Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation.

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4+CD45RBhigh T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4+ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4+ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4+ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

Metachronous Neoplasia and Local Recurrence after Colorectal Endoscopic Submucosal Dissection.

Several reports discussed colonoscopic surveillance after polypectomy and endoscopic mucosal resection (EMR) for colorectal polyps, but only a few reports focused on prognostic analyses, and none involved metachronous neoplasia after colorectal endoscopic submucosal dissection (ESD). We conducted the present study to assess the risk of adenoma recurrence requiring endoscopic treatment, and to establish appropriate post-ESD colonoscopic surveillance. We enrolled 116 patients who had undergone colorectal ESD at Okayama University Hospital between February 2008 and July 2014 and had been followed-up >12 months. We retrospectively analyzed clinicopathological features of 101 lesions from 101 patients. Metachronous adenomas were detected in 21 cases (20.8%). We divided the patients into 2 groups according to the occurrence of metachronous adenomas. Our comparison of clinicopathological characteristics between these groups showed that in the metachronous adenomas group the number of synchronous adenomas at index colonoscopy was high and the rate of laterally spreading tumor-nongranular (LST-NG) was higher. A multivariate analysis indicated that the number of synchronous adenomas was significantly associated with metachronous adenomas (HR: 2.54, 95%CI: 1.04-6.52, p<0.05). The colonoscopic surveillance planning after colorectal ESD should be more meticulous for patients with more synchronous adenomas.