Single-Cell Data Analysis Reveals Critical Hepatic Cells Subpopulations in the Progression of Non-alcoholic Fatty Liver Disease to Non-Alcoholic Steatohepatitis.

AIMS: The aim of this study was to reveal the hepatic cell landscape and function in the progression of NAFLD to NASH. BACKGROUND: Non-alcoholic steatohepatitis (NASH) is the progressive form and turning point of nonalcoholic fatty liver disease (NAFLD), which severely causes irreversible cirrhosis as well as hepatocellular carcinoma. The mechanism underlying the progression of NAFLD to NASH has not been revealed. Unraveling the mechanism of action of NAFLD-NASH is an important goal in improving the survival of patients with liver disease. OBJECTIVE: The aim of this study is to discover heterogeneous hepatic cells during the progression of NAFLD to NASH. METHODS: Single-nucleus RNA-seq (snRNA-seq) data containing NASH in NAFLD samples were obtained from the Gene Expression Omnibus (GEO) database. Cell types in liver tissues from NASH and NAFLD were identified after dimensionality reduction analysis, cluster analysis, and cell annotation. The cell pathways in which differences existed were identified by analyzing metabolic pathways in Hepatic cells. We also identified cell subpopulations in Hepatic cells. The developmental trajectories of Hepatic cells were characterized by pseudotime trajectory analysis. Single-cell regulatory network inference and clustering analysis identified key transcription factors and gene regulatory networks in Hepatic cells. Moreover, cell communication analysis determined the potential interactions between Hepatic cells and immune cells, and heapatic stellate cells. RESULTS: Seven cell types were identified in NAFLD and NASH. The proportion of Hepatic cells was lower in NASH and showed greater energy metabolism and glucose metabolism activity. Hepatic cells exhibited heterogeneity, showing two cell subpopulations, Hepatic cells 1 and Hepatic cells 2. Dysregulation of lipid metabolism in Hepatic Cell 2 resulted in lipid accumulation in the liver, which might be involved in the progression of NAFLD. Four key transcription factors, BHLHE40, NFEL2L, RUNX1, and INF4A, were primarily found in Hepatic cells 2. The transcription factors within the hepatic cells 2 subpopulation mainly regulated genes related to lipid metabolism, energy metabolism, and inflammatory response. The cell communication analysis showed that hepatocyte interactions with immune cells were associated with inflammatory responses, while interactions with hepatic astrocytes were associated with liver injury and hepatocyte fibrosis. CONCLUSION: The hepatic cells 2 might promote the progression of NAFLD to NASH by regulating metabolic activity, which might contribute to liver injury through inflammation.

Oncogenic transmembrane protein 158 drives the PI3K/Akt signaling pathway to accelerate gastric cancer cell growth.

Gastric cancer (GC) is a serious threat to human health and an important cause of cancer-related death. Herein, we evaluated the influence of transmembrane protein 158 (TMEM158) on GC cell growth. According to Genomic Spatial Event (GSE) and The Cancer Genome Atlas (TCGA) databases, TMEM158 content is amplified in GC tissues. The diagnostic value of TMEM158 expression in GC is huge. GC sufferers with high expression of TMEM158 were associated with poor overall survival. In addition, TMEM158 content was increased in GC cells. TMEM158 promoted GC cell proliferation by modulating the PI3K/Akt signaling pathway. Lack of TMEM158 reduced GC tumor growth. Collectively, TMEM158 accelerated GC cell proliferation by modulating the PI3K/Akt signaling pathway, making it a prospective biomarker for survival in GC patients.

Oncogenic transmembrane protein 158 drives the PI3K/Akt signaling pathway to accelerate gastric cancer cell growth

Gastric cancer (GC) is a serious threat to human health and an important cause of cancer-related death. Herein, we evaluated the influence of transmembrane protein 158 (TMEM158) on GC cell growth. According to Genomic Spatial Event (GSE) and The Cancer Genome Atlas (TCGA) databases, TMEM158 content is amplified in GC tissues. The diagnostic value of TMEM158 expression in GC is huge. GC sufferers with high expression of TMEM158 were associated with poor overall survival. In addition, TMEM158 content was increased in GC cells. TMEM158 promoted GC cell proliferation by modulating the PI3K/Akt signaling pathway. Lack of TMEM158 reduced GC tumor growth. Collectively, TMEM158 accelerated GC cell proliferation by modulating the PI3K/Akt signaling pathway, making it a prospective biomarker for survival in GC patients.

The effect of pantoprazole and somatostatin combined with thrombin in the treatment of non-esophagogastric varicosity upper gastrointestinal bleeding.

OBJECTIVE: To explore the effect of pantoprazole and somatostatin combined with thrombin in the treatment of non-esophagogastric varicosity upper gastrointestinal bleeding (UGB) as well as its influence on serum hs-CRP and coagulation function. METHODS: From June 2016 to May 2018, patients with upper gastrointestinal hemorrhage due to non-esophagogastric varices in our hospital were selected as research subjects. After screening, they were randomly divided into the combined group (57 cases) and the control group (57 cases). After the two groups are treated, the therapeutic effect was observed. The two groups of patients were followed up for 6 consecutive months, and the data were statistically analyzed. RESULTS: It was found that there wass no significant difference between the two groups in gender, age, amount of bleeding, and etiology (P > 0.05). It was found that the immediate hemostasis rate and the hemostasis rate within 24 hours in the combined group were distinctly higher compared to the control group. The difference has statistical significance (P < 0.05). The total effective rate of the combined group was distinctly higher compared to the control group (P < 0.05). By comparing the expression levels of hs-CRP and IL-6 protein in the serum of the two groups before and after treatment, it was found that there was no significant difference in the expression levels of hs-CRP and IL-6 protein before treatment. However, after treatment, it was found that the levels of hs-CRP and IL-6 protein in the combined group were distinctly lower compared to the control group (P < 0.05). By analyzing adverse reactions, it was found that the combined group had distinctly lower adverse reactions compared to the control group (P < 0.05). CONCLUSION: This work provides an experimental basis for the diagnosis and treatment of non-esophagogastric varicose UGB in the clinic.