TJs in MOJ patients with jaundice were disrupted in the intestinal epithelium, which may have resulted from the alterations in TJ-related protein expression. TJ interruption may be a key factor contributing to intestinal mucosal barrier injury and increased intestinal permeability.

No abstract

Esophageal cancer is the eighth most common malignant tumor in the world and is a common cause of tumor-related death. The development of esophageal cancer is a complex process involving many pathogenetic factors, multiple stages and accumulation of multiple gene mutations and interactions. This study aimed to investigate the effects of Raf kinase inhibitor protein (RKIP) on the proliferation, apoptosis and invasion of TE-1 esophageal cancer cells. Surgical specimens from esophageal cancer patients were classified into esophageal cancer tissues, tumor-adjacent tissues and normal esophageal tissues. The tissues were fixed in 4% paraformaldehyde solution for hematoxylin and eosin and immunohistochemical staining. RKIP expression in esophageal tissues was detected by immunohistochemical staining. The esophageal cancer cell line TE-1 was exposed to four different viruses: RKIP-RNAi-AD, NC-RNAi-GFP-AD, RKIP-AD and GFP-AD. Cell proliferation was detected by MTT assay and cell apoptosis was detected by flow cytometry. Cell invasion was determined by a Transwell coated with Matrigel. RKIP, phospho-RKIP, Raf-1, phospho-Raf-1, ERK1/2, phospho-ERK1/2, GRK-2 and GAPDH expression was assayed by western blotting. LIN28 and MMP-14 mRNA was assayed by qPCR. The results showed that RKIP expression was reduced in esophageal cancer tissues in comparison with expression in normal esophageal epithelium tissues and tumor-adjacent tissues. Reduced RKIP expression was associated with lymph node or distant metastasis in esophageal cancer. RKIP inhibited the invasive and metastatic abilities of esophageal cancer cell line TE-1 by downregulating mRNA expression of LIN28 and MMP-14. RKIP had no effect on the MAPK signaling pathway in the esophageal cancer cell line TE-1, but was involved in the G protein-coupled signaling pathway. Our findings clearly demonstrate that RKIP inhibits esophageal cancer cell invasion by downregulating the expression of GRK-2, LIN28 and MMP-14.

Stomach adenocarcinoma (STAD) is one of the most common malignancies. But the molecular mechanism is unknown. In this study, we downloaded the transcriptional profiles and clinical data of 344 STAD and 30 normal samples from The Cancer Genome Atlas (TCGA) database. Stromal and immune scores of STAD were calculated by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm, and association of stromal/immune scores with tumor differentiation/T/N/M stage and survival was investigated. The differentially expressed genes (DEGs) between high and low score groups (based on media) were identified, and prognostic genes over-/underexpressed in both STAD and stromal/immune signature were retrieved. Furthermore, proportions of 22 infiltrating immune cells for the cohort from TCGA were estimated by the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm, and association of 22 immune cells with tumor differentiation/T/N/M stage and survival was investigated. Next, coexpression analysis of 22 immune cells and intersection genes over-/underexpressed in both STAD and stromal signature was conducted. We found high stromal and immune scores and macrophage infiltration predicting poor tumor differentiation and severe local invasion, obtained a list of prognostic genes based on stromal-immune signature, and explored the interaction of collagen, chemokines such as CXCL9, CXCL10, and CXCL11, and macrophage through coexpression analysis and may provide novel prognostic biomarkers and immunotherapeutic targets for STAD.

Analysis of single-cell RNA sequencing (scRNA-seq) data of immune cells from the tumor microenvironment (TME) may identify tumor progression biomarkers. This study was designed to investigate the prognostic value of differentially expressed genes (DEGs) in intrahepatic cholangiocarcinoma (ICC) using scRNA-seq. We downloaded the scRNA-seq data of 33,991 cell samples, including 17,090 ICC cell samples and 16,901 ICC adjacent tissue cell samples regarded as normal cells. scRNA-seq data were processed and classified into 20 clusters. The immune cell clusters were extracted and processed again in the same way, and each type of immune cells was divided into several subclusters. In total, 337 marker genes of macrophages and 427 marker genes of B cells were identified by comparing ICC subclusters with normal subclusters. Finally, 659 DEGs were obtained by merging B cell and macrophage marker genes. ICC sample clinical information and gene expression data were downloaded. A nine-prognosis-related-gene (PRG) signature was established by analyzing the correlation between DEGs and overall survival in ICC. The robustness and validity of the signature were verified. Functional enrichment analysis revealed that the nine PRGs were mainly involved in tumor immune mechanisms. In conclusion, we established a PRG signature based on scRNA-seq data from immune cells of patients with ICC. This PRG signature not only reflects the TME immune status but also provides new biomarkers for ICC prognosis.