Analysis of immune related gene expression profiles and immune cell components in patients with Barrett esophagus.

Barrett's esophagus (BE) is a well-known precancerous condition of esophageal adenocarcinoma. However, the immune cells and immune related genes involved in BE development and progression are not fully understood. Therefore, our study attempted to investigate the roles of immune cells and immune related genes in BE patients. The raw gene expression data were downloaded from the GEO database. The limma package in R was used to screen differentially expressed genes (DEGs). Then we performed the least absolute shrinkage and selection operator (LASSO) and random forest (RF) analyses to screen key genes. The proportion of infiltrated immune cells was evaluated using the CIBERSORT algorithm between BE and normal esophagus (NE) samples. The spearman index was used to show the correlations of immune genes and immune cells. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of key genes in BE. A total of 103 differentially expressed immune-related genes were identified between BE samples and normal samples. Then, 7 genes (CD1A, LTF, FABP4, PGC, TCF7L2, INSR,SEMA3C) were obtained after Lasso analysis and RF modeling. CIBERSORT analysis revealed that resting CD4 T memory cells and gamma delta T cells were present at significantly lower levels in BE samples. Moreover, plasma cell and regulatory T cells were present at significantly higher levels in BE samples than in NE samples. INSR had the highest AUC values in ROC analysis. We identified 7 immune related genes and 4 different immune cells in our study, that may play vital roles in the occurrence and development of BE. Our findings improve the understanding of the molecular mechanisms of BE.

Decreased secretion of tumor necrosis factor-α attenuates macrophages-induced insulin resistance in skeletal muscle.

AIMS: Macrophages, as an important member of immune system, engulf and digest pathogens in innate immunity and help initiate adaptive immunity. However, macrophages also involve in occurrence and development of many diseases, such as obesity and type 2 diabetes. Here, we aimed to reveal how activated macrophages cause insulin resistance in skeletal muscle in vitro through simulating body environment. MAIN METHODS: We established RAW264.7 macrophages and C2C12 myotubes co-incubation model in vitro using Transwell filter to simulate body environment and investigated effects of RAW264.7 cells on insulin-regulated glucose metabolism in C2C12 myotubes. Immunofluorescence, Immunoblot and glucose uptake tests were used to assess metabolic changes in C2C12 myotubes. ELISA test detected secretions of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) from RAW264.7 cells. In addition, RNA interference and inhibitor treatment were used. KEY FINDINGS: Activated RAW264.7 cells attenuated insulin response in C2C12 myotubes. Activated RAW264.7 cells secreted a lot of TNF-α and IL-6. We found that TNFα, but not IL-6, caused insulin resistance of skeletal muscle in a dose-dependent manner. The results further indicated that activation of TNF-α downstream proteins, inhibitor of nuclear factor κ-B kinase (IKK) and the jun-N-terminal kinase 1 (JNK1) led to phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser residues and insulin resistance in C2C12 myotubes. SIGNIFICANCE: Our research provided further and direct demonstration on activated macrophage-induced insulin resistance in skeletal muscle, suggesting TNF-α might become a therapeutic target to ameliorate and treat type 2 diabetes.

Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials.

PURPOSE: The study sought to summarize the evidence of pre-procedural atorvastatin therapy to improve the prognosis of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS: We searched PubMed and Embase from inception to July 2018 for randomized controlled trials that compared loading dose atorvastatin pretreatment with no or low dose for the prevention of cardiovascular events. The primary end points were all-cause mortality and myocardial infarction (MI) at 30 days. The secondary end point was 30-day major adverse cardiovascular events (MACE), a composite of all-cause mortality, MI, and revascularization. RESULTS: Six trials with 4,991 individuals were included in our meta-analysis. High-dose atorvastatin preloading before PCI was associated with a 27% relative reduction in MI (OR: 0.73, 95% CI, 0.56-0.94, P=0.015). All-cause mortality was nonsignificantly reduced by early treatment with high-potency atorvastatin (OR: 0.94, 95% CI, 0.69-1.30, P=0.725). There was a 20% reduction in MACE in the group of patients treated with statin loading prior to PCI (OR: 0.80, 95% CI, 0.66-0.97, P=0.026). When stratified according to the diagnosis of ACS, the results of MACE were only significant for those ST-elevation myocardial infarction patients undergoing PCI (OR: 0.67, 95% CI, 0.48-0.94, P=0.022) and were not noted in the group of non-ST elevation ACS patients (OR: 0.65, 95% CI, 0.35-1.22, P=0.179). CONCLUSION: High-dose atorvastatin pretreatment leads to a significant reduction in MI and MACE at 30 days in ACS patients undergoing PCI, especially in ST-segment elevation MI.

Expression and clinical significance of Apollon in esophageal squamous cell carcinoma.

Apollon, an unusually large member of the inhibitors of apoptosis protein family, may be important for oncogenesis development. The aim of the present study was to assess the association between esophageal squamous cell carcinoma (ESCC) and Apollon expression levels, and to highlight the association between Apollon and the occurrence, development and prognosis of ESCC. Apollon expression was detected by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction in ESCC tissues, adjacent non­cancerous tissues and paired normal tissues respectively, in order to analyze the association between Apollon expression and the clinicopathological features of ESCC. Survival analysis was used to assess the prognostic significance of Apollon expression. It was determined that the mRNA and protein expression levels of Apollon were significantly higher in the carcinoma tissues compared with the adjacent non­cancerous tissues and normal control tissues (P<0.001). There was a significant difference in lymph node involvement and the tumor, nodes, and metastases stage in patients categorized according to different Apollon expression levels. The prognostic significance of Apollon was also determined using the log­rank method. The overexpression of Apollon was associated with shorter overall survival and disease-free survival rates. The present study indicates that Apollon expression is associated with the biological characteristics of ESCC, and may be a valuable prognostic factor and a novel chemotherapeutic target for ESCC treatment.