miR-381-3p inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1.

BACKGROUND: Hyperglycemia increases the risk of many cardiovascular diseases (CVD), and the dysregulation of proliferation and migration in vascular smooth muscle cells (VSMCs) also participates in the pathogenesis of CVD. miR-381-3p is known to suppress the proliferation and migration of multiple human cell types. Nevertheless, the function of miR-381-3p in VSMCs remains largely indistinct. METHODS: A quantitative real-time polymerase chain reaction (qRT-PCR) was employed to investigate miR-381-3p expression in high-glucose-induced VSMCs. Inflammatory cytokines tumor necrosis factor-α, interleukin-1ß and interleukin-6, as well as oxidative stress markers SOD and MDA, were determined by an enzyme-linked immunosorbent assay. Reactive oxygen species generation was examined using a 2,7'-dichlorofluorescein kit. The proliferation, migration and apoptosis of VSMCs were monitored by 3-(4,5-dimethylthiazl2-yl)-2,5-diphenyltetazolium bromide (MTT), transwell and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays. The TargetScan database (http://www.targetscan.org) was employed to seek the potential target gene of miR-381-3p. Interaction between miR-381-3p and HMGB1 was determined by a qRT-PCR, western blotting and a luciferase reporter assay. RESULTS: miR-381-3p expression was significantly reduced in a VSMCs dysfunction model induced by high-glucose in a dose- and time-dependent manner. Transfection of miR-381-3p mimics suppressed the inflammation, oxidative stress, proliferation and migration of VSMCs, whereas apoptosis of VSMCs was promoted, and the transfection of miR-381-3p inhibitors had the opposite effect. Mechanistically, HMGB1, an important factor in inflammation response, was confirmed as a target gene of miR-381-3p. CONCLUSIONS: miR-381-3p targets HMGB1 to suppress the inflammation, oxidative stress, proliferation and migration of high-glucose-induced VSMCs by targeting HMGB1.

Ablation of idiopathic ventricular arrhythmia using zero-fluoroscopy approach with equivalent efficacy and less fatigue: A multicenter comparative study.

The efficacy of a completely zero-fluoroscopy (ZF) approach for the catheter ablation of idiopathic ventricular arrhythmias (VAs) and whether it has advantages over the conventional fluoroscopy (F) approach are still unknown. The aim of this study was to compare the safety and efficacy of a completely ZF approach with those of the conventional F approach in the ablation of idiopathic VAs.We conducted a prospective study involving 7 centers in China. Consecutive patients (n = 489, mean age 45.3 ±â€Š15.3 years, 44.8% male) with idiopathic VAs were recruited. Eligible participants were assigned to either a ZF (n = 163) or F (n = 326) approach at a ratio of 1:2. The completely ZF approach was successful in 163 (100%) patients for electrophysiological study, and in 151 patients (94.4%) for arrhythmia ablation with 9 cases having to switch to the F approach due to the need for coronary angiography. There was no significant difference between the ZF approach and F approach in procedural success rate (84.1% vs 85.4%, respectively), arrhythmia recurrence (1.9% vs 2.2%), or severe complications (0.6% vs 0.9%). The medical staffs using the ZF approach did not wear heavy protective apparels, thus experienced significantly less fatigue compared with those using the F approach (2.1 ±â€Š0.7 vs 3.9 ±â€Š1.6, P < 0.05).The completely ZF approach is as safe and efficient as the conventional F approach for the electrophysiological study and the ablation of idiopathic VAs. The medical staffs using ZF approach felt less fatigue and received less exposure to radiation.

Possible association between serum alkaline phosphatase concentration and thoracicacute aortic dissection.

OBJECTIVES: Alkaline phosphatase (ALP) is an enzyme that catalyzes the hydrolysis of organic pyrophosphate. Accumulating data have demonstrated that the concentration of increased ALP is associated with C-reactive protein (CRP) concentration, and inflammation was complicated in the pathogenesis of acute aortic dissection (ADD). Therefore, the aim of our study was to examine the relationship between serum ALP concentration and thoracic ADD. METHODS: We retrieved demographic data and test results of biochemical data of 68 patients with thoracic ADD and 126 Non-thoracic ADD patients, retrospectively. RESULTS: A total of 194 patients were divided into thoracic ADD groups and non-thoracic ADD groups. Age, creatinine(Cr) and high-density lipoprotein cholesterol (HDL-C) were found to be statistical significance between the two groups. The mean ALP level was significantly higher in patients with thoracic ADD compared with Non-thoracic ADD patients (80.6±23.02 Vs. 65.9±16.49, P=0.001). Stepwise multiple logistic regression analyses revealed a significantly association of ALP with thoracic ADD (OR=1.038, 95% CI: 1.015-1.062, P=0.001). In addition, HDL-C was negative associated with thoracic ADD in multiple logistic regression analyses after adjustment for age, sex and Cr (OR=-0.083, 95% CI: 0.012-0.560, P=0.011). CONCLUSIONS: The present study suggests that the level of serum ALP is associated with thoracic ADD, and serum ALP concentration may be apotential risk factor for thoracic ADD.

Malignant potential of H22 hepatocarcinoma cells increases after recovery from IFN-γ-mediated inhibition.

IFN-γ (interferon γ) can effectively suppress tumours, but it has also been found to promote tumour progression. However, the underlying mechanisms by which it enhances malignancy have not been fully elucidated. By using a mouse model that expresses IFN-γ locally in muscle, we found that the growth potential of tumours was increased after a quick decrease of IFN-γ. Furthermore, the up-regulation of IRF-2 (IFN regulatory factor 2) and down-regulation of IRF-1 were also found in the tumour cells. Along these lines, IFN-γ led to down-regulated expression of cyclin-D1, Bcl-2 and Bcl-xL and up-regulated expression of p21WAF1 and Bax in tumour cells. Yet, the expression of these genes, as well as activation of ERK (extracellular signal-regulated kinase) and NF-κB (nuclear factor-κB), was also reversed shortly after a decrease in IFN-γ, all of which resulted in increase tumour cell proliferation and apoptosis resistance. These findings indicate that the malignant potential of tumour cells may be suppressed by interfering with IRF-2 signalling pathways during and after decreased IFN-γ in tumour microenvironments.