Hsa_ circ_0006867 regulates ox-LDL-induced endothelial injury via the miR-499a-3p/ADAM10 axis.

Circular RNAs (circRNAs) have been reported to participate in the development of various diseases. In this study, we investigated the potential mechanism underlying the role of circRNAs in atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with 100µg/mL oxidized low-density lipoprotein (ox-LDL) to simulate atherosclerosis. We observed that hsa_circ_0006867 (circ_0006867), a circRNA markedly increased in ox-LDL-treated endothelial cells, acted as a molecular sponge of miR-499a-3p and regulated its expression. This interaction led to changes in the downstream target gene ADAM10, thus affecting cell apoptosis and migration. Thus, our study suggests that circ_0006867 regulates ox-LDL-induced endothelial injury via the circ_0006867/miR-499a-3p/ADAM10 axis, indicating its potential as an exploitable therapeutic target for atherosclerosis.

Identification of hub genes and their correlation with immune infiltration in coronary artery disease through bioinformatics and machine learning methods.

Background: Coronary artery disease (CAD) is a multifactorial disease and its pathogenesis remains unclear. We aimed to explore the optimal feature genes (OFGs) for CAD and to investigate the function of immune cell infiltration of CAD. It will be helpful for better understanding of the pathogenesis and the development of genetic prediction of CAD. Methods: Datasets related to CAD were obtained from the Gene Expression Omnibus (GEO) database. Cases from the datasets met diagnostic criteria including clinical symptoms, electrocardiographic (ECG) and angiographic evidence. We identified differentially expressed genes (DEGs) and conducted functional enrichment analysis. OFGs were obtained from the least absolute shrinkage and selection operator (LASSO) algorithm, support vector machine recursive feature elimination (SVM-RFE) algorithm, and random forest (RF) algorithm. CIBERSORT was used to compare immune infiltration between CAD patients and normal controls, and the correlation between OFGs and immune cells was analyzed. Results: DEGs were involved in the interleukin (IL)-17 signaling pathway, nuclear factor (NF)-kappa B signaling pathway, and tumor necrosis factor (TNF) signaling pathway. Gene Ontology (GO) analysis revealed DEGs were enriched in lipopolysaccharide (LPS), tertiary granule, and pattern recognition receptor activity. Disease Ontology (DO) analysis suggested DEGs were enriched in lung disease, arteriosclerotic cardiovascular disease (CVD). Matrix metalloproteinase 9 (MMP9), Pellino E3 ubiquitin protein ligase 1 (PELI1), thrombomodulin (THBD), and zinc finger protein 36 (ZFP36) were screened by the intersection of OFGs obtained from LASSO, SVM-REF, and RF algorithms. CAD patients had a lower proportion of memory B cells (P=0.019), CD8 T cells (P<0.001), resting memory CD4 T cells (P<0.001), regulatory T cells (P=0.028), and gamma delta T cells (P<0.001) than normal controls, while the proportion of activated memory CD4 T cells (P=0.014), resting natural killer (NK) cells (P<0.001), monocytes (P<0.001), M0 macrophages (P=0.023), activated mast cells (P<0.001), and neutrophils (P<0.001) in CAD patients were higher than normal controls. MMP9, PELI1, THBD, and ZFP36 were correlated with immune cells. Conclusions: MMP9, PELI1, THBD, and ZFP36 may be predicted biomarkers for CAD. The OFGs and association between OFGs and immune infiltration may provide potential biomarkers for CAD prediction along with the better assessment of the disease.

A Sampling Survey of the Oral Health Status and Awareness among Primary School Students in Lhasa / 中国医学科学院学报

Objective To investigate the oral health status and awareness of urban children in Lhasa,aiming to provide a data basis for the prevention and treatment of children's caries and the promotion of oral health education. Methods A total of 504 Tibetan students were selected by cluster sampling from 2 primary schools in Chengguan District of Lhasa.All the participants were required to take oral health examination and complete a questionnaire about oral health awareness and behavior. Results The caries prevalence rate and mean decayed-missing-filled tooth(DMFT)of permanent teeth were 75.00% and 2.18±1.91,respectively.The rates of pit and fissure sealant and filling of permanent teeth were 3.77% and 6.81%,respectively.The caries prevalence rate of first permanent molars was 47.62%.The mean DMFT of permanent teeth and caries prevalence rate of first permanent molar were significantly higher in female group(

Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning.

BACKGROUND/AIMS: Previous studies have shown that heat shock protein 90 (HSP90)-mediated mitochondrial import of connexin 43 (Cx43) is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. METHODS: Cellular models of hypoxic postconditioning (HPC) from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS) production was assessed with the peroxide-sensitive fluorescent probe 2',7'-dichlorofluorescin in diacetate (DCFH-DA). The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA), ROS scavengers superoxide dismutase (SOD) and catalase (CAT), and small interfering RNA (siRNA) targeting Cx43 and HSP90 were also investigated. RESULTS: HPC significantly reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA) or siRNA targeting HSP90 prevented the protection of HPC and the HPC-induced association of Cx43, indicating that mitochondrial HSP90 was important for mitochondrial translocation of Cx43 during HPC. CONCLUSION: Mitochondrial HSP90 played a central role in HPC cardioprotection, and its activity was linked to the mitochondrial targeting of Cx43, the activation of which triggered ROS signaling and the subsequent reduction of redox stress. Consequently, its target gene, Bcl-2, was upregulated, and proapoptotic Bax was inhibited in the sarcolemma and mitochondria, ultimately attenuating H/R-induced cardiomyocyte apoptosis. These data reveal a novel mechanism of HPC protection.