作者机构：
[Tang, Chao-Ke; Yu, Xiao-Hua] Univ South China, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Tang, Chao-Ke; Yin, Kai] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.;[Fu, Yu-Chang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zhang, Da-Wei] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2S2, Canada.;[Zhang, Da-Wei] Univ Alberta, Grp Mol & Cell Biol Lipids, Edmonton, AB T6G 2S2, Canada.
通讯机构：
[Yin, Kai] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.
关键词：
ABCA1;ABCG1;ACAT1;AGE;ATP-binding cassette transporter A1;ATP-binding cassette transporter G1;Atherosclerosis;CD36;CE;ERK1/2;FC;Foam cells;HDL;LDLR;LXR;MAPK;PI3K;PKB;PKC;PPAR response elements;PPAR-gamma;PPREs;RCT;RXR;SR-A;SR-BI;TGF-beta;acyl coenzyme A:cholesterol acyltransferase-1;advanced glycation end products;apoA-I;apoE;apolipoprotein A-I;apolipoprotein E;cholesterol ester;extracellular signal-regulated kinases 1 and 2;free cholesterol;high-density lipoprotein;liver X receptor;low-density lipoprotein receptor;mitogen-activated protein kinase;nCEH;neutral cholesteryl ester hydrolase;ox-LDL;oxidized low-density lipoprotein;peroxisome proliferator-activated receptor-gamma;phosphatidylinositol 3-kinase;protein kinase B;protein kinase C;retinoid X receptor;reverse cholesterol transport;scavenger receptor BI;scavenger receptor class A;transforming growth factor-beta
摘要：
Atherosclerosis is a chronic disease characterized by the deposition of excessive cholesterol in the arterial intima. Macrophage foam cells play a critical role in the occurrence and development of atherosclerosis. The generation of these cells is associated with imbalance of cholesterol influx, esterification and efflux. CD36 and scavenger receptor class A (SR-A) are mainly responsible for uptake of lipoprotein-derived cholesterol by macrophages. Acyl coenzyme A:cholesterol acyltransferase-1 (ACAT1) and neutral cholesteryl ester hydrolase (nCEH) regulate cholesterol esterification. ATP-binding cassette transporters A1 (ABCA1), ABCG1 and scavenger receptor BI (SR-BI) play crucial roles in macrophage cholesterol export When inflow and esterification of cholesterol increase and/or its outflow decrease, the macrophages are ultimately transformed into lipid-laden foam cells, the prototypical cells in the atherosclerotic plague. The aim of this review is to describe what is known about the mechanisms of cholesterol uptake, esterification and release in macrophages. An increased understanding of the process of macrophage foam cell formation will help to develop novel therapeutic interventions for atherosclerosis. (c) 2013 The Authors. Published by Elsevier B.V. All rights reserved.
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience,2012年32(9):3044-3057 ISSN：1529-2401
通讯作者：
Liu, Wenlan
作者机构：
[Liu, Jie; Jin, Xinchun; Liu, Ke J.; Liu, Wenlan] Univ New Mexico, Coll Pharm, Hlth Sci Ctr, Albuquerque, NM 87131 USA.;[Liu, Ke J.] Univ New Mexico, Dept Neurol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.;[Liu, Jie] Univ South China, Sch Med, Dept Med Microbiol & Immunol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Liu, Wenlan] Univ New Mexico, Coll Pharm, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
摘要：
Blood-brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here, we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran and promoted the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis.
期刊：
Journal of Experimental & Clinical Cancer Research,2017年36(1):1-12 ISSN：1756-9966
通讯作者：
Zeng, Zhaoyang;Tang, Hailin
作者机构：
[Li, Xiaoling; Zeng, Zhaoyang; He, Rongfang; Li, Guiyuan; Xiong, Wei] Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Carcinogenesis, Changsha, Hunan, Peoples R China.;[Li, Xiaoling; Zeng, Zhaoyang; He, Rongfang; Li, Guiyuan; Xiong, Wei] Cent S Univ, Canc Res Inst, Chinese Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha, Hunan, Peoples R China.;[He, Rongfang] Univ South China, Affiliated Hosp 1, Dept Pathol, Hengyang, Hunan, Peoples R China.;[Tang, Hailin; Xie, Xiaoming; Liu, Peng] Sun Yat Sen Univ, Canc Ctr, Dept Breast Oncol, Guangzhou, Guangdong, Peoples R China.;[Tang, Hailin; Xie, Xiaoming; Liu, Peng] State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China.
通讯机构：
[Zeng, Zhaoyang] Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Carcinogenesis, Changsha, Hunan, Peoples R China.;[Zeng, Zhaoyang] Cent S Univ, Canc Res Inst, Chinese Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha, Hunan, Peoples R China.;[Tang, Hailin] Sun Yat Sen Univ, Canc Ctr, Dept Breast Oncol, Guangzhou, Guangdong, Peoples R China.;[Tang, Hailin] State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China.;[Tang, Hailin] Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China.
关键词：
Circular RNAs<&wdkj&>miR-34a<&wdkj&>GFRA1<&wdkj&>Competitive endogenous RNAs<&wdkj&>Triple negative breast cancer
摘要：
Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in triple negative breast cancer (TNBC) is largely unknown. We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in TNBC cell lines. Expression levels of a significantly upregulated circRNA, circGFRA1, was detected by quantitative real-time PCR (qRT-PCR) in TNBC cell lines and tissues. Kaplan-Meier survival analysis was used to explore the significance of circGFRA1 in clinical prognosis. Then, we examined the functions of circGFRA1 in TNBC by cell proliferation, apoptosis and mouse xenograft assay. In addition, luciferase assay was used to explore the miRNA sponge function of circGFRA1 in TNBC. Microarray analysis and qRT-PCR verified a circRNA termed circGFRA1 that was upregulated in TNBC. Kaplan-Meier survival analysis showed that upregulated circGFRA1 was correlated with poorer survival. Knockdown of circGFRA1 inhibited proliferation and promoted apoptosis in TNBC. Via luciferase reporter assays, circGFRA1 and GFRA1 was observed to directly bind to miR-34a. Subsequent experiments showed that circGFRA1 and GFRA1 regulated the expression of each other by sponging miR-34a. Taken together, we conclude that circGFRA1 may function as a competing endogenous RNA (ceRNA) to regulate GFRA1 expression through sponging miR-34a to exert regulatory functions in TNBC. circGFRA1 may be a diagnostic biomarker and potential target for TNBC therapy.
通讯机构：
[Tang, Chao-Ke] Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
Cholesterol transport system<&wdkj&>Atherosclerosis<&wdkj&>High-density lipoprotein
摘要：
Atherosclerosis, the pathological basis of most cardiovascular disease (CVD), is closely associated with cholesterol accumulation in the arterial intima. Excessive cholesterol is removed by the reverse cholesterol transport (RCT) pathway, representing a major antiatherogenic mechanism. In addition to the RCT, other pathways are required for maintaining the whole-body cholesterol homeostasis. Thus, we propose a working model of integrated cholesterol transport, termed the cholesterol transport system (CTS), to describe body cholesterol metabolism. The novel model not only involves the classical view of RCT but also contains other steps, such as cholesterol absorption in the small intestine, low-density lipoprotein uptake by the liver, and transintestinal cholesterol excretion. Extensive studies have shown that dysfunctional CTS is one of the major causes for hypercholesterolemia and atherosclerosis. Currently, several drugs are available to improve the CTS efficiently. There are also several therapeutic approaches that have entered into clinical trials and shown considerable promise for decreasing the risk of CVD. In recent years, a variety of novel findings reveal the molecular mechanisms for the CTS and its role in the development of atherosclerosis, thereby providing novel insights into the understanding of whole-body cholesterol transport and metabolism. In this review, we summarize the latest advances in this area with an emphasis on the therapeutic potential of targeting the CTS in CVD patients.
摘要：
Cerebral ischemia caused severe disability, and associated with a series of neurological events. Long non-coding RNA SNHG12 was found to be upregulated in mouse brain microvascular endothelial cells by cerebral ischemia. Moreover, it was reported that SNHG12 could directly interact with miR-199a and sirtuin 1 (SIRT1) as a direct target of miR-199a in other diseases. However, the function and mechanism of SNHG12 in cerebral ischemia and reperfusion (I/R) injury of neuronal cells remains unclear. The present study was thus designed to explore the potential effect of SNHG12 and to investigate the underlying mechanism in I/R neuronal cells. we found that SNHG12 was upregulated in primary neuronal cells and N2a cells and peaked at 12 h and 24 h after OGD/R treatment, respectively. Meanwhile, MTT assay showed that knockdown SNHG12 inhibited cell proliferation under OGD/R condition. And flow cytometry analyses revealed more apoptosis rate was caused by SNHG12 knockdown. Mechanistically, SNHG12 interacted with miR-199a and decreased the expression of miR-199a. Overexpression miR-199a largely inhibited the cell proliferation and induced the cell apoptosis. Meanwhile, SNHG12 was proven to target miR-199a and then activated SIRT1 expression, which finally led to activation of AMPK signaling pathway. In summary, we demonstrate SNHG12 targets miR-199a to upregulate SIRT1 expression, which attenuates cerebral ischemia/reperfusion injury through AMPK pathway activation. Our findings provide molecular mechanism by which SNHG12 attenuates cerebral I/R injury and facilitate development of therapeautical strategies for treating ischemia-induced stroke.
摘要：
Autophagy, which is tightly regulated by a series of autophagy-related genes (ATGs), is a vital intracellular homeostatic process through which defective proteins and organelles are degraded and recycled under starvation, hypoxia or other specific cellular stress conditions. For both normal cells and tumour cells, autophagy not only sustains cell survival but can also promote cell death. Autophagy-related signalling pathways include mTOR-dependent pathways, such as the AMPK/mTOR and PI3K/Akt/mTOR pathways, and non-mTOR dependent pathways, such as the P53 pathway. Additionally, autophagy plays a dual role in gastric carcinoma (GC), including a tumour-suppressor role and a tumour-promoter role. Long-term Helicobacter pylori infection can impair autophagy, which may eventually promote tumourigenesis of the gastric mucosa. Moreover, Beclin1, LC3 and P62/SQSTM1 are regarded as autophagy-related markers with GC prognostic value. Autophagy inhibitors and autophagy inducers show promise for GC treatment. This review describes research progress regarding autophagy and its significant role in gastric cancer.
