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Substantial progress has been made in cancer biology and treatment in recent years, but the clinical outcome of patients with renal cell carcinoma (RCC) remains unsatisfactory. The tumor microenvironment (TME) is a potential target. By analyzing single-cell RNA sequencing (sc-RNAseq) data from six RCC tumor samples, this study identified 11 different cell types in the RCC cellular microenvironment, indicating a high degree of intratumoral heterogeneity. Through re-dimensionality reduction clustering of epithelial cells, neutrophils, macrophages, and T cells, we deeply reveal differences in the RCC tumor microenvironment. By analyzing differentially expressed genes in normal epithelial cells and malignant epithelial cells, we identify RNASET2 and GATM as potential prognostic biomarkers in RCC. In addition, by transcriptional factor analysis, we found significant differences in the expression of GZMK-CD8 T cell and B cell transcription factors between cancer tissues and normal tissues. By cell correlation analysis, we found significant correlations between neutrophils and macrophages and between IL7R-CD4 T cells and T regulatory (Treg) cells in RCC, which may be involved in the formation of immune TMEs. By cell developmental trajectory analysis, we showed that macrophages may be derived from neutrophils, whereas Treg cells may be derived from IL7R-CD4 T cells. By cell communication analysis, we found a clear interaction between macrophages and endothelial cells, neutrophils, and GZMK-CD8 T cells. In addition, we found that ADGRE5 signaling was mainly derived from mast cells and GZMK-CD8 T cells, and had a significant communication effect with neutrophils. The COLLAGEN signaling pathway is mainly derived from fibroblasts and has a significant communication effect with mast cells. Finally, we verified that RNASET2, which is highly expressed in epithelial cells, promotes proliferation and migration of RCC in vitro. RNASET2 is likely to be a potential target for renal cell carcinoma therapy. The results based on sc-RNAseq data analysis help to further elucidate the cellular microenvironment of RCC and provide help for cancer heterogeneity studies. This will help to provide more accurate personalized treatment for patients in clinical diagnosis. [ABSTRACT FROM AUTHOR]

Previous studies reported that administration of somatostatin (SST) to human patients mitigated their diarrheal symptoms. Octreotide (an analog of SST) treatment in animals resulted in upregulation of sodium/hydrogen exchanger 8 (NHE8). NHE8 is important for water/sodium absorption in the intestine, and loss of NHE8 function results in mucosal injury. Thus we hypothesized that NHE8 expression is inhibited during colitis and that SST treatment during pathological conditions can restore NHE8 expression. Our data showed for the first time that NHE8 is expressed in the human colonic tissue and that NHE8 expression is decreased in ulcerative colitis (UC) patients. We also found that octreotide could stimulate colonic NHE8 expression in colitic mice. Furthermore, the somatostatin receptor 2 (SSTR2) agonist seglitide and the somatostatin receptor 5 (SSTR5) agonist L-817,818 could restore NHE8 expression via its role in suppressing ERK1/2 phosphorylation. Our study uncovered a novel mechanism of SST stimulation of NHE8 expression in colitis., (Copyright © 2016 the American Physiological Society.)

Tight junction plays a critical role in intestinal defence. The alteration and perturbation of tight junction proteins could induce intestine barrier damage, and lead to the malabsorption of electrolytes and water. Previous studies had showed that colonic infection and inflammation could lead to the alteration of tight junction function, and somatostatin could protect intestinal epithelia. Thus, this study could explore that whether somatostatin could regulate tight junction in colitis mice. Colitis mice with diarrhea were induced by Citrobacter rodentium (CR) and Dextran sulfate sodium (DSS). In CR infected model, cladudin-1 and claudin-3 expression significantly decreased compared with the control mice (P<0.05); after octreotide treatment, claudin-1 and claudin-3 expression significantly increased compared with untreated CR infected mice (P<0.05). In DSS colitis model, occludin and claudin-3 expression significantly decreased compared with the control mice (P<0.05); and octreotide treatment could only significantly upregulate claudin-3 expression compared with untreated DSS colitis mice (P<0.05). To testify our results in vivo, we repeated the models in caco-2 cells by exposed with enteropathogenic Escherichia coli (E. Coli) and Tumor necrosis factor α (TNF-α). The results in vitro were consistent with in vivo study. The results suggested that somatostatin play a role in intestinal barrier protection by modulating tight junction proteins expression.

Infection of Helicobacter pylori (H. pylori) changed the proliferation of gastric epithelial cells and decreased the expression of heat shock protein 70 (HSP70). However, the effects of H. pylori on the proliferation of gastric epithelial cells and the roles of HSP70 during the progress need further investigation. Objective. To investigate the effects of Helicobacter pylori (H. pylori) and heat shock protein 70 (HSP70) on the proliferation of human gastric epithelial cells. Methods. H. pylori and a human gastric epithelial cell line (AGS) were cocultured. The proliferation of AGS cells was quantitated by an MTT assay, and the expression of HSP70 in AGS cells was detected by Western blotting. HSP70 expression in AGS cells was silenced by small interfering RNA (siRNA) to investigate the role of HSP70. The siRNA-treated AGS cells were cocultured with H. pylori and cell proliferation was measured by an MTT assay. Results. The proliferation of AGS cells was accelerated by coculturing with H. pylori for 4 and 8 h, but was suppressed at 24 and 48 h. HSP70 expression was decreased in AGS cells infected by H. pylori for 48 h. The proliferation in HSP70-silenced AGS cells was inhibited after coculturing with H. pylori for 24 and 48 h compared with the control group. Conclusions. Coculture of H. pylori altered the proliferation of gastric epithelial cells and decreased HSP70 expression. HSP70 knockdown supplemented the inhibitory effect of H. pylori on proliferation of epithelial cells. These results indicate that the effects of H. pylori on the proliferation of gastric epithelial cells at least partially depend on the decreased expression of HSP70 induced by the bacterium.