rhamnocitrin were identified as key candidate compounds due to their relatively high abundance and confirmation as absorbed constituents in vivo. Network pharmacology and molecular docking indicated favorable interactions with hub targets (TNF, EGFR, and AKT1; binding energies < −5.0 kcal/mol) and highlighted the involvement of the AGE–RAGE signaling pathway and inflammation- and lipid metabolism-related processes. In vivo, AM significantly attenuated HFD-induced weight gain, decreased serum ALT and AST levels, and reduced hepatic lipid deposition. AM also alleviated oxidative stress by lowering malondialdehyde (MDA) and increasing superoxide dismutase (SOD) activity, while suppressing hepatic IL-1β and IL-6. Moreover, AM improved gut microbial homeostasis by restoring α-diversity and enriching beneficial genera, including Akkermansia and Bacteroides. Hepatic metabolomics further showed that AM partially normalized lipid metabolic disturbances, particularly glycerophospholipid and sphingolipid metabolism. Collectively, these results suggest that AM mitigates MASLD via a multi-component, multi-target mechanism, potentially through modulation of AGE–RAGE-associated inflammatory signaling and the gut–liver axis, supporting its development as a functional food-derived candidate for metabolic liver disorders. Full article

Background: The gut microbiota and plasma metabolites have been shown to contribute to the etiology of post-traumatic stress disorder (PTSD). The relationship between the gut microbiome and plasma metabolome in PTSD is poorly understood. This study aims to integrate the gut microbiome data and plasma metabolome data to elucidate microbial–metabolite associations specific for PTSD in a mouse model. Methods: A PTSD mouse model was induced by single prolonged stress and electric foot shock (SPS&S). We sequenced the gut microbiota composition by 16S rRNA gene sequencing and used ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) for the plasma metabolomic profiling to explore the association between the gut microbiota and the plasma metabolites in mice with PTSD. Results: The PTSD mice exhibited robust anxiety-like behaviors, significantly elevated plasma IL-1β and TNF-α, and profound gut dysbiosis characterized by a marked depletion of Muribaculaceae and Akkermansia and expansion of the Lachnospiraceae_NK4A136_group. The plasma metabolomics identified 24 significantly dysregulated metabolites, including upregulated L-arginine, palmitic acid, and oleic acid, and downregulated uridine. The pathway enrichment analysis revealed coordinated perturbations in arginine biosynthesis, pyrimidine metabolism, unsaturated fatty acid biosynthesis, and glycerophospholipid metabolism. Critically, genus-level correlation analysis uncovered biologically coherent associations. The Muribaculaceae abundance showed strong negative correlations with L-arginine and palmitic acid and positive correlations with L-glutamine and thymidine. Conclusions: This study provides an exploratory investigation into the association network between the gut microbiota and the plasma metabolites in a PTSD mouse model, offering preliminary insights into potential microbe–metabolite interactions in PTSD. Full article

Background/Objectives: Enteropathogenic Escherichia coli O157:H7 infection disrupts intestinal homeostasis, causing dysbiosis, barrier dysfunction, and inflammation. This study aimed to evaluate the protective efficacy and mechanisms of a novel probiotic, Bacteroides thetaiotaomicron type strain ATCC 29148, isolated from goat feces, against E. coli O157:H7-induced colitis. Methods: This study assessed the protective potential of the probiotic strain Bacteroides thetaiotaomicronBT6 and BT7 in vitro for GI tolerance, adhesion, and no adverse effects were observed. For the in vivo experiment, male C57BL/6J mice were divided into groups treated with Bacteroides thetaiotaomicron (BT6), PBS, E. coli O157:H7, or a combination. We employed integrated analyses including 16S rRNA gene sequencing, antioxidant status, cytokine profiling, and short-chain fatty acid (SCFA) measurement. Results: In vitro, Bacteroides thetaiotaomicron (BT6 and BT7) showed high gastrointestinal tolerance (71.89–93.22% survival). In vivo, it significantly mitigated infection-associated weight loss and disease activity (p < 0.05). Probiotic treatment enhanced barrier integrity, reduced colonic inflammation, and modulated systemic immune responses, notably increasing anti-inflammatory IL-10 while decreasing pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 (p < 0.05). It also alleviated oxidative stress by reducing malondialdehyde (MDA) and elevating antioxidant enzymes (SOD, CAT, GSH) and ATP. Fecal SCFA profiling revealed increased propionic and butyric acid. 16S sequencing indicated that B. thetaiotaomicron (BT6) administration increased beneficial families (Lactobacillaceae, Muribaculaceae) and suppressed pathobionts. Conclusions: B. thetaiotaomicron (BT6) probiotic with potential for mitigating enteropathogenic infection, an effect mainly determined by its capacity to reestablish the intestinal epithelial barrier and enhance global host health, and modulating the inflammatory response. Full article