作者： Zeng, Junfa;Tao, Jun;Xi, Linzhen;Wang, Zuo*;Liu, Lushan*

期刊： INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2021年47(4):1-10 ISSN：1107-3756

通讯作者： Wang, Zuo;Liu, Lushan

作者机构： [Xi, Linzhen; Wang, Zuo; Liu, Lushan; Tao, Jun; Zeng, Junfa] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang Med Coll,Hunan Int Sci & Technol Coopera, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Junfa] Univ South China, Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Wang, Z; Liu, LS] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang Med Coll,Hunan Int Sci & Technol Coopera, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： dye;JC 1 dye;oxidized low density lipoprotein;proprotein convertase 9;reactive oxygen metabolite;small interfering RNA;unclassified drug;UQCRC1 protein;low density lipoprotein;oxidized low density lipoprotein;PCSK9 protein, human;proprotein convertase 9;reactive oxygen metabolite;ubiquinol cytochrome c reductase;Article;concentration response;controlled study;disorders of mitochondrial functions;gene knockdown;gene overexpression;gene silencing;human;human cell;HUVEC cell line;inflammation;membrane potential;PCSK9 gene;protein expression;protein function;pyroptosis;real time polymerase chain reaction;signal transduction;staining;UQCRC1 ROS signaling pathway;vascular endothelial cell;Western blotting;enzyme linked immunosorbent assay;fluorescent antibody technique;genetics;metabolism;mitochondrial membrane potential;physiology;pyroptosis;reverse transcription polymerase chain reaction;umbilical vein endothelial cell;Blotting, Western;Electron Transport Complex III;Enzyme-Linked Immunosorbent Assay;Fluorescent Antibody Technique;Human Umbilical Vein Endothelial Cells;Humans;Lipoproteins, LDL;Membrane Potential, Mitochondrial;Proprotein Convertase 9;Pyroptosis;Reactive Oxygen Species;Reverse Transcriptase Polymerase Chain Reaction

摘要： The present study aimed to explore the role and mechanisms of proprotein convertase subtilisin/kexin type 9 (PcSK9) in the oxidized low-density lipoprotein (oxLdL)-induced pyroptosis of vascular endothelial cells. For this purpose, human umbilical vein endothelial cells (HUVEcs) were incubated with oxLdL (100 µg/ml) for 24 h to induce pyroptosis, which was detected using PI/hoechst33342 double staining. The expression of pyroptosis-associated mole- cules was measured by western blot analysis and RT-qPcR. Reactive oxygen species (ROS) and membrane potential were examined through ROS probe and Jc-1 staining, respectively. PcSK9 and mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQcRc1) protein were knocked down by small interfering RNA (siRNA). PcSK9 was overexpressed by lentivirus. The results revealed that oxLdL induced HUVEc injury, pyroptosis and inflammatory factor release, and upregu- lated the expression of PcSK9 protein in the HUVEcs in a concentration-dependent manner. The silencing of PcSK9 expression with siRNA suppressed the oxLdL-induced damage to HUVEcs, the release of inflammatory substances and the occurrence of pyroptosis. In addition, oxLdL inhibited UQcRc1expression,promotedmitochondrialmembranepoten- tial collapse and damaged mitochondrial function; however, these processes were reversed by the silencing of PcSK9. PcSK9 overexpression induced the pyroptosis of HUVEcs, the generation of ROS and the disorder of mitochondrial func- tion by inhibiting UQcRc1. Therefore, PcSK9 mediates the oxLdL-induced pyroptosis of vascular endothelial cells via the UQcRc1/ROS pathway. © 2021 Spandidos Publications. All rights reserved.

语种： 英文

作者： Tao, Jun;Xia, Linzhen;Cai, Zemin;Liang, Lingli;Chen, Yanjun;...

期刊： DNA AND CELL BIOLOGY,2021年40(1):101-115 ISSN：1044-5498

通讯作者： Meng, Jun;Wang, Zuo

作者机构： [Chen, Yanjun; Tao, Jun; Xia, Linzhen; Liang, Lingli; Wang, Zuo] Univ South China, Hengyang Med Coll, Hunan Int Sci & Technol Cooperat Base Arterioscle, Key Lab Arteriosclerol Hunan Prov,Inst Cardiovasc, Hengyang, Peoples R China.;[Cai, Zemin] Univ South China, Dept Pediat, Affiliated Hosp 1, Hengyang, Peoples R China.;[Meng, Jun] Univ South China, Funct Dept, Affiliated Hosp 1, 61 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;[Wang, Zuo] Univ South China, Heng Yang Med Sch, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Dis, Changsheng Rd, Hengyang City 421001, Peoples R China.

通讯机构： [Meng, Jun; Wang, Zuo] U;Univ South China, Funct Dept, Affiliated Hosp 1, 61 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Heng Yang Med Sch, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Dis, Changsheng Rd, Hengyang City 421001, Peoples R China.

关键词： DNA methylation;DNMTs;TET2;VSMCs;atherosclerosis;endothelia;hydroxymethylation;inflammation;microRNA

摘要： Atherosclerosis (AS) is a chronic inflammatory disease accompanied by complex pathological changes, such as endothelial dysfunction, foam cell formation, and vascular smooth muscle cell proliferation. Many approaches, including regulating AS-related gene expression in the transcriptional or post-transcriptional level, contribute to alleviating AS development. The DNA methylation is a crucial epigenetic modification in regulating cell function by silencing the relative gene expression. The microRNA (miRNA) is a type of noncoding RNA that plays an important role in gene post-transcriptional regulation and disease development. The DNA methylation and the miRNA are important epigenetic factors in AS. However, recent studies have found a mutual regulation between these two factors in AS development. In this study, recent insights into the roles of miRNA and DNA methylation and their interaction in the AS progression are reviewed.

语种： 英文

作者： 张凯;周支香;王佐;曾钧发;龚慧琴

期刊： 中华高血压杂志,2020年28(9):862-867 ISSN：1673-7245

作者机构： 南华大学附属第二医院重症医学科,湖南衡阳421001;南华大学衡阳医学院机能学实验中心;南华大学衡阳医学院心血管疾病研究所;南华大学附属南华医院心血管内科;[张凯; 曾钧发] 南华大学第二附属医院

关键词： 血管内皮细胞;微小RNA-126;肿瘤坏死因子α;炎症反应

摘要： 目的探究微小RNA(miR)-126模拟物在肿瘤坏死因子α(TNF-α)诱导的血管内皮细胞损伤中的作用及可能机制。方法体外培养人脐静脉内皮细胞株ECV304,随机进行如下处理:无特殊处理(对照组);加100 μg/L TNF-α(TNF-α组);转染Lipofectamine 2000+100 μg/L TNF-α(miR-126阴性组);转染miR-126模拟物+100 μg/L TNF-α(miR-126模拟物组),每组设置6个重复样品。实时荧光定量聚合酶链反应(qRT-PCR)法检测细胞中miR-126表达情况;MTT法检测细胞增殖活性;酶联免疫吸附试验法检测细胞中白细胞介素(IL)6、IL-1β水平;流式细胞术检测细胞凋亡情况;免疫印迹法检测细胞中内皮细胞黏附分子1(VCAM-1)、细胞间黏附分子1(ICAM-1)、高迁移率族蛋白B1(HMGB1)表达;双荧光霉素活性实验检测miR-126、HMGB1间的靶向关系。结果与对照组相比, TNF-α组、miR-126阴性组miR-126表达降低,细胞增殖率降低,IL-6、IL-1β水平升高,细胞凋亡率升高,VCAM-1、 ICAM-1、HMGB1蛋白表达升高(均P <0.05);与TNF-α组、miR-126阴性组相比,miR-126模拟组miR-126表达升高,细胞增殖率升高,IL-6、IL-1β水平降低,细胞凋亡率降低,VCAM-1、ICAM-1、HMGB1蛋白表达降低(均P < 0.05)。与miR-126阴性组+HMGB1 3’非编码区(UTR)-携带野生型(Wt)组相比,miR-126模拟物+HMGB1 3’UTR-Wt组荧光素酶活性降低(0.43±0.05比1.06±0.15,P <0.05)。结论miR-126模拟物可能通过降低炎症反应缓解TNF-α诱导的细胞损伤,实现对血管内皮细胞损伤的保护。

语种： 中文

作者： Tao, Jun;Xia, Lin-Zhen;Chen, Jiao-Jiao;Zeng, Jun-Fa;Meng, Jun*;...

期刊： JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH,2020年46(9):1690-1701 ISSN：1341-8076

通讯作者： Meng, Jun;Wu, ShiYuan;Wang, Zuo

作者机构： [Zeng, Jun-Fa; Tao, Jun; Xia, Lin-Zhen; Chen, Jiao-Jiao; Wang, Zuo] Univ South China, Key Lab Arteriosclerol Hunan Prov, Hunan Int Sci & Technol Cooperat Base Arterioscle, Inst Cardiovasc Dis,Hengyang Med Coll, Hengyang, Peoples R China.;[Meng, Jun] Univ South China, Funct Dept, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Wu, ShiYuan] YueYang Maternal Child Med Hlth Hosp, Hunan Prov Innovat Training Base Med Postgrad, Yueyang 416000, Hunan, Peoples R China.;[Wang, Zuo] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Heng Yang Med Sch, Hengyang City 421001, Peoples R China.

通讯机构： [Meng, Jun; Wang, Zuo] U;[Wu, ShiYuan] Y;Univ South China, Funct Dept, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;YueYang Maternal Child Med Hlth Hosp, Hunan Prov Innovat Training Base Med Postgrad, Yueyang 416000, Hunan, Peoples R China.;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Heng Yang Med Sch, Hengyang City 421001, Peoples R China.

关键词： glucose;messenger RNA;placental growth factor;Article;cell invasion;cell migration;cell proliferation;cell viability;controlled study;down regulation;fluorescence microscopy;human;human cell;immunofluorescence;preeclampsia;pregnancy diabetes mellitus;protein analysis;protein expression;protein function;real time polymerase chain reaction;trophoblast;Western blotting

摘要： Aim: This study aimed to investigate the effect of high glucose (HG) level on the proliferation, migration and invasion of trophoblasts and determine the role of placental growth factor (PLGF) in the process. Methods: HTR8-S/Vneo was treated with different concentrations of d-glucose (0, 10, 15, 20, 25 and 30 μM) at different times (0, 6, 12 and 24 h). qRT-PCR and Western blot analyses were used to measure PLGF expression. The protein level of PLGF was measured by immunofluorescence. Cell proliferation was assessed with CCK-8 analysis. Wound healing and transwell assays were used to evaluate cell migration and invasion. Intercellular ROS was detected with DCFH-DA. Results: After d-glucose treatment, the viability decreased in 25 and 30 μM groups. The HG group (25 μM) showed inhibited cell migration and invasion ability. The mRNA and protein levels of PLGF decreased under HG condition. Elevated ROS production was also detected in the HG group. Knocked-down PLGF expression enhanced increased ROS production and decreased cell migration and invasion, which reverted to the original levels after PLGF was overexpressed. Conclusion: High glucose treatment inhibited HTR8-S/Vneo viability, migration and invasion by downregulating PLGF expression. © 2020 Japan Society of Obstetrics and Gynecology

语种： 英文

作者： Luo, Lin;Zeng, Furen;Xie, Jiangbo;Fan, Jialong;Xiao, Shengying;...

期刊： JOURNAL OF MATERIALS CHEMISTRY B,2020年8(18):4080-4092 ISSN：2050-750X

通讯作者： Xie, Hailong;Liu, Bin

作者机构： [Xie, Hailong; Luo, Lin] Univ South China, Sch Med, Inst Canc Res, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.;[Xiao, Shengying; Zeng, Furen] Hunan Prov Peoples Hosp, Oncol Dept 2, Changsha 410082, Hunan, Peoples R China.;[Xie, Jiangbo] Cent South Univ, Xiangya Sch Med, Affiliated Canc Hosp, Hunan Canc Hosp, Changsha 410013, Hunan, Peoples R China.;[Liu, Bin; Fan, Jialong; Wang, Zhou] Hunan Univ, Coll Biol, Changsha 410082, Hunan, Peoples R China.

通讯机构： [Xie, Hailong] U;[Liu, Bin] H;Univ South China, Sch Med, Inst Canc Res, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.;Hunan Univ, Coll Biol, Changsha 410082, Hunan, Peoples R China.

关键词： Biomimetics;Blood;Chemotherapy;Controlled drug delivery;Cytology;Diseases;Drug interactions;Graphene;Lanthanum compounds;Mammals;Photosensitizers;Semiconductor quantum dots;Tumors;Biochemical parameters;Blood circulation;Cervical cancers;Drug transportations;Indocyanine Green;Photothermal therapy;Strong interaction;Targeted delivery systems;Targeted drug delivery;antineoplastic antibiotic;biomimetic material;doxorubicin;nanoparticle;photosensitizing agent;animal;apoptosis;Bagg albino mouse;cell proliferation;cell survival;chemistry;diagnostic imaging;drug effect;erythrocyte membrane;experimental neoplasm;female;fluorescence imaging;HeLa cell line;human;mouse;particle size;photochemotherapy;surface property;uterine cervix tumor;Animals;Antibiotics, Antineoplastic;Apoptosis;Biomimetic Materials;Cell Proliferation;Cell Survival;Doxorubicin;Erythrocyte Membrane;Female;HeLa Cells;Humans;Mice;Mice, Inbred BALB C;Nanoparticles;Neoplasms, Experimental;Optical Imaging;Particle Size;Photochemotherapy;Photosensitizing Agents;Surface Properties;Uterine Cervical Neoplasms

摘要： Due to the untargeted release of chemical drugs, the efficacy of chemotherapy is often compromised along with serious side effects on patients. Recently, the development of targeted delivery systems using nanomaterials as carriers has provided more alternatives for chemical drug transportation. In this study, we developed a novel targeted nanocomplex of GOQD-ICG-DOX@RBCM-FA NPs (GID@RF NPs). First, PEG modified graphene oxide quantum dots (GOQDs) were used to co-load the photosensitizer of indocyanine green (ICG) and DOX, to form GOQD-ICG-DOX NPs (GID NPs). Then, the red blood cell membrane (RBCM) was applied for GID NP camouflage to avoid immune clearance. Finally, folic acid was used to endow the targeting ability of GID@RF NPs. MTT assay showed that the survival rate of HeLa cells reduced by 71% after treatment with GID@RF NPs and laser irradiation. Meanwhile, membrane camouflage significantly prolonged the blood circulation time and enhanced the immune evading ability of GID NPs. Moreover, the drug accumulation at tumor sites was significantly improved through the strong interaction between FA and FA receptor highly expressed on the tumor cells. In vivo assay demonstrated the strongest tumor growth inhibition ability of the combinational chemo/photothermal therapy. H&E analysis indicated no significant abnormalities in the major organs of mice undergoing GID@RF NPs treatment. The level of blood and biochemical parameters remained stable as compared to the control. In summary, this combinational therapy system provides a safe, rapid and effective alternative for the treatment of cervical cancer in the future. © 2020 The Royal Society of Chemistry.

语种： 英文

作者： Lin Xiaolong;Guo Dongmin;Liu, Mihua;Wang Zuo;Hu Huijun;...

期刊： Journal of Cellular and Molecular Medicine,2020年24(9):4992-5006 ISSN：1582-1838

通讯作者： Zeng Zhaolin

作者机构： [Lin Jun; Lin Wensheng; Hu Huijun; Hu XueMei; Tan Qiufen; Lin Xiaolong; Pan Yuping] Guangzhou Med Univ, Huizhou Third Peoples Hosp, Dept Pathol, Huizhou City, Peoples R China.;[Wang Zuo; Zeng Zhaolin; Guo Dongmin] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang City, Peoples R China.;[Liu, Mihua] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis, Ctr Lipid Res, Chongqing, Peoples R China.;[Liu, Mihua] Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, Minist Educ,Inst Viral Hepatitis, Chongqing, Peoples R China.;[Liu, Mihua] Gannan Med Univ, Dept Lab Med, Affiliated Hosp 1, Ganzhou City, Peoples R China.

通讯机构： [Zeng Zhaolin] C;Chongqing Med Univ, Nanchuan Peoples Hosp, Dept Cardiol, Chongqing 408400, Peoples R China.

关键词： cholesterol oleate;complementary DNA;fat droplet;fibroblast growth factor 21;high density lipoprotein cholesterol;lentivirus vector;low density lipoprotein cholesterol;receptor for activated C kinase 1;short hairpin RNA;small interfering RNA;triacylglycerol;AMPK signaling;animal cell;animal experiment;animal model;animal tissue;Article;atherosclerosis;autophagy (cellular);blood sampling;cell stress;cholesterol transport;controlled study;genetic transfection;high performance liquid chromatography;lipid blood level;lipid degradation;lipid diet;male;mouse;nonhuman;phase contrast microscopy;plasmid;priority journal;real time polymerase chain reaction;signal transduction;transmission electron microscopy;upregulation;Western blotting

摘要： Fibroblast growth factor 21 (FGF21) acts as an anti-atherosclerotic agent. However, the specific mechanisms governing this regulatory activity are unclear. Autophagy is a highly conserved cell stress response which regulates atherosclerosis (AS) by reducing lipid droplet degradation in foam cells. We sought to assess whether FGF21 could inhibit AS by regulating cholesterol metabolism in foam cells via autophagy and to elucidate the underlying molecular mechanisms. In this study, ApoE−/− mice were fed a high-fat diet (HFD) with or without FGF21 and FGF21+3-Methyladenine (3MA) for 12weeks. Our results showed that FGF21 inhibited AS in HFD-fed ApoE−/− mice, which was reversed by 3MA treatment. Moreover, FGF21 increased plaque RACK1 and autophagy-related protein (LC3 and beclin-1) expression in ApoE−/− mice, thus preventing AS. However, these proteins were inhibited by LV-RACK1 shRNA injection. Foam cell development is a crucial determinant of AS, and cholesterol efflux from foam cells represents an important defensive measure of AS. In this study, foam cells were treated with FGF21 for 24hours after a pre-treatment with 3MA, ATG5 siRNA or RACK1 siRNA. Our results indicated that FGF21-induced autophagy promoted cholesterol efflux to reduce cholesterol accumulation in foam cells by up-regulating RACK1 expression. Interestingly, immunoprecipitation results showed that RACK1 was able to activate AMPK and interact with ATG5. Taken together, our results indicated that FGF21 induces autophagy to promote cholesterol efflux and reduce cholesterol accumulation in foam cells through RACK1-mediated AMPK activation and ATG5 interaction. These results provided new insights into the molecular mechanisms of FGF21 in the treatment of AS. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

语种： 英文

作者： Ma, Xiaofeng;Jiang, Zhisheng*;Wang, Zuo;Zhang, Zhuhua

期刊： JOURNAL OF CELLULAR PHYSIOLOGY,2020年235(3):2102-2112 ISSN：0021-9541

通讯作者： Jiang, Zhisheng

作者机构： [Ma, Xiaofeng; Jiang, Zhisheng; Wang, Zuo] Univ South China, Inst Cardiovasc Dis, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;[Ma, Xiaofeng; Jiang, Zhisheng; Wang, Zuo] Univ South China, Key Lab Arteriosclerol Hunan, Hengyang, Hunan, Peoples R China.;[Ma, Xiaofeng] Univ South China, Affiliated Nanhua Hosp, Dept Cardiol, Hengyang, Hunan, Peoples R China.;[Zhang, Zhuhua] Beijing Hosp Tradit Chinese Med, Dept Cardiol, Beijing, Peoples R China.;[Jiang, Zhisheng] Univ South China, Key Lab Arteriosclerol Hunan Prov, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Jiang, Zhisheng] U;Univ South China, Inst Cardiovasc Dis, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Key Lab Arteriosclerol Hunan Prov, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： cystathionine gamma lyase;DNA (cytosine 5) methyltransferase 1;DNA methyltransferase 3A;DNA methyltransferase 3B;homocysteine;hydrogen sulfide;interleukin 1beta;messenger RNA;metformin;methionine;tumor necrosis factor;cystathionine gamma lyase;hydrogen sulfide;interleukin 1beta;metformin;tumor necrosis factor;amino acid blood level;animal experiment;animal model;animal tissue;Article;atherosclerosis;bisulfite sequencing;C57BL 6 mouse;controlled study;cytokine production;disease severity;DNA methylation;drug effect;inflammation;luciferase assay;male;mouse;mRNA expression level;nonhuman;peritoneum macrophage;priority journal;promoter region;protein expression level;RAW 264.7 cell line;synthesis;THP-1 cell line;animal;atherosclerosis;C57BL mouse;cell line;metabolism;signal transduction;Animals;Atherosclerosis;Cell Line;Cystathionine gamma-Lyase;DNA Methylation;Hydrogen Sulfide;Interleukin-1beta;Macrophages, Peritoneal;Male;Metformin;Mice;Mice, Inbred C57BL;Promoter Regions, Genetic;RAW 264.7 Cells;Signal Transduction;Tumor Necrosis Factor-alpha

摘要： The therapeutic effect of metformin (Met) on atherosclerosis was studied here. Effects of methionine and Met on the induction of inflammatory response and H2S expression in peritoneal macrophages were evaluated. Enzyme-linked immunosorbent assay, immunohistochemistry assay, western blot, and quantitative reverse transcription polymerase chain reaction were conducted to observe the levels of cystathionine γ-lyase (CSE), DNA methyltransferases 1 (DNMT1), DNMT3a, DNMT3b, tumor necrosis factor (TNF- α), interleukin 1b (IL-1β), and hydrogen sulfide (H 2S). Luciferase and bisulfite sequencing assays were also utilized to evaluate the CSE promoter activity as well as the methylation status of CSE in transfected cells. Methionine significantly elevated Hcy, TNF-a, H 2S, and IL-1β expression while decreasing the level of CSE in C57BL/6 mice. In contrary, co-treatment with Methionine and Met reduced the detrimental effect of Methionine. Homocysteine (Hcy) decreased H 2S expression while promoting the synthesis of IL-1β and TNF-α in THP-1 and raw264.7 cells. Treatment of THP-1 and raw264.7 cells with methionine and Met reduced the activity of methionine in dose dependently. Moreover, Hcy increased the expression of DNMT and elevated the level of methylation in the CSE promoter, whereas the co-treatment with methionine and Met attenuated the effects of Hcy. Methionine significantly decreased plasma level of CSE while increasing the severity of inflammatory responses and plasma level of Hcy, which in turn suppressed H 2S synthesis and enhanced DNA hypermethylation of CSE promoter to promote the pathogenesis of atherosclerosis. In contrary, co-treatment with methionine and Met reduced the detrimental effect of methionine. © 2019 Wiley Periodicals, Inc.

语种： 英文

作者： Zeng Zhaolin;Chen Jiaojiao;Wu Peng;Liu Yami;Zhang Tingting;...

期刊： JOURNAL OF CELLULAR PHYSIOLOGY,2019年234(5):7475-7491 ISSN：0021-9541

通讯作者： Wang Zuo

作者机构： [Wang Zuo; Wei Dangheng; Zeng Zhaolin; Liu Yami; Tao Jun; Chen Jiaojiao; Wu Peng; Jiang Zhisheng] Univ South China, Inst Cardiovas Dis, Key Lab Atherosclerol Hunan Prov, Hengyang, Peoples R China.;[Wang Zuo; Wu Shiyuan; Wei Dangheng; Wu Peng; Xiao Jinyan] Univ South China, Cooperat Innovat Base, YueYang Maternal Child Med Hlth Hosp, Hengyang, Hunan, Peoples R China.;[Zhang Tingting] Sichuan Univ, West China Sch Med, School Rehabil Sci, Chengdu, Sichuan, Peoples R China.;[Wang Zuo] Univ South China, Cooperat Innovat Base, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Wang Zuo] U;Univ South China, Cooperat Innovat Base, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.

关键词： beta actin;cryopyrin;immunoglobulin enhancer binding protein;inflammasome;interleukin 18;interleukin 1beta;interleukin 1beta converting enzyme;microRNA;microRNA 125a;oxidized low density lipoprotein;procaspase 1;protein;reactive oxygen metabolite;tet2 protein;unclassified drug;cytokine;DNA binding protein;inflammasome;low density lipoprotein;microRNA;MIRN125 microRNA, human;oncoprotein;oxidized low density lipoprotein;TET2 protein, human;Article;atherosclerosis;controlled study;cytokine release;DNA methylation;enzyme linked immunosorbent assay;human;human cell;HUVEC cell line;mitochondrial membrane potential;priority journal;protein expression;pyroptosis;real time polymerase chain reaction;signal transduction;vascular endothelial cell;Western blotting;apoptosis;cell culture;endothelium cell;metabolism;mitochondrion;physiology;pyroptosis;Apoptosis;Atherosclerosis;Cells, Cultured;Cytokines;DNA Methylation;DNA-Binding Proteins;Endothelial Cells;Humans;Inflammasomes;Lipoproteins, LDL;MicroRNAs;Mitochondria;Proto-Oncogene Proteins;Pyroptosis;Reactive Oxygen Species

摘要： Pyroptosis participates in the formation and development of atherosclerosis (As) by promoting inflammatory factor release and is closely related to the stability of atherosclerotic plaque. MicroRNAs can regulate the expression of target genes at the posttranscriptional level. Previous studies have shown that miR-125a-5p increases in hyperlipidemic–hyperglycemic conditions and is involved in apoptosis, but its specific role in pyroptosis and As remains unclear. We propose that miR-125a-5p may be implicated in oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cells (VECs) pyroptosis and therefore conducted the current study. We observed that miR-125a-5p can inhibit tet methylcytosine dioxygenase 2 (TET2) expression at the posttranscription level, resulting in abnormal DNA methylation, mitochondrial dysfunction, and increased reactive oxygen species production, activated nuclear factor-κB that induces activation of inflammasome and maturation, release of proinflammatory cytokines interleukin (IL)-1β and IL-18, and pyroptosis. Given the role of VECs in vascular physiology, oxLDL-induced VEC pyroptosis may promote the development of As. Our current study reveals a novel pathway associated with pyroptosis program regulation, which comprises miR-125a-5p and TET2 in VECs. Modulation of their expression levels may serve as a potential target for therapeutic strategies of As. © 2018 Wiley Periodicals, Inc.

语种： 英文

作者： Peng, Wenxi;Cai, Guoding;Xia, Yiping;Chen, Jinna;Wu, Peng;...

期刊： DNA AND CELL BIOLOGY,2019年38(7):597-606 ISSN：1044-5498

通讯作者： Li, Guohua;Wei, Dangheng

作者机构： [Li, GH; Wei, Dangheng; Chen, Jinna; Li, Guohua; Peng, Wenxi; Wu, Peng; Wang, Zuo] Univ South China, Key Lab Arteriosclerol Hunan Prov, Hunan Int Sci & Technol Cooperat Base Arterioscle, Inst Cardiovasc Dis,Hengyang Med Sch, Hengyang 42001, Hunan, Peoples R China.;[Cai, Guoding] Univ South China, Affiliated Hosp 1, Dept Cardiothorac Surg, Hengyang, Peoples R China.;[Xia, Yiping] Univ South China Nursing, Hengyang, Peoples R China.

通讯机构： [Li, GH; Wei, DH] U;Univ South China, Key Lab Arteriosclerol Hunan Prov, Hunan Int Sci & Technol Cooperat Base Arterioscle, Inst Cardiovasc Dis,Hengyang Med Sch, Hengyang 42001, Hunan, Peoples R China.

关键词： atherosclerosis;endothelial cell;macrophage;mitochondrial dysfunction;smooth muscle cell

摘要： Mitochondria are highly dynamic organelles beyond powerhouses of a cell. These components also play important roles in cell homeostasis by regulating cell function and phenotypic modulation. Atherosclerosis is the leading cause of morbidity and mortality in developed and developing countries. Mitochondrial dysfunction has been increasingly associated with the initiation and progression of atherosclerosis by elevating the production of reactive oxygen species and mitochondrial oxidative stress damage, mitochondrial dynamics dysfunction, and energy supply. In this review, we describe the progression of the link between mitochondrial dysfunction and atherosclerosis and its potential regulation mechanisms.

语种： 英文

作者： Zeng Zhaolin;Li Guohua;Wu Shiyuan*;Wang Zuo*

期刊： Cell Proliferation,2019年52(2):e12563 ISSN：0960-7722

通讯作者： Wu Shiyuan;Wang Zuo

作者机构： [Wu Shiyuan; Wang Zuo; Zeng Zhaolin] Yueyang Maternal & Child Hlth Hosp, Yueyang, Peoples R China.;[Wang Zuo; Zeng Zhaolin; Li Guohua] Univ South China, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang, Peoples R China.

通讯机构： [Wu, SY; Wang, Z] Y;Yueyang Maternal & Child Hlth Hosp, Yueyang, Peoples R China.

关键词： atherosclerosis;cardiovascular disease;inflammation;pyroptosis

摘要： Cardiac function is determined by the dynamic equilibrium of various cell types and the extracellular matrix that composes the heart. Cardiovascular diseases (CVDs), especially atherosclerosis and myocardial infarction, are often accompanied by cell death and acute/chronic inflammatory reactions. Caspase-dependent pyroptosis is characterized by the activation of pathways leading to the activation of NOD-like receptors, especially the NLRP3 inflammasome and its downstream effector inflammatory factors interleukin (IL)-1beta and IL-18. Many studies in the past decade have investigated the role of pyroptosis in CVDs. The findings of these studies have led to the development of therapeutic approaches based on the regulation of pyroptosis, and some of these approaches are in clinical trials. This review summarizes the molecular mechanisms, regulation and cellular effects of pyroptosis briefly and then discusses the current pyroptosis studies in CVD research.

语种： 英文

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： <jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>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.</jats:p></jats:sec>

语种： 英文

作者： Guo, Feng;Yang, Li;Luo, Jingfei;Quan, Haiyan;Wang, Zhen;...

期刊： JOURNAL OF CELLULAR PHYSIOLOGY,2018年233(10):6910-6920 ISSN：0021-9541

通讯作者： Zhang, Liang;Qin, Xuping

作者机构： [Luo, Jingfei; Wang, Zhen; Li, Jie; Qin, Xuping; Yang, Li; Jiang, Zhisheng; Guo, Feng; Quan, Haiyan; Peng, Hongyan; Hong, Chenliang] Univ South China, Inst Pharm & Pharmacol, Key Lab Arteriosclerol Hunan Prov, Hengyang, Peoples R China.;[Zhang, Liang] Palmer Coll Chiropract, Palmer Lab Cell & Mol Biol, Port Orange, FL 32129 USA.;[Qin, Xuping] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.

通讯机构： [Zhang, Liang] P;[Qin, Xuping] U;Palmer Coll Chiropract, Palmer Lab Cell & Mol Biol, Port Orange, FL 32129 USA.;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.

关键词： calcitonin gene related peptide;caveolin 1;cycline;messenger RNA;mitogen activated protein kinase 3;receptor component protein;receptor protein;small interfering RNA;unclassified drug;calcitonin gene related peptide;caveolin 1;cycline;mitogen activated protein kinase;mitogen activated protein kinase 3;animal cell;Article;caveola;cell growth;cell proliferation;cell viability;controlled study;gene silencing;mechanotransduction;membrane microdomain;mouse;nonhuman;pressure;priority journal;protein expression;signal transduction;static pressure;vascular smooth muscle cell;animal;cell culture;cell line;cell proliferation;drug effect;MAPK signaling;metabolism;physiology;smooth muscle cell;vascular smooth muscle;Animals;Calcitonin Gene-Related Peptide;Caveolin 1;Cell Line;Cell Proliferation;Cells, Cultured;MAP Kinase Signaling System;Mice;Mitogen-Activated Protein Kinase 3;Mitogen-Activated Protein Kinases;Muscle, Smooth, Vascular;Myocytes, Smooth Muscle;Proliferating Cell Nuclear Antigen

摘要： Previous study suggested that the receptor component protein (RCP), one of the components of calcitonin gene-related peptide (CGRP) receptor, plays a multiple role in the cellular signal transduction. The study was designed to investigate whether or not the RCP involved in the regulation of caveolin-1/extracellular signal-regulated kinases-1 and -2 (ERK1/2) signal pathway in the vascular smooth muscle cells (VSMCs) proliferation induced by static pressure. Mouse-derived VSMCs line A10 (A10 VSMCs) was served as project in this experiment. Results showed that the A10 VSMCs viability and proliferating cell nuclear antigen (PCNA) expression which were increased by static pressure were inhibited by pretreatment of CGRP. In like manner, the expressions of the decreased-caveolin-1 and the increased-phosphorylated ERK1/2 (p-ERK1/2) induced by static pressure were significantly reversed by pretreatment of CGRP, respectively. Meanwhile, the expression of RCP was up-regulated by the static pressure. Silence of RCP gene with the small interrupt RNA (siRNA) not only significantly increased A10 VSMC proliferation but also increased the expression of p-ERK1/2 in response to static pressure. When treatment of A10 VSMCs with 120-mmHg static pressure for different time, however, the protein band of caveolin-1 and RCP was the least at time point of 10 min, but the p-ERK1/2 expression was the most maximum. In conclusion, RCP maybe involved in the static pressure-induced A10 VSMCs proliferation by regulation of caveolin-1/ERK1/2 signal pathway. © 2018 Wiley Periodicals, Inc.

语种： 英文

作者： 曾召林;陈姣姣;马小峰;王佐

期刊： 生命的化学,2018年38(3):464-472 ISSN：1000-1336

作者机构： 南华大学心血管疾病研究所, 动脉硬化学湖南省重点实验室, 衡阳, 421001;南华大学附属南华医院, 衡阳, 421002;[曾召林; 陈姣姣; 王佐] 南华大学心血管疾病研究所, 动脉硬化学湖南省重点实验室, 衡阳, 421001;[马小峰] 南华大学附属南华医院, 衡阳, 421002

关键词： 动脉粥样硬化;细胞焦亡;炎症;细胞死亡

摘要： 动脉粥样硬化是脂代谢紊乱和炎症共同作用的结果,在动脉粥样硬化中可以观察到细胞死亡,并且在动脉粥样硬化病变的发生发展中起重要作用.炎症是先天免疫的主要反应,被认为是动脉粥样硬化的启动者和驱动者.尽管大量研究揭示了凋亡、自噬和细胞坏死在动脉粥样硬化中的作用,但参与动脉粥样硬化的细胞死亡机制仍然在很大程度上是未知的.细胞焦亡是新近发现的一种程序性细胞死亡方式,其通过促使炎性因子释放而参与动脉粥样硬化的形成与进展,并与斑块的稳定性密切相关.本文就细胞焦亡在动脉粥样硬化中的作用作一综述.

语种： 中文

作者： Liu, Yami;Peng, Wen;Qu, Kai;Lin, Xiaolong;Zeng, Zhaolin;...

期刊： DNA AND CELL BIOLOGY,2018年37(6):517-523 ISSN：1044-5498

通讯作者： Wang, Zuo

作者机构： [Chen, Jiaojiao; Liu, Yami; Zeng, Zhaolin; Wang, Zuo; Wei, Dangheng] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Peng, Wen] Univ South China, Affiliated Hosp 1, Dept Spine Surg, Hengyang, Hunan, Peoples R China.;[Qu, Kai] Chongqing Univ, Coll Bioengn, Chongqing, Peoples R China.;[Lin, Xiaolong] Third Peoples Hosp Huizhou, Dept Pathol, Huizhou, Peoples R China.

通讯机构： [Wang, Zuo] U;Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.

关键词： atherosclerosis;DNA demethylation;inflammation;TET2

摘要： Atherosclerosis is the underlying cause of cardio-cerebrovascular disease. However, the mechanisms of atherosclerosis are still unclear. The modification of DNA methylation has an important role in atherosclerosis development. As a member of the Ten-eleven translocation (TET) family, TET methylcytosine dioxygenase 2 (TET2) can modify DNA methylation by catalyzing 5-methylcytosine to 5-hydroxymethylcytosine and mediate DNA demethylation. Recent findings suggest that TET2 is related to the phenotype transformation of vascular smooth muscle cells, endothelial dysfunction, and inflammation of macrophage, the key factors of atherosclerosis. Therefore, TET2 may be a potential target for atherosclerosis treatment. This review will elaborate the recent findings that suggest the role of TET2 in atherosclerosis.

语种： 英文

作者： Zeng Zhao-Lin;Chen Jiao-Jiao;Wang Zuo*

期刊： 生物化学与生物物理进展,2018年45(11):1115-1125 ISSN：1000-3282

通讯作者： Wang Zuo

作者机构： [Zeng Zhao-Lin; Wang Zuo; Chen Jiao-Jiao] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.

通讯机构： [Wang Zuo] U;Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.

关键词： 自噬;动脉粥样硬化;心血管疾病

摘要： 自噬作为一种进化上高度保守的细胞降解途径,其调节异常与心血管疾病的发生、发展密切相关.研究显示,在心血管系统中,基础水平自噬对维持心肌正常收缩和传导至关重要,而在缺血/再灌注损伤和心力衰竭等心血管病理状态下,自噬水平明显增强.细胞自噬是一种多基因参与的复杂过程,近年来越来越多的证据表明,microRNAs（miRNAs）在心血管系统发育、正常生理功能维持以及不同心血管疾病（cardiovascular disease,CVDs）自噬中具有重要调节作用.本文通过对miRNAs与CVDs自噬调节方面的进展进行归纳,针对miRNAs对CVDs自噬的潜在机制进行总结,望为心血管疾病的诊断和治疗提供新的方向.

语种： 中文

作者： Zhang, Yunsheng;Li, Fang;Liu, Luogen;Jiang, Hongtao;Jiang, Xiaorong;...

期刊： Life Sciences,2018年207:451-460 ISSN：0024-3205

通讯作者： Wang, Yi

作者机构： [Wang, Yi; Zhang, Yunsheng; Ge, Xin; Liu, Luogen] Univ South China, Affiliated Hosp 2, Clin Res Inst, 35 Jiefang Ave, Hengyang 421001, Hunan, Peoples R China.;[Li, Fang] Hunan Polytech Environm & Biol, Coll Nursing, Hengyang 421005, Peoples R China.;[Jiang, Hongtao] Univ South China, Affiliated Hosp 2, Dept Urol, Hengyang 421001, Peoples R China.;[Wang, Zhenggen; Zhang, Li; Jiang, Xiaorong] Univ South China, Affiliated Hosp 2, Dept Gastroenterol, Hengyang 421001, Peoples R China.;[Cao, Jingsong] Univ South China, Med Coll, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Peoples R China.

通讯机构： [Wang, Yi] U;Univ South China, Affiliated Hosp 2, Clin Res Inst, 35 Jiefang Ave, Hengyang 421001, Hunan, Peoples R China.

关键词： autophagy related protein;autophagy related protein 5;autophagy related protein 7;mammalian target of rapamycin;protein ATG3;protein kinase B;salinomycin;short hairpin RNA;unclassified drug;AKT1 protein, human;antineoplastic agent;ATG3 protein, human;autophagy related protein;green fluorescent protein;MTOR protein, human;protein kinase B;pyran derivative;salinomycin;target of rapamycin kinase;ubiquitin conjugating enzyme;Akt/mTOR signaling;antineoplastic activity;apoptosis;Article;ATG3 gene;ATG5 gene;ATG7 gene;autophagy;controlled study;down regulation;drug mechanism;drug screening;electron microscopy;flow cytometry;gene expression;gene silencing;human;human cell;immunofluorescence;PC 3 cell line;prostate cancer cell line;Western blotting;cell proliferation;drug effect;male;metabolism;prostate tumor;signal transduction;tumor cell line;Antineoplastic Agents;Apoptosis;Autophagy;Autophagy-Related Proteins;Cell Line, Tumor;Cell Proliferation;Green Fluorescent Proteins;Humans;Male;Prostatic Neoplasms;Proto-Oncogene Proteins c-akt;Pyrans;Signal Transduction;TOR Serine-Threonine Kinases;Ubiquitin-Conjugating Enzymes

摘要： Aims: This study evaluated the mechanism by which salinomycin-induced autophagy blocks apoptosis in PC-3 prostate cancer cells. Main methods: The anti-cancer effects of salinomycin in PC-3 cells were confirmed by flow cytometry, JC-1 staining and western blotting. Then, the autophagic effects were measured by western blotting, GFP-LC3 puncta formation assay, immunofluorescence staining and electron microscopy. Furthermore, we used lentivirus-mediated shRNA to silence ATG3, ATG5 and ATG7 expression in PC-3 cells to investigate the regulatory mechanisms of salinomycin-induced autophagy. Key findings: Salinomycin could induce apoptosis and autophagy in PC-3 cells. Interestingly, autophagy inhibition could enhance salinomycin-induced apoptosis. We further showed that ATG3, a known critical regulator of autophagy, was downregulated and involved in the inhibition of apoptosis by salinomycin-induced autophagy via the AKT/mTOR signaling axis. Significance: Our data indicated that salinomycin-induced autophagy blocks apoptosis via the ATG3/AKT/mTOR signaling axis in PC-3 cells, which provides new clues for the mechanisms of underlying the anti-cancer effects of salinomycin. © 2018

语种： 英文

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.

语种： 英文

作者： 钟丽园;彭田红;高安博;万炜;陈熙;...

期刊： 中国动脉硬化杂志,2018年26(2):139-143 ISSN：1007-3949

作者机构： 南华大学医学院应用解剖与生殖医学研究所,湖南省衡阳市,421001;南华大学医学院心血管疾病研究所,湖南省衡阳市,421001;[王莉; 万炜; 唐志晗; 吕运成; 王佐; 彭田红; 高安博; 钟丽园; 陈熙; 欧阳宇甲] 南华大学

关键词： 巨噬细胞;脂质蓄积;氧化型低密度脂蛋白;动脉粥样硬化

摘要： 目的 探讨分拣受体Sortilin对THP-1巨噬细胞内脂质代谢的影响.方法 用氧化型低密度脂蛋白(ox-LDL)孵育THP-1巨噬细胞.Western blot检测荷脂后THP-1巨噬细胞中Sortilin表达变化;THP-1巨噬细胞Sortilin高表达和沉默后,液体闪烁计数仪检测胞内胆固醇流出,高效液相色谱法检测细胞内脂质含量,油红O染色观察胞内脂滴情况.结果 THP-1巨噬细胞Sortilin表达呈ox-LDL剂量和时间依赖性增加;以50 mg/L ox-LDL处理24 h后THP-1巨噬细胞Sortilin表达水平达到高峰.与对照组相比,Sortilin过表达后巨噬细胞胆固醇流出减少,胞内脂质含量增加且脂滴明显增多,而Sortilin沉默后则刚好出现相反的结果.结论 Sortilin抑制巨噬细胞内胆固醇流出,促进胞内脂质蓄积.

语种： 中文

作者： Wang, Zigui;Wu, Peng;He, Zhilong;He, Hongyan;Rong, Weifeng;...

期刊： JOURNAL OF MATERIALS CHEMISTRY B,2017年5(36):7591-7597 ISSN：2050-750X

通讯作者： Zhou, Dongfang;Li, Jizhen

作者机构： [Huang, Yubin; Zhou, Dongfang; Wang, Zigui; He, Hongyan] Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Jilin, Peoples R China.;[Wang, Zigui] Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China.;[Li, Jizhen; Wu, Peng] Jilin Univ, Coll Chem, Changchun 130023, Jilin, Peoples R China.;[He, Zhilong] South China Univ, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Peoples R China.;[Rong, Weifeng] Shandong Inst Nonmetall Mat, Jinan 250031, Shandong, Peoples R China.

通讯机构： [Zhou, Dongfang] C;[Li, Jizhen] J;Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Jilin, Peoples R China.;Jilin Univ, Coll Chem, Changchun 130023, Jilin, Peoples R China.

关键词： Chemotherapy;Diseases;Nanoparticles;Silica;Tumors;Active targeting;Circulation time;Hepatocellular carcinoma;Lactobionic acid;Liver targeting;Mesoporous silica nanoparticles;Therapeutic efficacy;Therapeutic strategy;Platinum

摘要： Chemotherapy is the most common therapeutic strategy for the treatment of unresectable hepatocellular carcinoma. However, the therapeutic efficacy is limited by the low delivery efficiency of chemotherapeutics and severe toxicity towards healthy tissues. To address these challenges, active-targeting mesoporous silica nanoparticles conjugating a platinum(iv) prodrug were developed as a therapy for liver cancer for the first time. Taking advantage of liver-targeting lactobionic acid (LA), the smart nano-carriers not only enhanced the circulation time, but also effectively concentrated at the liver tumor site. Moreover, the conjugated platinum(iv) could be reduced in the reductive tumor environment for the fast release of active platinum(ii). The novel targeting and self-responsive drug-loading system offers new prospects for liver cancer chemotherapy. © 2017 The Royal Society of Chemistry.

语种： 英文

作者： Ma, Xiaofeng;Liu, Yami;Tan, Yanmei;Qu, Kai;He, Xinglan;...

期刊： Lipids in Health and Disease,2017年16(1):1-10 ISSN：1476-511X

通讯作者： Wang, Zuo;Zhang, Hai

作者机构： [Ma, Xiaofeng] Univ South China, Dept Cardiol, Affiliated Nanhua Hosp, Hengyang 421001, Peoples R China.;[Qu, Kai; Ma, Xiaofeng; Liu, Yami; Wang, Zuo] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Human Prov, Hengyang 421001, Peoples R China.;[Tan, Yanmei] Changde Vocat Tech Coll, Dept Pathol, Changde 415000, Peoples R China.;[He, Xinglan] Women & Children Healthcare Hosp Zhu Zhou, Zhuzhou 412000, Peoples R China.;[Zhang, Hai] Univ South China, Dept Pathol, Affiliated Hosp 1, Hengyang 421001, Peoples R China.

通讯机构： [Wang, Zuo; Zhang, Hai] U;Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Human Prov, Hengyang 421001, Peoples R China.;Univ South China, Dept Pathol, Affiliated Hosp 1, Hengyang 421001, Peoples R China.

关键词： Lipoprotein(a);Apolipoprotein(a);Diallyl disulfide;Extracellular regulated protein kinases;Mitogen-activated protein kinases;HepG2 cell

摘要： Background: Lipoprotein(a) [LP(a)] is implicated as a common and independent risk factor for cardiovascular diseases. The therapeutic options currently available for reducing plasma LP(a) concentrations are limited. Diallyl disulphide (DADS), the main component of garlic, regulates lipid metabolism in hepatocytes and adipocytes through ERK1/2 signalling. This study aimed to assess the effect of DADS on apolipoprotein(a) [apo(a)] in HepG2 cells. We also determined the effects of DADS on apo(a) expression and secretion in HepG2 cells as well as the underlying mechanisms. Methods: We examined the role of DADS on apo(a) expression in HepG2 cells by treating cell with different concentrations of DADS (10, 20, 40 and 80 μg/mL) for 24 h or treating cells with 40 μg/mL DADS for 0, 6, 12, 24 and 48 h. Then we used quantitative real-time PCR to analysis apo(a) mRNA levels, used Western blot to analysis apo(a) protein levels and used enzyme-linked immunosorbent assay to test apo(a) secreted levels. To farther determined the role of DADS, we applied Transfection of small interfering RNA to knockdown ELK-1levels and applied PD98059, a specific inhibitor of ERK1/2, to block ERK1/2 signal. Results: The results show DADS inhibited apo(a) at both the mRNA and protein levels in HepG2 cells in a dose-dependent manner. DADS-mediated inhibition of apoa(a) expression in HepG2 cells was attenuated when the cells were cultured in medium containing PD98059 (ERK1/2 inhibitor) or were transfected with siRNAs against MEK1 or ELK-1. Overexpression of apo(a) yielded similar results. Conclusions: This study reveals that DADS can downregulate apo(a) expression in a dose-dependent manner via the MEK-ERK12-ELK-1 pathway. © 2017 The Author(s).

语种： 英文