Aldo-keto reductase family 1, member B10 is secreted through a lysosome-mediated non-classical pathway
作者：
Luo, Di-xian;Huang, Mei C.;Ma, Jun;Gao, Zachary;Liao, Duan-fang* ;...
期刊：
Biochemical Journal ,2011年438(1):71-80 ISSN：0264-6021
通讯作者：
Liao, Duan-fang
作者机构：
[Liao, Duan-fang; Luo, Di-xian] Univ S China, Coll Pharm & Life Sci, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Luo, Di-xian; Ma, Jun; Gao, Zachary; Cao, Deliang] So Illinois Univ, Sch Med, Simmons Canc Inst, Dept Med Microbiol Immunol & Cell Biol, Springfield, IL 62794 USA.;[Huang, Mei C.] Mem Med Ctr, Dept Internal Med, Div Gastroenterol, Springfield, IL 62781 USA.;[Liao, Duan-fang] Hunan Univ Chinese Med, Sch Pharm, Dept Tradit Chinese Diagnost, Changsha 420108, Hunan, Peoples R China.
通讯机构：
[Liao, Duan-fang] U;Univ S China, Coll Pharm & Life Sci, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
aldo-keto reductase family 1;member B10 (AKR1B10);ATP-binding-cassette transporter (ABC transporter);calcium signalling;cancer marker;lysosomal exocytosis;non-classical protein-secretion pathway
摘要：
AKR1B10 (aldo-keto reductase family 1, member B10) protein is primarily expressed in normal human small intestine and colon, but overexpressed in several types of human cancers and considered as a tumour marker. In the present study, we found that AKR1B10 protein is secreted from normal intestinal epithelium and cultured cancer cells, as detected by a newly developed sandwich ELISA and Western blotting. The secretion of AKR1B10 was not affected by the protein-synthesis inhibitor cycloheximide and the classical protein-secretion pathway inhibitor brefeldin A, but was stimulated by temperature, ATP, Ca 2+ and the Ca 2+ carrier ionomycin, lysosomotropic NH 4Cl, the G-protein activator GTPγS and the G-protein coupling receptor N-formylmethionyl-leucyl-phenylalanine. The ADP-ribosylation factor inhibitor 2-(4-fluorobenzoylamino)-benzoic acid methyl ester and the phospholipase C inhibitor U73122 inhibited the secretion of AKR1B10. In cultured cells, AKR1B10 was present in lysosomes and was secreted with cathepsin D, a lysosomal marker. In the intestine, AKR1B10 was specifically expressed in mature epithelial cells and secreted into the lumen at 188.6-535.7 ng/ml of ileal fluids (mean = 298.1 ng/ml, n = 11). Taken together, our results demonstrate that AKR1B10 is a newsecretory protein belonging to a lysosome-mediated non-classical proteinsecretion pathway and is a potential serum marker. ©The Authors Journal compilation ©2011 Biochemical Society.
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英文
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AOPPs Inhibits Cholesterol Efflux by Down-regulating ABCA1 Expression in a JAK/STAT Signaling Pathway-Dependent Manner
作者：
Mo, Zhong-Cheng;Xiao, Ji;Liu, Xie-Hong;Hu, Yan-Wei;Li, Xiao-Xu;...
期刊：
Journal of Atherosclerosis and Thrombosis ,2011年18(9):796-807 ISSN：1340-3478
通讯作者：
Tang, Chao-Ke
作者机构：
[Tang, Chao-Ke; Li, Xiao-Xu; Hu, Yan-Wei; Liu, Xie-Hong; Tang, Ya-Ling; Mo, Zhong-Cheng; Yi, Guang-Hui; Wang, Zuo; Xiao, Ji] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
通讯机构：
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Advanced oxidation protein products;ATP-binding cassette transporter A1;JAK/STAT;Cholesterol efflux
摘要：
AIMS: Advanced oxidation protein products (AOPPs) are new independent risk factor for coronary artery disease. This study was to determine the effects and potential mechanisms of AOPPs on cholesterol efflux from human macrophage foam cells. METHODS: Human THP-1 monocytes were preincubated with Phorbol-12-myristate- 13-acetate (PMA) and oxidized low density lipoprotein (ox-LDL) to form foam cells. The protein and mRNA expression were examined by western immunoblotting assays and real-time quantitative PCR, respectively. Cellular cholesterol content was measured by HPLC. The cholesterol efflux was assessed by liquid scintillation counting. RESULTS: AOPPs significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and liver X receptor alpha (LXRalpha) and reduced cholesterol efflux from THP-1 macrophage- derived foam cells. AOPPs substantially activated NADPH oxidase and activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal pathway in THP-1-derived foam-like cells. Inhibiting NADPH oxidase by diphenyliodonium (DPI) effectively abolished the AOPPs-induced decrease in cholesterol efflux and the expression of ABCA1. Inhibiting JAK/STAT activation by its specific inhibitor AG-490 or by siRNA could also block AOPPs action on THP-1 cells. CONCLUSIONS: AOPPs may first down-regulate the expression of LXRalpha and ABCA1 through JAK/STAT signal pathway activation and then inhibit cholesterol efflux in THP-1-derived foam-like cells; therefore, our study may be useful for understanding the critical effects of AOPPs on the pathogenesis of atherosclerosis.
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英文
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MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signalling
作者：
Ling, Hong-Yan;Wen, Ge-Bo;Feng, Shui-Dong;Tuo, Qin-Hui;Ou, He-Sheng;...
期刊：
Clinical and Experimental Pharmacology and Physiology ,2011年38(4):239-246 ISSN：0305-1870
通讯作者：
Zhang, Liang
作者机构：
[Ling, Hong-Yan] Univ S China, Sch Med, Dept Physiol, Hengyang, Peoples R China.;[Wen, Ge-Bo; Ling, Hong-Yan] Univ S China, Affiliated Hosp 1, Inst Clin Res, Hengyang, Peoples R China.;[Feng, Shui-Dong] Univ S China, Sch Publ Hlth, Dept Epidemiol, Hengyang, Peoples R China.;[Gao, Zhi-Ping; Zhu, Bing-Yang; Ou, He-Sheng; Tuo, Qin-Hui; Liao, Duan-Fang] Univ S China, Inst Pharm & Pharmacol, Key Lab Pharmacoprote Hunan Prov, Hengyang, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Sch Pharm, Dept Tradit Chinese Diagnost, Changsha, Hunan, Peoples R China.
通讯机构：
[Zhang, Liang] P;Palmer Coll Chiropract Florida, Palmer Ctr Chiropract Res, Lab Cell & Mol Biol, 4705 S Clyde Morris Blvd, Port Orange, FL 32129 USA.
关键词：
3T3‐L1 adipocytes;differentiation;extracellular signal‐regulated kinases 1/2;microRNA‐375;obesity
摘要：
1. Adipocyte hypertrophy and hyperplasia are important processes in the development of obesity. To understand obesity and its associated diseases, it is important to elucidate the molecular mechanisms governing adipogenesis. MicroRNA-375 has been shown to inhibit differentiation of neurites, and participate in the regulation of insulin secretion and blood homeostasis. However, it is unknown whether miR-375 plays a role in adipocyte differentiation. 2. To investigate the role of miR-375 in adipocyte differentiation, we compared the miR-375 expression level between 3T3-L1 pre-adipocytes and adipocytes using miRNA microarray and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. Furthermore, we evaluated the effects of overexpression or inhibition of miR-375 on 3T3-L1 adipocyte differentiation. 3. In the present study, we found that miR-375 expression was increased after induction of adipogenic differentiation. Overexpression of miR-375 enhanced 3T3-L1 adipocyte differentiation, as evidenced by its ability to increase mRNA levels of both CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor-γ (PPARγ2), and induction of adipocyte fatty acid-binding protein (aP2) and triglyceride (TG) accumulation. Furthermore, we found overexpression of miR-375 suppressed phosphorylation levels of extracellular signal-regulated kinases 1/2 (ERK1/2). In contrast, anti-miR-375 increased ERK1/2 phosphorylation levels and inhibited mRNA expression of C/EBPα, PPARγ2 and aP2 in 3T3-L1 adipocyte, accompanied by decreased adipocyte differentiation. 4. Taken together, these data suggest that miR-375 promotes 3T3-L1 adipocyte differentiation, possibly through modulating the ERK-PPARγ2-aP2 pathway. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.
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英文
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Angiopoietin-1 protects myocardial endothelial cell function blunted by angiopoietin-2 and high glucose condition
作者：
Tuo, Qin-hui;Xiong, Guo-zuo;Zeng, Heng;Yu, Hei-di;Sun, Shao-wei;...
期刊：
中国药理学报 ,2011年32(1):45-51 ISSN：1671-4083
通讯作者：
Liao, Duan-fang
作者机构：
[Liao, Duan-fang; Zhu, Bing-yang; Tuo, Qin-hui; Ling, Hong-yan; Sun, Shao-wei] Univ S China, Sch Life Sci & Technol, Div Pharmacoprote, Hengyang 421001, Peoples R China.;[Yu, Hei-di; Zeng, Heng; Chen, Jian-xiong; Tuo, Qin-hui] Vanderbilt Univ, Med Ctr, Dept Pediat, Div Neonatol, Nashville, TN 37232 USA.;[Xiong, Guo-zuo] Univ S China, Affiliated Hosp 2, Dept Gen Surg, Hengyang 421001, Peoples R China.;[Liao, Duan-fang] Hunan Univ Chinese Med, Sch Pharm, Dept Tradit Chinese Diagnot, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Liao, Duan-fang] U;Univ S China, Sch Life Sci & Technol, Div Pharmacoprote, Hengyang 421001, Peoples R China.
关键词：
angiopoietin;Tie-2;myocardial endothelial cells;hyperglycemia;diabetic
摘要：
Aim:To evaluate the effects of angiopoietin-1 (Ang-1) on myocardial endothelial cell function under high glucose (HG) condition.Methods:Mouse heart myocardial endothelial cells (MHMECs) were cultured and incubated under HG (25 mmol/L) or normal glucose (NG, 5 mmol/L) conditions for 72 h. MTT was used to determine cellular viability, and TUNEL assay and caspase-3 enzyme linked immunosorbent assays were used to assay endothelial apoptosis induced by serum starvation. Immunoprecipitation and Western blot analysis were used to analyze protein phosphorylation and expression. Endothelial tube formation was used as an in vitro assay for angiogenesis.Results:Exposure of MHMECs to HG resulted in dramatic decreases in phosphorylation of the Tie-2 receptor and its downstream signaling partners, Akt/eNOS, compared to that under NG conditions. Ang-1 (250 ng/mL) increased Tie-2 activation, inhibited cell apoptosis, and promoted angiogenesis. Ang-1-mediated protection of endothelial function was blunted by Ang-2 (25 ng/mL).Conclusion:Ang-1 activates the Tie-2 pathway and restores hyperglycemia-induced myocardial microvascular endothelial dysfunction. This suggests a protective role of Ang-1 in the ischemic myocardium, particularly in hearts affected by hyperglycemia or diabetes. © 2011 CPS and SIMM All rights reserved.
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英文
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Two dimeric lignans with an unusual α,β-unsaturated ketone motif from Zanthoxylum podocarpum and their inhibitory effects on nitric oxide production
作者：
Zhou, Xiao-Jiang;Chen, Xiao-Liang;Li, Xue-Song;Su, Jia;He, Jiang-Bo;...
期刊：
Bioorganic & Medicinal Chemistry Letters ,2011年21(1):373-376 ISSN：0960-894X
通讯作者：
Cheng, Yong-Xian
作者机构：
[He, Jiang-Bo; Li, Yan; Li, Xue-Song; Cheng, Yong-Xian; Su, Jia; Chen, Xiao-Liang; Zhou, Xiao-Jiang; Wang, Yue-Hu] Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China.;[Li, Xue-Song; Zhou, Xiao-Jiang] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Cheng, Yong-Xian] C;Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China.
关键词：
Dimeric lignans;Nitric oxide production;Rutaceae;Zanthoxylum podocarpum;Zanthpodocarpins A and B
摘要：
Two new dimeric lignans, zanthpodocarpins A (1) and B (2), and five known lignans, eudesmin (3), (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4- dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (4), dimethoxysamin (5), rel-(1R,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octan-2-one (6), and magnone A (7), were isolated from the barks of Zanthoxylum podocarpum. Their structures were identified by using spectroscopic methods. Compounds 1 and 2 are rare dilignans bearing an unusual α,β-unsaturated ketone group from a natural source. Bioassay showed that compounds 1 and 2 could inhibit nitric oxide (NO) production in LPS stimulated RAW 264.7 cells with IC 50 values of 5.31 μM and 12.15 μM, respectively. © 2010 Elsevier Ltd. All rights reserved.
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英文
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Discovery of potent dipeptidyl peptidase IV inhibitors derived from β-aminoamides bearing substituted [1,2,3]-triazolopiperidines for the treatment of type 2 diabetes
作者：
Shan, Zhenwei;Peng, Min;Fan, Houxing;Lu, Qingtao;Lu, Peng;...
期刊：
Bioorganic & Medicinal Chemistry Letters ,2011年21(6):1731-1735 ISSN：0960-894X
通讯作者：
Chen, Yilang
作者机构：
[Lu, Qingtao; Shan, Zhenwei] Shandong Univ Tradit Chinese Med, Dept Med Chem, Jinan 250355, Shandong, Peoples R China.;[Fan, Houxing; Zhao, Chuansheng; Lu, Peng; Chen, Yilang] Shanghai Sun Sail Pharmaceut Sci & Technol Co Ltd, Dept Med Chem, Shanghai 201203, Peoples R China.;[Peng, Min] Hunan Univ Chinese Med, Dept Med Chem, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Chen, Yilang] S;Shanghai Sun Sail Pharmaceut Sci & Technol Co Ltd, Dept Med Chem, Shanghai 201203, Peoples R China.
关键词：
Dipeptidyl peptidase IV inhibitors;Type 2 diabetes;Triazolopiperidine
摘要：
A series of novel [1,2,3]-triazolopiperidine derivatives 5a-5y were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes, most of the compounds exhibited excellent in vitro potency (IC50 <50 nM) against DPP-4. Among these, compound 5d with potent in vitro activity against DPP-4 and good pharmacokinetic profiles exhibited pronounced in vivo efficacy in an oral glucose tolerance test (OGTT) in ICR mice. On the base of these properties, compound 5d was selected as a potential new candidate for the treatment of type 2 diabetes. © 2010 Elsevier Ltd. All rights reserved.
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英文
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小鼠间充质干细胞诱导分化成脂肪细胞miRNA表达的变化
作者：
凌宏艳;文格波;胡弼;奉水东;张恺芳;...
期刊：
中国应用生理学杂志 ,2011年27(4):391-395 ISSN：1000-6834
通讯作者：
Ling, H.Y.
作者机构：
南华大学生理学教研室,湖南衡阳,421001;南华大学附一医院临床研究所,湖南衡阳,421001;南华大学流行病学教研室,湖南衡阳,421001;湖南中医药大学药学院,长沙,410208;[杨丝丝; 奉水东; 凌宏艳; 张恺芳; 胡弼; 尹蔚兰; 何剑琴] 南华大学
关键词：
miRNA表达;骨髓间充质干细胞;分化;脂肪细胞
摘要：
目的：探讨小鼠间充质干细胞（MSCs）定向诱导分化成脂肪细胞微小RNA（miRNA）表达的变化，为进一步研究miRNA调控MSCs向脂肪细胞分化的分子机制奠定基础。方法：采用全骨髓体外分离结合差速贴壁法纯化扩增C57BL／6小鼠MSCs，形态学观察细胞生长情况，并用免疫组化方法鉴定细胞表面抗原CD29、CIM4和CD34的表达。脂肪细胞分化诱导剂诱导MSCs分化为脂肪细胞，利用油红O染色，判断MSCs成脂分化情况。运用rrfiRNA芯片技术检测MSC8和脂肪细胞中差异表达的miRNA。结果：①倒置显微镜下观察，传5代后可获得均一性较高的MSCs；免疫组化显示90％以上的骨髓间质干细胞CD29、CD44阳性，CD34阴性。MSCs经脂肪诱导剂诱导后，胞内大量脂滴形成，油红O染色阳性；②基因微阵列分析表明，小鼠MSCs分化成脂肪细胞差异表达的miRNA共75个，其中20个表达上调、55个表达下调。结论：MSCs分化成脂肪细胞存在miRNA表达的变化，某些miRNA很可能具有重要的调控MSCs成脂分化的作用。
语种：
中文
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银杏叶提取物对华法林人体内抗凝血功能和血药浓度的影响
作者：
周于禄;曾嵘
期刊：
中国中药杂志 ,2011年36(16):2290-2293 ISSN：1001-5302
通讯作者：
Zhou, Y.
作者机构：
[周于禄] 中南大学湘雅三医院;[曾嵘] 湖南中医药大学;湖南中医药大学药学院中药现代化重点实验室
通讯机构：
Third Xiangya Hospital, Central South University, China
关键词：
银杏叶提取物;华法林;药物相互作用;凝血;血药浓度
摘要：
目的:研究银杏叶提取物对华法林在人体内药动学和药效学的影响。方法:采用随机、单盲、双周期交叉、安慰荆对照试验设计。12名健康志愿者(男女各半)随机分为2组,连续5周每日分别服用银杏叶片(EGB,每片含总黄酮醇苷9.6 mg,萜类内酯2.4 mg)或安慰剂2粒,1日3次;29 d口服单剂量华法林5 mg;第2周期2组交叉服用安慰剂或银杏叶片,其余给药方案不变。按要求收集志愿者血样,分别以半自动血凝仪测定常见凝血指标,以HPLC测定华法林的血药浓度。结果:单独服用银杏叶提取物4周后,华法林凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)无显著变化。华法林药动学参数 Cmax,AUC_(0-144),AUC_(0-∞),t_(1/2)显著增加(P＜0.05);CL(F)显著减小(P＜0.05),t_(max)和V_d(F)没有显著变化。结论:银杏叶提取物可影响华法林的药动学指标,但不影响华法林的药效学;单独服用银杏叶提取物4周对凝血功能无明显影响。
语种：
中文
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Aryl Hydrocarbon Receptor Deficiency Enhances Insulin Sensitivity and Reduces PPAR-alpha Pathway Activity in Mice
作者：
Wang, Chun;Xu, Can-Xin;Krager, Stacey L.;Bottum, Kathleen M.;Liao, Duan-Fang;...
期刊：
ENVIRONMENTAL HEALTH PERSPECTIVES ,2011年119(12):1739-1744 ISSN：0091-6765
通讯作者：
Tischkau, Shelley A.
作者机构：
[Tischkau, Shelley A.; Wang, Chun; Xu, Can-Xin] So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA.;[Wang, Chun; Xu, Can-Xin] Univ S China, Coll Pharm & Life Sci, Inst Pharm & Pharmacol, Hengyang, Hunan, Peoples R China.;[Krager, Stacey L.; Bottum, Kathleen M.] So Illinois Univ, Sch Med, Dept Internal Med, Springfield, IL USA.;[Liao, Duan-Fang] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha, Hunan, Peoples R China.;[Tischkau, Shelley A.] 801 N Rutledge,Room 3354,POB 9629, Springfield, IL 62974 USA.
通讯机构：
[Tischkau, Shelley A.] 8;801 N Rutledge,Room 3354,POB 9629, Springfield, IL 62974 USA.
关键词：
aryl hydrocarbon receptor;BMAL1;circadian rhythm;diabetes;dioxins;PPAR-alpha
摘要：
BACKGROUND: Numerous man-made pollutants activate the aryl hydrocarbon receptor (AhR) and are risk factors for type 2 diabetes. AhR signaling also affects molecular clock genes to influence glucose metabolism. OBJECTIVE: We investigated mechanisms by which AhR activation affects glucose metabolism. METHODS: Glucose tolerance, insulin resistance, and expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and genes affecting glucose metabolism or fatty acid oxidation and clock gene rhythms were investigated in wild-type (WT) and AhR-deficient [knockout (KO)] mice. AhR agonists and small interfering RNA (siRNA) were used to examine the effect of AhR on PPAR-alpha expression and glycolysis in the liver cell line Hepa-1c1c7 (c7) and its c12 and c4 derivatives. Brain, muscle ARNT-like protein 1 (Bmal1) siRNA and Ahr or Bmal1 expression plasmids were used to analyze the effect of BMAL1 on PPAR-alpha expression in c7 cells. RESULTS: KO mice displayed enhanced insulin sensitivity and improved glucose tolerance, accompanied by decreased PPAR-alpha and key gluconeogenic and fatty acid oxidation enzymes. AhR agonists increased PPAR-alpha expression in c7 cells. Both Ahr and Bmal1 siRNA reduced PPAR-alpha and metabolism genes. Moreover, rhythms of BMAL1 and blood glucose were altered in KO mice. CONCLUSIONS: These results indicate a link between AhR signaling, circadian rhythms, and glucose metabolism. Furthermore, hepatic activation of the PPAR-alpha pathway provides a mechanism underlying AhR-mediated insulin resistance.
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英文
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Modeling Molecular Acidity with Electronic Properties and Hammett Constants for Substituted Benzoic Acids
作者：
Huang, Ying* ;Liu, Lianghong;Liu, Wanhui;Liu, Shaogang;Liu, Shubin
期刊：
Journal of Physical Chemistry A ,2011年115(51):14697-14707 ISSN：1089-5639
通讯作者：
Huang, Ying
作者机构：
[Huang, Ying; Liu, Lianghong] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Liu, Wanhui] Yantai Univ, Pharmaceut Sch, Yantai 264003, Shandong, Peoples R China.;[Liu, Shaogang] Cent S Univ, Modern Analyt Testing Ctr, Changsha 410078, Hunan, Peoples R China.;[Liu, Shubin] Univ N Carolina, Ctr Res Comp, Chapel Hill, NC 27599 USA.
通讯机构：
[Huang, Ying] H;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
摘要：
Molecular acidity is an important physiochemical property essential in many fields of molecular studies, but an efficient and reliable computational approach to make accurate predictions is still missing. In this work, based on our previous studies to use gas phase electronic properties such as molecular electrostatic potential and valence natural atomic orbitals of the acidic atom and leaving proton, we demonstrate here that different approaches can be employed to tackle this problem. To that end, we employ 196 singly, doubly, and triply substituted benzoic acids for the study. We show that two different approaches are possible, one focusing on the carboxyl group through its localized electronic properties and the other on the substituting groups via Hammett constants and their additivity rule. Our present results clearly exhibit that with the linear models built from the singly substituted species, one can accurately predict the pK<inf>a</inf> values for the doubly and triply substituted species with both of these two approaches. The predictions from these approaches are consistent with each other and agree well with the experimental data. These intrinsically different approaches are the two manifestations of the same molecular acidity property, both valid and complementary to each other. ©2011 American Chemical Society.
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英文
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Detection of intermediates for the Eschweiler-Clarke reaction by liquid-phase reactive desorption electrospray ionization mass spectrometry
作者：
Xu, Guangming;Chen, Bo;Guo, Bin* ;He, Dongxiu;Yao, Shouzhuo
期刊：
ANALYST ,2011年136(11):2385-2390 ISSN：0003-2654
通讯作者：
Guo, Bin
作者机构：
[Xu, Guangming; Yao, Shouzhuo] Hunan Univ, Coll Chem & Chem Engn, Ctr Biomed Engn, Changsha 410081, Hunan, Peoples R China.;[Guo, Bin; He, Dongxiu; Chen, Bo] Hunan Normal Univ, Minist Educ China, Key Lab Chem Biol & Tradit Chinese Med Res, Changsha 410081, Hunan, Peoples R China.;[Xu, Guangming] Hunan Univ Tradit Chinese Med, Coll Pharmaceut Sci, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Guo, Bin] H;Hunan Normal Univ, Minist Educ China, Key Lab Chem Biol & Tradit Chinese Med Res, Changsha 410081, Hunan, Peoples R China.
摘要：
Desorption electrospray ionization mass spectrometry (DESI-MS) has been developed dramatically as a powerful tool for the rapid analysis of samples in their native environment. Here a novel application of DESI-MS was demonstrated for direct probing of the reactive intermediates in the liquid-phase Eschweiler-Clarke reaction, a reductive amination reaction whereby a primary (or secondary) amine is successively N-methylated using excess formaldehyde and formic acid. The intermediates ion species of sodiated amino alcohol ([I + Na]+) and iminium ([II]+), along with the corresponding protonated molecules of amine reactant ([M + H]+) and end product ([III + H]+), were simultaneously and unambiguously characterized by the positive ion DESI-MS in the native liquid-phase reactive condition. The operating variables were optimized for better analytical performance including the spray solvent composition (such as formic acid concentration, proportion of methanol-water), voltage applied, spray spatial distance and incident angle. The feasibility of the reactive DESI-MS detection of acid-formaldehyde methylations was further validated using amines of a large variety of chemical types (2 primary and 3 secondary amines). Thus, the liquid-phase reactive DESI-MS technique allows the direct analysis of reaction intermediates occurring in complex liquid solutions without sample preparation to provide a valuable insight into chemical reaction mechanisms. © 2011 The Royal Society of Chemistry.
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英文
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二萜合酶的研究进展
作者：
何云飞;高伟;刘塔斯;李文渊;黄璐琦
期刊：
药学学报 ,2011年46(9):1019-1025 ISSN：0513-4870
通讯作者：
He, Y.-F.
作者机构：
[何云飞; 李文渊; 黄璐琦] 中国中医科学院中药研究所;[刘塔斯] 湖南中医药大学药学院;[高伟] 首都医科大学中医药学院
通讯机构：
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, China
关键词：
二萜合酶;生物合成途径;克隆;催化机制;合成生物学
摘要：
植物二萜类化合物广泛存在于自然界中,是一类重要的天然化合物。随着一些具有重要经济价值的二萜不断被发现,其生物合成中的二萜合酶也倍受关注。二萜合酶催化活性的多样性决定了终产物(二萜化合物)的丰富性。本文重点探讨了近年来二萜生物合成途径和二萜合酶的类型、克隆、催化机制及其合成生物学应用等研究进展。
语种：
中文
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补阳还五汤指纹图谱总量统计矩加合性的研究
作者：
段晓鹏;贺福元;周晋;曾姣丽;谢相贵;...
期刊：
中国中药杂志 ,2011年36(23):3247-3252 ISSN：1001-5302
通讯作者：
Duan, X.
作者机构：
[段晓鹏; 周晋; 曾姣丽; 谢相贵; 王海琴] 湖南中医药大学药学院;[贺福元] 湖南中医药大学
通讯机构：
Department of Pharmaceutics, Hunan University of Traditional Chinese Medicine, China
关键词：
补阳还五汤;指纹图谱;总量统计矩;加合性;溶度参数
摘要：
目的:采用总量统计矩法分析不同溶剂处理所获得的补阳还五汤HPLC指纹图谱,验证总量统计矩法的加合性。方法:采用水提醇沉法获取补阳还五汤总浸出物,依次用溶度参数11.4~23.40 Cal~(1/2).cm~(-3/2)的5种溶剂溶解制样;测定各溶剂浸出物的HPLC指纹图谱,计算并分析其总量统计矩参数的叠加规律。结果:以补阳还五汤总方液指纹图谱为参照峰,用正丁醇(11.4 Cal~(1/2).cm~(-3/2))、甲醇(13.5 Cal~(1/2).cm~(-3/2))、68%甲醇(16.67 Cal~(1/2).cm~(-3/2))、34%甲醇(20.03 Cal~(1/2).cm~(-3/2))、水(23.40 Cal~(1/2).cm~(-3/2))依次溶解所获得的浸出物指纹图谱的相似度分别为0.074,0.973,0.934,0.991,0.993,其总量零阶矩、一阶矩、二阶矩的RSD为63.04%,16.22%,69.38%,表明各指纹图谱差异性较大;按指纹图谱加合性公式计算的总量零阶矩、一阶矩、二阶矩分别为3.203×10~5 mAu.s,29.85 min,389.97 min~2,而实际测得的总方浸出物指纹图谱的总量零阶矩、一阶矩、二阶矩分别为6.548×10~4 mAu.s,29.44 min,389.00 min~2;两者极差绝对值百分率分别为2.209%,1.389%,0.248 4%。结论:中药指纹图谱总量统计矩法具有加合性,可用于中药多成分体系静态与动态的质量监控分析。
语种：
中文
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罗汉果中1个新的天然皂苷
作者：
李春;林丽美;罗明;马长福;王智民
期刊：
中国中药杂志 ,2011年36(6):721-724 ISSN：1001-5302
通讯作者：
Li, C.
作者机构：
[李春] Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. wenyeli@yahoo.com.cn
通讯机构：
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, China
关键词：
罗汉果;三萜皂苷;罗汉果皂苷ⅢA1
摘要：
目的:研究罗汉果中的化学成分. 方法:用各种色谱法分离和纯化化合物, 通过多种波谱数据鉴定其结构. 结果:从罗汉果乙醇提取物中分离鉴定了6个葫芦烷型三萜皂苷, 分别为罗汉果皂苷ⅢA1(mogrosideⅢA1)、赛门苷Ⅰ(siamenoside I)、罗汉果皂苷Ⅳa(mogrosideⅣa)、罗汉果皂苷Ⅳe(mogrosideⅣe)、罗汉果皂苷(mogrosideⅤ)、11-氧-罗汉果皂苷Ⅴ(11-oxo-mogrosideⅤ). 结论:mogrosideⅢA1为首次从天然产物中分离得到, 鉴定其结构为罗汉果醇-24-O-β-D-吡喃葡萄糖基(1→2)-[β-D-吡喃葡萄糖基(1→6)]-β-D-吡喃葡萄糖苷{Mogrol-24-O-β-D-glucopyranosyl(1→2)-[β-D-glucopyranosyl(1→6)]-β-D-glucopyranoside};其余5个化合物为已知化合物
语种：
中文
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蜂蜜对阿昔洛韦在兔眼内转运动力学特性的影响
作者：
何群;王适;张湘晖;张健;姜宇;...
期刊：
中国中药杂志 ,2011年36(19):2723-2726 ISSN：1001-5302
通讯作者：
He, Q.
作者机构：
[何群; 姜宇; 许江丽] 湖南中医药大学中药药剂学重点学科湖南中医药大学中药现代化实验室;[张湘晖; 张健] 湖南中医药大学第一临床学院;[王适] 湖南中医药大学第二临床学院
通讯机构：
Hunan Univ. of Traditional Chinese Med. and Drug Traditional Chinese Med. Pharmaceut. Key Subjects, Hunan University of Traditional Chinese Medicine, Drug Modernization Laboratory of Traditional Chinese Medicine and Drug, China
关键词：
蜂蜜;阿昔洛韦(ACV);单纯疱疹病毒性角膜炎(HSK);高效液相色谱法(HPLC);二室模型
摘要：
目的:从药动学角度探索蜂蜜增强阿昔洛韦(ACV)治疗单纯疱疹病毒性角膜炎(HSK)药效的作用机制,为2药合用处方及给药方案设计提供依据。方法:分别单次给予兔眼内含5%蜂蜜和0%蜂蜜的目安眼膏,于不同时间取兔眼房水,高效液相色谱法测房水内ACV含量,建立数学模型,通过数学及统计学处理提取药动学参数,比较各参数差异。结果:含5%蜂蜜和0%蜂蜜的目安眼膏在兔眼内的转运均属于二室模型,含5%蜂蜜的目安眼膏在房水中吸收半衰期为不含蜂蜜目安眼膏的2.30倍,分布半衰期为2.12倍,达峰浓度为1.17倍,达峰时间为1.36倍,AUC为1.41倍。结论:蜂蜜可显著提高ACV在眼内的浓度及生物利用度,延长ACV在靶细胞内的作用时间,提高ACV在靶分子的滞留能力,使ACV在靶组织药效持久,从而提高疗效。
语种：
中文
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中药多成分体系宏观质量表征的数学模型建立及实验研究
作者：
贺福元;邓凯文;石继连;刘文龙;皮风娟
期刊：
中国中药杂志 ,2011年36(22):3096-3103 ISSN：1001-5302
通讯作者：
He, F.
作者机构：
[贺福元; 石继连; 刘文龙; 皮风娟] 湖南中医药大学药学院;中药药性与药效国家中医药管理局重点实验室;湖南中医药大学现代中药制剂制备与评价实验室;[邓凯文] 湖南中医药大学第一附属医院
通讯机构：
Department of Pharmaceutics, Hunan University of Tradition Chinese Medicine, China
关键词：
中药质量;宏观质量;燃烧焓;信息熵;表观平衡常数;生物热焓;生物熵;Gibbs自由能;网通虹势
摘要：
目的:建立宏观状态数学模型与微观成分浓度相统一的中药材成分质量表征体系。方法:根据生物热力学定律建立中药材成分宏观状态函数关系式,并以大黄药材醇浸出物为对象,先测定燃烧焓,再建立指纹图谱,测定信息熵与信息量,再计算生物熵和表观平衡常数。结果:建立了中药成分的表观平衡常数、生物热焓、Gibbs自由能与生物熵等中药成分质量宏观状态函数模型。10批大黄的总摩尔浓度为0.153 4 mmol.g~(-1),RSD 28.26%;平均表观平衡常数为0.039 65,RSD6.020%;标准自由能为8 005 J.mol~(-1),RSD 1.860%;生物热焓为-2.408×10~7 J.mol~(-1),RSD 42.32%;生物熵为-8.078×10~4 J.K~(-1),RSD 42.31%。结论:中药宏观质量表征数学模型能表征中药多成分动态体系的内在质量,可达到远如森林近似树的综合作用结果。
语种：
中文
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Dual role of insulin-like growth factor-1 in acetyl-CoA carboxylase-alpha activity in human colon cancer cells HCT-8: downregulating its expression and phosphorylation
作者：
Luo, Di-Xian;Peng, Xu-hong;Xiong, Yan;Liao, Duan-Fang;Cao, Deliang;...
期刊：
Molecular and Cellular Biochemistry ,2011年357(1-2):255-262 ISSN：0300-8177
通讯作者：
Li, Longjiang
作者机构：
[Luo, Di-Xian; Cao, Deliang] So Illinois Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, Simmons Canc Inst, Springfield, IL 62702 USA.;[Li, Longjiang] Baoan Dist Peoples Hosp, Dept Urol Surg, Shenzhen 518101, Peoples R China.;[Luo, Di-Xian; Liao, Duan-Fang] Univ S China, Coll Pharmaceut & Life Sci, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Peng, Xu-hong] First Peoples Hosp, Dept Ultrasound Diag, Chenzhou City 423000, Peoples R China.;[Xiong, Yan] Guangzhou Med Univ, Dept Pharmacol, Guangzhou 510182, Guangdong, Peoples R China.
通讯机构：
[Li, Longjiang] B;Baoan Dist Peoples Hosp, Dept Urol Surg, 168 Longjing 2 Rd, Shenzhen 518101, Peoples R China.
关键词：
Acetyl-CoA carboxylase-alpha;Insulin-like growth factor-1;Fatty acid/lipid synthesis;ERK1/2;AMPK;HCT-8 cells
摘要：
Insulin-like growth factor-1 (IGF-1) plays the role in cellular lipid synthesis and cell proliferation. However, the role of IGF-1 on the growth of colon cancer cell line HCT-8 is not clear. In this study, HCT-8 cells were exposed to IGF-1 at 0, 10, 50, or 100 ng/ml in serum-free medium. Fatty acid/lipid synthesis in HCT-8 cells was examined by 2-14C-acetate incorporation. HCT-8 cell growth and proliferation were determined by MTT assay and Trypan blue exclusive viable cell counting. We found that in serum starvation conditions, IGF-1 at 10-100 ng/ml induced dose-dependent down regulation of both the ACCα expression and the phosphorylation in HCT-8 cells, maintaining a balance in ACCα activity and lipid synthesis. IGF-1 reduced p-ATM, p-AMPK, and then p-ACCα protein levels in HCT-8 cells. IGF-1 increased p-Akt levels, but decreased p-ERK1/2 levels, leading to the decrease in ACCα protein and mRNA levels. Similarly, ERK1/2 inhibitor PD98059 reduced ACCα expression. IGF-1 influences neither HCT-8 cell growth nor their p53 protein levels and PARP cleavage. In a word, IGF-1 reduced ACCα phosphorylation via an ATM/AMPK signaling pathway and suppressed ACCα expression through an ERK1/2 transduction, playing a dual role in regulating ACCα activity and lipogenesis. This may render a cell with survival advantages under a serum starvation crisis, representing a novel mitogenic role of IGF-1. © Springer Science+Business Media, LLC. 2011.
语种：
英文
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Solid-phase extraction and ultra high-performance liquid chromatography tandem mass spectrometry analysis of the gastrointestinal absorption of emodin in different digestive segments of rats
作者：
Kong, Weijun;Xia, Xinhua;Wang, Jiabo;Zhou, Canping;Fang, Fang;...
期刊：
Journal of Separation Science ,2011年34(3):260-267 ISSN：1615-9306
通讯作者：
Xiao, Xiaohe
作者机构：
[Zhou, Canping; Fang, Fang; Kong, Weijun; Xing, Xiaoyan; Wang, Jiabo; Zang, Qingce; Xiao, Xiaohe; Zhao, Yanling; Jin, Cheng] Mil Hosp China, China Mil Inst Chinese Mat Med, Beijing, Peoples R China.;[Fang, Fang; Kong, Weijun; Xing, Xiaoyan] Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu, Peoples R China.;[Xia, Xinhua; Zhou, Canping] Hunan Univ Chinese Med, Coll Pharmaceut Sci, Changsha, Hunan, Peoples R China.;[Zang, Qingce] Jiangxi Univ Tradit Chinese Med, Coll Pharm, Nanchang, Peoples R China.;[Xiao, Xiaohe] 302 Mil Hosp China, China Mil Inst Chinese Mat Med, Beijing 100039, Peoples R China.
通讯机构：
[Xiao, Xiaohe] 3;302 Mil Hosp China, China Mil Inst Chinese Mat Med, Beijing 100039, Peoples R China.
关键词：
Digestive segment;Emodin;Gastrointestinal absorption;SPE;UHPLC-ESI-MS/MS
摘要：
A rapid, simple and sensitive ultra high-performance liquid chromatography (UHPLC-MS/MS) method was established for determining the absorption amount of emodin in the five digestive segments of rat. Plasma samples were pre-purified by solid-phase extraction (SPE) with Oasis MAX cartridge. Separation of emodin and 1,8-dihydroxyanthraquinone (internal standard) was performed on an Acquity BEH UHPLC C<inf>18</inf> column (100mm ×- 2.1mm, 1.7Iμm) with gradient elution of methanol and 0.1% formic acid aqueous solution. The LC/MS system was operated under multiple reaction monitoring mode using electrospray ionization (ESI) in negative ion mode. The results showed that this established method was valid and sensitive for emodin within 0.04-16.4μg/mL, with low limits of detection and quantification of 0.6ng/mL and 2.4ng/mL, respectively and upper limit of quantification of 220.0ng/mL. The intra- and interday variations were below 4.9% of RSD. The extraction recoveries were 98.9-106.1% with RSD of 1.9-3.2%. The plasma concentration-time relationship showed that the absorption of emodin in stomach was faster than in intestine segments. The sequence of absorption amount was: ileum>jejunum>colon-duodenum>stomach. Most of emodin was absorbed in ileum, and the absorption amount was increased with prolonged retention of drug form in intestine, especially in ileum and jejunum. The developed UHPLC-ESI-MS/MS method was appropriate for determining the in vivo absorption of emodin in other herbal medicines or preparations containing this compound. Copyright ©2011 WILEY-VCH Verlag GmbH &Co. KGaA, Weinheim.
语种：
英文
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单面针茎中生物碱类成分研究
作者：
肖灿;袁园;丁扬洲;靳铁飞;裴刚
期刊：
中药材 ,2011年34(4):551-553 ISSN：1001-4454
通讯作者：
Xiao, C.
作者机构：
[肖灿; 袁园; 丁扬洲; 靳铁飞; 裴刚] 湖南中医药大学药学院
关键词：
单面针;生物碱
摘要：
目的:对单面针茎中的生物碱成分进行研究。方法:将0.5%盐酸渗滤得到酸水用氨水调pH值至11,以此提取单面针茎中总生物碱,采用氧化铝、硅胶柱层析法进行分离,并根据理化性质及光谱数据对单体化合物进行结构鉴定。结果:分离得到4个化合物,经鉴定分别为:两面针碱(Ⅰ)、血根碱(Ⅱ)、花椒棚碱(Ⅲ)、白鲜碱(Ⅳ)。结论:其中,化合物Ⅰ~Ⅲ为首次从单面针茎中分离得到。
语种：
中文
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基于环氧合酶抑制作用的人工麝香质量评价方法研究
作者：
罗云;金城;周健;温瑞卿;李兴丰;...
期刊：
药学学报 ,2011年46(4):438-442 ISSN：0513-4870
通讯作者：
Jin, C.
作者机构：
[罗云; 金城; 周健; 温瑞卿; 李兴丰; 肖小河] 解放军第三○二医院解放军中药研究所;[李瑞生] 解放军第三○二医院实验动物中心;[杨明] 江西中医学院
通讯机构：
China Military Institute of Chinese Materia Medica, 302 Military Hospital of China, China
关键词：
人工麝香;环氧合酶-2;酶免疫测定;抗炎;生物评价
摘要：
采用酶免疫（EIA）法,测定和计算人工麝香对环氧合酶Ⅱ（COX-2）的抑制率,构建人工麝香对COX-2抑制作用的量效关系,为建立人工麝香的体外抗炎效价测定方法提供研究基础。结果显示,人工麝香对COX-2具有明显抑制作用,半数抑制浓度（IC50）为2.26 mg·mL-1,在0.31～20.0 mg·mL-1内,具有明显的量效关系。结果表明,该方法快速、灵敏、准确、重现性好,可用于建立人工麝香抗炎生物效价检测方法,同时本文也为人工麝香的生物活性评价提供了新的研究思路和方法。
语种：
中文
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