Quercetin induces the selective uptake of HDL-cholesterol: Via promoting SR-BI expression and the activation of the PPARγ/LXRα pathway
作者：
Ren, Kun;Jiang, Ting;Zhao, Guo-Jun*
期刊：
FOOD & FUNCTION ,2018年9(1):624-635 ISSN：2042-6496
通讯作者：
Zhao, Guo-Jun
作者机构：
[Zhao, Guo-Jun; Jiang, Ting; Ren, Kun] Guilin Med Univ, Dept Histol & Embryol, Guilin 541004, Guangxi, Peoples R China.;[Ren, Kun] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Peoples R China.
通讯机构：
[Zhao, Guo-Jun] G;Guilin Med Univ, Dept Histol & Embryol, Guilin 541004, Guangxi, Peoples R China.
摘要：
Reverse cholesterol transport (RCT) is the process to deliver cholesterol to the liver for further excretion and involves scavenger receptor class B type I (SR-BI)-mediated selective lipid uptake (SLU) from high-density lipoprotein cholesterol (HDL-C). The up-regulation of hepatic SR-BI expression accelerates HDL-C clearance in circulation and impedes the development of atherosclerosis (AS). In the present study, we explored the modulation of hepatic SR-BI expression and SR-BI-mediated SLU by quercetin, a natural flavonoid compound in the diet with a favorable role in cardiovascular disorders. We found that quercetin significantly increased the expression level of SR-BI in HepG2 cells in a concentration- and time-dependent manner. Besides, quercetin had stimulatory effects on the binding of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (Dil)-labeled HDL to hepatocytes and 125I/3H-CE-HDL association. Treatment with small interfering RNA (siRNA) or SR-BI specific inhibitor, BLT-1, inhibited quercetin-induced Dil-HDL binding and selective HDL-C uptake. Treatment with quercetin increased both proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) levels. Additionally, the quercetin-induced expression of SR-BI, Dil-HDL binding and the selective uptake of HDL-C were significantly attenuated by treatment with PPARγ siRNA, LXRα siRNA, and their antagonists, respectively. In C57BL/6 mice, quercetin administration potently increased SR-BI, PPARγ and LXRα levels and lipid accumulation in the liver. Altogether, our results suggest that quercetin-induced up-regulation of SR-BI and subsequent lipid uptake in hepatocytes might contribute to its beneficial effects on cholesterol homeostasis and atherogenesis. © 2018 The Royal Society of Chemistry.
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英文
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Hydrogen sulfide ameliorates rat myocardial fibrosis induced by thyroxine through PI3K/AKT signaling pathway
作者：
Liu, Maojun;Li, Zining;Liang, Biao;Li, Ling;Liu, Shengquan;...
期刊：
Endocrine Journal ,2018年65(7):769-781 ISSN：0918-8959
通讯作者：
Yang, Jun;Chu, Chun
作者机构：
[Liu, Maojun; Li, Ling; Liu, Shengquan; Yang, Jun; Long, Junrong; Tang, Fen; Liang, Biao; Tan, Wenting; Li, Zining] Univ South China, Affiliated Hosp 1, Dept Cardiol, 69 Chuanshanrd, Hengyang 421001, Hunan, Peoples R China.;[Chu, Chun] Univ South China, Affiliated Hosp 2, Dept Pharm, 30 Jiefangrd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yang, Jun; Chu, Chun] U;Univ South China, Affiliated Hosp 1, Dept Cardiol, 69 Chuanshanrd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Dept Pharm, 30 Jiefangrd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Autophagy;Hydrogen sulfide;Myocardial fibrosis;PI3K/AKT;Thyroxine
摘要：
This study aims to investigate the role and regulatory mechanism of the Hydrogen sulfide (H2S) in amelioration of rat myocardial fibrosis induced by thyroxine through interfering the autophagy via regulating the activity of PI3K/AKT1 signaling pathway and the expression of relative miRNA. 40 adult male SD rats were randomly divided into 4 groups (n = 10): the control group, the thyroxine model group (TH group), the model group with H2S intervention (TH + H2S group) and the normal group with H2S intervention (H2S group). Pathological changes were observed via H&E staining and Masson staining, Expressions of MMPs/TIMPs, PI3K/AKT, autophagy-related proteins in myocardial tissues were detected via Western blotting, and the expressions of miR-21, miR-34a, miR-214 and miR-221 were detected via RT-qPCR. Compared with the control group, in the TH group, myocardial fibrosis was more significant, the expressions of proteins in PI3K/AKT and autophagy-related proteins were significantly decreased, as well as the expression of miR-221; while the expressions of miR-21, miR-34a and miR-214 were significantly elevated. By contrast, all above-mentioned changes were obviously reversed with H2S treatment, which demonstrated the positive function of H2S in amelioration of rat myocardial fibrosis induced by thyroxine. The mechanism of such amelioration may be correlated with autophagy activated by the upregulation of expression of PI3K/AKT signaling pathway and downregulation of expressions of miR-21, miR-34a and miR-214.
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英文
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PIG11 over-expression predicts good prognosis and induces HepG2 cell apoptosis via reactive oxygen species-dependent mitochondrial pathway
作者：
Wang, Yan;Liu, Xiaomin;Liu, Gang;Wang, Xiaojuan;Hu, Rong;...
期刊：
Biomedicine & Pharmacotherapy ,2018年108:435-442 ISSN：0753-3322
通讯作者：
Liang, Xiaoqiu
作者机构：
[Wang, Yan] Nantong Univ, Affiliated Hosp, Dept Pathol, Nantong 226001, Peoples R China.;[Liang, Xiaoqiu; Liu, Xiaomin; Wang, Xiaojuan; Hu, Rong; Wang, Yan] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.;[Liang, Xiaoqiu; Liu, Xiaomin; Wang, Xiaojuan; Hu, Rong; Wang, Yan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Liu, Gang] Inner Mongolia Univ, Coll Biol Sci, Hohhot 010021, Neimenggu, Peoples R China.
通讯机构：
[Liang, Xiaoqiu] U;Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.
关键词：
PIG11;Apoptosis;Hepatocellular carcinoma (HCC);HepG2 cell;Reactive oxygen species (ROS);Mitochondria
摘要：
P53-induced protein 11 (PIG11), one of the primeval transcriptional targets of p53, is up-regulated in apoptosis induced by multiple chemopreventive agents and is involved in tumorigenesis or tumor development. Nevertheless, the clinical value and biological role of PIG11 in hepatocellular carcinoma (HCC) are still unknown. In the present article, we explored the expression pattern of PIG11 in HCC tumor tissues, the prognostic value of PIG11 for HCC patients, and the biological functions on the apoptosis of HepG2 cells. We discovered that high PIG11 expression was negatively associated with certain clinical characteristics, and higher expression of PIG11 resulted in better prognosis of patients with HCC. PIG11 over-expression induced HepG2 cell apoptosis through the mitochondrial pathway, and reactive oxygen species played a regulatory role in this process. Hence, PIG11 may act as a candidate liver tumor suppressor and exhibit potential as a novel prognostic biomarker for HCC.
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英文
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Heat shock protein 70 accelerates atherosclerosis by downregulating the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway
作者：
Zhao, Zhen-Wang;Zhang, Min;Chen, Ling-Yan;Cong, Duo;Xia, Xiao-Dan;...
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS ,2018年1863(8):806-822 ISSN：1388-1981
通讯作者：
Tang, Chao-Ke
作者机构：
[Ou, Xiang; Tang, Chao-Ke; Cong, Duo; Zhao, Zhen-Wang; Wang, Si-Qi; Yu, Xiao-Hua; Chen, Ling-Yan; Xia, Xiao-Dan; Zhang, Min] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Med Res Expt Ct, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Ou, Xiang] First Hosp Changsha, Dept Endocrinol, Changsha 410005, Hunan, Peoples R China.;[Dai, Xiao-Yan] Guangzhou Med Univ, Guangdong Prov Key Lab Mol Target & Clin Pharmaco, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China.;[Dai, Xiao-Yan] Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Dept Biochem & Mol Biol, Libin Cardiovasc Inst Alberta, Hlth Sci Ctr, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
通讯机构：
[Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Med Res Expt Ct, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.
关键词：
HSP70;Atherosclerosis;Cholesterol efflux;ABCA1;ABCG1;Reverse cholesterol transport
摘要：
Background and aims: Recent studies have suggested that heat shock protein 70 (HSP70) may play critical roles in cardiovascular disease. However, the effects of HSP70 on the development of atherosclerosis in apoE−/− mice remain largely unknown. This study was to investigate the role and potential mechanism of HSP70 in atherosclerosis. Methods: HSP70 was overexpressed in apoE−/− mice and THP-1-derived macrophages with lentiviral vectors. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaque in apoE−/− mice fed the Western type diet. Moreover, immunostaining was employed to detect the expression of relative proteins in aortic sinus. Reporter gene and chromatin immunoprecipitation were performed to analyze the effect of Elk-1 on the promoter activity of ABCA1 and ABCG1; [3H] labeled cholesterol was used to assess the capacity of cholesterol efflux and reverse cholesterol transport (RCT). Results: Our results showed that HSP70 increased lipid accumulation in arteries and promoted the formation of atherosclerotic lesion. The capacity of cholesterol efflux was reduced in peritoneal macrophages isolated from HSP70-overexpressed apoE−/− mice. The levels of ABCA1 and ABCG1 expression were also reduced in the peritoneal macrophages and the aorta from apoE−/− mice in response to HSP70. The c-Jun N-terminal kinase (JNK) and ETS transcription factor (Elk-1) played a critical role in HSP70-induced downregulation ABCA1 and ABCG1. Further, HSP70 reduced RCT from macrophages to plasma, liver, and feces in apoE−/− mice. Conclusions: HSP70 promotes the progression of atherosclerosis in apoE−/− mice by suppressing the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway. © 2018 Elsevier B.V.
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英文
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Ginnalin A from Kujin tea (: Acer tataricum subsp. ginnala) exhibits a colorectal cancer chemoprevention effect via activation of the Nrf2/HO-1 signaling pathway
作者：
Bi, Wu;He, Chun-nian;Li, Xiao-xiao;Zhou, Liu-ying;Liu, Rui-jie;...
期刊：
FOOD & FUNCTION ,2018年9(5):2809-2819 ISSN：2042-6496
通讯作者：
Zhang, Peng-fei
作者机构：
[Liu, Rui-jie; Bi, Wu; Li, Xiao-xiao; Zhang, Sai; Zhou, Liu-ying; Zhang, Peng-fei; Chen, Zhu-chu] Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Canc Prote, Changsha 410008, Hunan, Peoples R China.;[He, Chun-nian] Chinese Acad Med Sci, Minist Educ, Inst Med Plant Dev, Key Lab Bioact Subst & Resources Utilizat Chinese, Beijing 100193, Peoples R China.;[He, Chun-nian] Peking Union Med Coll, Beijing 100193, Peoples R China.;[Li, Guo-qing] Univ South China, Sch Pharm & Life Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhang, Peng-fei] C;Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Canc Prote, Changsha 410008, Hunan, Peoples R China.
摘要：
Ginnalin A (also known as acertannin) is one of the most important phenolic compounds of several beverage Acer plants. In this study, it is reported for the first time that ginnalin A is an activator of the Nrf2 signaling pathway in human colon cancer cells. Ginnalin A, isolated from the leaves of Acer tataricum subsp. ginnala, exhibited promising preventive activity against colon cancer cells (HCT116, SW480 and SW620) with IC50 values of 24.8 μM, 22.0 μM and 39.7 μM, respectively. In addition, it significantly reduced the colony formation of these cells. Flow cytometry analysis indicated that ginnalin A suppressed cancer proliferation via the induction of cell cycle arrest at the S-phase. Real time PCR analysis demonstrated that ginnalin A can upregulate the mRNA expression levels of Nrf2-related antioxidant genes Nrf2, HO-1 and NQO1. Western blotting analysis revealed that ginnalin A promoted the Nrf2 nuclear translocation and upregulated the proteins Nrf2, HO-1 and NQO1. Moreover, the upregulation of p62 and the inhibition of Keap1 were also found by Western blotting analysis. Therefore, the activation of the Nrf2 signaling pathway was probably induced through the upregulation of p62 and the inhibition of Keap1. © 2018 The Royal Society of Chemistry.
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英文
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Spider Toxin Peptide Lycosin-I Functionalized Gold Nanoparticles for in vivo Tumor Targeting and Therapy
作者：
Tan, Huaxin;Huang, Yazhou;Xu, Jianghong;Chen, Bo;Zhang, Peng;...
期刊：
THERANOSTICS ,2017年7(12):3168-3178 ISSN：1838-7640
通讯作者：
Liu, Zhonghua;Xiao, Lehui
作者机构：
[Tan, Huaxin; Zhang, Peng; Liu, Zhonghua; Liang, Songping; Huang, Yazhou] Hunan Normal Univ, Coll Life Sci, Natl & Local Joint Engn Lab Anim Peptide Drug Dev, Changsha 410081, Hunan, Peoples R China.;[Tan, Huaxin; Xu, Jianghong; Ye, Zhongju; Xiao, Lehui; Chen, Bo] Hunan Normal Univ, Coll Chem & Chem Engn, Key Lab Phytochem R&D Hunan Prov, Changsha 410081, Hunan, Peoples R China.;[Xiao, Lehui] Nankai Univ, Coll Chem, State Key Lab Med Chem Biol, Tianjin Key Lab Biosensing & Mol Recognit, Tianjin 300071, Peoples R China.;[Tan, Huaxin] Univ South China, Dept Biochem & Mol Biol, Sch Pharmaceut & Biol Sci, Hengyang 421001, Peoples R China.
通讯机构：
[Liu, Zhonghua; Xiao, Lehui] H;[Xiao, Lehui] N;Hunan Normal Univ, Coll Life Sci, Natl & Local Joint Engn Lab Anim Peptide Drug Dev, Changsha 410081, Hunan, Peoples R China.;Hunan Normal Univ, Coll Chem & Chem Engn, Key Lab Phytochem R&D Hunan Prov, Changsha 410081, Hunan, Peoples R China.;Nankai Univ, Coll Chem, State Key Lab Med Chem Biol, Tianjin Key Lab Biosensing & Mol Recognit, Tianjin 300071, Peoples R China.
关键词：
*Gold nanorods;*Intracellular delivery;*Photothermal therapy.;*Spherical gold nanoparticles;*Spider anticancer peptide lycosin-I
摘要：
Cell penetrating peptides (CPPs) are commonly Cell penetrating peptides (CPPs) are commonly utilized for intracellular delivery of functional materials to circumvent biomembrane barrier. However, further application of CPPs is hindered by lacking selectivity toward targeted cells. The spider venom peptide, lycosin-I, is a CPP with potent cytotoxicity to cancer cells, which might enable lycosin-I to deliver functional materials into cancer cells selectively. In this study, we demonstrated that the lycosin-I-conjugated spherical gold nanoparticles (LGNPs) not only exhibited efficient cellular internalization efficiency toward cancer cells but also displayed unprecedented selectivity over noncancerous cells. Although LGNPs were removed from the living circulatory system via reticuloendothelial system-dominant clearance modes without noticeable adverse effects to animals, they actually displayed active tumor-targeting effects and efficient accumulation in tumors in vivo. Furthermore, the potential application of this platform for cancer therapy was explored by lycosin-I-conjugated gold nanorods (LGNRs). LGNRs exhibited selective intracellular translocation towards cancer cells and efficient photothermal effect under near infrared (NIR, 808 nm) irradiation, which consequently killed cancer cells in vitro and in vivo effectively. Therefore, the established LGNPs and LGNRs possessed great potential in cancer-targeting delivery and photothermal therapy. © Ivyspring International Publisher.
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英文
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miR-467b regulates the cholesterol ester formation via targeting ACAT1 gene in RAW 264.7 macrophages
作者：
Wang, Bo;He, Ping-Ping;Zeng, Gao-Feng;Zhang, Tao;Yang, Xin-Ping Ou
期刊：
Biochimie ,2017年132:38-44 ISSN：0300-9084
通讯作者：
Tao Zhang<&wdkj&>Xin-Ping Ou Yang
作者机构：
[Wang, Bo; Zeng, Gao-Feng] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang 421001, Hunan, Peoples R China.;[He, Ping-Ping; Yang, Xin-Ping Ou] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[He, Ping-Ping; Yang, Xin-Ping Ou] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[He, Ping-Ping] Univ South China, Sch Nursing, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Tao] Univ South China, Dept Urol, Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tao Zhang] D;[Xin-Ping Ou Yang] I;Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China<&wdkj&>Department of Physiology, The Neuroscience Institute, Medical College, University of South China, Hengyang, Hunan 421001, China<&wdkj&>Departments of Urology, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China
关键词：
ABCA1;ACAT1;Atherosclerosis;CE:FC ratio;miR-467b
摘要：
Previous studies have shown that miR-467b plays a central role in the progression of atherosclerosis via regulating LPL expression. However, the regulatory mechanism of miR-467b in regulateing the CE and FC formation is still unclear. Interestingly, computational analysis demonstrated that ACAT1 which converts intracellular FC into the storage form of CE, and ABCA1 which promotes cellular FC efflux may be target gene of miR-467b. Here, we examined whether miR-467b could target ACAT1 and ABCA1, thereby affecting the CE and FC formation in oxLDL-treatment RAW 264.7 cells. We found that miR-467b regulates the CE:FC ratio in oxLDL-treatment RAW 264.7 macrophages, and the luciferase activity of ACAT1 is regulated by the miR-467b, but the luciferase activity of ABCA1 has no effect. Furthermore, our data suggested that miR-467b highly regulates the endogenous levels of ACAT1 expression, thereby affecting the CE formation in oxLDL-treatment RAW 264.7 macrophages. Taken together, our findings demonstrate that ACAT1 is a target gene of miR-467b, and miR-467b regulated the CE and FC formation via directly target the ACAT1 3'UTR. © 2016
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英文
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Selenophenes: Introducing a New Element into the Core of Non-Steroidal Estrogen Receptor Ligands
作者：
Zhang, Silong;Wang, Zhiyong;Hu, Zhiye;Li, Changhao;Tang, Chu;...
期刊：
ChemMedChem ,2017年12(3):235-249 ISSN：1860-7179
通讯作者：
Zhou, Hai-Bing;Huang, Jian
作者机构：
[Zhang, Silong; Zhou, Hai-Bing; Tang, Chu; Wang, Zhiyong; Dong, Chune; Luo, Junjie; Hu, Zhiye] Wuhan Univ, State Key Lab Virol, Key Lab Combinatorial Biosynth & Drug Discovery, Sch Pharmaceut Sci,Minist Educ, 185 East Lake Rd, Wuhan 430071, Peoples R China.;[Li, Changhao; Huang, Jian] Wuhan Univ, Coll Life Sci, 299 Bayi Rd, Wuhan 430072, Peoples R China.;[Carlson, Kathryn E.; Katzenellenbogen, John A.] Univ Illinois, Dept Chem, 600 South Mathews Ave, Urbana, IL 61801 USA.;[Zhou, Hai-Bing] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构：
[Zhou, Hai-Bing; Huang, Jian] W;[Zhou, Hai-Bing] U;Wuhan Univ, State Key Lab Virol, Key Lab Combinatorial Biosynth & Drug Discovery, Sch Pharmaceut Sci,Minist Educ, 185 East Lake Rd, Wuhan 430071, Peoples R China.;Wuhan Univ, Coll Life Sci, 299 Bayi Rd, Wuhan 430072, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
breast cancer;estrogen receptor;structural diversity;relative binding affinity;selenophenes
摘要：
The importance of the heterocyclic core elements with peripheral phenolic and alkyl substituents as a dominant structural motif of ligands for the estrogen receptor (ER) has been well recognized. In this study we expanded the structural diversity of core elements by preparing selenium-containing heterocycles and exploring the activities of these selenophenes on the two ERs, ERα and ERβ. Careful structure–activity relationship (SAR) analysis of their ER binding affinities showed that most selenophenes are ERβ-selective, with the position of the phenol substituents on the selenophene core and the nature of these substituents having a marked effect on their binding affinities. The compound bis(2-fluoro-4-hydroxyphenyl)selenophene (2 f) has the highest relative binding affinity (RBA) of 24.3 for ERβ. In transcription assays, most selenophenes were found to exhibit partial to full agonist activity for both ER subtypes, with compounds bis(2-methyl-4-hydroxyphenyl)selenophene (2 b), bis(4-fluoro-3-hydroxyphenyl)3-bromoselenophene (6 f), and 2,3,5-tris(hydroxyphenyl)thiophenes (8 b and 8 d) profiling as superagonists for ERα; however, several compounds display a range of ERα or ERβ antagonistic activities. A few selenophenes exhibited antiproliferative activity, with compound 8 c showing antiproliferative effects similar to that of 4-hydroxytamoxifen in breast cancer MCF-7 cells while being nontoxic to normal VERO cells. These new ligands could act as models for the development of novel agents leading to improved therapeutics that target the estrogen receptor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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英文
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The role of Krüppel-like factor 14 in the pathogenesis of atherosclerosis
作者：
Xie, Wei;Li, Liang;Zheng, Xi-Long;Yin, Wei-Dong* ;Tang, Chao-Ke*
期刊：
Atherosclerosis ,2017年263:352-360 ISSN：0021-9150
通讯作者：
Yin, Wei-Dong;Tang, Chao-Ke
作者机构：
[Tang, Chao-Ke; Yin, Wei-Dong; Tang, CK; Li, Liang; Xie, Wei] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Xie, Wei] Univ South China, Lab Clin Anat, Hengyang 421001, Hunan, Peoples R China.;[Li, Liang] Univ South China, Dept Pathophysiol, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Cumming Sch Med, Dept Biochem & Mol Biol,Libin Cardiovasc Inst Alb, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
通讯机构：
[Yin, WD; Tang, CK] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.
关键词：
*Atherosclerosis;*Inflammation;*KLF14;*Lipid metabolism;*Pathogenesis;*Type 2 diabetes
摘要：
The Krüppel-like factor (KLF) family, as the SP/XKLF transcription factors, plays important roles in regulating the expression of genes required for the proper execution of important biological and pathological processes. Recent studies have demonstrated that KLF14, a member of the KLF family, participates in the initiation and progression of atherosclerotic cardiovascular disease (CVD). From the molecular function aspect, this review focuses on the impact of KLF14-mediated regulation in major atherosclerosis-related diseases and pathological processes, such as insulin resistance, type 2 diabetes, dyslipidemia, inflammation, obesity, metabolic syndrome, cell proliferation and differentiation. This review was designed to help understand the roles of KLF14 in the pathogenesis of atherosclerosis and define KLF14 as a potential disease biomarker and a novel therapeutic target in CVD.
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英文
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A new anthraquinone and a new naphthoquinone from the whole plant of Spermacoce latifolia
作者：
Luo, Ying;Shen, Hai-Yan;Shen, Qing-Xiang;Cao, Zhao-Hui;Zhang, Min;...
期刊：
亚洲天然物产研究(英文版) ,2017年19(9):869-876 ISSN：1028-6020
通讯作者：
Tan, Jian-Wen
作者机构：
[Luo, Ying; Long, Shi-Yin; Wang, Zong-Bao; Cao, Zhao-Hui; Zhang, Min] Univ South China, Sch Pharm & Biol Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Educ Dept, Hengyang 421001, Peoples R China.;[Luo, Ying; Tan, Jian-Wen] Chinese Acad Sci, South China Bot Garden, Guangdong Prov Key Lab Appl Bot, Guangzhou 510650, Guangdong, Peoples R China.;[Shen, Hai-Yan] Univ South China, Inst Pathogen Biol, Hengyang 421001, Peoples R China.;[Shen, Qing-Xiang] Univ South China, Affiliated Hosp 2, Dept Obstet & Gynaecol, Hengyang 421001, Peoples R China.
通讯机构：
[Tan, Jian-Wen] C;Chinese Acad Sci, South China Bot Garden, Guangdong Prov Key Lab Appl Bot, Guangzhou 510650, Guangdong, Peoples R China.
关键词：
Rubiaceae;Spermacoce latifolia;anthraquinone;antibacterial activity;naphthoquinone;alpha-glucosidase inhibitor
摘要：
A phytochemical study on the whole plant of Spermacoce latifolia led to the isolation of a new anthraquinone, 1,2,6-trihydroxy-5-methoxy-9,10-anthraquinone (1), and a new naphthoquinone, (2R)-6-hydroxy-7-methoxy-dehydroiso-α-lapachone (2), together with three known anthraquinones (3–5). Their structures were established on the basis of detailed spectroscopic analysis, including one- and two-dimensional NMR, ESI–MS, and HR–ESI–MS techniques. All the compounds were isolated from S. latifolia for the first time. Compounds 1, 2, 4, and 5 showed significant antibacterial activity toward Bacillus subtilis with MIC values ranging from 0.9 to 31.2 μg/ml, and compound 4 aslo exhibited antibacterial activity against Bacillus cereus with a MIC value 62.5 μg/ml. Compound 1 was further revealed to show significant in vitro α-glucosidase inhibitory activity with IC 50 value of 0.653 mM. © 2017 Informa UK Limited, trading as Taylor & Francis Group.
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英文
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Apelin/APJ system: A novel promising therapy target for pathological angiogenesis
作者：
Wu, Lele;Chen, Linxi;Li, Lanfang*
期刊：
Clinica Chimica Acta ,2017年466:78-84 ISSN：0009-8981
通讯作者：
Li, Lanfang
作者机构：
[Li, Lanfang; Wu, Lele; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hunan Prov Cooperat Innovat Centerfor Mol Target, Hengyang 421001, Peoples R China.;[Li, Lanfang] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
通讯机构：
[Li, Lanfang] U;Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
关键词：
APJ;Angiogenesis-related diseases;Apelin
摘要：
Apelin is the endogenous ligand of the G protein-coupled receptor APJ. Both Apelin and APJ receptor are widely distributed in various tissues such as heart, brain, limbs, retina and liver. Recent research indicates that the Apelin/APJ system plays an important role in pathological angiogenesis which is a progress of new blood branches developing from preexisting vessels via sprouting. In this paper, we review the important role of the Apelin/APJ system in pathological angiogenesis. The Apelin/APJ system promotes angiogenesis in myocardial infarction, ischemic stroke, critical limb ischemia, tumor, retinal angiogenesis diseases, cirrhosis, obesity, diabetes and other related diseases. Furthermore, we illustrate the detailed mechanism of pathological angiogenesis induced by the Apelin/APJ system. In conclusion, the Apelin/APJ system would be a promising therapeutic target for angiogenesis-related diseases. © 2016 Elsevier B.V.
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英文
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Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway
作者：
Xu, Man;Xie, Yafeng;Jiang, Chuanhao;Xiao, Yongjian;Kuang, Xingxing;...
期刊：
Immunobiology ,2017年222(5):709-718 ISSN：0171-2985
通讯作者：
Wu, Yimou
作者机构：
[Wu, Yimou; Zhao, Feijun; Xie, Yafeng; Tan, Manyi; Kuang, Xingxing; Tan, Yuan; Wen, Yating; Xu, Man; Zeng, Tiebing] Univ South China, Med Coll, Inst Pathogen Biol, Hengyang 421001, Peoples R China.;[Wu, Yimou; Zhao, Feijun; Xie, Yafeng; Tan, Manyi; Kuang, Xingxing; Tan, Yuan; Wen, Yating; Xu, Man; Zeng, Tiebing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wu, Yimou; Zhao, Feijun; Xie, Yafeng; Tan, Manyi; Kuang, Xingxing; Tan, Yuan; Wen, Yating; Xu, Man; Zeng, Tiebing] Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Peoples R China.;[Xie, Yafeng; Xiao, Yongjian] Univ South China, Affiliated Hosp 2, Dept Clin Lab, Hengyang 421001, Peoples R China.;[Jiang, Chuanhao] Cent S Univ, Xiangya Hosp 2, Dept Lab Med, Changsha 410011, Hunan, Peoples R China.
通讯机构：
[Wu, Yimou] U;Univ South China, Med Coll, Inst Pathogen Biol, Hengyang 421001, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Peoples R China.
关键词：
Flagellin;Human monocytes;Inflammation;TLR5 signaling;Treponema pallidum
摘要：
The tissue damage caused by syphilis infection may be associated with inflammation. However, the virulence factors of Treponema pallidum are still unclear, nor are the molecular mechanisms for leading to the productions of proinflammatory cytokines. Flagellin, a classic pathogen-associated molecular pattern (PAMP), is a potent immunogen that induces inflammation. In the present study, we have demonstrated that stimulations of human monocytes with Treponema pallidum FlaB1, FlaB2, and FlaB3 result in the up regulation of interleukin (IL)-6 and IL-8. Moreover, silencing of the Toll-like receptor 5 (TLR5) gene by using small interfering RNA was found to abrogate the T. pallidum flagellins-induced IL-6 and IL-8 expressions. Similarly, transfection with the dominant negative plasmid encoding MyD88 (pDeNy-hMyD88) was also giving rise to the down regulation of IL-6 and IL-8. We further investigated the relative contributions of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling to transcriptions and translations of IL-6 and IL-8. Western Blot and immuno fluorescence experiments revealed that flagellins-mediated IL-6 and IL-8 expressions are heavily dependent on ERK, p38, and NF-κB. In addition, inhibitions of p38 kinase, ERK, and NF-κB were found to attenuate the productions of IL-6 and IL-8. Taken together, our results indicate that T. pallidum flagellins can upregulate IL-6 and IL-8 generations via TLR5 and MAPK/NF-κB signaling pathways in THP-1 cells, which will improve our understanding of the pathogenesis of T. pallidum. © 2017 Elsevier GmbH
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英文
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Tail vein injection of mmLDL upregulates mouse mesenteric artery ETB receptors via activation of the ERK1/2 pathway
作者：
Liu, Yang;Chen, Xiao-Lan;Xu, Cang-Bao;Cao, Lei;Lin, Jie;...
期刊：
Vascular Pharmacology ,2017年96-98:33-39 ISSN：1537-1891
通讯作者：
Li, Jie
作者机构：
[Li, Jie; Liu, Yang] Univ South China, Inst Pharm & Pharmacol, Hengyang, Hunan, Peoples R China.;[Chen, Xiao-Lan; Chen, Gen; Li, Jie; Lin, Jie] Xiangnan Univ, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.;[Xu, Cang-Bao] Xian Med Univ, Inst Basic & Translat Med, Xian, Shaanxi, Peoples R China.;[Cao, Lei] Xi An Jiao Tong Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Pharmacol, Xian, Shaanxi, Peoples R China.
通讯机构：
[Li, Jie] X;Xiangnan Univ, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
关键词：
*5-hydroxytryptamine (PubChem CID: 21,701,104);*Acetylcholine (PubChem CID: 187);*Dimethylsulfoxide (PubChem CID: 21,584,481);*ERK1/2;*ET(B) receptor;*ICAM-1;*Mesenteric artery;*Sarafotoxin 6c (PubChem CID: 16,132,429);*Tail vein injection;*U0126 (PubChem CID: 3,006,531);*VCAM-1;*mmLDL
摘要：
Minimally modified low density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. This study investigated the effect of mmLDL on mouse mesenteric artery endothelin type B (ETB) receptors and its molecular mechanism. Mice were injected with normal saline (NS group), mmLDL in the tail vein (mmLDL group), or with both mmLDL and an intraperitoneal injection of the ERK1/2 pathway-specific inhibitor U0126 (mmLDL + U0126 group). The dose-response curve of mesenteric artery contraction induced by sarafotoxin 6c (S6c), the ETB receptor agonist, was measured using a sensitive myograph system. ELISAs, RT-PCR and Western blot were used to determine the serum concentrations of mouse oxidized low density lipoprotein (oxLDL), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well as the expression of ETB receptors, ICAM-1, VCAM-1 and phosphorylated-extracellular signal-regulated kinase 1/2 (p-ERK1/2). The S6c-induced contraction dose-response curve was significantly enhanced by mmLDL treatment and showed a significantly higher Emax value than in the NS group (P < 0.001), and the ETB receptor mRNA and protein expression in the vascular wall was significantly higher than in the NS group. The serum concentration and expression of ICAM-1 and VCAM-1 were also increased by mmLDL treatment, but intraperitoneal injection of U0126 inhibited these changes as well as the increase in p-ERK1/2 protein in the vessel wall caused by mmLDL. ICAM-1 and VCAM-1 serum concentrations were positively correlated with the S6c-induced maximum contraction of blood vessels. Increased in vivo levels of mmLDL increased the serum concentrations and expression of ICAM-1 and VCAM-1 by activating the ERK1/2 pathway, resulting in the expression of ETB receptors and the enhancement of contractile function in vascular smooth muscle. Understanding the effect of mmLDL on ETB receptors and its mechanism can provide ideas for cardiovascular disease prevention and treatment.
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英文
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Proprotein convertase furin/PCSK3 and atherosclerosis: New insights and potential therapeutic targets
作者：
Ren, Kun;Jiang, Ting;Zheng, Xi-Long;Zhao, Guo-Jun*
期刊：
Atherosclerosis ,2017年262:163-170 ISSN：0021-9150
通讯作者：
Zhao, Guo-Jun
作者机构：
[Zhao, Guo-Jun; Jiang, Ting; Ren, Kun] Guilin Med Univ, Dept Histol & Embryol, Guilin 541004, Guangxi, Peoples R China.;[Ren, Kun] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Dept Biochem & Mol Biol, Libin Cardiovasc Inst Alberta, Hlth Sci Ctr, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
通讯机构：
[Zhao, Guo-Jun] G;Guilin Med Univ, Dept Histol & Embryol, Guilin 541004, Guangxi, Peoples R China.
关键词：
*Atherosclerosis;*Furin;*Inflammation;*Lipid metabolism
摘要：
Furin, a member of the mammalian proprotein convertases family, can promote the proteolytic maturation of proproteins. It is known that furin is predominantly present in certain cell types of human atherosclerotic lesions and neointima in animal models, including vascular smooth muscle cells, endothelial cells and mononuclear inflammatory cells. Evidence suggests that furin participates in the initiation and progression of atherosclerosis through regulation of lipid and cholesterol metabolism, inflammatory response, blood pressure and the formation of atherosclerotic lesions. This review provides a panorama of the roles of furin in atherosclerosis and the insights into the prevention and treatment of atherosclerosis and cardiovascular disease.
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英文
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deSUMOylation signaling: a novel mechanism of liver CSC properties and hepatocarcinogenesis in hypoxia
作者：
Zhao, Hong;Yao, Pingbo;Fu, Nian;Chen, Linxi
期刊：
生物化学与生物物理学报 ,2017年49(12):1135-1137 ISSN：1672-9145
通讯作者：
Nian Fu<&wdkj&>Linxi Chen
作者机构：
[Fu, Nian; Chen, Linxi; Zhao, Hong] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang, 421001, China;[Yao, Pingbo] Intensive Care Units of the Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, China
通讯机构：
[Nian Fu; Linxi Chen] I;Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang, China
关键词：
hypoxia;liver
摘要：
Hepatocellular carcinoma (HCC),one of the most common malignant cancers, is the third leading cause of cancer-related mortality worldwide. The etiological factors of HCC include alcohol intake, smoking, viral infections, cirrhosis, non-alcoholic steatohepatitis, hemochromatosis, and diabetes. Nowadays, despite much advance in HCC treatment, the 5-year survival rate for patients keeps dismal due to recurrence and metastases of HCC. Cancer stem cells (CSCs), also termed tumor-initiating cells, have the capability for unrestricted cell division, contributing to heterogeneous cell progenies. CSCs exist in both solid tumors and hematological malignancy. Till now, some cell surface markers are widely used to identify a subpopulation of cells with CSC features in liver such as CD24,CD 133, and epithelial cell adhesion molecule. Therefore, identification of CSC subpopulations in tumor will provide a novel understanding for cancer progress.
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英文
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Hsp27 promotes ABCA1 expression and cholesterol efflux through the PI3K/PKCζ/Sp1 pathway in THP-1 macrophages
作者：
Kuang, Hai-Jun;Zhao, Guo-Jun;Chen, Wu-Jun;Zhang, Min;Zeng, Gao-Feng;...
期刊：
European Journal of Pharmacology ,2017年810(1):57-62 ISSN：0014-2999
通讯作者：
Tang, Chao-Ke
作者机构：
[Tang, Chao-Ke; Chen, Wu-Jun; Kuang, Hai-Jun; Zhang, Min] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Guo-Jun] Guilin Med Univ, Dept Histol & Embryol, 1 Zhiyuan Rd, Guilin 541100, Guangxi, Peoples R China.;[Kuang, Hai-Jun; Zeng, Gao-Feng] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
通讯机构：
[Tang, Chao-Ke] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.
关键词：
ABCA1;Atherosclerosis;Cholesterol efflux;Hsp27
摘要：
Heat shock protein 27 (Hsp27) is a putative biomarker and therapeutic target in atherosclerosis. This study was to explore the potential mechanisms underlying Hsp27 effects on ATP-binding cassette transporter A1 (ABCA1) expression and cellular cholesterol efflux. THP-1 macrophage-derived foam cells were infected with adenovirus to express wild-type Hsp27, hyper-phosphorylated Hsp27 mimic (3D Hsp27), antisense Hsp27 or hypo-phosphorylated Hsp27 mimic (3A Hsp27). Wild-type and 3D Hsp27 were found to up-regulate ABCA1 mRNA and protein expression and increase cholesterol efflux from cells. Expression of antisense or 3A Hsp27 suppressed the expression of ABCA1 and cholesterol efflux. Furthermore, over-expression of wild-type and 3D Hsp27 significantly increased the levels of phosphorylated specificity protein 1 (Sp1), protein kinase C ζ (PKCζ) and phosphatidylinositol 3-kinase (PI3K). In addition, the up-regulation of ABCA1 expression and cholesterol efflux induced by 3D Hsp27 was suppressed by inhibition of Sp1, PKCζ and PI3K with specific kinase inhibitors. Taken together, our results revealed that Hsp27 may up-regulate the expression of ABCA1 and promotes cholesterol efflux through activation of the PI3K/PKCζ/Sp1 signal pathway in THP-1 macrophage-derived foam cells. Our findings may partly explain the mechanisms underlying the anti-atherogenic effect of Hsp27. © 2017 Elsevier B.V.
语种：
英文
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The influence of HK2 blood group antigen on human B cell activation for ABOi-KT conditions
作者：
Cao, Jingsong;Liu, Luogen;Zhang, Yunsheng;Xiao, Jianhua* ;Wang, Yi*
期刊：
BMC Immunology ,2017年18(1):1-8 ISSN：1471-2172
通讯作者：
Xiao, Jianhua;Wang, Yi
作者机构：
[Xiao, Jianhua; Cao, Jingsong] Univ South China, Med Coll, Inst Pathogen Biol, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Hunan, Peoples R China.;[Xiao, Jianhua; Cao, Jingsong] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Wang, Yi; Zhang, Yunsheng; Xiao, JH; Wang, Y; Xiao, Jianhua; Liu, Luogen; Cao, Jingsong] Univ South China, Affiliated Hosp 2, Inst Pathogen Biol, Clin Res Ctr,Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Wang, Yi] Univ South China, Affiliated Hosp 2, Urinary Surg, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xiao, Jianhua; Xiao, JH; Wang, Y] U;Univ South China, Med Coll, Inst Pathogen Biol, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Inst Pathogen Biol, Clin Res Ctr,Med Coll, Hengyang 421001, Hunan, Peoples R China.
关键词：
Blood group B antigen;Blood group B antibody;HK2;B cells activation;ABOi-KT
摘要：
Background: It is well known that ABO blood group system incompatible kidney transplantation (ABOi-KT) is an effective strategy for end-stage renal disease. The main barrier for ABOi-KT is how to keep host B cell activation and blood group antibody titer in low levels. Moreover, the mechanism of B cell activation induced by blood group antigen was unclear in ABOi-KT. Results: In this study, HK2 cells were identified to express blood group B antigen when cocultured with lymphocytes of blood group A. Optical microscope observation demonstrated that HK2 cells in coculture group gradually decreased. Furthermore, flow cytometer assay identified that T cell phenotypes (CD3+, CD3+CD4+ and CD3+CD8+) had no significant change and B cell phenotypes (CD19+ and CD138+) were all significantly enhanced (3.07 and 3.02 folds) at day 4. In addition, immunoturbidimetry analysis demonstrated that blood group B antibody was significantly increased to 2.35 fold at day 4, IgG was significantly increased to 3.60 and 2.81 folds at days 4 and 8 respectively, while IgM had no significant change at the measured time points. Conclusions: Taken together, B cells were activated and secreted blood group B antibody after treatment with HK2 expressing blood group B antigen. The results of this study maybe useful for further determination of the mechanism of B cell activation after ABO incompatible kidney endothelial cells stimulation. © 2017 The Author(s).
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英文
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Inhibition of long non-coding RNA ROR reverses resistance to Tamoxifen by inducing autophagy in breast cancer
作者：
Li, Yuehua;Jiang, Baohong;Zhu, Hongbo;Qu, Xiaofei;Zhao, Liqin;...
期刊：
Tumor Biology ,2017年39(6):1010428317705790 ISSN：1010-4283
通讯作者：
Wu, Xiaoping
作者机构：
[Qu, Xiaofei; Tan, Yeru; Zhu, Hongbo; Li, Yuehua; Jiang, Yiling; Liao, Mingchu; Wu, Xiaoping] Univ South China, Affiliated Hosp 1, Dept Oncol, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Baohong] Univ South China, Affiliated Hosp 1, Dept Pharm, Hengyang, Peoples R China.;[Zhao, Liqin] Univ South China, Affiliated Hosp 1, Dept Hematol, Hengyang, Peoples R China.
通讯机构：
[Wu, Xiaoping] U;Univ South China, Affiliated Hosp 1, Dept Oncol, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Long non-coding RNA ROR;breast cancer;autophagy;Tamoxifen;endocrine therapy;drug resistance
摘要：
This study explored the mechanism underlying long non-coding RNA ROR regulating autophagy on Tamoxifen resistance in breast cancer. Cancer tissues and adjacent normal tissues were collected from 74 breast cancer patients. Human breast cancer BT474 cells were assigned into blank, phosphate buffered saline, Tamoxifen, negative control + Tamoxifen, siROR + Tamoxifen, 3-methyladenine + Tamoxifen, and siROR + 3-methyladenine + TA groups. The expression of long non-coding RNA ROR and expressions of multi-drug resistance-associated P-glycoprotein and glutathione S-transferase-π messenger RNA were detected using quantitative real-time polymerase chain reaction. The expressions of light chain 3, Beclin 1, multi-drug resistance-associated P-glycoprotein, and glutathione S-transferase-π protein were determined using western blotting. Cell proliferation, invasion, and migration abilities were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell assay, and scratch test, respectively. The long non-coding RNA ROR expression was higher in the breast cancer tissues than that in the adjacent normal tissues. Compared with the blank group, light chain 3 and Beclin 1 expressions were increased in the siROR + Tamoxifen group but decreased in the 3-methyladenine + Tamoxifen group; these data indicated that downregulated long non-coding RNA ROR promoted autophagy. In comparison with the blank group, multi-drug resistance-associated P-glycoprotein and glutathione S-transferase-π messenger RNA and protein expressions were reduced in the siROR + Tamoxifen group but elevated in the 3-methyladenine + Tamoxifen group, suggesting that downregulated long non-coding RNA ROR suppressed the drug resistance to Tamoxifen and the inhibition of autophagy reversed the effect of long non-coding RNA ROR on drug resistance. Compared with the Tamoxifen, negative control, and siROR + 3-methyladenine + Tamoxifen groups, the cell proliferation, invasion, and migration in the siROR + Tamoxifen group were much decreased; these results implied that downregulated long non-coding RNA ROR suppressed BT474 cell proliferation, invasion, and migration and reversed the effect of Tamoxifen on the BT474 cells. These results indicate that inhibition of long non-coding RNA ROR reverses resistance to Tamoxifen by inducing autophagy in breast cancer. © The Author(s) 2017.
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英文
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Myocardin: A novel player in atherosclerosis
作者：
Xia, Xiao-Dan;Zhou, Zhen;Yu, Xiao-hua;Zheng, Xi-Long;Tang, Chao-Ke*
期刊：
Atherosclerosis ,2017年257:266-278 ISSN：0021-9150
通讯作者：
Tang, Chao-Ke
作者机构：
[Tang, Chao-Ke; Yu, Xiao-hua; Xia, Xiao-Dan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov,Med Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Xia, Xiao-Dan] Univ South China, Affiliated Nanhua Hosp, Dept Hand Surg, Hengyang 421002, Hunan, Peoples R China.;[Zhou, Zhen] Univ South China, Affiliated Nanhua Hosp, Dept Cardiothorac Surg, Hengyang 421002, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
通讯机构：
[Tang, Chao-Ke] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov,Med Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词：
*Abca1;*Atherosclerosis;*Inflammation;*Lipid metabolism;*Myocardin;*VSMC
摘要：
Myocardin (MYOCD) the most important coactivator of serum response factor (SRF), plays a critical role specifically in the development of cardiac myocytes and vascular smooth muscle cells (VSMCs). Binding of Myocardin to the SRF on the CArG box-containing target genes can transcriptionally activate a variety of downstream muscle-specific genes, such as Sm22 alpha, Acta2, Myh11, and several other signaling pathways. Myocardin expression represents a contractile and differentiated SMC phenotype. Loss of Myocardin, however, represents a synthetic and dedifferentiated phenotype, a hallmark in atherosclerosis. Growing evidence shows that Myocardin is involved in lipid metabolism and vascular inflammation, the primary pathogenesis of atherosclerosis. Moreover, Myocardin expression level is altered in atherosclerotic patients and animal models, suggesting more extensive and important roles for Myocardin in atherosclerosis. In the current review, we summarized recent progress on the regulation and signaling of Myocardin, and highlighted its impacts on atherosclerotic disease. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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英文
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Curcumin enhances vascular contractility via induction of myocardin in mouse smooth muscle cells
作者：
Sun, Shao-wei;Tong, Wen-juan;Guo, Zi-fen;Tuo, Qin-hui;Lei, Xiao-yong;...
期刊：
中国药理学报 ,2017年38(10):1329-1339 ISSN：1671-4083
通讯作者：
Liao, Duan-fang
作者机构：
[Guo, Zi-fen; Lei, Xiao-yong; Zhang, Cai-ping; Sun, Shao-wei] Univ South China, Sch Life Sci & Technol, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Tong, Wen-juan] Univ South China, Affiliated Hosp 1, Dept Gynecol & Obstet, Hengyang 421001, Peoples R China.;[Liao, Duan-fang; Chen, Jian-xiong; Tuo, Qin-hui] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Hunan, Peoples R China.;[Chen, Jian-xiong] Univ Mississippi, Med Ctr, Sch Med, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA.
通讯机构：
[Liao, Duan-fang] H;Hunan Univ Chinese Med, Med Sch, Changsha 410208, Hunan, Peoples R China.
关键词：
courcumin;smooth muscle;vascular contractility;myocardin;caveolin-1;Notch1
摘要：
A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin (100 mg·kg~(-1)·d~(-1), ig) for 6 weeks, the contractile responses of the thoracic aorta to KCI and phenylephrine were significantly enhanced compared with the control group. Furthermore, the contractility of vascular smooth muscle (SM) was significantly enhanced after incubation in curcumin (25 pmol/L) for 4 d, which was accompanied by upregulated expression of SM marker contractile proteins SM22a and SM a-actin. In cultured vascular smooth muscle cells (VSMCs), curcumin (10, 25, 50 µmol/L) significantly increased the expression of myocardin, a “master regulator” of SM gene expression. Curcumin treatment also significantly increased the levels of caveolin-1 in VSMCs. We found that as a result of the upregulation of caveolin-1, curcumin blocked the activation of Notch 1 and thereby abolished Notchl-inhibited myocardin expression. Knockdown of caveolin-1 or activation of Notch 1 signaling with Jagged 1 (2 pg/mL) diminished these effects of curcumin in VSMCs. These findings suggest that curcumin induces the expression of myocardin in mouse smooth muscle cells via a variety of mechanisms, including caveolin-l-mediated inhibition of Notch 1 activation and Notch 1-mediated repression of myocardin expression. This may represent a novel pathway, through which curcumin protects blood vessels via the beneficial regulation of SM contractility.
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