Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin salicylate derivatives
作者:
Deng, Xiangping;Zhao, Zihao;Xiong, Shujuan;Xiong, Runde;Liu, Juan;...
期刊:
Natural Product Research ,2018年32(18):2178-2186 ISSN:1478-6419
通讯作者:
Liu, Yunmei;Tang, Guotao
作者机构:
[Wang, Zhe; Liu, Yunmei; Zou, Liu; Liu, Juan; Tang, Guotao; Zheng, Xing; Deng, Xiangping; Xie, Zhizhong; Liu, YM; Tang, GT; Lei, Xiaoyong; Xiong, Shujuan; Zhao, Zihao; Xiong, Runde; Cao, Xuan] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Zhao, Zihao] Xiangtan Cent Hosp, Pharm Dept, Xiangtan, Peoples R China.;[Chen, Yanming] Mu Dan Jiang You Bo Pharmacert Co Ltd, Mudanjiang, Peoples R China.
通讯机构:
[Liu, YM; Tang, GT] U;Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.
关键词:
Chrysin;salicylate derivatives;synthesis;antitumour
摘要:
A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-803cells and MFC cells. Among them, compound 3f showed the most potent activity against MGC-803 cells and MFC cells with IC50 values of 23.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The flow cytometry assay reconfirmed that compound 3f promoted the occurrence of tumour cells’ G1/S block under the inhibiting effect of compound 3f. Compound 3f possessed higher antitumour efficacy in tumour-bearing mice, compared with the positive control 5-Fu and the blank control saline.
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英文
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miR-23b-3p and miR-125b-5p downregulate apo(a) expression by targeting Ets1 in HepG2 cells
作者:
Zeng, Jun-fa;Zeng, Zhao-lin;Zhang, Kai;Zhao, Yue;Liu, Ya-mi;...
期刊:
Cell Biology International ,2018年42(3):313-323 ISSN:1065-6995
通讯作者:
Wang, Zuo
作者机构:
[Zeng, Jun-fa; Zhang, Kai] Univ South China, Hosp 2, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Zhao-lin; Zhao, Yue; Chen, Jiao-jiao; Jiang, Zhi-sheng; Wei, Dang-heng; Liu, Ya-mi; Wang, Zuo] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Tong, Hai] Univ South China, Hosp 1, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Wang, Zuo] U;Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词:
atherosclerosis;Lipoprotein (a);miR-23b-3p;miR-125b-5p
摘要:
High concentrations of plasma lipoprotein(a) [Lp(a)] have been inferred to be an independent risk factor for cardiovascular and cerebrovascular diseases, such as coronary artery diseases, restenosis, and stroke. Apolipoprotein(a) [apo(a)] is one of the most important components of Lp(a) and contributes greatly to the increased concentration of plasma Lp(a). As a critical positive transacting factor of apo(a) gene, Ets1 has been proven as a target gene of several miRNAs, such as miR-193b, miR-125b-5p, miR-200b, miR-1, and miR-499. In this study, a series of experiments on miRNAs and relative miRNAs inhibitor delivered HepG2 cells were conducted, and two miRNAs that downregulate the apo(a) by targeting the 3′-UTR of Ets1 were identified. Results showed that apo(a) and Ets1 were differentially expressed in SMMC7721 and HepG2 cell lines. Meanwhile, apo(a) and Ets1 were inversely correlated with several hepatic endogenous miRNAs, such as miR-125b-5p, miR-23b-3p, miR-26a-5p, and miR-423-5p, which were predicted to bind to Ets1. Results show that miR-125b-5p and miR-23b-3p mimics could inhibit the synthesis of apo(a) by directly targeting Ets1 in HepG2, thereby reducing the plasma Lp (a) concentration. © 2017 International Federation for Cell Biology
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英文
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Immunogenicity and protective efficacy against Treponema pallidum in New Zealand rabbits immunized with plasmid DNA encoding flagellin
作者:
Zheng, Kang;Xu, Man;Xiao, Yongjian;Luo, Haodang;Xie, Yafeng;...
期刊:
Emerging Microbes & Infections ,2018年7(1):1-10 ISSN:2222-1751
通讯作者:
Wu, Yimou
作者机构:
[Yu, Jian; Wu, Yimou; Zhao, Feijun; Li, Yumeng; Tan, Manyi; Luo, Haodang; Zheng, Kang; Xu, Man; Zeng, Tiebing] Univ South China, Med Coll, Inst Pathogen Biol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Xie, Yafeng; Xiao, Yongjian] Univ South China, Affiliated Hosp 2, Clin Lab, Hengyang 421001, Peoples R China.;[Yu, Jian] Univ South China, Med Coll, Dept Expt Zool, Hengyang 421001, Peoples R China.
通讯机构:
[Wu, Yimou] U;Univ South China, Med Coll, Inst Pathogen Biol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
摘要:
Plasmid DNA encoding flagellin FlaB3 was used as a vaccination candidate for the evaluation of immunogenicity and protection against Treponema pallidum subsp. pallidum dissemination. First, intramuscular injection of the flagellin encoded by the plasmid DNA into New Zealand rabbits elicited both humoral and cellular immune responses. Total IgG production increased in response to flagellin. In addition, serum IFN-γ secretion and CD8+ cells were substantially greater in the rabbits immunized with the plasmid encoding flagellin FlaB3 than those in the rabbits immunized with recombinant flagellin. The flagellin encoded by the plasmid DNA induced significant upregulation of serum IL-6 and IL-8 compared to that of the control rabbits. Subsequently, intradermal challenge of the vaccinated New Zealand rabbits with 1 × 10 7 T. pallidum resulted in a significant reduction of the bacterial organ burden in the blood, liver, spleen, and testicles in the flagellin plasmid DNA-vaccinated rabbits. Furthermore, the histopathological analysis demonstrated that the rabbits immunized with the plasmid DNA-encoded flagellin (FlaB3) showed better immune protection. These findings provide evidence that plasmid DNA-encoded flagellin (FlaB3) may be useful as a potential immunization route for future development of a vaccine to inhibit T. pallidum dissemination in related animals. © 2018, The Author(s).
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英文
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Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin-resistant breast cancer by binding to enhancer of zeste homolog 2
作者:
Jiang, Baohong;Li, Yuehua* ;Qu, Xiaofei;Zhu, Hongbo;Tan, Yeru;...
期刊:
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE ,2018年42(5):2801-2810 ISSN:1107-3756
通讯作者:
Li, Yuehua
作者机构:
[Jiang, Baohong] Univ South China, Affiliated Hosp 1, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Qu, Xiaofei; Tan, Yeru; Zhu, Hongbo; Li, Yuehua; Jiang, Yiling; Liao, Mingchu; Fan, Qun; Wu, Xiaoping] Univ South China, Affiliated Hosp 1, Dept Med Oncol, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, Yuehua] U;Univ South China, Affiliated Hosp 1, Dept Med Oncol, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
breast cancer;drug-resistance;cancer susceptibility candidate 9;enhancer of zeste homolog 2;multidrug resistance protein 1
摘要:
The present study aimed to investigate the effect of the long noncoding RNA cancer susceptibility candidate 9 (CASC9) on doxorubicin (DOX)-resistant breast cancer and to reveal the potential underlying mechanisms. The expression of CASC9 in breast cancer tissues and cell lines, in addition to drug-resistant breast cancer cells (MCF-7/DOX), was detected by reverse transcription-quantitative polymerase chain reaction. Subsequently, MCF-7/DOX cells were transfected with the silencing vector pS-C ASC9, containing enhancer of zeste homolog 2(EZH2), multidrug resistance protein 1 (MDR1) or control small interfering (si)RNAs. The viability, apoptosis, migration and invasion of the transfected cells were assessed via an MTT assay, flow cytometry and a Transwell assay, respectively. The expression levels of apoptosis-associated proteins (apoptosis regulator Bcl-2, apoptosis regulator BAX, caspase-3 and caspase-9) were determined by western blotting. An RNA pull-down assay was performed to identify CASC9-binding candidates. In addition, the expression levels of the MDR1 gene and its encoded protein, P-glycoprotein, were detected. CASC9 expression was upregulated in breast cancer tissues and cell lines, and drug-resistant breast cancer cells. CASC9 knockdown significantly inhibited the growth and metastasis of drug-resistant breast cancer cells, and decreased the half-maximal inhibitory concentration DOX in MCF-7/DOX cells. The RNA pull-down assay revealed that CASC9 engaged EZH2; EZH2 siRNA significantly inhibited the cell growth, metastasis and chemoresistance of MCF-7/DOX cells. Additionally, EZH2 may regulate the MDR1 gene. The present study demonstrated the oncogenic role of CASC9 in drug-resistant breast cancer by binding to EZH2 and regulating the MDR1 gene. Modulation of CASC9 expression may be a promising target in the therapy of breast cancer and drug-resistant breast cancer. © 2018 Spandidos Publications. All rights reserved.
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英文
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Mechanisms of MAFG Dysregulation in Cholestatic Liver Injury and Development of Liver Cancer
作者:
Liu, Ting;Yang, Heping;Fan, Wei;Tu, Jian;Li, Tony W. H.;...
期刊:
Gastroenterology ,2018年155(2):557-571.e14 ISSN:0016-5085
通讯作者:
Lu, Shelly C.
作者机构:
[Li, Tony W. H.; Yang, JinWon; Lu, Shelly C.; Wang, Jiaohong; Fan, Wei; Seki, Ekihiro; Xiong, Ting; Tu, Jian; Yang, Heping; Noureddin, Mazen; Liu, Ting] Cedars Sinai Med Ctr, Div Digest & Liver Dis, Los Angeles, CA 90048 USA.;[Liu, Ting] Cent S Univ, Xiangya Hosp, Dept Gastroenterol, Changsha, Hunan, Peoples R China.;[Liu, Ting] Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Canc Prote, Changsha, Hunan, Peoples R China.;[Fan, Wei] Guangzhou First Peoples Hosp, Dept Geriatr, Guangzhou, Guangdong, Peoples R China.;[Fan, Wei] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China.
通讯机构:
[Lu, Shelly C.] C;Cedars Sinai Med Ctr, Davis Bldg,Room 2097,8700 Beverly Blvd, Los Angeles, CA 90048 USA.
关键词:
FXR;Obeticholic Acid;S-Adenosylmethionine;Ursodeoxycholic Acid
摘要:
Background & Aims: MAF bZIP transcription factor G (MAFG) is activated by the farnesoid X receptor to repress bile acid synthesis. However, expression of MAFG increases during cholestatic liver injury in mice and in cholangiocarcinomas. MAFG interacts directly with methionine adenosyltransferase α1 (MATα1) and other transcription factors at the E-box element to repress transcription. We studied mechanisms of MAFG up-regulation in cholestatic tissues and the pathways by which S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) prevent the increase in MAFG expression. We also investigated whether obeticholic acid (OCA), an farnesoid X receptor agonist, affects MAFG expression and how it contributes to tumor growth in mice. Methods: We obtained 7 human cholangiocarcinoma specimens and adjacent non-tumor tissues from patients that underwent surgical resection in California and 113 hepatocellular carcinoma (HCC) specimens and adjacent non-tumor tissues from China, along with clinical data from patients. Tissues were analyzed by immunohistochemistry. MAT1A, MAT2A, c-MYC, and MAFG were overexpressed or knocked down with small interfering RNAs in MzChA-1, KMCH, Hep3B, and HepG2 cells; some cells were incubated with lithocholic acid (LCA, which causes the same changes in gene expression observed during chronic cholestatic liver injury in mice), SAMe, UDCA (100 μM), or farnesoid X receptor agonists. MAFG expression and promoter activity were measured using real-time polymerase chain reaction, immunoblot, and transient transfection. We performed electrophoretic mobility shift, and chromatin immunoprecipitation assays to study proteins that occupy promoter regions. We studied mice with bile-duct ligation, orthotopic cholangiocarcinomas, cholestasis-induced cholangiocarcinoma, diethylnitrosamine-induced liver tumors, and xenograft tumors. Results: LCA activated expression of MAFG in HepG2 and MzChA-1 cells, which required the activator protein-1, nuclear factor–κB, and E-box sites in the MAFG promoter. LCA reduced expression of MAT1A but increased expression of MAT2A in cells. Overexpression of MAT2A increased activity of the MAFG promoter, whereas knockdown of MAT2A reduced it. MAT1A and MAT2A had opposite effects on the activator protein-1, nuclear factor–κB, and E-box–mediated promoter activity. Expression of MAFG and MAT2A increased, and expression of MAT1A decreased, in diethylnitrosamine-induced liver tumors in mice. SAMe and UDCA had shared and distinct mechanisms of preventing LCA-mediated increased expression of MAFG. OCA increased expression of MAFG, MAT2A, and c-MYC, but reduced expression of MAT1A. Incubation of human liver and biliary cancer cells lines with OCA promoted their proliferation; in nude mice given OCA, xenograft tumors were larger than in mice given vehicle. Levels of MAFG were increased in human HCC and cholangiocarcinoma tissues compared with non-tumor tissues. High levels of MAFG in HCC samples correlated with hepatitis B, vascular invasion, and shorter survival times of patients. Conclusions: Expression of MAFG increases in cells and tissues with cholestasis, as well as in human cholangiocarcinoma and HCC specimens; high expression levels correlate with tumor progression and reduced survival time. SAMe and UDCA reduce expression of MAFG in response to cholestasis, by shared and distinct mechanisms. OCA induces MAFG expression, cancer cell proliferation, and growth of xenograft tumors in mice. © 2018 AGA Institute
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英文
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Advances in the T7 phage display system
作者:
Deng, Xiangying;Wang, Li;You, Xiaolong;Dai, Pei;Zeng, Yanhua*
期刊:
MOLECULAR MEDICINE REPORTS ,2018年17(1):714-720 ISSN:1791-2997
通讯作者:
Zeng, Yanhua
作者机构:
[Dai, Pei; Wang, Li; Deng, Xiangying; Zeng, Yanhua; You, Xiaolong] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Special Pathogens Prevent & Co, Inst Pathogen Biol,Med Coll, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Deng, Xiangying] Cent S Univ, Canc Res Inst, Key Lab Carcinogenesis & Canc Invas, Chinese Minist Educ, Changsha 410078, Hunan, Peoples R China.
通讯机构:
[Zeng, Yanhua] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Special Pathogens Prevent & Co, Inst Pathogen Biol,Med Coll, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
T7 phage;T7 phage display;protein interaction;antigen discovery;vaccine development;cancer diagnosis and treatment
摘要:
The present review describes the advantages and updated applications of the T7 phage display system in bioscience and medical science. Current phage display systems are based on various bacteriophage vectors, including M13, T7, T4 and f1. Of these, the M13 phage display is the most frequently used, however, the present review highlights the advantages of the T7 system. As a phage display platform, M13 contains single-stranded DNA, while the T7 phage consists of double-stranded DNA, which exhibits increased stability and is less prone to mutation during replication. Additional characteristics of the T7 phage include the following: The T7 phage does not depend on a protein secretion pathway in the lytic cycle; expressed peptides and proteins are usually located on the C-terminal region of capsid protein gp10B, which avoids problems associated with steric hindrance; and T7 phage particles exhibit high stability under various extreme conditions, including high temperature and low pH, which facilitates effective high-throughput affinity elutriation. Recent applications of the T7 phage display system have been instrumental in uncovering mechanisms of molecular interaction, particularly in the fields of antigen discovery, vaccine development, protein interaction, and cancer diagnosis and treatment.
语种:
英文
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The role of FTO variants in the susceptibility of polycystic ovary syndrome and in vitro fertilization outcomes in Chinese women
作者:
Liu, Ai Ling;Liao, Hong Qing;Zhou, Jing;Nie, Yu Lin;Zhou, Cui Lan;...
期刊:
Gynecological Endocrinology ,2018年34(8):719-723 ISSN:0951-3590
通讯作者:
Peng, Cui Ying
作者机构:
[Li, Zhi Liang; Peng, Cui Ying; Liu, Ai Ling; Zhu, Yun Hua] Univ South China, Sch Pharmaceut & Biol Sci, Inst Biol, Hengyang, Peoples R China.;[Peng, Cui Ying; Liu, Ai Ling] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Peng, Cui Ying; Liu, Ai Ling] Key Lab Biol Toxicol & Ecol Restorat Hengyang Cit, Hengyang, Peoples R China.;[Nie, Yu Lin; Zhou, Jing; Liao, Hong Qing] Univ South China Hengyang City, Affiliated Hosp 2, Hengyang, Peoples R China.;[Zhou, Cui Lan] Univ South China, Dept Anat, Hengyang, Peoples R China.
通讯机构:
[Peng, Cui Ying] U;Univ South China, Sch Pharmaceut & Biol Sci, Inst Biol, Hengyang, Peoples R China.
关键词:
BMI;FTO;IVF;Polycystic ovary syndrome;polymorphism
摘要:
We investigated the association between single nucleotide polymorphisms (SNPs) in the fat mass and obesity associated (FTO) gene (rs9926289 A/G, rs79206939 A/G, rs9930506 A/G, rs8050136 A/C, and rs1588413 C/T) and polycystic ovary syndrome (PCOS), as well as outcomes of in vitro fertilization (IVF). A case-control study consisting of 147 PCOS patients and 120 healthy controls was conducted. FTO SNPs were genotyped by PCR to determine allelic frequencies, and IVF outcomes were analyzed. The results showed that FTO rs8050136 (p =.025) and rs1588413 (p =.042) were significantly associated with PCOS susceptibility, and women with risk alleles were often found to be obese (p <.05). For SNP rs8050136, women with AA + AC genotypes had higher body mass indexes (BMIs), oral glucose tolerance test/2 h (OGTT) levels and implantation rates but lower follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) day progesterone levels and ovulation numbers (all p <.05) than those with the CC genotype. For SNP rs1588413, women carrying risk alleles exhibited higher BMIs, implantation rate, and levels of luteinizing hormone (LH), estradiol, and OGTT/2 h (all p <.05) compared with those with non-risk genotypes. Therefore, these findings suggest that rs8050136 and rs1588413 are associated with PCOS susceptibility, and that women with risk alleles have less ovulation numbers but higher implantation rates than those with other genotypes. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
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英文
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MicroRNA-182 promotes lipoprotein lipase expression and atherogenesisby targeting histone deacetylase 9 in apolipoprotein E-knockout mice
作者:
Cheng, Hai-Peng;Gong, Duo;Zhao, Zhen-Wang;He, Ping-Ping;Yu, Xiao-Hua;...
期刊:
Circulation Journal ,2018年82(1):28-38 ISSN:1346-9843
通讯作者:
Yin, Wei-Dong;Tang, Chao-Ke
作者机构:
[Gong, Duo; Cheng, Hai-Peng; He, Ping-Ping; Ouyang, Xin-Ping; Xia, Xiao-Dan; Zhang, Min; Tang, Chao-Ke; Tan, Yu-Lin; Zhao, Zhen-Wang; Yu, Xiao-Hua; Li, Liang; Yin, Wei-Dong; Xie, Wei; Huang, Chong; Chen, Ling-Yan] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang, Hunan, Peoples R China.;[Zhang, Xin; Wang, Zong-bao] Univ South China, Sch Pharm & Life Sci Coll, Hengyang, Hunan, Peoples R China.;[Ye, Qiong; Tian, Guo-Ping] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Hengyang, Hunan, Peoples R China.;[Ye, Qiong; Tian, Guo-Ping] Univ South China, Dept Cardiovasc Med, Affiliated Hosp 2, Hengyang, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Libin Cardiovasc Inst Alberta, Cumming Sch Med, Dept Biochem & Mol Biol,Hlth Sci Ctr, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
通讯机构:
[Yin, WD; Tang, CK] U;Univ South China, Inst Cardiovasc Res, 28 W Chengsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
Atherosclerosis;Histone deacetylase 9 (HDAC9);Inflammation;Lipoprotein lipase (LPL);MicroRNA-182
摘要:
Background: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis. Methods and Results: Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targeting HDAC9 in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson’s trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. Conclusions: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targeting HDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice. © 2017, Japanese Circulation Society. All rights reserved.
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英文
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Expression and Purification of Tag-removed Human IL37 by Digestion on Beads in Escherichia coli
作者:
Wu, Daichao;Li, Guoqing;Ma, Yao;Liu, Jin;Li, Yukun;...
期刊:
PROTEIN AND PEPTIDE LETTERS ,2018年25(11):996-1002 ISSN:0929-8665
通讯作者:
Chen, Yongheng;Tan, Sijie;Li, Meixiang
作者机构:
[Li, Yukun; Tan, Sijie; Bai, Junhui; Liu, Jin; Li, Meixiang; Wu, Daichao; Wang, Juan] Univ South China, Hengyang Med Coll, Inst Clin Anat & Reprod Med, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Wu, Daichao; Li, Guoqing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Ma, Yao] Univ South China, Network Informat Ctr, Hengyang 421001, Hunan, Peoples R China.;[Chen, Yongheng] Cent S Univ, XiangYa Hosp, Chinese Minist Hlth, Lab Struct Biol,Key Lab Canc Prote, Changsha 410008, Hunan, Peoples R China.;[Chen, Yongheng] Cent S Univ, XiangYa Hosp, Changsha 410008, Hunan, Peoples R China.
通讯机构:
[Chen, Yongheng] C;[Tan, SJ; Li, MX] U;Cent S Univ, XiangYa Hosp, Changsha 410008, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Hengyang 421000, Peoples R China.
关键词:
Soluble expression;purification;interleukin 37;Escherichia coli;digestion on beads;inflammatory diseases.
摘要:
Background: Human Interleukin 37 (IL37), a unique anti-inflammatory cytokine of IL1 family member, plays critical roles in innate and adaptive immunity and inflammation. Objective: Preparation of high purity and tag-removed recombinant IL37 protein (rIL37) is critical for its clinical application. Method: In this study, we constructed an N-terminal cleavable GST-fused IL37 expression vector for recombinant expression. Results: Subsequent to transformation and optimization of the induction temperature, the soluble expression level of rIL37 was 306.5 mg/L of culture medium at 18 °C induction in Escherichia coli. Meanwhile, rIL37 was digested on beads by GST-HRV3C protease during GST affinity chromatography. After further purification, the purity of rIL37 was higher than 99 %. Finally, the anti-inflammatory activity of tag-removed protein was verified by the results showing that rIL37 suppressed IL1β production in PBMCs. Conclusion: This work presents a protocol to produce high purity and tag-removed rIL37 with anti-inflammatory activity, which provides the firm basis for advancing clinical application in human IL37-related inflammatory diseases. © 2018 Bentham Science Publishers.
语种:
英文
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The P2X7 purinergic receptor: An emerging therapeutic target in cardiovascular diseases
作者:
Chen, Zhe;He, Lu;Li, Lanfang* ;Chen, Linxi*
期刊:
Clinica Chimica Acta ,2018年479:196-207 ISSN:0009-8981
通讯作者:
Li, Lanfang;Chen, Linxi
作者机构:
[Li, Lanfang; Li, LF; Chen, Linxi; He, Lu; Chen, Zhe] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构:
[Li, LF; Chen, LX] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词:
The P2X7 receptor;Myocardial ischemia-reperfusion injury;Dilated cardiomyopathy;Autoimmune myocarditis;Atherosclerosis;Diabetic retinopathy
摘要:
The P2X7 purinergic receptor, a calcium permeable cationic channel, is activated by extracellular ATP. Most studies show that P2X7 receptor plays an important role in the nervous system diseases, immune response, osteoporosis and cancer. Mounting evidence indicates that P2X7 receptor is also associated with cardiovascular disease. For example, the P2X7 receptor activated by ATP can attenuate myocardial ischemia-reperfusion injury. By contrast, inhibition of P2X7 receptor decreases arrhythmia after myocardial infarction, prolongs cardiac survival after a long term heart transplant, alleviates the dilated cardiomyopathy and the autoimmune myocarditis process. The P2X7 receptor also mitigates vascular diseases including atherosclerosis, hypertension, thrombosis and diabetic retinopathy. This review focuses on the latest research on the role and therapeutic potential of P2X7 receptor in cardiovascular diseases.
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英文
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Effects of rapamycin on growth hormone receptor knockout mice
作者:
Fang, Yimin* ;Hill, Cristal M.;Darcy, Justin;Reyes-Ordonez, Adriana;Arauz, Edwin;...
期刊:
Proceedings of the National Academy of Sciences of the United States of America ,2018年115(7):E1495-E1503 ISSN:0027-8424
通讯作者:
Fang, Yimin
作者机构:
[Hill, Cristal M.; Osland, Jared; Darcy, Justin; McFadden, Samuel; Fang, Yimin; Bartke, Andrzej; Yuan, Rong] Southern Illinois Univ, Dept Internal Med, Sch Med, Springfield, IL 62702 USA.;[Chen, Jie; Arauz, Edwin; Reyes-Ordonez, Adriana] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.;[Zhang, Chi] Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.;[Gao, John] Southern Illinois Univ, Dept Pathol & Lab Med, Sch Med, Springfield, IL 62702 USA.;[Zhang, Tian] Southern Illinois Univ, Dept Surg, Sch Med, Springfield, IL 62702 USA.
通讯机构:
[Fang, Yimin] S;Southern Illinois Univ, Dept Internal Med, Sch Med, Springfield, IL 62702 USA.
关键词:
mTORC2;rapamycin;longevity;homeostasis;GHR-KO
摘要:
It is well documented that inhibition of mTORC1 (defined by Raptor), a complex of mechanistic target of rapamycin (mTOR), extends life span, but less is known about the mechanisms by which mTORC2 (defined by Rictor) impacts longevity. Here, rapamycin (an inhibitor of mTOR) was used in GHR-KO (growth hormone receptor knockout) mice, which have suppressed mTORC1 and up-regulated mTORC2 signaling, to determine the effect of concurrently decreased mTORC1 and mTORC2 signaling on life span. We found that rapamycin extended life span in control normal (N) mice, whereas it had the opposite effect in GHR-KO mice. In the rapamycin-treated GHR-KO mice, mTORC2 signaling was reduced without further inhibition of mTORC1 in the liver, muscle, and s.c. fat. Glucose and lipid homeostasis were impaired, and old GHR-KO mice treated with rapamycin lost functional immune cells and had increased inflammation. In GHR-KO MEF cells, knockdown of Rictor, but not Raptor, decreased mTORC2 signaling. We conclude that drastic reduction of mTORC2 plays important roles in impaired longevity in GHR-KO mice via disruption of whole-body homeostasis. © 2018 National Academy of Sciences.All Rights Reserved.
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Elabela-APJ axis contributes to embryonic development and prevents pre-eclampsia in pregnancy
作者:
Qionglin Zhou;Kai Zhang;Yu Guo;Linxi Chen;Lanfang Li
期刊:
生物化学与生物物理学报 ,2018年50(3):319-321 ISSN:1672-9145
通讯作者:
Linxi Chen<&wdkj&>Lanfang Li
作者机构:
[Zhou Qionglin; Zhang Kai; Guo Yu; Chen Linxi; Li Lanfang] Institute of Pharmacy and Pharmacology, University of South China, Learning Key Laboratory for Pharmacoproteomics;[Zhou Qionglin; Zhang Kai; Guo Yu; Chen Linxi; Li Lanfang] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001
通讯机构:
[Linxi Chen; Lanfang Li] I
关键词:
pregnancy;embryologic development
摘要:
APJ is a seven-transmembrane G protein coupled receptor. Apelin is an endogenous ligand of APJ [1]. It is well known that Apelin and APJ receptor are widely distributed in a variety of organs including the heart, brain, kidney, stomach, lung, adipose tissues, endothelium, vascular smooth muscle cells, testis, ovary, and gland, particularly in the cardiovascular system. The Apelin/APJ system plays multiple important roles in various physiological and pathological processes such as regulation of blood pressure, cardiac contractility, water homeostasis, immunity, glucose metabolism, fat metabolism, inflammation, liver fibrosis, cardiovascular development, apoptosis, revascularization, as well as cell proliferation.
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英文
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Selection and identification of novel peptides specifically targeting human cervical cancer
作者:
Liu, Xiaomin;Peng, Jingwen;He, Jie;Li, Qiaoran;Zhou, Jianbin;...
期刊:
Amino Acids ,2018年50(5):577-592 ISSN:0939-4451
通讯作者:
Liang, Xiaoqiu;Tang, Shengsong
作者机构:
[He, Jie; Li, Qiaoran; Liang, Xiaoqiu; Liu, Xiaomin; Peng, Jingwen] Univ South China, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;[He, Jie; Li, Qiaoran; Liang, Xiaoqiu; Liu, Xiaomin; Peng, Jingwen] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Zhou, Jianbin] Univ South China, Dept Gynecol & Obstet, Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Biomed Res Ctr, Huaihua 418000, Hunan, Peoples R China.
通讯机构:
[Liang, Xiaoqiu; Tang, Shengsong] U;[Tang, Shengsong] H;Univ South China, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst, 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, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
关键词:
Peptides;Tumor targeting;Cervical cancer;Phage display
摘要:
Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer deaths among females in underdeveloped countries. This study aimed to identify several novel cervical cancer-specific targeting peptides (CSPs) to provide new methods for the effective diagnosis and treatment of cervical cancer. Peptide library screening in vivo was performed on human cervical cancer xenografts with Ph.D.™-12 and C7C phage display peptide libraries. Two specific peptide sequences (GDALFSVPLEVY and KQNLAEG), which were enriched in tumors, were screened, and respectively, named CSP-GD and CSP-KQ through three rounds of biopanning. The in vivo tumor-targeting ability of these peptides was identified by injecting them into mice with cervical cancer xenograft. CSPs were compounded and labeled with fluorescein isothiocyanate (FITC). The specificity and affinity of FITC-CSPs were evaluated in human cervical cancer cell lines and tissue microarrays in vitro by immunofluorescent staining. Results showed that FITC-CSP-GD and FITC-CSP-KQ evidently and specifically bound to the cell membrane and cytoplasm of SiHa, ME-180, and C-33A cells in vitro. In human cervical cancer tissue, FITC-CSP-GD and FITC-CSP-KQ strongly targeted human cervical adenocarcinoma and cervical squamous cell carcinoma tissues, respectively. A bright FITC signal was located mainly on the cell membrane and cytoplasm of tumor cells. In conclusion, the novel 12-residue peptide CSP-GD and 7-residue peptide CSP-KQ could specifically target human cervical cancer and may have the potential to be used in the diagnosis and targeted therapy of cervical cancer. © 2018, Springer-Verlag GmbH Austria, part of Springer Nature.
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Nonpathogenic colonization with Chlamydia in the gastrointestinal tract as oral vaccination for inducing transmucosal protection
作者:
Wang, Luying;Zhu, Cuiming;Zhang, Tianyuan;Tian, Qi;Zhang, Nu;...
期刊:
Infection and Immunity ,2018年86(2) ISSN:0019-9567
通讯作者:
Xue, Min;Zhong, Guangming
作者机构:
[Xue, Min; Wang, Luying] Cent S Univ, Xiangya Hosp 3, Changsha, Hunan, Peoples R China.;[Tian, Qi; Zhu, Cuiming; Wang, Luying; Zhang, Tianyuan; Zhang, Nu; Zhong, Guangming] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol Immunol & Mol Genet, San Antonio, TX 78229 USA.;[Zhu, Cuiming] Univ South China, Dept Microbiol, Hengyang, Hunan, Peoples R China.;[Morrison, Sandra; Morrison, Richard] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA.
通讯机构:
[Xue, Min] C;[Zhong, Guangming] U;Cent S Univ, Xiangya Hosp 3, Changsha, Hunan, Peoples R China.;Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol Immunol & Mol Genet, San Antonio, TX 78229 USA.
关键词:
Chlamydia muridarum;oral inoculation;transmucosal immunity;nonpathogenic;Chlamydia;gastrointestinal infection;mucosal immunity;oral vaccines
摘要:
Chlamydia has been detected in the gastrointestinal tracts of humans and animals. We now report that gastrointestinal Chlamydia muridarum is able to induce robust transmucosal protection in mice. C. muridarum colonization in the gastrointestinal tract correlated with both a shortened course of C. muridarum genital tract infection and stronger protection against subsequent genital tract challenge infection. Mice preinoculated intragastrically with C. muridarum became highly resistant to subsequent C. muridarum infection in the genital tract, resulting in prevention of pathology in the upper genital tract. The transmucosal protection in the genital tract was rapidly induced, durable, and dependent on major histocompatibility complex (MHC) class II antigen presentation but not MHC class I antigen presentation. Although a deficiency in CD4+ T cells only partially reduced the transmucosal protection, depletion of CD4+ T cells from B cell-deficient mice completely abolished the protection, suggesting a synergistic role of both CD4+ T and B cells in the gastrointestinal C. muridarum-induced transmucosal immunity. However, the same protective immunity did not significantly affect C. muridarum colonization in the gastrointestinal tract. The long-lasting colonization with C. muridarum was restricted to the gastrointestinal tract and was nonpathogenic to either gastrointestinal or extragastrointestinal tissues. Furthermore, gastrointestinal C. muridarum did not alter the gut microbiota or the development of gut mucosal resident memory T cell responses to a nonchlamydial infection. Thus, Chlamydia may be developed into a safe and orally deliverable replicating vaccine for inducing transmucosal protection. © 2018 American Society for Microbiology.
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The Olfactory Receptor Pseudo-pseudogene: A Potential Therapeutic Target in Human Diseases
作者:
CHEN Zhe;HUANG Zhen;CHEN Lin Xi
期刊:
生物医学与环境科学:英文版 ,2018年31(2):168-170 ISSN:0895-3988
通讯作者:
HUANG, Z.
作者机构:
[CHEN Zhe; HUANG Zhen; CHEN Lin Xi] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan, China
通讯机构:
[HUANG, Z.] I;Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China
关键词:
嗅觉;受体;治疗学;疾病;神经原;醋酸;基因;果蝇
摘要:
Recently, Prieto-Godino et al. found that the olfactory receptor 75a (Ir75a) gene is a functional pseudo-pseudogene in Drosophila sechellio. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons (OSNs). Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechellia lr75a gene is generally recognized as a pseudogene in OSNs. Nevertheless, the D. sechellia Ir75a gene is not a simple pseudogene. Prieto-Godino et al. found that D. sechellia Ir75a is sensitive to propionic, butyric, and 2-oxopentanoic acids. Therefore, the D. sechellia Ir75a gene encodes a functional olfactory receptor (OR) that induces different olfactory responses.
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Apelin/APJ system: A novel promising target for anti-aging intervention
作者:
Zhou, Qionglin;Chen, Linxi;Tang, Mingzhu;Guo, Yu;Li, Lanfang*
期刊:
Clinica Chimica Acta ,2018年487:233-240 ISSN:0009-8981
通讯作者:
Li, Lanfang
作者机构:
[Guo, Yu; Li, Lanfang; Zhou, Qionglin; Tang, Mingzhu; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
通讯机构:
[Li, Lanfang] U;Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
关键词:
Aging;Apelin/APJ system;Cardiovascular disease;Diabetes;Obesity
摘要:
Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is widely expressed in various organs. Recent research has indicated that the Apelin/APJ system plays an important role in aging. Apelin and APJ receptor expression are down-regulated with increasing age. In murine models, Apelin and APJ knockouts exhibit accelerated senescence whereas Apelin-restoration results in enhanced vigor and rejuvenated behavioral and circadian phenotypes. Furthermore, aged Apelin knockout mice develop progressive impairment of cardiac contractility associated with systolic dysfunction. Apelin is crucial to maintain cardiac contractility in aging. Moreover, the Apelin/APJ system appears to be involved in regulation of renin-angiotensin-aldosterone system (RAAS), apoptosis, inflammation and oxidative stress which promotes aging. Likewise, the Apelin/APJ system regulates autophagy, stem cells and the sirtuin family thus contributing to anti-aging. In this review, we describe the relationship between Apelin/APJ system and aging. We elaborate on the role of the Apelin/APJ system in aging stimulators, aging inhibitors and age-related diseases such as obesity, diabetes and cardiovascular disease. We conclude that Apelin/APJ system might become a novel promising therapeutic target for anti-aging.
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英文
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Use of recombinant Lactobacillus sakei for the prevention and treatment of radiation-induced enteritis
作者:
He, Jun-yan;Wang, Wu-zhou;Qi, Hui-zhou;Ma, Yun;He, Shu-ya*
期刊:
Medical Hypotheses ,2018年119:37-40 ISSN:0306-9877
通讯作者:
He, Shu-ya
作者机构:
[He, Shu-ya; Wang, Wu-zhou; He, Jun-yan; Ma, Yun; Qi, Hui-zhou] Univ South China, Med Coll, Hengyang, Peoples R China.;[He, Shu-ya; Wang, Wu-zhou; He, Jun-yan; Ma, Yun] Univ South China, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.
通讯机构:
[He, Shu-ya] U;Univ South China, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.
摘要:
Radiation-induced enteritis is one of the most common complications in patients under radiotherapy at abdominal or pelvic cavity. Up to 50% of patients treated with pelvic radiotherapy has been reported radiation-induced acute enteritis, and half of them developed chronic enteritis. Overproduction of free radicals, activation of inflammatory pathways and vascular endothelial dysfunction were considered as the primary mechanisms of radiation-induced enteritis. Because probiotics have been demonstrated as a promising potential candidate for treating intestinal diseases, it may be a safer and more effective radioprotector for the enteritis compared to conventional chemical agents with inherent toxicities. Here, we propose that a recombinant Lactobacillus sakei would decrease the complications or symptoms significantly through against different pathogenic mechanisms simultaneously. Therefore, application of higher radiation dose for tumor control would be feasible when co-treating with recombinant Lactobacillus sakei.
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英文
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MicroRNAs: Important Regulators of Induced Pluripotent Stem Cell Generation and Differentiation
作者:
Zeng, Zhao-Lin;Lin, Xiao-long;Tan, Li-Lan;Liu, Ya-Mi;Qu, Kai;...
期刊:
Stem Cell Reviews and Reports ,2018年14(1):71-81 ISSN:2629-3269
通讯作者:
Wang, Zuo
作者机构:
[Tan, Li-Lan; Qu, Kai; Zeng, Zhao-Lin; Liu, Ya-Mi; Wang, Zuo] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Lin, Xiao-long] Guangzhou Med Univ, Huizhou Peoples Hosp 3, Dept Pathol, Huizhou 516002, Guangdong, Peoples R China.
通讯机构:
[Wang, Zuo] U;Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词:
Induced pluripotent stem cell;MicroRNA;Generation;Differentiation
摘要:
Induced pluripotent stem (iPS) cells can differentiate into nearly all types of cells. In contrast to embryonic stem cells, iPS cells are not subject to immune rejection because they are derived from a patient’s own cells without ethical concerns. These cells can be used in regenerative medical techniques, stem cell therapy, disease modelling and drug discovery investigations. However, this application faces many challenges, such as low efficiency, slow generation time, partially reprogrammed colonies and tumourigenicity. Numerous techniques have been formulated in the past decade to improve reprogramming efficiency and safety, including the use of different transcription factors, small molecule compounds and non-coding RNAs. Recently, microRNAs (miRNAs) were found to promote the generation and differentiation of iPS cells. The miRNAs can more effectively and safely generate iPS cells than transcription factors. This process ultimately leads to the development of iPSC-based therapeutics for future clinical applications. In this comprehensive review, we summarise advances in research and the application of iPS cells, as well as recent progress in the use of miRNAs for iPS cell generation and differentiation. We examine possible clinical applications, especially in cardiology. © 2017, Springer Science+Business Media, LLC, part of Springer Nature.
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英文
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Design, synthesis and biological evaluation of chrysin benzimidazole derivatives as potential anticancer agents
作者:
Wang, Zhe;Deng, Xiangping;Xiong, Shujuan;Xiong, Runde;Liu, Juan;...
期刊:
Natural Product Research ,2018年32(24):2900-2909 ISSN:1478-6419
通讯作者:
Zheng, Xing;Tang, Guotao
作者机构:
[Wang, Zhe; Liu, Yunmei; Zou, Liu; Liu, Juan; Zheng, X; Tang, GT; Tang, Guotao; Zheng, Xing; Deng, Xiangping; Xie, Zhizhong; Lei, Xiaoyong; Xiong, Shujuan; Xiong, Runde; Cao, Xuan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Chen, Yanming] Mu Dan Jiang You Bo Pharmacert Co Ltd, Mudanjiang, Peoples R China.
通讯机构:
[Zheng, X; Tang, GT] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang, Peoples R China.
关键词:
Chrysin;benzimidazole;synthesis;anticancer
摘要:
A series of chrysin benzimidazole derivatives were synthesised and evaluated for their anticancer activity in the search for potential anticancer agents. Among them, compound 18 displayed the most potent anti-proliferative activity against MFC cells with IC50 values of 25.72 ± 3.95 μM. The flow cytometry results displayed that compound 18 induced apoptosis of MFC cells in a dose-dependent manner and caused the cell cycle to be arrested in the G0/G1 phase. Furthermore, the preliminary anticancer activity in vivo was also studied in tumour-bearing mice, and the compound 18 exerted good inhibition effect on tumour growth. These results suggested that compound 18 had good anticancer activity, which could be a potential anticancer agent after further optimisation and evaluation.
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英文
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Apigenin retards atherogenesis by promoting ABCA1-Mediated cholesterol efflux and suppressing inflammation
作者:
Ren, Kun;Jiang, Ting;Zhou, Hui-Fang;Liang, Yin;Zhao, Guo-Jun*
期刊:
Cellular Physiology and Biochemistry ,2018年47(5):2170-2184 ISSN:1015-8987
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.;[Liang, Yin; Ren, Kun; Zhou, Hui-Fang] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang, Peoples R China.
通讯机构:
[Zhao, Guo-Jun] G;Guilin Med Univ, Dept Histol & Embryol, Guilin 541004, Guangxi, Peoples R China.
关键词:
ATP-binding cassette transporter A1;Atherosclerosis;Inflammation;Nuclear factor-kappaB;Toll-like receptor 4
摘要:
Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4', 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE -/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE -/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE -/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation. © 2018 The Author(s). Published by S. Karger AG, Basel.
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英文
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