Prognostic value and immunological roles of GPX3 in gastric cancer.

Objective: The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. Methods: The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. Results: A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Conclusions: Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints.

Development and validation of a nomogram based on neutrophil-to-lymphocyte ratio and fibrinogen-to-lymphocyte ratio for predicting recurrence of colorectal adenoma.

Background: There are many risk factors for the recurrence of colorectal adenoma (CRA). The purpose of this study was to explore the predictive performance of fibrinogen-to-lymphocyte ratio (FLR) and neutrophil-to-lymphocyte ratio (NLR) on the recurrence of CRA and to construct a predictive model. Methods: This study analyzed the clinicopathological features of 421 CRA patients who underwent colonoscopy and adenectomy, and evaluated the recurrence of polyps under colonoscopy. Among them, 301 were training cohort and 120 were validation cohort. Multivariate logistic regression was used to identify independent risk factors associated with CRA recurrence. Established a nomogram model to predict the risk of recurrence in CRA patients using independent risk factors. The receiver operating characteristic (ROC) curves were used to verify the nomogram model discrimination. Calibration curves were used to verify the model calibration degree. The decision curve analysis (DCA) curves were used to verify the clinical efficacy of the nomogram model. Results: Totally, six independent predictors, including smoking, diabetes, adenoma number, adenoma size, NLR, and FLR, were enrolled in the nomogram. In the training cohort and validation cohort, the area under the curve (AUC) of the nomogram for predicting the risk of CRA recurrence was 0.846 and 0.841, respectively. The calibration curves displayed a good agreement. DCA curves showed that this model had a high net clinical benefit. Conclusions: Smoking, diabetes, adenoma number, adenoma size, NLR, and FLR were influencing factors for CRA recurrence.

Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review.

Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.

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.

Vertical distribution of gas exchanges and their integration throughout the entire canopy in a maize field.

Fluxes of carbon and water along a vertical profile within a canopy, particularly the associations between canopy and ecosystem levels, are not well studied. In this study, gas exchange along the vertical profile in a maize canopy was examined. The relationships between leaf- and ecosystem-level carbon and water fluxes were compared. The results from research conducted over two growing seasons showed that during vegetative growth, the top and middle leaf layers in the canopy contribute most to the carbon and water fluxes of the entire canopy. During the grain-filling stage, gas exchange processes were performed mostly in the middle leaves with and near the ears. Significant relationships were observed between the net ecosystem CO2 exchange rate (NEE) plus soil respiration and the assumed canopy levels (Acanopy) and between evapotranspiration rates at the ecosystem (ET) and assumed canopy levels (Ecanopy). This highlights the close associations between these parameters by integrating the leaf gas exchange rates measured in a conventional leaf cuvette and those at the ecosystem level via the eddy covariance technique. These results improve our understanding of how carbon assimilation varies vertically within a canopy, highlighting the critical role of ear leaves.

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.

Efficacy and safety of endoscopic submucosal dissection for gastrointestinal neuroendocrine tumors: a 10-year data analysis of Northern China.

Objective: Endoscopy is the main method to treat gastrointestinal neuroendocrine tumors (GI-NETs), but the specific indications are still controversial. We aim to investigate the clinical outcomes of GI-NETs patients who experienced endoscopic submucosal dissection (ESD). Methods: We retrospectively reviewed the clinical features and prognosis of 65 GI-NETs patients who underwent ESD between 2008 and 2018. Results: A total of 65 patients diagnosed with GI-NETs pathologically, bearing 75 lesions, were found by endoscopy incidentally for other symptoms. The locations of these lesions were stomach (n = 24), duodenal bulb (n = 4) and rectum (n = 47). The diameter of 75 tumors were as follows: size ≤ 1 cm (78.7%), 1 cm < size ≤ 2 cm (17.3%), 2 cm < size ≤ 3.5 cm (4.0%). Endoscopic ultrasonography (EUS) suggested that 72 lesions were confined to submucosa and 3 lesions invaded into muscularis propria. The rates of en bloc resection and complete resection were all 100% and the rates of intraoperative bleeding and perforation were 2.7% and 1.3%, respectively. None of the 65 patients had lymph nodes and distant metastasis during the period of study. Conclusion: For GI-NETs without lymph nodes and distant metastases, the lesion confined to submucosa with the diameter ≤1 cm is absolute indication of ESD. For rectal neuroendocrine tumors limited in submucosa with the diameter between 1 and 2 cm, and Type 1 gastric neuroendocrine tumors predicted to be T2, ESD should be prioritized to preserve gastrointestinal volume and function at initial treatment.