Prolonged colonic inflammation and ulcerative colitis lead to colon cancer. The rapid growth and treatment-resistant nature of these tumors are primarily influenced by an immunosuppressive tumor microenvironment, which is led by tumor-associated macrophages (TAMs). However, factors influencing or regulating the immunosuppressive nature of TAMs have not been sufficiently studied. In this manuscript, we use a mouse model of colitis-associated colorectal cancer (CRC) to demonstrate that WNT expression in TAMs regulates their immunosuppressive function by inhibiting Glycogen synthase kinase-3 beta (GSK-3β) within the macrophages, possibly through an autofeedback loop. GSK3β is a positive regulator of PD-1 and PD-L1 expression in macrophages and promotes an immunosuppressive microenvironment. Therefore, GSK-3β inhibition alters the immunosuppressive nature of the immune microenvironment and effectively controls tumor growth. In Csf1r.iCre; Porcnfl/fl mice, the absence of macrophage-derived WNT promotes tumor growth in the model of colitis-associated colon cancer. Absence of macrophage-derived WNT stabilizes GSK-3β in macrophages and promotes an immunosuppressive tumor microenvironment. We also show that pharmacological inhibition of GSK-3β in a macrophage-specific manner, achieved by systemic delivery of a lipo-GSK3β inhibitor, effectively inhibits tumor growth. Therefore, this manuscript demonstrates for the first time that the macrophage-specific modulation of GSK3β can be a potential target to treat colitis-associated colon cancer.

Single nucleotide variants in the CYP2C19 gene, as well as some non-genetic factors, are associated with the effectiveness of most proton pump inhibitors used for stress ulcer prophylaxis and should be considered in personalized treatment. In this study, we aimed to determine the CYP2C19*2 and *17 haplogenotypes by qPCR and the concentration of lansoprazole and its metabolites using HPLC in 50 burn patients from the European population on their first-ever lansoprazole prophylaxis. While CYP2C19 pharmacogenetic profiling in patients with burns played no significant role in predicting their ability to metabolize lansoprazole, associations of non-genetic factors with lansoprazole metabolism, such as age, sex, BMI, smoking, or substance abuse, were detected. Our results suggest that when prescribing lansoprazole to prevent stress ulcers in burn patients from the European population, the effect of genetic predispositions might be lower than that of other factors. Generalizability to other populations with different genetic backgrounds is, however, limited, and further studies with larger groups of CYP2C19*2 carriers in an acute setting are needed.

This critical review aims to highlight the publications on Behçet's syndrome (BS) during 2025. Recent studies have further elucidated the immunopathogenesis of BS, highlighting the interplay between innate and adaptive immune responses. Neutrophil hyperactivation, macrophage heterogeneity, and T cell imbalance emerge as central mechanisms, with growing evidence supporting the role of intercellular crosstalk and epigenetic regulation. Monocytes and non-coding RNAs emerge as areas of interest, while confirming the already established role of Th1/Th17 immune activation. These findings contribute to a more integrated understanding of disease mechanisms and may inform future targeted therapeutic strategies. While most studies are limited by small patient numbers and lack of validation in independent cohorts, the overall direction of research is encouraging. BS remains a diagnostically challenging systemic vasculitis. A meaningful proportion of patients develop significant organ damage without satisfying formal classification criteria. There is growing interest in the diagnostic utility of multimodal imaging for Behçet's uveitis. Phenotypic clustering offers a promising modality for understanding disease mechanisms, but there are substantial methodological inconsistencies across cohorts. Roflumilast and dusquetide might be promising agents for severe oral ulcers.Vascular involvement appears to be the most frequent de novo manifestation during treatment with monoclonal TNF inhibitors. High CRP level and large aneurysm diameter are associated with the need of surgery in patients with arterial involvement.

Chronic venous disease (CVD) causes substantial symptom burden and healthcare cost, driven not only by venous hypertension but by a persistent molecular cascade of endothelial activation, glycocalyx degradation, and inflammation within the vein wall. Venoactive drugs (VADs) - a heterogeneous class of flavonoid, synthetic, animal-derived, and plant-derived compounds - target this cascade and are recommended by international guidelines as adjuncts to compression therapy, endovenous intervention, and wound care in venous leg ulcer (VLU) management. This review synthesizes the pharmacological rationale and clinical evidence for VADs across these three adjunct settings. The evidence base is strongest for VAD use alongside compression, supported by multiple Cochrane-grade meta-analyses; MPFF and ruscus extracts have the most robust symptom evidence, while MPFF, pentoxifylline, and sulodexide have the strongest evidence for VLU healing. Evidence in the peri-interventional setting remains the weakest, limited to open-label studies of MPFF. Priorities for future research include stratified and biomarker-guided prescribing, combination pharmacotherapy, and larger, adequately powered VLU healing trials.

Diarrhea is a hallmark of Crohn's disease (CD) and ulcerative colitis (UC), often linked to a leaky epithelial barrier and an impaired fluid and electrolyte absorption. This study investigates whether a defect in enterocyte differentiation contributed to reduced absorptive, but increased leak protein expression in patients with Inflammatory bowel disease (IBD). Segmental biopsies from the terminal ileum to the rectum were collected from IBD patients and healthy controls (HC). mRNA and protein levels of key absorptive ion transporters and markers of cell proliferation and differentiation were analyzed. Disease activity and diarrhea severity were assessed using clinical data, endoscopy, histopathology, and proinflammatory cytokine expression. In healthy subjects, ion transporters such as Na+/H+ exchanger NHE3 (SLC9a3), Cl-/HCO3- exchanger DRA (SLC26A3), short-chain fatty acid transporter MCT1 (SLC16A1), and epithelial Na+ channel ENaC showed distinct segment-specific expression patterns. Compared with HC, inflamed segments from IBD patients exhibited significantly reduced ion transporter expression, and increased expression of the leak-promoting tight junction protein claudin 2. Markers of absorptive enterocyte differentiation-including villin, intestinal alkaline phosphatase (iALP), and HES1-were reduced, whereas the proliferative marker KI67 was elevated. Goblet cell differentiation was also impaired in highly inflammed areas. High diarrhea scores correlated with lower transporter expression. Together, our findings suggest that inflammation-driven defects in epithelial differentiation may represent an important contributing mechanism to IBD-associated diarrhea, alongside other established mechanisms, including direct inflammation- and cytokine-mediated regulation of epithelial ion transporters. Mucosal healing restored normal segmental transporter expression, highlighting the reversibility of these defects.

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated gastrointestinal disorders with a recognized epidemiologic association, yet the clinical phenotype of overlapping disease remains incompletely characterized. We performed a retrospective cohort study using the All of Us Research Program Controlled Tier dataset mapped to the Observational Medical Outcomes Partnership common data model. Adults with EoE were identified using International Classification of Diseases, Ninth Revision (ICD-9), International Classification of Diseases, Tenth Revision (ICD-10), and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) codes requiring ≥2 distinct diagnosis dates. IBD overlap was identified using Crohn's disease (CD) and ulcerative colitis (UC) diagnoses. Analyses evaluated disease sequence, atopic comorbidities, medication exposure, symptom burden, and fibrostenotic complications. Among 797 patients meeting EoE criteria, 28 (3.5%) had overlapping IBD (13 CD, 17 UC), representing a 3.2-fold enrichment over the general All of Us cohort (1.1%). Overlap patients had higher rates of asthma (57.1% vs 36.8%; OR 2.29, P = 0.045) and allergic rhinitis (71.4% vs 48.5%; OR 2.65, P = 0.020). Corticosteroid exposure was substantially greater, including systemic (96.4% vs 66.1%; OR 13.8, P < 0.001) and topical corticosteroids (75.0% vs 48.1%; OR 3.23, P = 0.006). Disease sequence was bidirectional, with IBD preceding EoE in 53.6% and EoE preceding IBD in 42.9%. Despite greater treatment exposure, overlap patients demonstrated similar rates of dysphagia, food impaction, stricture, and esophageal dilation. Patients with overlapping EoE and IBD demonstrate a distinct phenotype characterized by increased atopic comorbidity without increased fibrostenotic severity. The bidirectional temporal relationship supports shared immune susceptibility rather than unidirectional disease progression.