miR­155 inhibition represents a potential valuable regulator in mitigating myocardial hypoxia/reoxygenation injury through targeting BAG5 and MAPK/JNK signaling.

Increasing evidence has indicated that miR­155 is closely associated with apoptosis, which may protect the myocardium and diminish the infarct area in myocardial ischemia reperfusion injury (IRI). In addition, studies have revealed that miR­155 serves a leading role in promoting fibroblast inflammation, cardiac dysfunction and other aspects of myocardial injury. The present study aimed to uncover the function and potential biological mechanism of miR­155 in myocardial IRI. The rat H9c2 myocardial cells was treated with hypoxia/reoxygenation (H/R) to simulate IRI in vitro. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to detect the expression levels of miR­155 mRNA. Cell Counting Kit­8 and flow cytometry assays and western blot analysis were applied to determine the biological behaviors of the H/R­treated cells. The association between miR­155 and BAG family molecular chaperone regulator 5 (BAG5) was predicted by bioinformatics software and was confirmed by dual luciferase assay. RT­qPCR and western blot analysis were used to analyze the expression of BAG5. The key proteins involved in mitogen­activated protein kinase (MAPK)/JNK signaling pathway were detected by western blot analysis. The data from the RT­qPCR assay indicated that the expression of miR­155 was markedly upregulated in the H/R model, and that downregulation of miR­155 may promote cell proliferation and inhibit cell apoptosis, and vice versa. BAG5, which was downregulated in the H/R model, was confirmed as a target of miR­155 and negatively modulated by miR­155. The key proteins involved in MAPK/JNK signaling, which were highly expressed in the H/R model, were suppressed by treatment with the miR­155 inhibitor, and overexpression of BAG5 promoted the protective effect of miR­155 inhibition on cell injury caused by H/R. In addition, the expression patterns of hypoxia­inducible factor 1­α and von Hippel­Lindau were altered following different treatments. Taken together, the data from the present study indicated that miR­155 inhibition represented a potential treatment strategy to improve myocardial H/R injury, which may be associated with targeting BAG5 and inhibition of the MAPK/JNK pathway.

MiR-16, as a potential NF-κB-related miRNA, exerts anti-inflammatory effects on LPS-induced myocarditis via mediating CD40 expression: A preliminary study.

The purpose of this study was to investigate the biological effect of miR-16 on myocarditis and the underlying molecular mechanism. H9c2 cells were treated with 10 µg/mL lipopolysaccharide (LPS) for 12 hours to form a myocarditis injury model. We observed that LPS treatment distinctly decreased the level of miR-16 in H9c2 cells. Upregulation of miR-16 increased cell proliferation and reduced cell apoptosis. Then, CD40 was predicted and verified as a target gene of miR-16 by TargetScan and luciferase reporter assay, respectively. Furthermore, the messenger RNA and protein expression of CD40 are negatively regulated by miR-16. The relative expression of inflammatory factors was dramatically decreased by the miR-16 mimic. Cells cotransfected with miR-16 mimic and si-CD40 could significantly abolish the injury of cardiomyocytes caused by myocarditis. Our study illustrated that the upregulation of miR-16 has a protective effect on LPS-damaged H9c2 cells, which may be achieved by regulating CD40 and the nuclear factor kappa B pathway.

Plasma oxidized high-density lipoprotein and glycated apolipoprotein A-I concentrations in ST-segment elevation myocardial infarction patients with stress hyperglycaemia or high thrombus burden.

BACKGROUND: High-density lipoprotein (HDL) particles exert many beneficial actions that may help protect against cardiovascular disease. However, recent work has demonstrated that HDL can be oxidized and glycated under certain circumstances and may become pro-atherogenic. The present study investigated the impact of oxidized high-density lipoprotein (ox-HDL) and glycated apolipoprotein A-I (gly-ApoA-I) in patients presenting with ST-elevation myocardial infarction (STEMI). METHODS: We assessed 55 consecutive patients with STEMI. Patients were divided into: (1) a stress hyperglycaemia (SH) and a no SH group; and (2) a high thrombus burden (HTB) group and a low thrombus burden (LTB) group. Meanwhile, 48 healthy volunteers were recruited as controls. Plasma ox-HDL and gly-ApoA-I concentrations were measured on admission and 7 days after admission. RESULTS: Higher concentrations of ox-HDL and gly-ApoA-I were found in the STEMI group than in the control group on admission and at d7. Further subgroup analysis showed that ox-HDL and gly-ApoA-I were higher in the SH group than in the no SH group at both time points; the HTB group had higher ox-HDL and ox-HDL/HDL-C levels than the LTB group on admission and at d7. However, gly-ApoA-I and the relative intensity of ApoA-I glycation showed no significant differences between the HTB and LTB groups. CONCLUSIONS: The present data indicate that: (1) SH is associated with increased plasma concentrations of ox-HDL and gly-ApoA-I and therefore aggressive treatment is recommended; and (2) that ox-HDL and ox-HDL/HDL-C were higher in the HTB group and may be used to quantify thrombus burden.

Correlation between the methylation of APC gene promoter and colon cancer.

The present study was planned to explore the correlation between the methylation of APC (adenomatous polyposis coli) and colon carcinogenesis. Colon cancer tissues and tumor-adjacent normal tissues of 60 colon cancer patients (who received surgical operation in our hospital from January 2012 to December 2014) were collected. SW1116 cells in human colon cancer tissues were selected for culturing. 5-aza-2c-deoxycytidine (5-aza-dC) was utilized as an inhibitor of the methylation for APC gene. Methylation specific PCR (MSP) was utilized for detection of APC methylation in SW1116 cells. The MTT and Transwell assays were performed to detect the effect of the methylation of APC gene on the proliferation and invasive abilities of SW1116 cells. The correlation between the methylation of APC gene and pathological parameters of colon cancer patients was analyzed. MSP results revealed that 41 cases (68.33%) showed methylation of APC gene in colon cancer tissues. No methylation of APC gene was found in tumor-adjacent normal tissues. 5-aza-dC was able to inhibit the methylation of APC gene in SW1116 cells. APC gene methylation was correlated with tumor size, differentiation degree, lymph node metastasis and Dukes staging. In conclusion, the levels of the methylation of APC in colon cancer tissues and SW1116 cells are relatively high. The methylation of APC promoted the proliferation and invasion abilities of SW1116 cells. Furthermore, methylation is correlated with a variety of clinicopathological features of colon cancer patients.