Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats

Background

Mesenchymal stem cell transplantation is a promising new therapy to improve cardiac function after myocardial infarction (MI). The electrophysiological consequences of MSC implantation has not been systematically studied.

Methods

We investigated the electrophysiological and arrhythmogenic effects of mesenchymal stem cells (MSCs) therapy in experimental infarction model. Rats were subjected to MI operation by LAD ligation and randomly allocated to receive intramyocardially injection PBS (MI-PBS) or 5 × 10⁵ EGFP labeled MSCs (MI-MSCs). Electrophysiological study, histological examination, and western blotting were performed 2 weeks after cell transplantation.

Results

Programmed electrical stimulation (PES) showed a significant reduced inducible ventricular tachycardias (VTs), raised ventricular fibrillation threshold (VFT) and prolonged ventricular effective refractory period (VERP) in MSC-treated rats compared to PBS-treated animals. MSC implantation led to markedly longer action potential duration (APD) and shorter activation time (AT) in infarcted border zone (IBZ) of left ventricular epicardium compared with PBS-treated hearts. Histological study revealed that fibrotic area and collagen deposition in infarcted region were significantly lower in MI-MSC group than in MI-PBS group. Abnormal alterations of Connexin 43 including reduction and lateralization were significantly attenuated by MSC treatment.

Conclusions

This study provide strong evidence that MSC implantation ameliorates interstitial fibrosis and the remodeling of gap junction, attenuates focal heterogeneity of reporlarization and conduction and reduces vulnerability to VTs. The results suggest that MSC transplantation might emerge as a new preventive strategy against VAs besides improving cardiac performance in ischemic heart disease.     

高碘对新生鼠大脑神经生长相关蛋白表达的影响

目的 研究新生鼠大脑内神经生长相关蛋白的分布及高碘对黄表达的影响。和碘化油诱导建立高碘大鼠动物模型；采用甲状腺激素定量测定、免疫细胞化学方法结合图像分析研究了高碘及正常新生鼠大脑内神经生长相关蛋白表达的差异。结果 ①高碘可引起血清甲状腺激素（Ｔ３↓，Ｔ３／Ｔ４↑）；②高碘及正常新生鼠顶叶皮质及海巴结构内生长相关蛋白的分布趋势相似，表现为顶叶皮质分子层染色深，海马结构表现为腔隙层、放射层及始层梯度染     

HPV16 E6 Controls the Gap Junction Protein Cx43 in Cervical Tumour Cells

Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43), a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G) Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this cytoplasmic pool of Cx43. E6 siRNA depletion in W12T cells resulted in restoration of Cx43 and hDlg trafficking to the cell membrane. In C33a HPV-negative cervical tumour cells expressing HPV16 or 18 E6, Cx43 was located primarily in the cytoplasm, but mutation of the 18E6 C-terminal hDlg binding motif resulted in redistribution of Cx43 to the membrane. The data indicate for the first time that increased cytoplasmic E6 levels associated with malignant progression alter Cx43 trafficking and recycling to the membrane and the E6/hDlg interaction may be involved. This suggests a novel E6-associated mechanism for changes in Cx43 trafficking in cervical tumour cells.     

肥胖与非肥胖2型糖尿病患者外周血T淋巴细胞亚群研究

以免疫荧光双标记单克隆抗体及流式细胞仪检测外周血淋巴细胞亚群，在非肥胖2型糖尿病患者外周血CD3^ CD8^ 阳性细胞数显著低于肥胖2型糖尿病患者和健康对照组，而CD4/CD8比值增高。在非肥胖2型糖尿病患者可能存在明显的细胞免疫功能异常。