Circ-JA760602 promotes the apoptosis of hypoxia-induced cardiomyocytes by transcriptionally suppressing BCL2.

Acute myocardial infarction (AMI) is myocardial necrosis caused by the complete or partial obstruction of a coronary artery. Circular RNAs (circRNAs) have been proven as regulators in the progression of various human diseases, including AMI. However, the role of novel circ-JA760602 in AMI remains unknown. Here, we investigated the role of circ-JA760602 in modulating the apoptosis of hypoxia-induced AMI cells using the AC16 cardiomyocyte in vitro cell model. The expression of circ-JA760602 in AC16 cardiomyocytes subjected to hypoxia was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was measured by cell counting kit-8 (CCK-8) assay. Apoptosis of cardiomyocytes was evaluated by TUNEL assay and flow cytometry analysis. The cellular location of circ-JA760602 was identified through fluorescence in situ hybridization (FISH) assay and subcellular fractionation assay. The downstream molecular mechanisms of circ-JA760602 were demonstrated by luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. Rescue assays were performed to demonstrate the effects of BCL2 knockdown on circ-JA760602 silencing-mediated cardiomyocyte apoptosis. Circ-JA760602 expression was elevated after hypoxia treatment. Knockdown of circ-JA760602 enhanced viability and curbed apoptosis of hypoxia-treated cardiomyocytes. EGR1 and E2F1 could activate BCL2 transcription. Cytoplasmic circ-JA760602 bound with EGR1 and E2F1 to thus inhibit their nuclear translocation. BCL2 knockdown reversed the effects of circ-JA760602 silencing on the apoptosis of hypoxia-treated AC16 cells. Circ-JA760602 promotes hypoxia-induced apoptosis of cardiomyocytes by binding with EGR1 and E2F1 to inhibit the transcriptional activation of BCL2.

1,25-Vitamin D3 protects against cooking oil fumes-derived PM2.5-induced cell damage through its anti-inflammatory effects in cardiomyocytes.

The functional role of 1,25-vitamin D3 in cooking oil fumes (COFs)-derived PM2.5-induced cell damage is largely unexplored. The present study investigated the protective role of 1,25-vitamin D3 against cell injury by possible involvement of JAK/STAT and NF-κB signaling pathways in cardiomyocytes. Cell viability was measured using CCK-8 assay, and cell apoptosis was analyzed by flow cytometry, qRT-PCR and Western blot in cultured rat neonatal cardiomyocytes treated with 1,25-vitamin D3 and COFs-derived PM2.5. Expressions of JAK/STAT and NF-κB signaling pathway were measured by Western blot. The results suggested that treatment with COFs-derived PM2.5 significantly decreased cell viability and increased apoptosis and oxidative stress in cultured rat neonatal cardiomyocytes. 1,25-vitamin D3 pretreatment alleviated the cell injury by increasing cell viability and decreasing apoptosis in the cardiomyocytes. 1,25-vitamin D3 pretreatment also decreased the ROS level and inflammation in the cardiomyocytes. Furthermore, 1,25-vitamin D3 pretreatment alleviated COFs-derived PM2.5-evoked elevation of JAK/STAT and NF-κB signaling pathways. Our study showed that 1,25-vitamin D3 pretreatment protected cardiomyocytes from COFs-derived PM2.5-induced injury by decreasing ROS, apoptosis and inflammation level via activations of the JAK/STAT and NF-κB signaling pathways.

Association between maternal tumor necrosis factor-α G308A polymorphism and interferon-γ A874T polymorphism and risk of preterm birth: a meta-analysis.

OBJECTIVE(S): This article was undertaken to investigate the association between tumor necrosis factor-α (TNF-α) G308A polymorphism and interferon-γ (INF-γ) A874T polymorphism and risk of preterm birth (PTB) by performing a meta-analysis of available studies. STUDY DESIGN: Articles were chosen based on PubMed, EMBASE, Web of science, and China Biology Medicine (CBM) databases with no language restriction from their inceptions to 1 March, 2014. Specific inclusion criteria were used to evaluate articles. Meta-analysis was performed by using a random or fixed effect model with STATA 11.0 software. We estimated the summary odds ratios (ORs) with its corresponding 95% confidence interval (95%CI) to assess the association. RESULTS: 21 eligible case-control studies with a total of 2103 cases and 5070 controls were finally included into this meta-analysis. Pooled analysis showed that A allele of TNF-α G308A was not associated with increased PTB risk (OR=0.84, 95%CI: 0.65-1.07, p=0.167 for G vs. A). Stratifying analysis for ethnicity and different definition of PTB also indicated that A allele was not associated with increased PTB risk. However, the meta-analysis showed that INF-γ A874T polymorphism was associated with the increased risk of PTB (OR=1.14, 95%CI: 1.11-1.73, p=0.004 for A vs. T). Stratifying analysis was not performed due to the small sample size. CONCLUSION(S): TNF-α G308A polymorphism was not associated with an increased risk of PTB, but INF-γ A874T polymorphism may contribute to increasing susceptibility to PTB. Detection of polymorphism of INF-γ A874T might be a promising biomarker for the diagnosis and prognosis of preterm delivery.