潰瘍性大腸炎

Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the colonic mucosa, whose pathogenesis is intricately linked to metabolic reprogramming within both immune and epithelial compartments. The mechanistic target of rapamycin (mTOR) signaling pathway serves as a central immunometabolic hub that integrates nutrient availability, microbial cues, and inflammatory signals to orchestrate glycolytic flux, thereby profoundly shaping the functional plasticity of diverse intestinal cell populations. This review systematically delineates, from a cell-type-specific perspective, the divergent regulatory roles of the mTOR-glycolysis axis in intestinal immunity and mucosal barrier homeostasis. We first outline the core molecular architecture of mTORC1/mTORC2-driven glycolytic reprogramming, highlighting key regulatory nodes including GLUT1/3-mediated glucose uptake, HK2-dependent rate-limiting phosphorylation, and PKM2-governed metabolic-transcriptional switching. Subsequently, we examine how aberrant mTOR-glycolysis axis activation in neutrophils, macrophages, type 3 innate lymphoid cells, and CD4+ T effector subsets propagates a feed-forward inflammatory loop-exacerbating oxidative burst, NETosis, M1 polarization, and Th17 pathogenicity-while simultaneously undermining the metabolic fitness and suppressive integrity of regulatory T cells. Moreover, we discuss the metabolic rewiring of intestinal epithelial cells via the mTOR-glycolysis axis, which compromises barrier integrity, disrupts epithelial regeneration, and initiates a "metabolic-secretory" crosstalk that perpetuates mucosal inflammation. Collectively, this review positions the mTOR-glycolysis axis as a rheostat governing the transition from homeostatic immunosurveillance to pathogenic inflammation in UC, and proposes that cell-selective metabolic checkpoint targeting-rather than broad systemic inhibition-represents a promising precision strategy for future therapeutic intervention.

OBJECTIVE: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate that targets the folate receptor-alpha and is used for the treatment of platinum-resistant ovarian cancer, though post-marketing safety data remain limited. This study aimed to perform a post-marketing safety assessment of MIRV based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Adverse event (AE) reports of MIRV as the primary suspected drug were collected from the FAERS database (Q4 2022 to Q4 2025). Four main methods of disproportionality analysis, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, were employed for signal detection. Additionally, clinical priority and time-to-onset characteristics were assessed. RESULTS: Two thousand five hundred eighty-two AEs associated with MIRV were identified in 1,252 unique patients. The system organ classes of eye and gastrointestinal disorders were the most frequently affected by MIRV. Thirty-nine preferred terms (PTs) were detected as positive safety signals. The most frequently reported AEs were vision blurred, neuropathy peripheral, cataract, diarrhea, abdominal pain and pneumonitis. Several unexpected safety signals, including blindness, colitis, pulmonary fibrosis, glaucoma, intestinal perforation, and ulcerative keratitis, were also identified. None of the positive PTs were classified as strong clinical priority. Furthermore, exploratory findings suggest the peak onset period for MIRV-associated AEs appears to be the first month of treatment. CONCLUSION: This study confirms the known safety profile of MIRV and identifies several unexpected safety signals. However, as these unexpected safety signals are only hypothesis-generating, prospective studies are still required to confirm causality.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), where dysregulated microRNAs (miRNAs) may play a role in the immune imbalance and injury to the mucosa. miR-21 and miR-146 have been associated with inflammatory signaling pathways. OBJECTIVE: The aim of this study was to evaluate the expression levels of miR-21 and miR-146 in blood and colonic tissue of patients newly diagnosed with Ulcerative Colitis (UC) compared to healthy controls. METHODS: A case-control study was performed from January to October 2025. Patients who have recently been diagnosed with UC. The age range of the study subjects was 15-65 years and they were recruited at the time of diagnosis from gastroenterology/endoscopy services inxx and from collaborating clinics and healthy individuals as controls. Total RNA extracted from peripheral blood and colonic tissue, and expression of miR-21 and miR-146 levels were quantified by qRT-PCR, Relative miRNA expression levels were calculated by the 2^-ΔCt method after normalization with the endogenous reference gene. The relative expression levels was calculated to the control groups. RESULTS: Expression of miR-21 and miR-146 in blood and tissue was significantly lower in patients than in the controls. CONCLUSIONS: The new findings were that miR-21 and miR-146 were down-regulated in blood and much more strongly suppressed in colonic tissue in newly diagnosed UC. The results further confirm miR-21 and miR-146 as potential biomarker candidates for UC characterization, and as potential starting points for miRNA-based therapeutic approaches. These patterns should be confirmed in larger cohorts of patients and correlated to disease severity, extent and treatment response using formal inferential statistics in future studies.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disorder characterized by epithelial barrier disruption, oxidative stress, and gut microbiota dysbiosis. Although epigallocatechin-3-gallate (EGCG) exhibits potent anti-inflammatory and antioxidant activities, its clinical application is limited by poor stability and low colonic bioavailability. Herein, EGCG-loaded Eudragit® S100-coated chitosan microparticles (EG@euCS MPs) were developed as a colon-targeted oral delivery platforms integrating mucoadhesive retention with pH-responsive release. EG@euCS MPs effectively protected EGCG during gastrointestinal transit and achieved sustained release under colonic conditions. In vitro, EG@euCS MPs enhanced cellular uptake, reduced oxidative stress, promoted anti-inflammatory macrophage polarization, and restored epithelial barrier integrity. In a dextran sulfate sodium (DSS)-induced colitis mice, EG@euCS MPs achieved prolonged colonic retention and significantly alleviated disease severity, as evidenced by improved clinical symptoms, reduced inflammatory responses, restored colon morphology, and enhanced tight junction expression. Importantly, integrated 16S rRNA sequencing, short-chain fatty acid profiling, and untargeted metabolomics revealed that EG@euCS MPs restored microbial and metabolic homeostasis, characterized by enrichment of beneficial taxa, including Akkermansia, increased acetate, propionate, and butyrate production, recovery of antioxidant and tryptophan-related metabolites, and attenuation of inflammatory lipid mediators. Collectively, EG@euCS MPs coordinate the regulation of inflammatory, microbial, and metabolic pathways, representing promising colon targeted therapeutics for UC.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis which can present as an extraintestinal manifestation of ulcerative colitis (UC). There is significant overlap in the pathophysiology of both diseases, including interleukin (IL)-23 overexpression. Guselkumab, a selective IL-23 inhibitor, has been shown to be an effective treatment option in UC and has successfully treated PG in case reports. However, there is limited literature on concomitantly treating PG and UC. We present a case in which guselkumab contributed to the treatment of PG in a patient with UC, while also maintaining clinical remission of UC.