Project description:Genome-scale DNA methylation profiling using the Infinium DNA methylation 450K BeadChip platform and samples from gastric cancer (intestinal and diffuse), precursor lesions (multifocal chronic atrophic gastritis and inestina metaplasia), non-atrophic gastritis and normal gastric mucosa.
Project description:Intestinal-type gastric cancer is preceded by premalignant lesions including chronic atrophic gastritis and intestinal metaplasia. In this study, we performed a scRNA-seq survey of 56,440 cells from thirteen gastric antral mucosa biopsies from nine patients with Non-atrophic gastritis (NAG), CAG, IM or early gastric cancer (EGC), and constructed a single-cell transcriptome atlas for gastric premalignant and early-malignant lesions. The thirteen biopsies, including three wild superficial gastritis (NAG) ones, three CAG ones, six IM ones and one EGC , spanned the cascade from gastritis to early gastric cancer.For each biopsy, we isolated single cells without prior selection for cell types and utilized the 10x Chromium platform to generate RNA-seq data. After removing low-quality cells (Methods), a total of 32, 332 cells that passed the quality control were retained for subsequent analysis, which yielded a median of 1941 detected genes per cell.
Project description:BackgroundThe role of the gastric microbiome in development or persistence of equine glandular gastric disease (EGGD) remains to be investigated.Hypothesis/objectivesThe objective was to characterize the glandular mucosal and gastric fluid microbiomes of horses with and without EGGD. It was hypothesized that differences in the mucosal microbiome are associated with EGGD.AnimalsTwenty-four horses were enrolled.MethodsGastroscopy was performed and EGGD scores recorded (score 0, n = 6; score 1, n = 8; score ≥2, n = 10). Gastric fluid and pinch biopsies of healthy glandular mucosa and EGGD lesions were collected via gastroscope. 16S rRNA amplicon sequencing of the gastric fluid and glandular mucosal biopsies was performed. Relationships between gastric fluid and mucosal microbial community composition were evaluated among EGGD score groups (EGGD 0-BX, EGGD 1-BX, EGGD ≥2-BX) and among endoscopic appearances: controls from horses without EGGD and normal areas, hyperemic areas, and lesions from horses with EGGD.ResultsMicrobial community structure of mucosal biopsies differed among EGGD score groups (Jaccard similarity index; P = .009). Principal coordinate analysis showed separate clusters for EGGD 0-BX and EGGD ≥2-BX.Conclusions and clinical importanceA modest difference was detected in the community structure of the gastric glandular mucosal microbiome in association with EGGD score.
Project description:To investigate the changes in molecular expression, biological processes, stemness, immune microenvironment, tumor hallmark activities and co-expression relationships during intestinal-type gastric cancer carcinogenesis and to excavate the prognostic information contained in the carcinogenesis process. RNA expression profiles of ninety-four gastroscope biopsy samples with different stages of precancerous lesions or early gastric cancers and their paired controls were detected by Agilent Microarray.
Project description:To elucidate the molecular mechanism by which A4gnt-null mice develop gastric adenocarcinoma, gastric mucosa was isolated from the stomachs of wild-type and A4gnt-null mice, and microarray analysis was performed. Total RNA was isolated from the gastric mucosa stripped from the muscular layer of the glandular stomach of A4gnt-null and wild-type mice at 5, 10, and 50 weeks of age (one mouse per each group was analyzed).
Project description:Equine glandular gastric disease (EGGD) is a common disease among athletic horses that can negatively impact health and performance. The pathophysiology of this EGGD remains poorly understood. Previous studies using controlled populations of horses identified differences in the gastric glandular mucosal microbiome associated with disease. The objective of this study was to compare the gastric microbiome in horses with EGGD and those without across multiple barns and differing management practices. We hypothesized that alterations in the microbiome of the gastric glandular mucosa are associated with EGGD. A secondary objective was to perform a risk factor analysis for EGGD using the diet and management data collected. Microbial populations of biopsies from normal pyloric mucosa of horses without EGGD (control biopsies), normal pyloric mucosa of horses with EGGD (normal biopsies) and areas of glandular mucosal disruption in horses with EGGD (lesion biopsies) were compared. Lesion biopsies had a different microbial community structure than control biopsies. Control biopsies had a higher read count for the phylum Actinomycetota compared to lesion biopsies. Control biopsies also had an enrichment of the genera Staphylococcus and Lawsonella and the species Streptococcus salivarius. Lesion biopsies had an enrichment of the genera Lactobacillus and Actinobacillus and the species Lactobacillus equigenerosi. These results demonstrate differences in the gastric glandular microbiome between sites of disrupted mucosa in horses with EGGD compared to pyloric mucosa of horses without EGGD. Risk factor analysis indicated that exercise duration per week was a risk factor for EGGD.
Project description:Modern pharmacology has proved that Codonopsis Radix and its active ingredients can treat stomach diseases by ameliorating gastrointestinal motility and regulating oxidase levels. However, the detailed molecular mechanism is still unclear. In this study, we systematically evaluated the pharmacodynamic effects of Codonopsis Radix in Gastric Precancerous Lesions animal models. Considering the combination of proteomics and metabolomics, we found that CR could significantly reversed the biological pathways related to energy metabolism which were disturbed by GPL model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix contained serum could ameliorate gastritis injury, and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in above cells.
Project description:This study evaluates whether Helicobacter pylori eradication improves precancerous lesions including glandular atrophy and intestinal metaplasia as well as metachronous cancers or dysplasias after endoscopic mucosal resection for gastric cancer.
Project description:Gastric cancer continues to be one of the most common cancers, with the third highest cancer-related mortality in the world. After infection with Helicobacter pylori, a cascade of inflammatory events that can lead to gastric cancer is triggered. This inflammatory response to the infection is characterized by the infiltration of mononuclear and polymorphonuclear cells into the infected mucosa. The transition of these cells from the circulation to the tissues is mediated through the interaction of receptors on the immune cells and their ligands in the endothelial compartment. CD44 is the receptor for hyaluronan, but it also interacts with osteopontin and collagen, among other molecules. Previous reports have shown that CD44 expression is increased in advanced gastric lesions. However, the association of this molecule with the progression of these lesions over time has not been investigated. In addition, there is a lack of understanding of the CD44-dependent cellular processes that lead to gastritis, and possibly to gastric cancer. Here we studied a subset of subjects from a cohort of individuals with various degrees of gastric inflammation to determine gene expression changes associated with disease progression over a period of six years. We report that CD44 expression is significantly increased in individuals whose gastric lesions progressed over time (from multifocal atrophic gastritis to intestinal metaplasia or from intestinal metaplasia to dysplasia) along the gastric precancerous cascade. We also show that CD44-/- mice develop less severe and less extensive Helicobacter pylori-induced metaplasia, and show fewer infiltrating Gr1+ cells compared to wild type mice. Thus, we present data suggesting that CD44 is associated with disease progression. Mechanisms associated with these effects include induction of interferon gamma responses.