Search Results (2,871)

Background: Edwardsiella piscicida is a significant intracellular pathogen of channel catfish (Ictalurus punctatus) and a major threat to U.S. aquaculture. A recently developed recombinant attenuated vaccine strain (χ16016) uses arabinose-regulated murA expression to trigger delayed cell wall lysis in vivo, ensuring biological containment while conferring strong protection against virulent challenge. Although its efficacy has been demonstrated, the host immune programs underlying protection remain incompletely defined. Methods: We used RNA sequencing to characterize tissue-specific transcriptomic responses in the intestines and kidneys of channel catfish at 7 days post-vaccination. Fish were vaccinated with χ16016 by either bath immersion or intracoelomic (IC) injection, and differentially expressed genes and enriched immune pathways were analyzed to determine how the vaccine delivery route shapes systemic and mucosal immune responses. Results: Across comparisons, 19,101 differentially expressed genes revealed pronounced route- and tissue-dependent immune remodeling. As aquaculture vaccination strategies increasingly prioritize scalability and practical deployment, understanding how the delivery route shapes immune outcomes is critical. Here, IC vaccination induced broader systemic transcriptional changes, particularly in the intestine, whereas bath immunization elicited a more focused yet coordinated mucosal response. Overall, intestinal tissue exhibited greater transcriptional responsiveness than kidney tissue, underscoring its central role in early vaccine-induced immunity. Functional enrichment analyses identified the activation of innate recognition pathways, MAPK and calcium signaling cascades, complement components, antigen processing machinery, and cell adhesion networks. Notably, bath immunization enriched the intestinal immune network for IgA production pathway, which represents an orthology-based mapping of conserved mucosal immune components, alongside the upregulation of IL-6, CXCL12–CXCR4, integrins (α4β7), MHC class II, complement C3, and polymeric immunoglobulin receptor (pIgR). Given that catfish rely primarily on IgM in mucosal immunity, these findings indicate the induction of IgM-mediated mucosal defense rather than classical mammalian IgA responses. Concurrent complement and scavenger receptor signatures suggest a transition toward efficient opsonophagocytic clearance with controlled inflammation at this subacute stage. Conclusions: This study provides the first systems-level view of host transcriptomic responses to a regulated-lysis E. piscicida vaccine in channel catfish. The findings demonstrate that immersion vaccination, although transcriptionally less expansive than injection, effectively activates coordinated mucosal innate and adaptive immune programs, supporting its practical use as a scalable vaccination strategy for aquaculture. Full article

We evaluated the antimicrobial and antioxidant capabilities of a bacteriocin purified from a recently identified marine Lactococcus lactis (L. lactis) NAN6399 strain, a lactic acid bacterium recovered from Mediterranean coastal waters near Alexandria, Egypt, and identified by combined API 50 CHL phenotypic profiling and 16S rRNA gene sequencing. Bacteriocin purification was achieved by sequential ammonium sulfate precipitation and reverse-phase high-performance liquid chromatography (RP-HPLC). The purified bioactive fraction had an approximate molecular weight of 20 kDa by SDS-PAGE and a 106-amino-acid N-terminal sequence that, upon BLAST alignment, returned 98.1% overall identity to the Lactococcin 972 family bacteriocin AAK06118.1 from L. lactis IL1403, with divergence confined exclusively to the terminal two C-terminal residues. This sequence is structurally and functionally distinct from canonical Lcn972 (L. lactis IPLA 972): the two peptides share an identical 25-residue signal peptide but diverge entirely in their mature bioactive domains, which exhibit only 9.1% sequence identity. Canonical Lcn972 operates through Lipid II-mediated septum disruption and inhibits only Lactococcus species; the NAN6399 peptide, correctly designated as a novel member of the Lcn972-like peptide family, demonstrated broad-spectrum antimicrobial efficacy against multiple indicator organisms (Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis), producing inhibition zones of up to 30 mm and minimum inhibitory concentration (MIC) values as low as 1.25 μg/mL against S. aureus. Antioxidant capacity was assessed using the DPPH radical scavenging assay, with the purified preparation achieving 73.14 ± 0.34% inhibition. Collectively, these data establish L. lactis NAN6399 as the producer of a bifunctional Lcn972-family bacteriocin with both antimicrobial and antioxidant potential, provide the first experimental characterization of the antimicrobial activity of this Lcn972-family branch, and highlight marine LAB as a productive reservoir for novel bioactive peptide discovery. Full article

Inflammation at the superior airway level has multiple manifestations, and allergic rhinitis and chronic rhinosinusitis with or without polyps are two of the most frequent and troublesome of them, with innate and adaptive immunity being implicated. Dendritic cells, epithelial cells, neutrophils, macrophages, mucosal mast cells, eosinophils, basophils, innate lymphoid cells (ILCs), and NK cells are the players in innate immunity, while regulatory T (Treg), TH1, TH2, TH17, T follicular helper, and B cells are components of the adaptative immune system. Th9 cells, a subset of T helper cells discovered in 2008 that produce interleukin-9 (IL-9), play a vital role in the adaptive immune response and have advantageous and harmful effects in different diseases due to the induction pattern. We queried international databases for current, up-to-date information regarding the interplay between interleukin 9 (IL-9) and helper T cells (especially Th9 cells), and by other immune cells. Interleukin-9 has multiple immunological functions, acting on various target cells through its specific receptor (IL-9R), such as the following: the regulation of allergic (Th2-type) immune responses; effects on epithelial and mucosal cells, mast cells, and eosinophils; chronic inflammation; and autoimmunity. Thus, there is a further need to translate laboratory findings into clinical practice regarding IL-9. Full article

The evolution of herbicide resistance can increase, decrease, or have no effect on the growth rate, competitive ability, and fitness of field-selected populations. The growth response of an ACCase-resistant (R) johnsongrass [Sorghum halepense (L.) Pers.] population harboring an Ile1781Leu mutation, and a susceptible (S) population was studied in pot experiments under intraspecific and interspecific competition with corn or sunflower, using a target-neighborhood design. The R population in the intraspecific competition indicated greater fitness-related traits such as height (H), tiller number (TN), aboveground fresh weight (AFW), and rhizome fresh weight (RFW) than the S population. Aggressiveness, competitive ratio, competition intensity index, and relative competition intensity indices confirmed also the superiority of the R population. Similarly, the R population grown in interspecific competition with corn or sunflower produced greater H, TN, and AFW than the S population. In addition, both R and S populations growing in competition with corn produced more H, TN, and AFW than those growing in competition with sunflower. Furthermore, the R population in competition with corn hybrids resulted in a greater reduction in H and AFW in corn plants. These findings strongly support the evidence of fitness advantage in the R population harboring the 1781Leu mutant allele as compared to the S counterpart. Full article

Concurrent alcohol and cannabis use (“crossfading”) is increasingly prevalent, especially among adolescents, yet its toxicological impact on pulmonary innate immunity remains largely unexplored. Alveolar macrophages (AMs) orchestrate inflammatory responses in the lung, and dysregulated macrophage polarization is a hallmark of alcohol-associated lung disease. Although alcohol and cannabinoids individually modulate immune function, the mechanisms by which their co-exposure alters macrophage activation and inflammatory signaling in the lung are largely unknown. AMs are highly sensitive to xenobiotic exposure and play a central role in regulating inflammatory and cytotoxic responses. In this study, we investigated how acute ethanol exposure, synthetic cannabinoid exposure, and their combined exposure affect macrophage viability, polarization, and the release of inflammatory mediators via cannabinoid receptor (CB1R/CB2R)-dependent pathways. Human THP-1-derived macrophages and KG-1 macrophage-like cells were exposed to ethanol, the CB1/CB2 agonist WIN 55,212-2, or both, with selective pharmacological antagonism of CB1R and CB2R. Ethanol exposure activated and polarized macrophages toward a pro-inflammatory M1 phenotype, accompanied by increased secretion of pro-inflammatory cytokines MCP-1, TGF-α, IFN-β, IL-6, and TNF-α. In contrast, WIN 55,212-2 promoted anti-inflammatory M2 polarization and increased IL-10 and IL-4 production. Notably, co-exposure to ethanol and WIN produced an antagonistic immunomodulatory response, characterized by the suppression of ethanol-induced M1 polarization and attenuation of pro-inflammatory cytokine release. Mechanistically, pharmacological CB1R blockade reduced ethanol-induced M1 polarization and cytokine secretion, whereas CB2R blockade exacerbated these effects, underscoring divergent roles for cannabinoid receptors in regulating pulmonary macrophage responses. This study provides novel findings demonstrating the mechanism by which alcohol–cannabinoid co-use reshapes macrophage immune phenotypes and identifies the endocannabinoid system as a potential therapeutic target for alcohol-related inflammatory lung disease. Full article

Background: Acquired resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib, often mediated by EGFR triple mutations, poses a major clinical challenge in non-small cell lung cancer (NSCLC) treatment. Among these, some rare mutations, such as L858R/T790M/L792H and L858R/T790M/G796R, create steric hindrance that directly interferes with osimertinib binding, yet effective targeted therapeutic strategies for these specific mutations remain lacking. Cudratricusxanthone A (CTXA), a natural xanthone derivative isolated from Cudrania tricuspidata Bur., has demonstrated various pharmacological activities, but its effects against EGFR triple-mutant NSCLC have not been systematically investigated. Methods: Stable Ba/F3 and NIH/3T3 cell lines expressing EGFR L858R/T790M/L792H or L858R/T790M/G796R triple mutations were generated via electroporation. The antiproliferative effects of CTXA were evaluated by MTT/MTS assays, colony formation, and wound healing assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression of EGFR signaling pathway components (p-EGFR, p-ERK, p-AKT, p-STAT3) and cell cycle regulators (Cyclin D1, CDK4) were examined by Western blotting. Molecular docking and 200 ns molecular dynamics simulations were performed to investigate the stability and binding modes of CTXA to the mutant EGFR kinase domains. Results: The successfully established triple-mutant cell lines exhibited high EGFR expression, IL-3-independent growth, and significant resistance to osimertinib. CTXA inhibited the proliferation of all triple-mutant cell lines in a time- and concentration-dependent manner, with 48 h IC₅₀ values ranging from 0.362 to 2.488 μM. Mechanistically, CTXA suppressed EGFR autophosphorylation and downregulated downstream p-ERK, p-AKT, and p-STAT3. CTXA induced G1 phase cell cycle arrest by downregulating Cyclin D1 and CDK4, significantly promoted apoptosis, and inhibited cell migration. Molecular docking revealed that while osimertinib binding was blocked by steric hindrance from His-792 or Arg-796, CTXA adapted to the mutated ATP-binding pockets through multiple hydrogen bonds and extensive hydrophobic interactions. Molecular dynamics simulations confirmed the stable binding of CTXA to both mutant EGFR proteins over the 200 ns simulations. Conclusions: This study demonstrates for the first time that the natural compound CTXA possesses antitumor efficacy against EGFR L858R/T790M/L792H and L858R/T790M/G796R mutants by regulating EGFR-ERK/AKT/STAT3 signaling. Our findings position CTXA as a promising lead compound for tackling this challenging form of acquired resistance and highlight the value of natural products in multi-target antitumor drug discovery. Full article

Mussel foot proteins (Mfps) are renowned for their underwater adhesion, whereas their biotechnological potential for cutaneous wound repair remains largely underexplored. In this study, we identified and characterized a cysteine-rich mussel foot protein, Mfp6-1, from Mytilus coruscus and investigated its therapeutic potential for wound healing. Sequence analysis showed that Mfp6-1 is enriched in cysteine (11.0%) and tyrosine (~16.5%). We successfully expressed recombinant Mfp6-1 (rMfp6-1) in E. coli. Structural prediction based on the mature peptide sequence suggested that rMfp6-1 adopts a relatively compact fold containing several short β-structural elements. In vitro assays demonstrated that rMfp6-1 possesses antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and alkylation experiments suggested that cysteine residues contribute importantly to this activity. Dithio-bis-nitrobenzoic acid (DTNB)-based thiol quantification further demonstrated that rMfp6-1 contained abundant accessible free sulfhydryl groups, supporting an important contribution of cysteine-derived thiols to its antioxidant activity. Experiments on a full-thickness mouse wound model showed that rMfp6-1 treatment resulted in significantly faster wound contraction. Morphological analysis further revealed that rMfp6-1 optimizes the healing microenvironment by promoting collagen accumulation and re-epithelialization. Additionally, the treatment was found to trigger vascular endothelial growth factor (VEGF)-mediated angiogenesis, thereby improving the overall quality of the regenerated tissue. Furthermore, rMfp6-1 treatment significantly reduced interleukin-6 (IL-6) expression, suggesting that its antioxidant capacity creates a permissive microenvironment for tissue regeneration by suppressing excessive inflammation. These findings indicate that recombinant rMfp6-1 is a promising bioactive candidate for wound-healing applications. Full article

Hematologic malignancies arise and progress within a systemic ecosystem in which the gut microbiota is an increasingly recognized, partially modifiable component. Across acute leukemias, chronic lymphocytic leukemia, plasma cell disorders, lymphomas, and clonal myeloid neoplasms, human studies consistently report reduced microbial diversity, depletion of barrier-supportive, short-chain fatty acid-producing commensals, and enrichment of Gram-negative, pro-inflammatory, or hospital-adapted taxa. These alterations are associated with pre-leukemic clonal expansion, adverse genetic and immunological features, progression from precursor conditions, and inferior outcomes after chemotherapy, immunochemotherapy, chimeric antigen receptor T-cell therapy, and allogeneic hematopoietic stem cell transplantation. Mechanistic work in animal models and ex vivo systems demonstrates that microbiota-derived signals and metabolites—including Th17/IL-17-skewing consortia and the lipopolysaccharide intermediate ADP heptose sensed by the cytosolic receptor ALPK1—can actively modulate hematopoietic stem and progenitor cell fitness, inflammatory circuits, and malignant cell survival, supporting a causal role in disease biology. At the same time, major knowledge gaps remain because most human cohorts are small, single-center, and cross-sectional, frequently rely on 16S rRNA profiling, and are vulnerable to dietary, geographic, and treatment-related confounding. Within this context, three translational domains appear particularly promising: pharmaco-microbiomics, microbiome-informed risk stratification, and rational microbiota-targeted interventions, particularly diet-based strategies and antimicrobial stewardship. Here, we provide an integrated, disease-spanning synthesis of these data, emphasizing clonal hematopoiesis and myeloid neoplasms as emerging examples of microbiota–marrow crosstalk and outlining practical priorities for embedding microbiome science into future hematologic trials. Routine microbiome profiling or empiric microbiota-directed therapies cannot yet be recommended in everyday hematology practice, but integrating microbiome science into prospective therapeutic and transplant trials offers a realistic path to improved disease modeling, biomarker development, and rational adjunctive strategies to enhance outcomes for patients with hematologic malignancies. Full article

Emphysema is a well-recognized risk factor for lung cancer; however, its influence on the immunologic tumor microenvironment in lung adenocarcinoma remains poorly defined. In this pilot, hypothesis-generating study, immune-related gene expression profiling was performed using archival formalin-fixed paraffin-embedded tumor specimens from 12 patients with lung adenocarcinoma, including the Never-smoker group (never-smokers without emphysema; n = 4), the Smoker 1 group (smokers without emphysema; n = 3), and the Smoker 2 group (smokers with CT-defined emphysema; n = 5). Expression of 770 immune-related genes was analyzed using the nCounter PanCancer IO 360 Panel (NanoString Technologies, Seattle, WA, USA). Compared with the Never-smoker group, tumors from the Smoker 1 group showed marked upregulation of SFRP1, SERPINB5, and IL6, whereas tumors from the Smoker 2 group exhibited increased expression of KIR2DL3, BLK, and WNT2B. Relative to the Smoker 1 group, the Smoker 2 group demonstrated significant upregulation of MMP7, TDO2, and CCL18. Pathway enrichment analysis revealed cytokine–cytokine receptor interaction as the most prominently enriched pathway in both smoker groups, while the IL-17 signaling pathway was preferentially enriched in the Smoker 2 group. In addition, diffusing capacity for carbon monoxide showed significant correlations with immune-related genes including IL-6 and IL-6R. Collectively, these preliminary findings suggest that lung adenocarcinoma arising in emphysematous lungs may be characterized by a distinct pro-inflammatory immune microenvironment. Given the small sample size and potential confounders, these results should be regarded as hypothesis-generating. Emphysema-associated immune remodeling may nevertheless represent an important biological factor worthy of validation in larger, independent cohorts. Full article

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