作者机构：
[Tang, Chao-ke; Liao, Duan-fang; Sun, Shao-wei] Univ S China, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Chen, Lin-xi; Liao, Duan-fang; Lei, Xiao-yong; Tuo, Qin-hui; Sun, Shao-wei; Zu, Xu-yu] Univ S China, Inst Pharm & Pharmacol, Prov Key Lab Pharmacoprotom, Hengyang 421001, Peoples R China.;[Liao, Duan-fang] Hunan Univ Chinese Med, Dept Tradit Chinese Diagnost, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Li, Kai] Suzhou Univ, Mol Med Ctr, Suzhou 215004, Peoples R China.;[Li, Kai] Suzhou Univ, Affiliated Hosp 2, Suzhou 215004, Peoples R China.
通讯机构：
[Tang, Chao-ke] Univ S China, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.
关键词：
caveolae;caveolin-1;oxidized low density lipoprotein;atherosclerosis;transcytosis;human umbilical vein endothelial cells
摘要：
Aim: To explore the mechanisms involved in ox-LDL transcytosis across endothelial cells and the role of caveolae in this process. Methods: An in vitro model was established to investigate the passage of oxidized low density lipoprotein (ox-LDL) through a tight monolayer of human umbilical vein endothelial cells (HUVEC) cultured on a collagen-coated filter. Passage of Dil-labeled ox-LDL through the monolayer was measured using a fluorescence spectrophotometer. The uptake and efflux of ox-LDL by HUVEC were determined using fluorescence microscopy and HPLC. Results: Caveolae inhibitors - carrageenan (250 μg/mL), filipin (5 μg/mL), and nocodazole (33 μmol/L)-decreased the transport of ox-LDL across the monolayer by 48.9%, 72.4%, and 79.8% as compared to the control group. In addition, they effectively decreased ox-LDL uptake and inhibited the efflux of ox-LDL. Caveolin-1 and LOX-1 were up-regulated by ox-LDL in a time-dependent manner and decreased gradually after depletion of ox-LDL (P<0.05). After treatment HUVEC with ox-LDL and silencing caveolin-1, NF-KB translocation to the nucleus was blocked and LOX-1 expression decreased (P<0.05). Conclusion: Caveolae can be a carrier for ox-LDL and may be involved in the uptake and transcytosis of ox-LDL by HUVEC
摘要：
Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport (RCT) that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells (VSMCs) and macrophages, which are the most important original cells of foam cells. This novel model consists of 1) a caveolae transport center, 2) an intracellular trafficking system of the caveolin-1 complex, 3) a transmembrane transport system of the ABC-A1 complex, 4) a transmembrane transport system of the SR-B1 complex, and 5) an extracelluar trafficking system of HDL/Apo-A1. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-A1. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic process of atherosclerosis.
摘要：
Doxorubicin (DOX), a widely used anti-tumor drug, can give rise to severe cardiotoxicity by oxidative stress and cell apoptosis, which restricts its clinical application. α-Linolenic acid (ALA) has been shown to serve as a potent cardioprotective agent. The aim of this study was to explore the protective effects of ALA on DOX-induced cardiotoxicity and the underlying molecular mechanisms for this cardioprotection in rats. Rats were randomly divided into four groups and administrated with normal saline, ALA (500 µg/kg), DOX (2.5 mg/kg), or ALA (500 µg/kg) plus DOX (2.5 mg/kg) for 17 days. The results showed that DOX treatment significantly increased the heart weight/body weight, liver wet weight (WW)/dry weight (DW), lung WW/DW, serum levels of brain natriuretic peptide, creatine kinase-MB, lactate dehydrogenase, and cardiac troponin I, myocardial necrosis and myocardial malondialdehyde content, and induced the mRNA expression of Nrf2 in the nucleus, cleaved caspase-3, Bax, and superoxide dismutase (SOD). In addition, DOX led to a significant decrease in left ventricular end-diastolic volume, stroke volume, ejection fraction, SOD, glutathione-peroxidase, catalase, as well as the expression of Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm, phospho-AKT, phospho-ERK, and Bcl-2. Co-treatment with ALA significantly eliminated these changes induced by DOX except further reduction of Keap1 and elevation of Nrf2 and SOD mRNA. These results showed the cardioprotective effects of ALA on DOX-induced cardiotoxicity in rats. The mechanisms might be associated with the enhancement of antioxidant defense system through activating Keap1/Nrf2 pathway and anti-apoptosis through activating protein kinase B/extracellular signal regulated kinase pathway. Our results suggested a promising future of ALA-based preventions and therapies for myocardial damage after administration of DOX.
作者机构：
[Zhao, Guo-jun; Tang, Chao-ke; Liu, Mei-mei; Tan, Chun-zhi; Liu, Xie-hong; Yin, Wei-dong; Yin, Kai; Jiang, Jin; Mo, Zhong-cheng; Cui, Li-bao; Xiao, Ji; Chen, Si-guo] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Xiao, Ji] Univ S China, Dept Anesthesiol, Affiliated Hosp 2, Hengyang 421001, Peoples R China.;[Chen, Si-guo] Xiangnan Univ, Dept Physiol, Chenzhou 423000, Peoples R China.
通讯机构：
[Tang, Chao-ke] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
ATP-binding membrane cassette transporter A-l;ATP-binding membrane cassette transporter G-l;ibrolipim;liver X receptor α;atherosclerosis;RNA interference;high density lipoprotein;apolipoprotein;cholesterol;ATP-binding membrane cassette transporter A-l;ATP-binding membrane cassette transporter G-l;ibrolipim;liver X receptor α;atherosclerosis;RNA interference;high density lipoprotein;apolipoprotein;cholesterol
摘要：
To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis. Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays. Ibrolipim 5 and 50 μmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the ibrolipim treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by ibrolipim. Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.
期刊：
Acta Biochimica et Biophysica Sinica,2012年44(2):119-128 ISSN：1672-9145
通讯作者：
Tang, Chaoke
作者机构：
[Yu, Xiaohua; Zhao, Guojun; Yin, Kai; Li, Xiaoxu; Tang, Chaoke; Jiang, Zhisheng; Xiao, Ji; Mo, Zhongcheng] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Yu, Xiaohua] Univ S China, Sch Nursing, Hengyang 421001, Peoples R China.;[Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zha, Xiaohui] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada.
通讯机构：
[Tang, Chaoke] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Niemann–Pick type C1;oxLDL;ERK1/2;COX-2;PPARα;cholesterol
摘要：
The Niemann–Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane. It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression. However, the detailed mechanisms are not fully understood. In this study, we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages. Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. In addition, oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2) mRNA and protein expression in the macrophages, and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment. OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels, which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages. OxLDL dramatically elevated cellular cholesterol efflux, which was abrogated by inhibiting ERK1/2 and/or COX-2. In addition, oxLDL-induced NPC1 expression and cellular cholesterol efflux were reversed by PPARα siRNA or GW6471, an antagonist of PPARα. Taken together, these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.
摘要：
Background Macrophage migration inhibitory factor (MIF) is an upstream regulator in immune and inflammatory responses. However, its role in viral myocarditis remains unknown. In this study, we investigated the role of the MIF in coxsackievirus B3 (CVB3)-induced myocarditis. Methods Mice were randomized into two groups receiving either Eagle’s minimal essential medium (EMEM, control group) or virus solution (infected group). Subsets of mice in the infected group were sacrificed on days 3, 7, 14 and 28 after inoculation. Expression of MIF was detected using an enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction and immunohistochemistry. A neutralizing antibody (Ab) to MIF was injected intraperitoneally from day 0 to 7 after inoculation. Disease severity was estimated by histopathology of the heart and by the heart weight to body weight ratio, and the interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the myocardium were measured by ELISA on day 14. Results The serum MIF concentration and expression levels of myocardial MIF mRNA and protein were significantly elevated in mice on days 7 and 14 post-infection. The survival rate was markedly higher and disease severity was obviously less in mice treated with anti-MIF Ab. Furthermore, MIF blockade significantly decreased the IL-1β and TNF-α in the myocarditic heart. Conclusion These results demonstrate that MIF is an important naturally occurring inflammatory cytokine in CVB3-induced myocarditis, and anti-MIF Ab may lessen the inflammatory response.
作者机构：
[Zhu Bing-Yang; Luo Di-Xian; Xu Can-Xin; Wang Chun; Gao Zhi-Ping; Liao Duan-Fang] Univ S China, Life Sci Res Ctr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Liao Duan-Fang] Hunan Univ Chinese Med, Dept Tradit Chinese Diagnost, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Liao Duan-Fang] Univ S China, Life Sci Res Ctr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
期刊：
Chinese Physics Letters,2009年26(1):368-371 ISSN：0256-307X
通讯作者：
Guo Ping
作者机构：
[He Ji-Shan; Xiong Ping; Guo Ping] Cent S Univ, Sch Infophys & Geomat Engn, Changsha 410083, Peoples R China.;[Li Xin-Xia; Guo Ping] Univ S China, Dept Nucl Phys, Hengyang 421001, Peoples R China.
通讯机构：
[Guo Ping] Cent S Univ, Sch Infophys & Geomat Engn, Changsha 410083, Peoples R China.
关键词：
field emission;molybdenum dioxide;enhancement factor
摘要：
The transport and capture of therapeutic magnetic nanoparticles in human microvasculature is studied numerically. The nanoparticles are injected into a vascular system upstream from malignant tissue, and are captured at the tumour site with the aid of a local applied magnetic field positioned outside the body. Taking into account the dominant magnetic and fluidic forces on the particles, our study shows that the nanoparticles can be directed to and concentrated at the desired zone that is within a few centimetres from the surface of the body. In addition, influence of the particles size, average blood flow velocity and the diameter of the blood vessel on the captured efficiency are parametrically analysed.
作者机构：
[王程] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, China;[王程] Department of Spine Surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China;[王文军; 晏怡果; 杨威] Department of Spine Surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China;[于小华] Life Science Research Center, University of South China, Hengyang 421001, China;[张健] Department of Hand and Micro-surgery, the First Affiliated Hospital, University of South China, Hengyang 421001, China
期刊：
Chinese Physics Letters,2015年32(3): 035202-1-035202-4 ISSN：0256-307X
通讯作者：
Xiang Nong
作者机构：
[Li Xin-Xia] Univ South China, Dept Nucl Phys, Hengyang 421001, Peoples R China.;[Li Xin-Xia; Gan Chun-Yun; Xiang Nong] Chinese Acad Sci, Inst Plasma Phys, Hefei 230031, Peoples R China.
通讯机构：
[Xiang Nong] Chinese Acad Sci, Inst Plasma Phys, Hefei 230031, Peoples R China.
关键词：
EAST
摘要：
The effect of the wave accessibility condition on the lower hybrid current drive in the experimental advanced superconductor Tokamak (EAST) plasma with H-mode operation is studied. Based on a simplified model, a mode conversion layer of the lower hybrid wave between the fast wave branch and the slow wave branch is proved to exist in the plasma periphery for typical EAST H-mode parameters. Under the framework of the lower hybrid wave simulation code (LSC), the wave ray trajectory and the associated current drive are calculated numerically. The results show that the wave accessibility condition plays an important role on the lower hybrid current drive in EAST plasma. For wave rays with parallel refractive index n_‖ = 2.1 or n_‖ = 2.5 launched from the outside midplane, the wave rays may penetrate the core plasma due to the toroidal geometry effect, while numerous reflections of the wave ray trajectories in the plasma periphery occur. However, low current drive efficiency is obtained. Meanwhile, the wave accessibility condition is improved if a higher confined magnetic field is applied. The simulation results show that for plasma parameters under present EAST H-mode operation, a significant lower hybrid wave current drive could be obtained for the wave spectrum with peak value n_(‖) = 2.1 if a toroidal magnetic field B_T = 2.5 T is applied.
期刊：
Acta Biochimica et Biophysica Sinica,2017年49(3):277-283 ISSN：1672-9145
通讯作者：
Wang, Deming;Peng, Liangyu
作者机构：
[Tang, Dan; Ou, Weiwei; Wang, Deming; Chen, Quan; Wang, Jiazheng; Xiao, Ji] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;[Mo, Zhongcheng] Univ South China, Dept Histol & Embryol, Hengyang 421001, Peoples R China.;[Tang, Chaoke] Univ South China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Peng, Liangyu] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
通讯机构：
[Wang, Deming] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;[Peng, Liangyu] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
关键词：
liver X receptor;cytokine;mRNA decay;tristetraprolin;mitogen-activated protein kinase
摘要：
Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in post-transcriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1β, IL-6 and TNFa mRNA degradation. Moreover, T0901317 destabilized TNFa mRNA through its 3'-untranslated region. In addition, T0901317 increased the expression of tristetraprolin (TTP), while antagonizing TTP with siRNA abrogated T0901317-mediated inflammatory cytokine mRNA decay. Interestingly, T0901317 repressed LPS-induced phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) in THP-1 macrophages. The evidence presented here confirms that LXR activation with T0901317 inhibits the phosphorylation of ERK1/2 and p38 MAPK, likely resulting in the increased expression of TTP and the decay of LPS-induce inflammatory cytokine mRNAs.
