Background: Gankyrin (GK) is an oncoprotein which regulates inflammatory responses and its inhibition is considered as a possible anti-inflammatory therapy for inflammatory bowel disease (IBD). Methods: In this study, we investigated the role of GK in epithelial cells using mice with intestinal epithelial cell-specific GK deletion in (i) the entire small intestine and colon (Villin-Cre;Gankyrin^f/f) and (ii) the distal intestine and colon (Cdx2-Cre;Gankyrin^f/f). Result: Unexpectedly, GK-deficiency in the upper small bowel augmented inflammatory activity compared with control mice when colitis was induced with dextran sodium sulfate. Biochemical analyses have revealed GK-deficiency to have caused reduction in the expression of antimicrobial peptides, α-Defensin-5 and -6, in the upper small bowel. Examination of human samples have further confirmed that the reduction of GK expression in the small bowel is associated with colonic involvement in human Crohn’s disease. Through the sequencing of bacterial 16S rRNA gene amplicons, bacteria potentially deleterious to intestinal homeostasis such as Helicobacter japonicum and Bilophila were found to be over-represented in colitis induced Villin-Cre;Gankyrin^f/f mice when compared to Gankyrin^f/f control mice under the same condition. Conclusion: These results highlight the distinct site dependence of the pro- and anti-inflammatory functions of GK and provide important insights into the pathogenesis of IBD.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing-remitting course that often requires hospitalization during flares. While prolonged fasting has traditionally led to high-calorie intravenous nutrition, excessive caloric intake may induce hyperglycemia, increase infection risk, and inhibit autophagy. This study aimed to evaluate the impact of a short-term, calorie-restricted regimen (≤400 kcal/day), designed to promote autophagy, on clinical outcomes in hospitalized patients with UC. A retrospective analysis was conducted on 38 patients admitted for UC exacerbation between January 2022 and December 2024. Patients were categorized into a calorie-restricted group (≤400 kcal/day) or a standard nutrition group (>400 kcal/day) based on their total caloric intake. The calorie-restricted group received only intravenous fluids and noncaloric beverages. The primary endpoint was clinical remission at day 14, while secondary endpoints included the length of hospital stay and incidence of adverse events. The clinical remission at day 14 following treatment initiation was significantly higher in the calorie-restricted group (86% [12/14]) compared to the standard nutrition group (42% [10/24]) (P < .05). The mean duration of hospitalization was also significantly shorter in the calorie-restricted group (11.0 ± 3.3 days) compared to the standard nutrition group (22.1 ± 8.9 days) (P < .01). The calorie-restricted group experienced mild, transient adverse events but no serious complications. In contrast, the standard nutrition group experienced serious adverse events such as catheter-related infections and myocarditis. Caloric restriction during hospitalization for UC exacerbation may be associated with increased clinical remission and a shorter hospital stay. That nutritional strategy offers a potentially novel and cost-effective approach distinct from conventional bowel rest. Further prospective, multicenter studies are warranted to validate these findings.

Aims: Tofacitinib (TOF), an oral pan‐Janus kinase (JAK) inhibitor, is a therapeutic option for moderate to severe ulcerative colitis (UC). While short‐term efficacy has been reported, its long‐term real‐world outcomes—particularly in Asian populations—and optimal dose reduction timing are incompletely understood. Methods and Results: This single‐center, retrospective study included 63 patients with UC treated with TOF between October 2018 and April 2025. Clinical outcomes—response, remission, steroid‐free remission, and adverse events—were assessed at Weeks 26, 52, and 104. The impact of dose reduction (20–10 mg/day) was analyzed, focusing on endoscopic mucosal healing (Mayo endoscopic subscore 0–1). At Week 26, clinical response and remission rates were 63% and 53%, respectively; 43% of patients achieved steroid‐free remission by Week 52, and 41% maintained it at Week 104. Early responders were associated with treatment efficacy in a lower partial Mayo score (OR = 1.724, 95% CI: 0.994–2.988, p = 0.052). Among 26 patients with dose reduction, relapse occurred in 5.6% with mucosal healing versus 62.5% without. Significant factors associated with relapse/exacerbation were TOF dose reduction based on clinical remission alone without endoscopic confirmation ( p = 0.003, OR = 5.26) and disease duration ( p = 0.019, OR = 0.86). Adverse events were infrequent and manageable, with no malignancies or deaths reported. Conclusion: TOF demonstrated sustained effectiveness and safety in UC. Mucosal healing was strongly associated with successful dose de‐escalation, representing a key treatment target. These findings support treat‐to‐target strategies incorporating endoscopic assessment to guide TOF dose reduction.

Background/Objectives: Ulcerative colitis (UC)-associated neoplasia (UCAN) often presents as flat lesions with indistinct margins, and biopsy sensitivity is limited. Therefore, we evaluated endoscopic criteria to distinguish UCAN from sporadic neoplasia, assessing the accuracy of endoscopic ultrasonography (EUS) for invasion depth and the role of endoscopic submucosal dissection (ESD) as a “total biopsy.” Methods: We reviewed 212 endoscopically treated neoplastic lesions in UC-affected mucosa (April 2016–January 2025). We compared preoperative diagnoses using macroscopic type, pit pattern, and the Japan Narrow-Band Imaging Expert Team classification with final histology. We compared depth estimates with pathology in 10 UCAN-suspected lesions undergoing EUS. Lesions < 2 cm underwent conventional endoscopic resection, whereas those ≥ 2 cm underwent ESD. Results: No UCAN was found in 189 lesions < 2 cm. Among 23 ESD lesions, 8 suspected sporadic lesions were non-UCAN. Of 15 UCAN-suspected lesions, 8 were UCAN, 6 sporadic, and 1 inflammatory. For positive T1b or deeper invasion, the sensitivity, specificity, positive and negative predictive values, and overall accuracy of EUS were 50.0%, 100%, 100%, 88.9%, and 90.0%, respectively. EUS depth assessment agreed with pathology in 9/10 cases; nine lesions were T1a or shallower, and one was T1b. Third-layer thickening occurred in two lesions—both UCAN—including the T1b cancer. In ESD cases, redness and a VI pit pattern were independent predictors of UCAN. Conclusions: EUS-based depth assessment is useful for determining optimal treatment strategies. Beyond therapy, ESD enables comprehensive histologic assessment of the entire lesion, functioning as a total biopsy to guide management while preserving bowel function.