摘要：
Acetyl-CoA carboxylases (ACCs) play a rate-limiting role in fatty acid biosynthesis in plants, microbes, mammals and humans. ACCs have the activity of both biotin carboxylase (BC) and carboxyltransferase (CT), catalyzing carboxylation of Acetyl-CoA to malonyl-CoA. In the past years, ACCs have been used as targets for herbicides in agriculture and for drug discovery and development of human diseases, such as microbial infections, diabetes, obesity and cancer. A great number of small molecule ACC inhibitors have been developed, including natural and non-natural (artificial) products. These chemicals target BC reaction, CT reaction or ACC phosphorylation. This article provides a comprehensive review and updates of ACC inhibitors, with a focus on their therapeutic application in metabolic syndromes and malignant diseases. The patent status of common ACC inhibitors is discussed.
期刊：
Cardiovascular & Hematological Disorders - Drug Targets,2012年12(2):- ISSN：1871-529X
作者机构：
Key Laboratory for Atherosclerology of Hunan Province, Institute of Cardiovascular Research, University of South China, Hengyang, Hunan, China<&wdkj&>
作者机构：
[Tang, Huifang; Yang, Xiaoyan; Yin, Jie; Xiang, Qiong; Lei, Xiaoyong; Yu, Jia] Univ S China Hengyang, Affiliated Hosp 1, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Yang, Xiaoyan] Univ S China, Coll Pharm & Life Sci, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yang, Xiaoyan] U;Univ S China, Coll Pharm & Life Sci, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
摘要：
Recently, we have reported tissue- and stage-specific expression of miR-195 in human hepatocellular carcinoma cells and so far, not many reports discuss the function of this microRNA (miRNA). Expression profiling of miRNAs revealed a limited set of miRNAs with altered expression in drug resistant hepatocellular carcinoma cell line BEL-7402/5-FU compared to its parental BEL-7402 cell line. Real-time PCR confirmed down-regulation of miR-195 in BEL-7402/5-FU cells. Western blots were performed to determine protein levels of LATS2, P53 and CDK2. MTT analysed the cell proliferation activity. Flow cytometry were performed to determine apoptosis rate. Up-regulation of miR-195 increased expression of LATS2 and increased apoptosis of HCC cells, while Anti-miR-195 treatment inhibited expression of LATS2. miR-195 over-expression inhibited the luciferase activity of a LATS2 3' untranslated region-based reporter construct in BEL-7402/5-FU cells. These results indicate that miR-195 could increase cell apoptosis by targeting LATS2 in hepatocellular carcinoma cells.
摘要：
Pregnancy-associated plasma protein-A (PAPP-A) has been involved in the atherosclerotic process through regulation of local expression of IGF-1 that mediates the activation of the phosphatidylinositol-3 (PI3-K) and Akt kinase (Akt) signaling cascades which lead to constitutive nitric oxide formation, with its attending vasodilator, antiplatelet and insulin-sensitizing actions. In addition, IGF-1 may decreased cholesterol efflux through reductions of expression in ABCA1 and SR-B1 by the PI3-K/Akt signaling pathway. In the current study, we examined whether PAPP-A was involved in LXRα regulation and in expression of ABCA1, ABCG1 or SR-B1 through the IGF-I-mediated signaling pathway (IGF/PI3-K/Akt). Results showed that PAPP-A significantly decreased expression of ABCA1, ABCG1 and SR-BI at both transcriptional and translational levels in a dose-dependent and time-dependent manner. Cellular cholesterol content was increased while cholesterol efflux was decreased by PAPP-A treatment. Moreover, LXRα which can regulate the expression of ABCA1, ABCG1 and SR-B1, was also down-regulated by PAPP-A treatment. LXRα-specific activation by LXRα agonist almost rescued the down-regulation of ABCA1, ABCG1 and SR-B1 expression by PAPP-A. In addition, PAPP-A can induce the IGF-1/PI3-K/Akt pathway in macrophages. Furthermore, our results indicate that the decreased levels observed in LXRα, ABCA1, ABCG1 and SR-B1 mRNA and protein levels upon treating cells with PAPP-A were strongly impaired with the PI3-K inhibitors or IGF-1R siRNA while the MAPK cascade inhibitor did not execute this effect, indicating that the process of ABCA1, ABCG1 and SR-BI degradation by PAPP-A involves the IGF-1/PI3-K/Akt pathway. In conclusion, PAPP-A may first down-regulate expression of LXRα through the IGF-1/PI3-K/Akt signaling pathway and then decrease expression of ABCA1, ABCG1, SR-B1 and cholesterol efflux in THP-1 macrophage-derived foam cells. Therefore, our study provided one of the mechanisms for understanding the critical effect of PAPP-A in pathogenesis of atherosclerosis.
作者：
Ling, H. -y.;Hu, B.;Hu, X. -b.;Zhong, J.;Feng, S. -d.;...
期刊：
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES,2012年120(9):553-559 ISSN：0947-7349
通讯作者：
Liao, D. -f.
作者机构：
[Ling, H. -y.; Hu, B.] Univ S China, Sch Med, Dept Physiol, Hengyang, Peoples R China.;[Liao, D. -f.] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.;[Ling, H. -y.] Univ S China, Ctr Basic Med Postdoctoral Studies, Hengyang, Peoples R China.;[Hu, X. -b.] Univ S China, Sch Life Sci & Technol, Dept Biochem & Mol Biol, Hengyang, Peoples R China.;[Wen, G. -b.; Zhong, J.] Univ S China, Affiliated Hosp 1, Inst Clin Res, Hengyang, Peoples R China.
通讯机构：
[Liao, D. -f.] H;Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.
摘要：
A novel small molecule probe, aptamer beacon (AB), was introduced for adenosine (Ade) recognition and quantitative analysis. The Ade aptamer was engineered into an aptamer beacon by adding a gold nanoparticle-modified nucleotide sequence which is complementary to aptamer sequence (FDNA) at the 3'-end of FDNA. The fluorescence signal "turning on" was observed when AB was bound to Ade, which is attributed to a significant conformational change in AB from a FDNA/QDNA duplex to a FDNA-Ade complex. The Ade measurement was carried out in 20 mmol L-1 Tris-HCl buffer solution of pH 7.4, Delta F signal linearly correlated with the concentration of Ade over the range of 2.0 x 10(-8) to 1.8 x 10(-6) mol L-1. The limit of detection (LOD) for Ade is 6.0 x 10(-9) mol L-1 with relative standard deviations (R.S.D) of 3.64-5.36%, and the recoveries were 98.6%, 100%, 102% (n = 6), respectively. The present method has been successfully applied to determine Ade in human urine samples, and the obtained results were in good agreement with those obtained by the HPLC method. Our investigation shows that the unique properties of the AB could provide a promising potential for small molecules detection, and be benefit to extend the application of aptamer beacon technique. (C) 2012 Elsevier B.V. All rights reserved.
摘要：
The role of microRNA-195 in developing acquired drug resistance in hepatocellular carcinoma cells was investigated. Expression pro fi ling of miRNAs revealed a limited set of miRNAs with altered expression in drug resistant hepatocellular carcinoma cell line BEL-7402/5-FU compared to its parental BEL-7402 cell line. Real-time PCR confirmed down-regulation of miRNA-195 in BEL-7402/5-FU cells. Overexpression of miRNA-195 sensitized BEL-7402/5-FU cells to anticancer drugs. Consistent with these findings, miR-195 antisense oligonucleotide induced drug resistance in BEL-7402/5-FU cells. Also, the basal levels of the anti-apoptotic protein Bcl-w were high in BEL-7402/5-FU cells and miR-195 overexpression repressed Bcl-w protein level and inhibited the luciferase activity of a Bcl-w 3' untranslated region-based reporter construct in both BEL-7402/5-FU and BEL-7402 cells. These results indicate that miR-195 could improve the drug sensitivity at least in part by targeting Bcl-w to increase cell apoptosis in hepatocellular carcinoma cells.
作者：
Qin, Li;Bromberg-White, Jennifer L.;Qian, Chao-Nan*
期刊：
Advances in Cancer Research,2012年113:191-239 ISSN：0065-230X
通讯作者：
Qian, Chao-Nan
作者机构：
[Qian, Chao-Nan; Qin, Li] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China.;[Qin, Li] Univ S China, Inst Pharm & Pharmacol, Div Pharmacoprote, Hengyang, Hunan, Peoples R China.;[Qian, Chao-Nan; Bromberg-White, Jennifer L.] Van Andel Res Inst, Lab Canc & Dev Cell Biol, Grand Rapids, MI USA.
通讯机构：
[Qian, Chao-Nan] S;Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China.
作者机构：
[刘玉玲; 李金兰; 赵绿英; 高治平; 黄红林] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang Hunan 421001, China
通讯机构：
[Zhao, L.-Y.] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, China
关键词：
染料木素;高脂血症;食饵性;大鼠;C-反应蛋白;对氧磷酶
摘要：
目的探讨染料木素(genistein,Gen)对大鼠食饵性高脂血症对氧磷酶(paraoxonase,PON1)活性及C-反应蛋白(C-reactive protein,CRP)的影响。方法健康SD大鼠40只,♀♂各半,随机分为以下5组:①普食组;②高脂血症模型组;③低剂量Gen(0.5 mg·kg~(-1)·d~(-1))组;④高剂量Gen(5 mg·kg~(-1)·d~(-1))组;⑤辛伐他汀(5 mg·kg~(-1)·d~(-1))阳性药物对照组;除普食组给以普通饲料喂养外,其他组均饲以高脂饲料喂养加敌百虫(10 mg·kg~(-1)·d~(-1))腹腔注射,建立食饵性高脂血症模型。各组大鼠连续喂养及同时用药8周,每2周测1次体重,根据体重调整用药量;定期取血检测胆碱酯酶(acetylcholine esterase,AChE)、血脂、丙二醛(ma-lonaldehyde,MDA)、PON1和CRP的含量,用苏木精/伊红(hematoxylin/eosin,HE)染色检测大鼠肝脏及主动脉弓病理形态变化。结果与模型组相比,高剂量Gen组与辛伐他汀组大鼠总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及动脉粥样硬化指数(atherosclerotic index,AI)明显降低,高密度脂蛋白胆固醇(high density lipoprotein cholesterol/total cholesterol,HDL-C)与TC比值(HDL-C/TC)明显升高,血清MDA含量也明显降低,同时还能明显降低高脂饲料喂养加低剂量敌百虫腹腔注射致高脂血症大鼠血清CRP含量,提高PON1活性,改善大鼠肝与主动脉弓形态变化。结论Gen可以减轻高脂饲料喂养加敌百虫诱发的大鼠高脂血症;其作用机制可能与逆转血脂障碍,抑制过氧化脂质作用抗氧化,降低炎症因子CRP抗炎及通过PON1酶的调节有关。
