Myocardial infarction (MI) is the most common event in cardiovascular disease. Carvedilol, a β-blocker with multiple pleiotropic actions, is widely used for the treatment cardiovascular diseases. However, the underlying mechanisms of carvedilol on alleviating MI are not fully understood. The aim of the present study was to investigate whether the beneficial effects of carvedilol were associated with regulation of microRNA-1 (miR-1). It was demonstrated that carvedilol ameliorated impaired cardiac function and decreased infarct size in a rat model of MI induced by coronary artery occlusion. Similarly, carvedilol reversed the H
2
O
2
-induced decrease in cardiomyocyte viability in a dose-dependent manner. The
in vivo
and
in vitro
models demonstrated the downregulation of miR-1 following treatment with carvedilol. Overexpression of miR-1, a known pro-apoptotic miRNA, decreased cell viability and induced cell apoptosis. Transfection of miR-1 abolished the beneficial effects of carvedilol. The expression of heat shock protein 60 (HSP60), a direct target of miR-1, was identified to be decreased in MI and H
2
O
2
-induced apoptosis, which was associated with a decrease in Bcl-2 and an increase in Bax; expression was restored following treatment with carvedilol. It was concluded that carvedilol partially exhibited its beneficial effects by downregulating miR-1 and increasing HSP60 expression. miR-1 has become a member of the group of carvedilol-responsive miRNAs. Future studies are required to fully elucidate the potential overlapping or compensatory effects of known carvedilol-responsive miRNAs and their underlying mechanisms of action in the pathophysiology of cardiovascular diseases.
Purpose:
A retrospective study was first performed to assess the multidrug resistant (MDR) pathogen in severe acute pancreatitis (SAP) patients who were treated using the step-up approach. We aim to assess the risk factors between MDR pathogen and potential covariates in SAP patients.
Methods:
The clinical data of 51 SAP patients who were treated from June, 2013 to December, 2016 were retrospectively collected. A total of 23 patients in the MDR group and 28 patients in the non-MDR group were reviewed. The risk factors for MDR pathogen-induced infections in SAP patients were analyzed.
Results:
Hyperlipidemia was the leading cause of SAP in our study. The mean duration of hospital stay was significantly longer in the patients with MDR pathogen infections (P=0.0135). The hospitalization expenses of MDR group were much higher than those in non-MDR group. The mortality of MDR group (56.5%) was higher than that in non-MDR group (28.6%) (P=0.0436). Gram-negative isolates (63.8%) were commonly detected in SAP patients. Acinetobacter baumannii was the most common MDR pathogens. Systemic disease (P
= 0.0136), initial use of carbapenem (P
= 0.0438), and open necrosectomy (P
= 0.0002) were the potential risk factors for MDR pathogen-induced infections in SAP. Furthermore, the logistic regression analysis revealed that open necrosectomy was the independent variable for MDR infections (OR: 15.6, 95% CI: 2.951–82.469, P
= 0.0012).
Conclusions:
MDR pathogen-induced infections were common in SAP patients and Acinetobacter baumannii was the main pathogen. Meanwhile, open necrosectomy was the independent risk factor for the infection of MDR pathogen.
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