Rebamipide attenuates alcohol-induced gastric epithelial cell injury by inhibiting endoplasmic reticulum stress and activating autophagy-related proteins.

Apoptosis of gastric mucosa epithelial cells caused by the abuse of alcohol produces injury to the gastric mucosa and acute or chronic gastritis. In recent years, it has been demonstrated that endoplasmic reticulum stress (ERS) is involved in mediating apoptosis, and that autophagy has a protective effect on survival of cells. Rebamipide is a gastric mucosal protectant used to treat gastritis and stomach ulcers. In this study, ethanol was used to overstimulate gastric mucosal epithelial cells and gavage mice. It was found that 400 mmol/L ethanol overstimulation could activate ERS and induce apoptosis (control vs ethanol treatment: 15.24 ± 1.10% vs 33.80 ± 1.47%, P < 0.001); but could not activate the autophagy pathway. Rebamipide intervention can reduce apoptosis rate (20.78 ± 1.63%), and significantly inhibit the activation of ERS and the active ERS-related downstream NF-κB signaling pathway. Additionally, rebamipide can activate the expression of autophagy-related pathway proteins and increase the expression of p-ERK and p-p38. In addition, rebamipide relieved oxidative stress after an ethanol insult. In the present study, molecular evidence of rebamipide inhibition of ERS and regulation of the protein expression of autophagy pathway components were produced using an acute alcoholic gastric mucosal injury model. This model provides a new approach for investigating the effects of rebamipide treatment on alcohol-induced gastric mucosal damage.

Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota.

Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.

A novel robust nomogram based on preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) for predicting lymph node metastasis of gastric cancer.

BACKGROUND: Accurate assessment of lymph node status in gastric cancer (GC) patients can help to select appropriate treatment strategies for GC, but the diagnostic accuracy of conventional methods needs to be improved. The aim of this study was to investigate the predictive value of preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) on lymph node status in GC patients and to construct a risk prediction model. METHODS: This study retrospectively analyzed the clinicopathological characteristics of 349 patients with GC who underwent radical gastrectomy, among which 250 patients were recruited in the training cohort and 99 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified as independent variables in multivariate logistic regression analysis, which were then incorporated and presented in a nomogram. Receiver operating characteristic (ROC) curves, Calibration curve and decision curve analysis (DCA) curves were used to evaluate the discrimination, prediction accuracy and clinical effectiveness of the model. RESULTS: Multifactorial logistic regression analysis showed that alcohol use (OR =2.203, P=0.036), Depth of invasion (OR =7.756, P<0.001), differentiation (OR =2.252, P=0.018), carcinoembryonic antigen (CEA) (OR =2.443, P=0.017), carbohydrate antigen 19-9 (CA199) (OR =2.715, P=0.008) and HALP (OR =2.276, P=0.032) were independent risk factors for lymph node metastasis (LNM) in GC. We used these factors to construct a nomogram for predicting LNM in GC patients, and the ROC curves showed good discrimination of the model with AUC values of 0.854 (training cohort) and 0.868 (validation cohort), respectively, and the calibration curves showed good predictive ability of the nomogram, in addition to the DCA curves results showed the clinical usefulness of the model. CONCLUSIONS: In conclusion, we established a nomogram for predicting LNM in patients with GC.