摘要：
The disorder of lipid metabolism is pathologically linked to hyperlipidemia, lipid storage disease, obesity and other related diseases. Intriguingly, recent studies have revealed that lipid metabolism disorders play an important role in carcinogenesis and development as well, since they cause abnormal expression of various genes, proteins, and dysregulation of cytokines and signaling pathways. More importantly, lipid-lowering drugs and anti-lipid per-oxidation treatment have been showing their advantages in clinic, in comparison with other anti-cancer drugs with high toxicity. Thus, further elucidation of molecular mechanism between lipid metabolism and cancer is essential in developing novel diagnostic biomarkers and therapeutic targets of human cancers.
期刊：
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics),2017年10603 LNCS:672-683 ISSN：0302-9743
摘要：
Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors.
摘要：
目的：探讨宫腔镜检查诊断异常子宫出血（AUB）的临床价值。方法选择2012年10月—2015年10月于湖南省中医药研究院附属医院院进行治疗的100例 AUB 患者，均进行 B 超检查及宫腔镜检查，比较两种检查的诊断准确率。结果宫腔镜检查诊断正确率高于 B 超，差异有统计学意义（P ﹤0.05）。结论宫腔镜检查诊断AUB 的效果较为明显，可以在很大程度上提高诊断准确率，使患者得到及时治疗，为患者生活质量提供保障。
期刊：
EXPERIMENTAL AND THERAPEUTIC MEDICINE,2014年8(1):3-8 ISSN：1792-0981
通讯作者：
Qin, L
作者机构：
[Guo, Qiong; Zhu, Neng; Yang, Luoyan] Cent S Univ, Xiangya Hosp 2, Dept Urol, Changsha 410011, Hunan, Peoples R China.;[Luo, Zhigang; Zhu, Neng] South China Univ, Affiliated Hosp 2, Dept Urol, Hengyang 421001, Hunan, Peoples R China.;[Qin, Li] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duanfang; Qin, Li] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Qin, Li] Univ South China, Inst Pharm & Pharmacol, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Qin, L ] U;Univ South China, Inst Pharm & Pharmacol, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Wnt5a;cancer;metastasis;signaling pathway
摘要：
Wnt5a is a noncanonical signaling member of the wingless-related/mouse mammary tumor virus integration family, which is involved in a wide range of cellular processes, particularly in cancer development and metastasis. Accumulating evidence indicates that Wnt5a exhibits paradoxical effects in various types of cancer metastasis. Therefore, the Wnt5a signaling cascade in cancer metastasis appears to be complex and may depend on binding receptors, downstream effectors, exogenous inhibitors and tumor microenvironments, as well as the extracellular matrix, particularly cell/tissue-tropic contexts. The aim of the present study was to summarize the previous findings on the roles of Wnt5a and the potential mechanisms in various types of cancer metastasis. Furthermore, it is reasonable to hypothesize that Wnt5a and the involved signaling pathways may become molecular targets in the treatment of cancer metastasis.
作者机构：
[Li, Chun-yu] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu 610000, Peoples R China.;[Zhang, Ya-ming; Yan, Dan; Li, Qi; Zhao, Yan-ling; Li, Chun-yu; Wang, Zhe-wei; Wang, Jia-bo; Tu, Can; Jiang, Bing-qian; Zeng, Ling-na] 302 Mil Hosp, China Mil Inst Chinese Med, Beijing 100039, Peoples R China.;[Ma, Zhi-jie; Li, Qi] Capital Med Univ, Dept Tradit Chinese Med, Beijing Friendship Hosp, Beijing 100050, Peoples R China.;[Zhang, Ping] 302 Mil Hosp, Integrat Med Ctr, Beijing 100039, Peoples R China.;[Tan, Rui; Wang, Zhe-wei] Southwest Jiaotong Univ, Sch Life Sci & Engn, Chengdu 610031, Peoples R China.
通讯机构：
[Wang, JB ] 3;302 Mil Hosp, China Mil Inst Chinese Med, Beijing 100039, Peoples R China.
关键词：
Powder needleless injection;Insulin;Transdermal drug delivery;Skin irritation
摘要：
Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.
摘要：
Aim: To investigate the mechanisms of anti-atherosclerotic action of ezetimibe in rat vascular smooth muscle cells (VSMCs) in vitro. Methods: VSMCs of SD rats were cultured in the presence of Chol:M beta CD (10 mu g/mL) for 72 h, and intracellular lipid droplets and cholesterol levels were evaluated using Oil Red O staining, HPLC and Enzymatic Fluorescence Assay, respectively. The expression of caveolin-1, sterol response element-binding protein-1 (SREBP-1) and ERK1/2 were analyzed using Western blot assays. Translocation of SREBP-1 and ERK1/2 was detected with immunofluorescence. Results: Treatment with Chol:M beta CD dramatically increased the cellular levels of total cholesterol (TC), cholesterol ester (CE) and free cholesterol (FC) in VSMCs, which led to the formation of foam cells. Furthermore, Chol:M beta CD treatment significantly decreased the expression of caveolin-1, and stimulated the expression and nuclear translocation of SREBP-1 in VSMCs. Co-treatment with ezetimibe (3 mu mol/L) significantly decreased the cellular levels of TC, CE and FC, which was accompanied by elevation of caveolin-1 expression, and by a reduction of SREBP-1 expression and nuclear translocation. Co-treatment with ezetimibe dose-dependently decreased the expression of phosphor-ERK1/2 (p-ERK1/2) in VSMCs. The ERK1/2 inhibitor PD98059 (50 mu mol/L) altered the cholesterol level and the expression of p-ERK1/2, SREBP-1 and caveolin-1 in the same manner as ezetimibe did. Conclusion: Ezetimibe suppresses cholesterol accumulation in rat VSMCs in vitro by regulating SREBP-1 and caveolin-1 expression, possibly via the MAPK signaling pathway.
摘要：
<jats:title>Summary</jats:title><jats:p>Cholesterol accumulation is a critical step during the development and progression of atherosclerosis. Recently, Wnt5a expression has been found to be markedly upregulated in both murine and human atherosclerotic lesions. However, the effect and mechanism of Wnt5a in atherosclerosis is poorly understood. In the present study, we investigated the effects and potential mechanisms of Wnt5a on cholesterol accumulation during atherosclerosis. We used <jats:styled-content style="fixed-case">RAW</jats:styled-content>264.7 and vascular smooth muscle cells (<jats:styled-content style="fixed-case">VSMC</jats:styled-content>) treated with oxidized low‐density lipoprotein (ox<jats:styled-content style="fixed-case">LDL</jats:styled-content>) as lipid‐loaded cell models. We found that expression of Wnt5a protein was increased in a concentration (25, 50, 75 and 100μg/mL)‐ and time (24, 48 and 72h)‐dependent manner by ox<jats:styled-content style="fixed-case">LDL</jats:styled-content> treatment. To explore the underlying mechanism, we used Wnt5a short interference (si) RNA to knockdown Wnt5a expression in both <jats:styled-content style="fixed-case">RAW</jats:styled-content>264.7 cells and <jats:styled-content style="fixed-case">VSMC</jats:styled-content>, or applied recombinant Wnt5a (rWnt5a) to stimulate Wnt5a signalling. After Wnt5a knockdown, total cholesterol (<jats:styled-content style="fixed-case">TC</jats:styled-content>) and free cholesterol (<jats:styled-content style="fixed-case">FC</jats:styled-content>) content in both cell types increased significantly (<jats:italic>P</jats:italic><0.05) upon exposure to ox<jats:styled-content style="fixed-case">LDL</jats:styled-content>. Conversely, the <jats:styled-content style="fixed-case">TC</jats:styled-content> and <jats:styled-content style="fixed-case">FC</jats:styled-content> content decreased markedly (<jats:italic>P</jats:italic><0.05) after treatment of cells with rWnt5a. More importantly, both protein and m<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression of Caveolin‐1 and <jats:styled-content style="fixed-case">ATP</jats:styled-content>‐binding cassette transporter A1 (<jats:styled-content style="fixed-case">ABCA</jats:styled-content>1) was significantly reduced after exposure of wnt5a si<jats:styled-content style="fixed-case">RNA</jats:styled-content>‐treated cells to ox<jats:styled-content style="fixed-case">LDL</jats:styled-content>, whereas rWnt5a treatment of cells resulted in increased Caveolin‐1 and <jats:styled-content style="fixed-case">ABCA</jats:styled-content>1 protein expression after exposure of cells to ox<jats:styled-content style="fixed-case">LDL</jats:styled-content>. Together, these findings demonstrate, for the first time, that Wnt5a reduces the accumulation of cholesterol in lipid‐loaded cells by regulating the <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression of <jats:italic>Caveolin‐1</jats:italic> and <jats:italic>ABCA1</jats:italic>, which are involved in reverse cholesterol transport. This may present a novel mechanism of Wnt5a‐mediated cholesterol transportation in macrophages and <jats:styled-content style="fixed-case">VSMC</jats:styled-content>. Therefore, targeting the Wnt5a signalling pathway may have clinical implications in atherosclerosis.</jats:p>
期刊：
Evidence-Based Complementary and Alternative Medicine,2013年2013:186573 ISSN：1741-427X
通讯作者：
Wang, JB
作者机构：
[Ma, Zhi-Jie; Pu, Shi-Biao; Li, Qi; Wang, Jia-Bo; Liu, Fei-Fei; Zeng, Ling-Na; Zhao, Yan-Ling] 302 Mil Hosp, China Mil Inst Chinese Med, Beijing 100039, Peoples R China.;[Ma, Zhi-Jie] Chengdu Univ Tradit Chinese Med, Coll Tradit Chinese Med, Chengdu 610075, Sichnan, Peoples R China.;[Zhong, Yan-Wei] 302 Mil Hosp, Pediat Liver Dis erapy & Res Ctr, Beijing 100039, Peoples R China.;[Yang, Hui-Yin; Wang, Rui-Lin; Xiao, Xiao-He; Bai, Yun-Feng; Li, Jian-Yu] 302 Mil Hosp, Integrat Med Ctr, Beijing 100039, Peoples R China.;[Xiao, Da-Ke] China Pharmaceut Univ, Coll Pharm, Nanjing 211198, Jiangsu, Peoples R China.
通讯机构：
[Wang, JB ] 3;302 Mil Hosp, China Mil Inst Chinese Med, Beijing 100039, Peoples R China.
摘要：
<jats:p>Some recent clinical reports have shown that the combination of oxymatrine, a phyto-derived drug, with lamivudine (3TC) could improve its curative effect against hepatitis B virus (HBV) infection. However, the experimental data in support of this combination strategy are lacking. In this study, we investigated the anti-HBV activity of the combination of 3TC and either oxymatrine or matrine on HepG2 2.2.15<jats:italic>in vitro</jats:italic>. The activities of the combination and the solo compound, each in different concentrations, were compared on the 3rd, 6th, and 9th experimental days. The cytotoxicity results showed that the nontoxic concentrations of both oxymatrine and matrine to HepG2 2.2.15 cells were 800 <jats:italic>μ</jats:italic>g/mL. We found that the single use of oxymatrine below 100 <jats:italic>μ</jats:italic>g/ml, matrine below 200 <jats:italic>μ</jats:italic>g/ml, and 3TC below 30 <jats:italic>μ</jats:italic>g/ml showed weak inhibitory effects on the secretion of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV-DNA in culture media; the combination of 3TC (30 <jats:italic>μ</jats:italic>g/ml) with oxymatrine (100 <jats:italic>μ</jats:italic>g/ml) or matrine (100 <jats:italic>μ</jats:italic>g/ml) showed significant inhibitory effects that were higher than or equivalent to the single use of 3TC at 100 <jats:italic>μ</jats:italic>g/ml. The results provide a new impetus to develop novel, multicomponent anti-HBV drugs through the combination of natural products with nucleoside analogs to enhance their activity.</jats:p>
作者机构：
Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha;Institute of Pharmacy & Pharmacology, University of South China, Hengyang Hunan, China
