Helicobacter pylori CagA Promotes the Formation of Gallstones by Increasing the Permeability of Gallbladder Epithelial Cells.

BACKGROUND: The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms. METHODS: scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (n = 6) and liver transplant donor gallbladder mucosal samples (n = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation. RESULTS: Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified Helicobacter pylori as a key bacterium associated with gallbladder chronic inflammation and stone formation. CONCLUSIONS: Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified H. pylori as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.

Global trends in PANoptosis research: bibliometrics and knowledge graph analysis.

PANoptosis has recently been discovered as a new type of cell death. PANoptosis mainly refers to the significant interaction among the three programmed cell death pathways of apoptosis, necroptosis, and pyroptosis. Despite this, only a few studies have examined the systematic literature in this area. By analyzing the bibliometric data for PANoptosis, we can visualize the current hotspots and predicted trends in research. This study analyzed bibliometric indicators using the Histcite Pro 2.0 tool, which searches the Web of Science for PANoptosis literature published between 2016 and 2022. A bibliometric analysis was performed using Histcite Pro 2.0, while research trends and hotspots were visualized using VOSviewer, CiteSpace and BioBERT. The output of related literature was low in the four years from the first presentation of PANoptosis in 2016 to 2020. The volume of relevant literature grew exponentially between 2020 and 2022. The United States and China play a leading role in this field. Although China started late, its research in this field is developing rapidly. As research progressed, more focus was placed on the relationship between PANoptosis and pyroptosis, as well as apoptosis and necrosis. Now is a rapid development stage of PANoptosis research. Most of the research focuses on the cellular level, and the focus is more on the treatment of tumor-related diseases. The current focus of this area is PANoptosis mechanisms in cancer and inflammation. It can be seen from the burst analysis of keywords that caspase1 and host defense have consistently been research hotspots in the field of PANoptosis, while the frequency of NLRC4, causes of autoinflammation, recognition, NLRP3, and Gasdermin D has gradually increased, all of which have become research hotspots in recent years. Finally, we used the BioBERT biomedical language model to mine the most documented genes and diseases in the PANoptosis field articles, pointing out the direction for subsequent research steps. According to a bibliometric analysis, researchers have shown an increased interest in PANoptosis over the past few years. Researchers initially focused on the molecular mechanism of PANoptosis and pyroptosis, apoptosis, and necroptosis. The role of PANoptosis in diseases and conditions such as inflammation and tumors is one of the current research hotspots in this area. The focus is more on treating inflammation-related diseases, which will become the key development direction of future research.

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma.

Ferroptosis is a recently discovered mode of cell death that inhibits tumor growth. Single-cell RNA sequencing (scRNA-seq) is a powerful tool for analyzing tumor heterogeneity and the immune microenvironment at the single-cell level. We used CIBERSORT to identify cellular immune scores and found that monocytes had significantly infiltrated and were correlated with prognosis in cholangiocarcinoma. scRNA-seq data were extracted from the Gene Expression Omnibus database, and the FindCluster() package was used for cell cluster analysis, which obtained 21 cell clusters, and there was increased TNFSF13B-TFRC intercellular communication between monocytes and cholangiocytes. A weighted correlation network analysis was performed with the WGCNA package to obtain monocyte-related gene modules. Univariate and multivariate Cox analyses were then performed to further establish the signature, and the reliability of the signature was assessed by receiver operating characteristic curve and decision curve analysis. A nomogram signature based on the Kaplan-Meier survival analysis was established. We found that the communication between monocytes and malignant cells in cholangiocarcinoma may be a regulatory factor of ferroptosis in cancer cells. The prognostic stratification system of the three-gene signature related to monocytes and ferroptosis can accurately assess the prognostic risk for cholangiocarcinoma.

ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.

High expression of fibronectin 1 indicates poor prognosis in gastric cancer.

Fibronectin 1 (FN1) is involved in the occurrence and development of various tumors and is upregulated in multiple cancer types. FN1 has been demonstrated to promote cell proliferation and migration in gastric cancer cell lines. However, the relationship between the expression of FN1 and clinicopathological factors and prognosis is not clear in gastric cancer (GC). The aim of the present study was to investigate the association between FN1 expression and clinicopathology and prognosis of gastric cancer. In this study, 17 publicly available GC cohorts (n=2,376) with gene expression data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine databases were tested. In addition, FN1 protein expression was validated by immunohistochemistry in a separate cohort (n=190). The meta-analysis results demonstrated an increase in FN1 expression at the protein and mRNA level in GC tissues, and the FN1 gene was highly expressed at the mRNA level in the advanced T stage (T2 + T3 + T4) group compared with that in the early T stage (T1) group. In addition, the expression of epithelial FN1 at the protein level was positively correlated with tumor size. FN1 expression at the protein and mRNA level was a predictor of poor prognosis following radical resection of GC. In conclusion, the expression of FN1 in GC tissues is upregulated compared with adjacent normal tissues, and it is a potential biomarker of poor prognosis in patients with GC.

The opposite role of alternatively spliced isoforms of LINC00477 in gastric cancer.

Background: Aberrant transcript alternative splicing is an important regulatory process closely connected with oncogenesis. Purpose: The objective of this study was to determine the phenotype and function of a novel long noncoding RNA (lncRNA) LINC00477 in gastric cancer. Patients and methods: The gastric cancer samples of 140 from Oncomine database and 17 from our own hospital, as well as three gastric cancer cell lines MKN-45, AGS and KATO III were used in this study. The expression of the spliced isoforms of LINC00477 were tested. The tumor effects of LINC00477 on gastric cancer were investigated in vitro and in vivo. The mechanism of LINC00477 interacted with aconitase 1 (ACO1) was further examined by RIP and pull down assay. Results: The overall expression of LINC00477 was reduced in gastric cancers compared to normal gastric tissues. The isoform 1 of LINC00477 was down-regulated while the isoform 2 was up-regulated in gastric cancer cells. The opposite role of isoforms 1 and 2 in the proliferation and migration of cancer cells in vitro and in vivo was observed. Furthermore, isoform 1 of LINC00477 was determined to interact with ACO1 and suppress the conversion ability from citrate to isocitrate by ACO1. Conclusion: we presented the important roles of the spliced isoforms of long noncoding RNA, LINC00477 in gastric carcinogenesis.