DNMT3a-Mediated Enterocyte Barrier Dysfunction Contributes to Ulcerative Colitis via Facilitating the Interaction of Enterocytes and B Cells.

Objective: Dysfunction of the enterocyte barrier is associated with the development of ulcerative colitis (UC). This study was aimed at exploring the effect of DNMT3a on enterocyte barrier function in the progression of UC and the underlying mechanism. Method: Mice were given 3.5% dextran sodium sulphate (DSS) in drinking water to induce colitis. The primary intestinal epithelial cells (IECs) were isolated and treated with lipopolysaccharide (LPS) to establish an in vitro inflammatory model. We detected mouse clinical symptoms, histopathological damage, enterocyte barrier function, B cell differentiation, DNA methylation level, and cytokine production. Subsequently, the effect of DNMT3a from IECs on B cell differentiation was explored by a cocultural experiment. Result: DSS treatment significantly reduced the body weight and colonic length, increased disease activity index (DAI), and aggravated histopathological damage. In addition, DSS treatment induced downregulation of tight junction (TJ) protein, anti-inflammatory cytokines (IL-10 and TGF-ß), and the number of anti-inflammatory B cells (CD1d+) in intestinal epithelial tissues, while upregulated proinflammatory cytokines (IL-6 and TNF-α), proinflammatory B cells (CD138+), and DNA methylation level. Further in vitro results revealed that DNMT3a silencing or TNFSF13 overexpression in IECs partly abolished the result of LPS-induced epithelial barrier dysfunction, as well as abrogated the effect of IEC-regulated B cell differentiation, while si-TACI transfection reversed these effects. Moreover, DNMT3a silencing decreased TNFSF13 methylation level and induced CD1d+ B cell differentiation, and the si-TNFSF13 transfection reversed the trend of B cell differentiation but did not affect TNFSF13 methylation level. Conclusion: Our study suggests that DNMT3a induces enterocyte barrier dysfunction to aggravate UC progression via TNFSF13-mediated interaction of enterocyte and B cells.

Lower gastrointestinal bleeding: role of 64-row computed tomographic angiography in diagnosis and therapeutic planning.

AIM: To determine the value of computed tomographic angiography (CTA) for diagnosis and therapeutic planning in lower gastrointestinal (GI) bleeding. METHODS: Sixty-three consecutive patients with acute lower GI bleeding underwent CTA before endovascular or surgical treatment. CTA was used to determine whether the lower GI bleeding was suitable for endovascular treatment, surgical resection, or conservative treatment in each patient. Treatment planning with CTA was compared with actual treatment decisions or endovascular or surgical treatment that had been carried out in each patient based on CTA findings. RESULTS: 64-row CTA detected active extravasation of contrast material in 57 patients and six patients had no demonstrable active bleeding, resulting in an accuracy of 90.5% in the detection of acute GI bleeding (57 of 63). In three of the six patients with no demonstrable active bleeding, active lower GI bleeding recurred within one week after CTA, and angiography revealed acute bleeding. The overall location-based accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the detection of GI bleeding by 64-row CTA were 98.8% (249 of 252), 95.0% (57 of 60), 100% (192 of 192), 100% (57 of 57), and 98.5% (192 of 195), respectively. Treatment planning was correctly established on the basis of 64-row CTA with an accuracy, sensitivity, specificity, PPV and NPV of 98.4% (248 of 252), 93.3% (56 of 60), 100% (192 of 192), 100% (56 of 56), and 97.5% (192 of 196), respectively, in a location-based evaluation. CONCLUSION: 64-row CTA is safe and effective in making decisions regarding treatment, without performing digital subtraction angiography or surgery, in the majority of patients with lower GI bleeding.