作者机构：
[Li, Jie; Huang, Chunlin] Univ S China, Sch Pharm & Life Sci, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Guo, Bin; Wang, Xiaoying; Zhu, Weitao; Chen, Bo; Yao, Shouzhuo] Hunan Normal Univ, Minist Educ China, Key Lab Chem Biol & Tradit Chinese Med Res, Changsha 410081, Hunan, Peoples R China.;[Ouyang, Shan] Shenzhen Entry Exit Inspect & Quarantine Bur Peop, Food Inspect & Quarantine Ctr, Shenzhen 518067, Peoples R China.
通讯机构：
[Guo, Bin] H;Hunan Normal Univ, Minist Educ China, Key Lab Chem Biol & Tradit Chinese Med Res, Changsha 410081, Hunan, Peoples R China.
关键词：
Animal tissues;Dispersive solid-phase extraction;Multi-residue;Semi-targeted screening;Sulfonamides;Triple-quadrupole linear ion trap mass spectrometer
摘要：
A generic and efficient homolog-targeted approach was used to expand screening and detection of target class of sulfonamides and structural analogs, based on a fast single-tube extraction/partitioning-multifunction adsorption cleanup (SEP/MAC) for class-specific fragmentation-dependent acquisition with a liquid chromatography-hybrid triple-quadrupole linear ion trap mass spectrometer (LC-QqLIT). By combining the two-stage process conducted in a single tube as one-pot protocol, the straightforward SEP/MAC procedure was optimized to offer clean extracts with reasonable recovery (71-109% with RSDs < 20%) and decreased matrix interferences (-9 to 19%) of multiresidual sulfonamide extraction from different tissue samples. The novel use of neutral loss scan of 66 Da (NLS) or precursor ion scanning of m/z 108 (PreS) in positive ion mode was found to achieve more comprehensive coverage of protonated molecular ions of a wide array of sulfonamides including N-4-acetyl and hydroxylamine metabolites plus their possible dimers. Moreover, the PreS-triggered automatically enhanced product ion spectral acquisition enabled simultaneous screening, profiling and confirmation of an unlimited number of analytes belonging to the sulfonamide class within a single analysis. The validation and application results of the generic SEP/MAC-based LC-QqLIT strategy consistently demonstrated favorable performances with acceptable accuracy (67-116%), precision (RSDs < 25%), and sensitivity (LOQs <= 7.5 ng g(-1)) to meet the acceptance criteria for all the sulfonamide-tissue combinations. Thus, the integration of the matrix-independent SEP/MAC procedure and the multiparameter matching algorithm with the unit-resolution LC-QqLIT instrument can serve as a valuable semi-targeted discovery strategy for rapid screening and reliable quantitative/confirmatory analysis of real samples. (C) 2012 Elsevier B.V. All rights reserved.
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.
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.
期刊：
MOLECULAR MEDICINE REPORTS,2012年5(3):753-760 ISSN：1791-2997
通讯作者：
Wang, Xiaochun
作者机构：
[Zhou, Feng; Liu, Lipeng; Tian, Zhi; Su, Min; Huang, Chunxia; Liu, Meiling; Guo, Xiaofang; Long, Yu] Changsha Med Univ, Dept Biochem & Mol Biol, Changsha 410219, Hunan, Peoples R China.;[Wang, Xiaochun] Cent S Univ, Dept Med Lab Examinat, Changsha 410013, Hunan, Peoples R China.;[Yu, Xiaohua] Nanhua Univ, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Wu, Xinhua] Cent S Univ, Xiangya Hosp, Dept Obstet & Gynecol, Changsha 410078, Hunan, Peoples R China.
通讯机构：
[Wang, Xiaochun] C;Cent S Univ, Dept Med Lab Examinat, Changsha 410013, Hunan, Peoples R China.
关键词：
Apoptosis;Bcl-2;HeLa;MiR-143;Proliferation
摘要：
microRNAs (miRNAs) are small non-coding RNA molecules of 21-24 nt that regulate the expression of other genes by transcriptional inhibition or translational repression. Multiple lines of evidence suggest that miRNAs play important roles in tumor development and progression. We identified 24 mi RNAs markedly and aberrantly expressed in human cervical cancer. The most significantly deregulated was miR-143 as determined by miRNA microarray analysis. miR-143 was introduced into He La cells and it was found that the overexpression of miR-143 significantly inhibited He La cell proliferation and promoted apoptosis; anti-miR-143 rescued the effects. He La cells transfected with pre-miR-143, pre-anti-miR-143 or control mi RNA precursor were injected subcutaneously into the flanks of female athymic nude mice, and the overexpression of miR-143 suppressed the formation of tumors. Compared with normal cervical tissues, the levels of Bcl-2 were increased in miR-143-downregulated tissues. Sustained overexpression of miR-143 in He La cells resulted in suppression of Bcl-2 expression, and knockdown of miR-143 by anti-miR-143 increased Bcl-2 expression. In addition, overexpression of Bcl-2 partially reversed the inhibition of proliferation and promotion of apoptosis in the He La cells caused by miR-143. Furthermore, miR-143 suppressed the activity of a luciferase reporter carrying the 3'-UTR of Bcl-2, which was abolished by mutation of the predicted miR-143-binding site, indicating that Bcl-2 is a miR-143 target gene. Our study revealed a molecular link between miR-143 and Bcl-2. Direct involvement in the regulation of Bcl-2 may be one of the mechanisms through which mi R-143 may play a role in the pathogenesis of cervical cancer.
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.
作者机构：
[Lu, Chunxue; Peng, Bo; Gong, Siqi; Zhong, Guangming] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA.;[Lu, Chunxue; Wu, Yimou; Peng, Bo; Zhong, Guangming] Univ S China, Dept Microbiol, Hengyang, Hunan, Peoples R China.;[Bailey, Robin L.; Mabey, David W.; Holland, Martin J.] London Sch Hyg & Trop Med, Dept Clin Res, London WC1E 7HT, England.;[Holland, Martin J.] MRC Labs, Banjul, Gambia.;[Zhong, Guangming] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
通讯机构：
[Zhong, Guangming] U;Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
摘要：
PURPOSE. Chlamydia trachomatis is the leading infectious cause of blindness. The goal of the current study was to search for biomarkers associated with C. trachomatis-induced ocular pathologies. METHODS. We used a whole genome scale proteome array to systematically profile antigen specificities of antibody responses to C. trachomatis infection in individuals from trachoma-endemic communities with or without end-stage trachoma (trichiasis) in The Gambia. RESULTS. When 61 trichiasis patients were compared with their control counterparts for overall antibody reactivity with organisms of different chlamydial species, no statistically significant difference was found. Both groups developed significantly higher titers of antibodies against C. trachomatis ocular serovars A and B than ocular serovar C, genital serovar D, or Chlamydia psittaci, whereas the titers of anti-Chlamydia pneumoniae antibodies were the highest. When antisera from 33 trichiasis and 26 control patients (with relatively high titers of antibodies to C. trachomatis ocular serovars) were reacted with 908 C. trachomatis proteins, 447 antigens were recognized by at least 1 of the 59 antisera, and 10 antigens by 50% or more antisera, the latter being designated as immunodominant antigens. More importantly, four antigens were preferentially recognized by the trichiasis group, with antigens CT414, CT667, and CT706 collectively reacting with 30% of trichiasis antisera but none from the normal group, and antigen CT695 reacting with 61% of trichiasis but only 31% of normal antisera. On the other hand, eight antigens were preferentially recognized by the control group, with antigens CT019, CT117, CT301, CT553, CT556, CT571, and CT709 together reacting with 46% of normal antisera and none from the trichiasis group, whereas antigen CT442 reacted with 35% of normal and 19% of trichiasis antisera respectively. CONCLUSIONS. The current study, by mapping immunodominant C. trachomatis antigens and identifying antigens associated with both ocular pathology and protection, has provided important information for further understanding chlamydial pathogenesis and the development of subunit vaccines. (Invest Ophthalmol Vis Sci. 2012;53:2551-2559) DOI:10.1167/iovs.11-9212
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：
[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：
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.
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.
期刊：
Journal of Atherosclerosis and Thrombosis,2011年18(9):796-807 ISSN：1340-3478
通讯作者：
Tang, Chao-Ke
作者机构：
[Tang, Chao-Ke; Li, Xiao-Xu; Hu, Yan-Wei; Liu, Xie-Hong; Tang, Ya-Ling; Mo, Zhong-Cheng; Yi, Guang-Hui; Wang, Zuo; Xiao, Ji] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
通讯机构：
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Advanced oxidation protein products;ATP-binding cassette transporter A1;JAK/STAT;Cholesterol efflux
摘要：
AIMS: Advanced oxidation protein products (AOPPs) are new independent risk factor for coronary artery disease. This study was to determine the effects and potential mechanisms of AOPPs on cholesterol efflux from human macrophage foam cells. METHODS: Human THP-1 monocytes were preincubated with Phorbol-12-myristate- 13-acetate (PMA) and oxidized low density lipoprotein (ox-LDL) to form foam cells. The protein and mRNA expression were examined by western immunoblotting assays and real-time quantitative PCR, respectively. Cellular cholesterol content was measured by HPLC. The cholesterol efflux was assessed by liquid scintillation counting. RESULTS: AOPPs significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and liver X receptor alpha (LXRalpha) and reduced cholesterol efflux from THP-1 macrophage- derived foam cells. AOPPs substantially activated NADPH oxidase and activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal pathway in THP-1-derived foam-like cells. Inhibiting NADPH oxidase by diphenyliodonium (DPI) effectively abolished the AOPPs-induced decrease in cholesterol efflux and the expression of ABCA1. Inhibiting JAK/STAT activation by its specific inhibitor AG-490 or by siRNA could also block AOPPs action on THP-1 cells. CONCLUSIONS: AOPPs may first down-regulate the expression of LXRalpha and ABCA1 through JAK/STAT signal pathway activation and then inhibit cholesterol efflux in THP-1-derived foam-like cells; therefore, our study may be useful for understanding the critical effects of AOPPs on the pathogenesis of atherosclerosis.
期刊：
Microbes and Infection,2011年13(5):419-425 ISSN：1286-4579
通讯作者：
Liu, Shuwen
作者机构：
[Xia, Chenglai; Yu, Xiaoling; Liu, Shuwen; Jiang, Shibo] So Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Guangdong, Peoples R China.;[Xia, Chenglai] Guangzhou Med Univ, Affiliated Hosp 3, Dept Pharm, Guangzhou 510150, Guangdong, Peoples R China.;[Luo, Dixian] Univ S China, Coll Sci & Technol, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10065 USA.;[Liu, Shuwen] So Med Univ, Sch Pharmaceut Sci, 1838 No Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China.
通讯机构：
[Liu, Shuwen] S;So Med Univ, Sch Pharmaceut Sci, 1838 No Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China.
摘要：
Neurological complications associated with HIV-1 are being recognized as a common disorder in AIDS patients, especially patients with HIV-associated dementia (HAD). However, our knowledge of the complicated pathogenesis and clinical symptoms of HAD is limited by an incomplete understanding of the biology of HIV-1 in the nervous system. Therefore, this review focuses on the pathogenesis of HAD in the context of novel highly active antiretroviral therapy (HARRT) regimens.
