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MicroRNA (miRNA) are non-coding small RNA that regulate gene expression. MiR-328 is reported to influence breast cancer resistance protein (BCRP) expression in cancer cells. As a large inter-individual difference in BCRP levels is observed in various human tissues, the contribution of miR-328 to these differences is of interest. We hypothesized that DNA methylation in the miR-328 promoter region is responsible for the difference in miR-328 levels, leading to inter-individual variability in BCRP levels in human placenta. The association between placental miR-328 and BCRP levels was analyzed, and then DNA methylation in the miR-328 5'-flanking region and regulatory mechanisms causing inter-individual differences in miR-328 and BCRP levels were examined. MiR-328 expression was significantly correlated with BCRP mRNA (Rs = -0.560, P < 0.01) and protein (Rs = -0.730, P < 0.01) levels. It was also up-regulated by the demethylating agent 5-aza-2’-deoxycytidine in BCRP-expressing cells. Luciferase assays with differentially methylated reporter constructs indicated that methylation in the miR-328 5’-flanking region including a predicted CpG island remarkably decreased transcriptional activity compared to that in unmethylated constructs. We selected CCAAT/enhancer binding protein α (C/EBPα), located within the predicted CpG island, by in silico analysis. To elucidate the role of C/EBPα in miR-328 expression, a chromatin immunoprecipitation assay, promoter deletion analysis, and electrophoretic mobility shift assay (EMSA) were performed. C/EBPα-binding site-truncated constructs showed significantly decreased promoter activity, and EMSA indicated that the C/EBPα-binding sites were located in the CpG island. Finally, the methylation patterns of several CpG dinucleotides proximal to two C/EBPα-binding sites in the miR-328 5’-flanking region were correlated negatively with miR-328 levels, and positively with BCRP levels in human placental samples. These results suggest that methylation patterns in the miR-328 5’-flanking region are involved in the inter-individual difference in BCRP levels in human placenta. [ABSTRACT FROM AUTHOR]

Introduction: There were few studies that investigated the association between serum zinc concentration and acute myocardial infarction (AMI) in percutaneous coronary intervention era. Objective: We assessed the relationships between serum zinc concentration, complications, and prognosis in AMI patients after primary percutaneous coronary intervention. Methods: We conducted a single-center, prospective, observational study including 50 patients with AMI. We divided patients into two groups (High-zinc group and Low-zinc group) by median serum zinc concentration and compared two groups about clinical outcomes up to 1 year follow up. Results: The mean age of patients was 66.2 ± 11.8 years old. Patients in the Low-zinc group had ST-segment elevation more frequently than those in the High-zinc group (96.0% vs. 72.0%, P = 0.02). All-cause mortality at 1 year was similar in both groups (P (log-rank) = 0.33). However, the lengths of hospital stay and in coronary care unit were longer in patients in the Low-zinc group than in those in the High-zinc group (15.6 ± 9.2 days vs. 11.9 ± 2.9 days, P = 0.06; 3.9 ± 2.8 days vs. 2.3 ± 0.8 days, P = 0.01). Multivariate regression analysis showed that low serum zinc concentration was associated with the use of cardiac or respiratory assist devices (adjusted odds ratio, 17.79; 95% CI 1.123 to 1216.5; P = 0.04). Conclusions: Although there was no significance difference in mortality in Low-zinc and High-zinc groups, low serum zinc concentration was associated with longer stay in the coronary care unit, and was one of the independent predictors for the use of cardiac or respiratory assist devices. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular disease is an important contributor to the mortality rate of patients with systemic lupus erythematosus (SLE), which is related to SLE disease activity. Fragmented QRS (fQRS) complexes, defined by additional spikes in the QRS complex, are useful for identifying myocardial scars on electrocardiography and can be an independent predictor of cardiac events. We aimed to assess the relationship between disease activity in patients with SLE and fQRS at the time of diagnosis. Methods: Forty-four patients with SLE were included. Patients with cardiac diseases, other rheumatic diseases, and prior treatment at the time of electrocardiography measurement were excluded. The appearance of fQRS represented exposure. The primary outcome was SLE Disease Activity Index 2000 (SLEDAI-2K). Multiple regression analysis was conducted to assess the association between fQRS and SLEDAI-2K adjusted for age, sex, and time from the estimated onset date to the date of diagnosis. Results: Among patients with SLE at diagnosis, 26 (59.1%) had fQRS. The median SLEDAI-2K was 18 (interquartile range [IQR], 12–22) and 9 (IQR, 8–15) in the fQRS(+) and fQRS(-) groups, respectively. SLEDAI-2K was significantly higher in the fQRS(+) group than in the fQRS(-) group (regression coefficient, 2.69; 95% confidence interval, 0.76–4.61; p = 0.008). Conclusion: Our results suggested that fQRS(+) patients with SLE had high disease activity. fQRS could likely detect subclinical myocardial involvement in patients with SLE and predict long-term occurrence of cardiac events. [ABSTRACT FROM AUTHOR]