Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2018-01-25 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To investigate the effect of exenatide on chemotactic migration of adipose-derived stem cells (ADSCs) and confirm that Rho GTPase is the downstream effector protein of SDF-1/CXCR-4 migration pathway. Methods ADSCs were isolated, cultured, identified by flow cytometry and induced to differentiate in vitro. RTCA xCELLigence system was used to analyze the effect of exenatide on ADSC proliferation. The effects of exenatide at different concentrations, AMD3100 (CXCR-4 antagonist), and CCG-1423 (Rho GTPase antagonist) on chemotactic migration of ADSCs were tested using Transwell assay. The expression of CXCR-4 in exenatide-treated ADSCs was measured by flow cytometry and Western blotting. Active Rhopull-down detection kit was used to detect the expression of Rho GTPase. Laser confocal microscopy was used to observe the formation of stress fibers in ADSCs with different treatments. Result Exenatide treatment for 24 h had no significant effect on ADSC proliferation. Exenatide obviously promoted chemotactic migration of ADSCs in a concentration-dependent manner, and this effect was blocked by either AMD3100 or CCG-1423. Both flow cytometry and Western blotting showed that exenatide dose-dependently up-regulated CXCR-4 expression in ADSCs. Western blotting showed that the expression of Rho GTPase was related to SDF-1/CXCR-4 pathway and laser confocal microscopy revealed that the formation of stress fibers in ADSCs was related to SDF-1/CXCR-4/ Rho GTPase pathway. Conclusion Exenatide promotes chemotactic migration of ADSCs, and Rho GTPase is the downstream effector protein of SDF-1/CXCR-4 pathway.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-27 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To analyze the distribution of trimethylamine N-oxide (TMAO) in healthy adults with different risk factors and explore its association with gut microbiota. Methods We collected fasting blood samples and fresh fecal samples from 181 subjects without atherogenesis in the carotid arteries. Plasma TMAO levels of the subjects were determined using stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). The fecal DNA was extracted, and the 16S rRNA V4 tags were amplified and sequenced by Illumina HiSeq 2000. The association between TMAO and classical cardiovascular risk factors were analyzed. Gut microbial community structure was analyzed with QIIME, and LEfSe was used to identify the biomarkers. Results The median (IQR) TMAO level was 2.66 (1.96-4.91) μmol/L in the subjects. TMAO level was significantly correlated with body mass index and operational taxonomic units (OTU). Individuals with high TMAO levels were found to have abundant Clostridiales, Phascolarctobacterium, Oscillibacter, and Alistipes but less abundant Anaerosprobacter. Conclusion Chinese subjects have in general low levels of TMAO. TMAO levels are not significantly correlated with the classical cardiovascular risk factors or the gut microbial structures.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To compare the long-term outcomes of patients receiving percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or medical therapy for treatment of chronic total coronary occlusion (CTO). Methods The patients with CTO were selected from a consecutive cohort of patients who underwent coronary angiography (CAG) between 2008 and 2009. The patients with multiple CAG were excluded. The patients received treatments with PCI, CABG, or conservative medication therapy and were followed for major adverse cardiovascular events (MACE) within 5 years. Results A total of 253 patients were enrolled in this study, including 192 receiving PCI, 48 receiving CABG, and 13 treated conservatively with medications. The baseline clinical characteristics were similar among the 3 groups except for increased low-density lipoprotein (LDL) and total cholesterol (TC) in the medication group, and increased Syndax score in CABG group. During the follow-up, the incidences of MACE, AMI, death, stroke or heart failure did not differ significantly among the 3 groups (P> 0.05). However, CABG group showed a higher incidence of the stroke than the other two groups although this difference did not reach a statistically significantly level (P=0.06). Conclusion Our study did not demonstrate that recanalization offers greater long-term benefits than medications for treatment of CTO, and the patients receiving CABG appeared to have a higher incidence of stroke.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To investigate the effect of liraglutide, an analogue of glucagon-like peptide-1, on the proliferation and migration of cardiac microvascular endothelial cells (CMECs) and explore the mechanism. Methods In vitro cultured CMECs of SD rats were purified by differential adhesion method and identified immunocytochemically using CD31 antibody and factor VIII. MTT assay was performed to assess the proliferation of the first-generation cells exposed to different concentrations (0-1000 nm/L) of liraglutide. Western blotting was used to detect the activation of PI3K/Akt and MAPK/ERK signaling pathways. BrdU fluorescent labeling and scratch assay were performed to observe the proliferation and migration of CMECs following liraglutide treatment, and PI3K/Akt and MAPK/ERK pathway inhibitors LY294002 and PD98059, respectively, were used to further confirm the role of these signaling pathways in regulating the proliferation and migration of CMECs. Results Immunocytochemical staining demonstrated a proportion of double positive cells exceeding 95%. The cells exhibited a logarithmic growth 48 h after plating. Liraglutide exposure concentration-dependently promoted the proliferation of CMECs with the optimal concentration of 100 nmol/L (P<0.05). Liraglutide exposure of the cells for 24 h significantly increased the levels of intracellular phosphorylated Akt and ERK (P<0.05), but pretreatment of the cells with Akt and ERK signaling pathway inhibitors 1 h before liraglutide obviously reversed such effect (P<0.05). BrdU and scratch assay showed that 100 nmol/L liraglutide significantly promoted the proliferation and migration of CMECs (P<0.05), but such effects were obviously suppressed by Akt and ERK inhibitors (P<0.05). Conclusion Liraglutide promotes the proliferation and migration of CMECs in vitro via PI3K/Akt and MAPK/ERK signaling pathways.
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