Retinoic acid-inducible gene I (RIG-I) plays a pivotal role in the regulation of cytokine production induced by pathogens. The RIG-I also augments the production of IFN and other cytokines via an amplification circuit. Because the production of cytokines is closely controlled, up-and down-regulation of RIG-I signaling also needs strict regulation. The mechanism of this regulation, however, remains elusive. Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.innate immunity ͉ signal transduction

By preventing tumor ingrowth and migration, covered SEMSs with an anti-migration system had a longer duration of patency than uncovered SEMSs, which recommends their use in the palliative treatment of patients with biliary obstruction due to pancreatic carcinomas.

Several changes in gut microbiota were associated with age and sex. Stool consistency and gut microbiota associations emphasized the importance of stool consistency assessments to understand intestinal function.

Background and study aims: Linked color imaging (LCI) is a new image-enhanced endoscopy technique using a laser light source to enhance slight differences in mucosal color. The aim of this study was to compare the usefulness of LCI and conventional white light imaging (WLI) endoscopy for diagnosing Helicobacter pylori (H. pylori). Patients and methods: We retrospectively analyzed images from 60 patients examined with WLI and LCI endoscopy between October 2013 and May 2014. Thirty patients had H. pylori infections, and other thirty patients tested negative for H. pylori after eradication therapy. Four endoscopists evaluated the 2 types of images to determine which was better at facilitating a diagnosis of H. pylori infection. Results: H. pylori infection was identified with LCI by enhancing the red appearance of the fundic gland mucosa. The accuracy, sensitivity, and specificity for diagnosing H. pylori infection using WLI were 74.2 %, 81.7 %, and 66.7 %, respectively, while those for LCI were 85.8 %, 93.3 %, and 78.3 %, respectively. Thus, the accuracy and sensitivity for LCI were significantly higher than those for WLI (P = 0.002 and P = 0.011, respectively). The kappa values for the inter- and intraobserver variability among the 4 endoscopists were higher for LCI than for WLI. Conclusions: H. pylori infection can be identified by enhancing endoscopic images of the diffuse redness of the fundic gland using LCI. LCI is a novel image-enhanced endoscopy and is more useful for diagnosing H. pylori infection than is WLI.

Background and study aim This study aimed to assess the safety and feasibility of endoscopic submucosal dissection (ESD) using a scissors‐type knife with prophylactic closure using over‐the‐scope clip (OTSC) for superficial non‐ampullary duodenal epithelial tumors (SNADETs). Patients and methods Consecutive patients who underwent ESD for SNADETs >10 mm between January 2009 and July 2019 were retrospectively enrolled. We performed ESD using either a needle‐type knife (Flush Knife‐ESD) or a scissors‐type knife (Clutch Cutter‐ESD). Mucosal defects were prophylactically closed using three methods: conventional clip, laparoscopic closure, or OTSC. Results A total of 84 lesions were resected using the Flush Knife‐ESD and the Clutch Cutter‐ESD (37 and 47 patients, respectively), and conventional clip, laparoscopic closure, and OTSC for mucosal defect closure after ESD were applied in 13, 13, and 56 lesions, respectively. The R0 resection rate was significantly higher in the Clutch Cutter‐ESD than that in the Flush Knife‐ESD (97.9% vs 83.8%, respectively, P = 0.040). The intraoperative perforation rate was significantly lower in the Clutch Cutter‐ESD than in the Flush Knife‐ESD (0% vs 13.5%, respectively, P = 0.014). Complete closure rates of conventional clip, laparoscopic closure, and OTSC were 76.9%, 92.3%, and 98.2%, respectively (P = 0.021); and delayed perforation rates were 15.4%, 7.7%, and 1.8%, respectively (P = 0.092). Conclusions Endoscopic submucosal dissection using a scissors‐type knife with prophylactic OTSC closure is safe and feasible for the low‐invasive treatment of SNADETs.

ESD effectively achieved a high rate of en bloc resection. However, the perforation rate was substantial; hence, improvement in the ESD method is required. The outcomes of ESD, especially for early colorectal malignancies, need to be assessed further.

BLI was useful for the diagnosis of colorectal polyps.

Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux and prevent gastric ulcers, and have been considered as low risk. However, recent studies have identified possible associations between PPI use and gut microbiota, suggesting that PPIs use increases the risk of enteric infections, including Clostridium difficile infection. To investigate gut microbiota in Japanese PPIs users, we conducted 16S metagenomics analysis of fecal samples collected from PPI users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control subjects) matched by age and sex were recruited and fecal samples were obtained to analyze the gut microbiome using 16S rRNA gene sequencing. There were significant differences in the microbial structure between PPI non-users and PPI users. In contrast, the analysis of α-diversity revealed no significant differences between PPI non-users and PPI users. When comparing in genus level between these two groups, the genera Streptococcus was significantly abundant and the genera Faecalibacterium was significantly decreased in PPI users. Our findings indicate a probable association between PPI use and the alternation of microbiota. These alterations might provide a mechanism by which PPIs predispose enteric infection such as Clostridium difficile infection.