Exendin-4 promotes paracrine action of adipose-derived stem cells through PI3K/Akt signaling pathways / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism by which exendin-4 promotes paracrine secretion of cytokines by adipose-derived stem cells (ADSCs).</p><p><b>METHODS</b>In vitro cultured SD rat ADSCs (fourth passage) with or without exendin-4 treatment underwent flow cytometry to characterize the surface markers. MTT assay was performed to assess the proliferation of the cells exposed to different concentrations (0-20 nm/L) of exendin-4, and the paracrine secretion of cytokines (bFGF, VEGF, HGF, and IGF-1) by the ADSCs was evaluated by qPCR. The changes in the expressions of p-Akt in the cells were analyzed by Western blotting and qPCR in response to exendin-4 (10 nm/L) with or without exposure to PI3K/Akt inhibitor LY-294002 (50 nm/L); bFGF, VEGF, HGF, and IGF-1 production in the cells were detected using ELISA kits.</p><p><b>RESULTS</b>Treatment with exendin-4 for 12 h did not affect the surface marker profile of the ADSCs but promoted the cell proliferation (P<0.05). Exendin-4 significantly increased the mRNA expressions of VEGF, bFGF, HGF, and IGF-1 in a concentration-dependent manner, and 10 nm/L was the optimum concentration (P<0.05). Exendin-4 treatment resulted in significantly increased p-Akt expressions in the ADSCs, and PI3K/Akt inhibitor not only reversed such effects of exendin-4 on p-Akt but also diminished the exendin-4- mediated up-regulation of the paracrine cytokines.</p><p><b>CONCLUSION</b>Exendin-4 can concentration-dependently promote the proliferative and paracrine capacities of ADSCs partially through the PI3K/Akt signaling pathway without affecting the surface marker profile of the cells.</p>

Predictors of the no-reflow phenomenon after primary percutaneous coronary intervention for acute myocardial infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify the risk factors for no-reflow (NR) phenomenon after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction.</p><p><b>METHODS</b>A total of 843 patients with AMI underwent primary PCI within 12 h following onset of the ischemic symptoms. According to TIMI flow grade and myocardial blush grade, the patients were divided into reflow group and NR group after primary PCI, and the clinical data, angiography findings and surgical data were compared to analyze the factors contributing to NR.</p><p><b>RESULTS</b>NR occurred in 15.9% of the AMI patients after primary PCI. Univariate analysis showed that previous myocardial infarction, Killip classes of MI, time to reperfusion, IABP use before PCI, TIMI flow grade before primary PCI, long target lesion, pre-PCI thrombus score and method of reperfusion were correlated to NR (P<0.05 ). Multiple logistic analysis identified the time to reperfusion (OR=1.60; 95% CI: 1.02-2.73), TIMI flow grade before primary PCI (OR=1.1; 95% CI: 1.04-1.16), long target lesion (OR=1.40; 95% CI: 1.19-1.69), and pre-PCI thrombus score (OR=2.02; 95% CI: 1.47-2.76) as the independent predictors of NR after primary PCI.</p><p><b>CONCLUSION</b>The time to reperfusion, TIMI flow grade before primary PCI, long target lesion, and pre-PCI thrombus score are independent predictors of NR after primary PCI for AMI.</p>

Transferring Novel Gene into Human Hematopoietic Cells by Adeno-Associated Virus / 中国肿瘤生物治疗杂志

Objective: To investigate the expression of MDR1 and GFP in the human hematopoietic cells mediated by adeno-associated virus. Methods: The GFP gene was transferred into the human hematopoietic cells by AAV vectors and created strong visible fluorescence by purely molecular biological means. Using adeno-associated virus vectors, we have transferred human mdr-1 gene into human hematopoietic cells and investigated the drug resistence of human hematopoietic cells modified with mdr-1 gene. PCR analysis confirmed that mdrl cDNA had been successfully transferred into the human hematopoietic cells. An assay of MTT proved that the human hematopoietic cells modified by mdrl gene had resistance to colchicine. Results: It was about 30% of the hematopoietic cells that expressed the green fluorescent proteins. The resistance of hematopoietic cells was increased parently when the cells were infected by the crude virus stocks. Conclusion: It is conducted that the AAV vector could successfully transfer the foreign gene into the human hematopoietic cells. The cells modified with mdrl gene have increased the resistance to drugs.

Hepatocyte growth factor protects cultured rat cardiomyocytes against apoptosis induced by gamma ray irradiation / 解放军医学杂志

Objective Hepatocyte growth factor (HGF) has been proposed to be used as an endogenous cardioprotective agent. The aim of the present study was to investigate the anti-apoptosis effect of HGF on rat cardiomyocytes after being irradiated by single dose gamma ray. Methods The study was performed using primary cell cultures of cardiomyocytes isolated from hearts of new-born rats. After being cultured for 72h in vitro, cardiomyocytes were irradiated with gamma ray in a single dose of 20Gy. In the HGF treated groups, cells were incubated with HGF in the dose of 20 and 40ng/ml 3h prior to irradiation, respectively. At 48h post-irradiation, the concentration of LDH in the supernatant of cell culture was determined. Apoptosis and cell cycle were determined with flow cytometry. Results LDH concentration in the supernatant of cell culture of irradiated cardiomyocytes was increased significantly compared to that of un-irradiated cells (P

Effects of local heart irradiation with ?-rays on cardiac function ex vivo in rats / 解放军医学杂志

Objective To investigate the pathophysiological changes in irradiation-induced heart injury in rats in order to provide preventive and therapeutic strategies for irradiation-induced heart disease(RIHD).Methods Experiments were performed using female Wistar rats with body weight of approximately 220g.12 female Wistar rats were randomly assigned to two groups(sham-irradiated group and irradiated group).Heart of rats was locally irradiated with 60Co ?-ray at a dosage of 20 Gy.During the post-radiation period,the intake of food and activities of the animals were observed daily and the body weight was recorded monthly.On the 120th day after irradiation,myocardial perfusion was tested using real time myocardial contrast echocardiography(RTMCE).On the 180th day after irradiation,the hearts were isolated from the rats of the both groups,and they were perfused with a Langendorff apparatus.Hemodynamic measurements,including peak systolic LV pressure(LVSP),maximal rate of LV pressure rise(LV dp/dtmax)and fall(LV dp/dtmin)were studied.Then the hearts were examined pathologically with HE staining.Results Animals irradiated with single dose of 20Gy locally were apparently in a good condition during the observation period of 180 days.No differences in food intake,physical activities and body weight were observed between irradiated and control animals.However,myocardial blood velocity(beta)of irradiated rats was significantly lower than that of sham irradiated group(P