CpG oligodeoxynucleotide preconditioning improves cardiac function after myocardial infarction via modulation of energy metabolism and angiogenesis.

Unmethylated CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to protect against myocardial ischemia/reperfusion injury. However, the potential effects of CpG-ODN on myocardial infarction (MI) induced by persistent ischemia remains unclear. Here, we investigated whether and how CpG-ODN preconditioning protects against MI in mice. C57BL/6 mice were treated with CpG-ODN by i.p. injection 2 hr prior to MI induction, and cardiac function, and histology were analyzed 2 weeks after MI. Both 1826-CpG and KSK-CpG preconditioning significantly improved the left ventricular (LV) ejection fraction (LVEF) and LV fractional shortening (LVFS) when compared with non-CpG controls. Histological analysis further confirmed the cardioprotection of CpG-ODN preconditioning. In vitro studies further demonstrated that CpG-ODN preconditioning increases cardiomyocyte survival under hypoxic/ischemic conditions by enhancing stress tolerance through TLR9-mediated inhibition of the SERCA2/ATP and activation of AMPK pathways. Moreover, CpG-ODN preconditioning significantly increased angiogenesis in the infarcted myocardium compared with non-CpG. However, persistent TLR9 activation mediated by lentiviral infection failed to improve cardiac function after MI. Although CpG-ODN preconditioning increased angiogenesis in vitro, both the persistent stimulation of CpG-ODN and stable overexpression of TLR9 suppressed the tube formation of cardiac microvascular endothelial cells. CpG-ODN preconditioning significantly protects cardiac function against MI by suppressing the energy metabolism of cardiomyocytes and promoting angiogenesis. Our data also indicate that CpG-ODN preconditioning may be useful in MI therapy.

MicroRNA-34c Suppresses Breast Cancer Migration and Invasion by Targeting GIT1.

Abnormal expression of microRNAs plays important role in tumor metastasis. Migration and invasion of cancer cells accord for the metastasis and deterioration of breast cancer. However, the regulatory role of microRNAs in the invasion and migration of breast cancer cells has not completely understood yet. Here we found that microRNA-34c (miR-34c) was significantly downregulated in metastatic tissue of breast cancer. In vitro study showed that miR-34c negatively regulated GIT1 protein expression by binding to the 3'UTR of GIT1 mRNA. Consistently, GIT1 protein expression was found upregulated significantly in metastatic breast cancer. Moreover, miR-34c overexpression suppressed the expression of GIT1 protein, and this effect was restored by AMO-miR-34c in breast cancer cells. Overexpression of miR-34c suppressed cell migration and invasion in both MCF-7 and MDA-MD-231 breast cancer cells. Furthermore, knockdown of endogenous GIT1 expression reduced the migration and invasion of both two breast cancer cells. Collectively, miR-34c downregulation in breast cancer cells resulted in the upregulation of GIT1, which in turn enhanced the migration and invasion of breast cancer. This study highlights molecular mechanism of migration and invasion of breast cancer cells.

[Midterm results of thoracic aortic dissection endovascular repair in conjunctions with the location of Adamkiewicz artery].

OBJECTIVE: To evaluate the effects of using longer xenografts in conjunctions with the location of Adamkiewicz artery (AKA) on midterm outcomes of endovascular treatment for thoracic aortic dissection. METHODS: From March 2005 to September 2011, 217 patients with type B dissection were recruited. There were 143 males and 74 females with a mean age of 65 ± 11 years. Among them, 43 patients were from Fifth Affiliated Hospital of Sun Yat-Sen University while another 174 patients from Affiliated Zhongshan Hospital of Fudan University. They were divided into 2 groups according to whether AKA was identified or not pre-operatively. Endovascular repairs were performed for all patients. Distal landing levels of xenografts were recorded. The thrombosis of false lumen and the complications of spinal cord injury and endoleak were analyzed. RESULTS: AKA was detected in 121 (55.8%) patients (group A) but not in 96 (44.2%) patients (group B). According to the levels of AKA, the patients of group A obtained the stabilization of affected thoracic aorta over a longer distance. And the ratio of patients with distal landing levels at T8-T10 was significantly higher than in group B (59.5% vs 12.5%, χ² = 49.85, P < 0.01). Also, during the follow-up period of 7.3 months, the ratio of patients with total thrombosis of false lumen in group A was significantly higher than that in group B (32.1% vs 19.1%, χ² = 4.34, P < 0.05). CONCLUSION: During the endovascular repair of thoracic aortic dissection, selecting a longer device may provide a better structural stability of affected aorta and promote false lumen thrombosis.