作者:
Peng, Cui Ying*;Xie, Hui Jun;Guo, Zi Fen;Nie, Yu Lin;Chen, Jun;...
期刊:
Journal of Assisted Reproduction and Genetics,2014年31(9):1211-1219 ISSN:1058-0468
通讯作者:
Peng, Cui Ying
作者机构:
[Guo, Zi Fen; Nie, Yu Lin; Yin, Jie; Xie, Hui Jun; Chen, Jun; Peng, Cui Ying; Zhou, Jun Mei] Univ South China, Dept Pharm & Biol Sci, Heng Yang 421001, Hunan, Peoples R China.
通讯机构:
[Peng, Cui Ying] U;Univ South China, Dept Pharm & Biol Sci, Heng Yang 421001, Hunan, Peoples R China.
摘要:
PURPOSE: Many studies have been carried out to confirm the relationship between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome (PCOS), without consistent results. Hence we conducted the current study to research this relationship. METHODS: 224 Chinese Han women with PCOS and 223 in vitro fertilization and embryo transplantation (IVF-ET) infertile women with tubal factor or male infertility served as the controls were recruited in our study. PCR-based assays were applied to genotype the (CAG)n repeat alleles. A meta-analysis including 1,536 PCOS patients and 1,807 controls was conducted to produce a pooled estimate. RESULTS: We observed that the CAG bi-allelic mean lengths were similar in PCOS patients and controls (22.65 +/- 2.5 vs. 23.09 +/- 2.1, P = 0.116). When CAG bi-allelic were divided into two categories (mean repeats </=22, >22), the short AR-CAG bi-allelic showed more frequent in PCOS group than in controls (56.25% vs 29.14%, P < 0.001). Further analysis presented that, in PCOS, there was a lower mean CAG repeat lengths in mean bi-allelic lengths (22.3 +/- 2.5 vs. 23.9 +/- 2.2, P = 0.008) and long bi-allelic lengths (24.3 +/- 1.4 vs. 25.9 +/- 1.6, P = 0.05) among patients with testosterone less than 0.7 ng/ml compared with those whose testosterone was more than 0.7 ng/ml. Besides, the testosterone were positively correlated with the CAG polymorphism (r = 0.237, P = 0.008), which accorded with our meta-analysis results. CONCLUSIONS: The distribution of AR-CAG allele differed between PCOS patients and controls, and polymorphism of CAG repeat lengths may contribute to hyperandrogenism in PCOS.
摘要:
Rationale: Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis. Objective: We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis. Methods and results: In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages. Conclusion: These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
摘要:
Background: Both clinical data and basic science studies suggest that advanced oxidation protein products (AOPPs) may contribute to the progression of atherosclerosis. The aim of this study was to investigate the effects of AOPPs on ATP-binding cassette transporter (ABC) A1 and ABCG1 expression, lipid accumulation and atherosclerotic lesions in apolipoprotein E knockout (apoE-KO) mice. Methods and Results: Male 8-week-old apoE-KO mice were fed a high-fat/high-cholesterol diet. Mice received intraperitoneal injections of AOPPs (5 mg/kg) and/or Janus Kinase (JAK) inhibitor AG-490 (5 mg/kg) once every other day for 8 weeks. As shown in our data, AOPPs increased lipid levels of plasma, and promoted advanced lesions in the aortic regions in apoE-KO mice. The ABCA1, ABCG1 and liver X receptor alpha (LXR alpha) expression were down-regulated in apoE-KO mice treated with AOPPs, whereas the lesions in the aortas were decreased, and the ABCA1, ABCG1 and LXR alpha expression were upregulated in mice treated with AOPPs plus AG-490, compared to the mice treated with AOPPs only. The ABCA1 and LXR alpha expressions of aortas, liver and intestine were downregulated in the AOPPs group, while the expressions were upregulated in the AOPP5-plus-AG-490 group when compared to the AOPPs group. The same results can be also observed in peritoneal macrophages. Conclusions: AOPPs increase accumulation of lipids and exacerbate atherosclerosis through downregulation of ABCA1 and ABCG1 expression, and the JAK-LXR alpha signaling pathway in apoE-KO mice.
摘要:
Chrysin is one of flavones constituents of Orocylumineicum vent. It has been a hot spot as a potential chemopreventive agent and as a natural molecule with numerous biological activities such as antioxidant, antitumor, antiviral, anti-hypertension, anti-diabetic, antibacterial, and so on in recent years. Because of its poor solubility, small intestinal absorption, and the rapid metabolism of glycosylation, a large number of efforts had been made by domestic and foreign researchers on designing its analogs and conjugates to obtain compounds with improved efficacy and selectivity for developing more active drugs for clinic. This article reviews the current research of studying on chrysin derivatives including their properties and possible applications. Additionally, this article also presents the basic information concerning chemical reactivity of chrysin, relevant to the synthesis of its derivatives.
作者机构:
Department of Histology and Embryology, School of Medicine, University of South China, Hu'nan Hengyang, 421001, China;Laboratory of Cell Differentiation and Apoptosis, School of Medicine, University of South China, Hu'nan Hengyang, 421001, China;[Zeng G.-Q.] Nursing Research Institute, School of Life Science and Technology, University of South China, Hu'nan Hengyang, 421001, China;[庾江东] Otolaryngology Department, Hengyang Central Hospital, Hu'nan Hengyang, 421001, China;[黄欣琼; 龙治峰; 王惠洁; 石金凤; 杜雅兰; 谢远杰; 李美香] Department of Histology and Embryology, School of Medicine, University of South China, Hu'nan Hengyang, 421001, China, Laboratory of Cell Differentiation and Apoptosis, School of Medicine, University of South China, Hu'nan Hengyang, 421001, China
通讯机构:
[Li, M.-X.] L;Laboratory of Cell Differentiation and Apoptosis, School of Medicine, University of South China, Hu'nan Hengyang, China
关键词:
鼻咽癌;转移;转染;免疫组织化学;人
摘要:
目的探讨外源表达periostin蛋白对鼻咽癌(NPC)6-10B细胞侵袭和迁移能力的影响及机制。方法采用脂质体转染技术建立稳定高表达periostin的6-10B细胞,RT-PCR结合Western blotting检测转染效率,Tanswell分析periostin高表达后6-10B细胞侵袭和迁移能力的改变,明胶酶谱法检测基质金属蛋白酶(MMPs)活性的变化;免疫组织化学检测整合素(integrin)α_vβ_5在转染periostin前后6-10B细胞中的表达以及其与periostin在鼻咽癌和正常鼻咽黏膜组织中的表达, image-pro Plus 6.0软件进行图像分析及吸光度测定,统计学分析鼻咽癌组织中periostin和integrinα_vβ_5表达强度的相关性。结果 Periostin过表达的6-10B细胞侵袭、迁移能力明显增强,细胞培养上清中MMP-2、MMP-9活性增加,integrin α_vβ_5在periostin过表达的6-10B细胞及NPC组织的表达明显强于对照组,Spearman相关性分析显示, integrin α_vβ_5和 periostin 在 NPC 组织中的表达强度成正相关(r =0.682, P =0.000)。结论外源表达periostin能促进NPC的侵袭和转移,其机制可能是通过与NPC细胞膜上integrinα_vβ_5受体结合而提高MMPs的活性。