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| 1 | Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells显示文摘AIM:To determine the effect of ellagic acid on apop-tosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid. METHODS:The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization,caspase activity,mitochondrial membrane potential and DNA fragmentation;and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells,and in isolated mitochondria. Nuclear factor kB(NF-kB) activity was measured by electromobility shift assay(EMSA) . RESULTS:We show that ellagic acid,a polyphenolic compound in fruits and berries,at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further,ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization,cytochrome C release,and the downstream caspaseactivation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kB binding activity. Furthermore,inhibition of NF-kB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION:Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosu-rvival transcription factor NF-kB. | Mouad Edderkaoui Irina Odinokova Izumi Ohno Ilya Gukovsky Vay Liang W Go Stephen J Pandol Anna S Gukovskaya | 2008 | World Journal of Gastroenterology2008，14，23： | 30 |
| 2 | Alcoholic hepatitis: The pivotal role of Kupffer cells显示文摘Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis(AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides(LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called tolllike receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis. | Duminda B Suraweera Ashley N Weeratunga Robert W Hu Stephen J Pandol Richard Hu | 2015 | World Journal of Gastrointestinal Pathophysiology2015，6，4： | 3 |
| 3 | Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting显示文摘瞄准:如果与推延的 portasystemic 有关的 T 房间激活通过 RANKL 依赖的小径引起调停骨破折的骨头损失,学习。如果用 rapamycin 的 T 房间抑制将在老鼠免于骨头损失,我们也调查了。方法:推延的 Portasystemic 在男 Sprague-Dawley 老鼠和 rapamycin 被执行 0.1 mg/kg 被管饲法为 15 wk 管理。老鼠收到了 powderized 食物并且补加喂在骨头作文上阻止营养不良的效果。重量获得和生长在推延的动物在外科以后被恢复。在结束,骨头周转和量的骨头组织学的生物化学的参数被估计。T 房间激活,煽动性的 cytokine 生产,和 RANKL 依赖的小径的标记被测量。另外, IGF-1 和性腺机能减退的角色被调查。结果:推延的 Portasystemic 引起了是 RANKL 独立人士的低周转骨质疏松症。包括 IL-1, IL-6 和 TNFalpha,骨头再吞 cytokine 层次没在浆液和 TNFalpha 被增加, RANKL 表示不起来在 PBMC 调整了。推延的 Portasystemic 增加了传播 CD8+T 房间人口。Rapamycin 减少了传播 CD8+T 房间人口,增加了 CD8+CD25+T 规章的房间人口并且改进了骨头周转的所有参数。结论:推延的 portasystemic 引起的骨质疏松症可以被 rapamycin 部分在肝的骨营养不良的老鼠模型改善。 | Schalk W van der Merwe Maria M Conradie Robert Bond Brenda J Olivier Elongo Fritz Martin Nieuwoudt Rhena Delport Tomas Slavik Gert Engelbrecht Del Kahn Enid G Shephard Maritha J Kotze Nico P de Villiers Stephen Hough | 2006 | World Journal of Gastroenterology2006，12，28： | 2 |
| 4 | Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing显示文摘 | Chan K C Allen Jiang Peiyong Zheng Yama W L Liao Gary J W Sun Hao Wong John Siu Shing Shun N Chan Wing C Chan Stephen L Chan Anthony T C Lai Paul B S Chiu Rossa W K Lo Y M D | 2013 | Clinical Chemistry2013，，1： | 2 |
| 5 | Biomarker-guided sequential targeted therapies to overcome therapy resistance in rapidly evolving highly aggressive mammary tumors显示文摘组合指向的治疗在由堵住治疗癌症是更有效的绕过机制或导致的合成致命性。然而,他们的临床的申请被抵抗和毒性妨碍。遇见这重要挑战,我们用 ErbB2-overexpressing/PTEN-low 开发了并且测试各种各样的指向的治疗的指导 biomarker 的顺序的应用程序的一个新奇概念,高度好攻击的乳癌作为我们的模型。惊人地,从遗传上设计的鼠标与 intratumoral 异质从病人和乳房的肿瘤在两 PTEN-low/trastuzumab-resistant 乳癌支撑了 ErbB2 和下游的小径驱动器 trastuzumab 抵抗的激活。尽管 lapatinib 开始禁止了 trastuzumab 抵抗的鼠标肿瘤,肿瘤由激活表明由量的蛋白质数组出现的网络的 PI3K/mTOR 绕过抑制。有趣地,小径也是的 mTOR 的激活在 neoadjuvant 观察了表明 lapatinib 抵抗的对待 lapatinib 的病人。Trastuzumab + lapatinib 抵抗被一个 PI3K/mTOR 双 kinase 禁止者(BEZ235 ) 的顺序的申请有效地没有重要毒性克服。然而,我们的 p-RTK 数组分析证明 BEZ235 治疗在遗传上设计的老鼠肿瘤导致了增加的 ErbB2 表示和 phosphorylation,导致 BEZ235 抵抗并且在 3-D,然而并非 2-D,文化。机械学地,我们作为 BEZ235 抵抗的新奇机制识别了 ErbB2 蛋白质稳定和激活,它被随后的治疗与 lapatinib + BEZ235 联合颠倒。显著地, biomarker 指导的指向的治疗的这个顺序的应用程序在很快发展加倍的抵抗的肿瘤改变忍受极其好攻击的肿瘤的鼠标的寿命。使用的这条根本上新奇的途径有效地在一个顺序的顺序罐头指向了治疗目标和改编在在治疗期间发展抵抗的癌症的发信号的网络。 | Ozgur Sahin Qingfei Wang Samuel W Brady Kenneth Ellis Hai Wang Chia-Chi Chang Qingling Zhang Preety Priya Rui Zhu Stephen T Wong Melissa D Landis William J Muller Francisco J Esteva Jenny Chang Dihua Yu | 2014 | Cell Research2014，24，5： | 2 |
| 6 | How Relational Norms Affect Compliance in Industrial Buying显示文摘 | Joshi A W Stephen J A | 1996 | Journal of Business Research1996，35，1： | 1 |
| 7 | Consequences of the Allee effect for behaviour, ecology and censer?vation显示文摘 | Stephens P A Sutherland W J | 1999 | Trends in Ecology and Evolution1999，14，10： | 1 |
| 8 | Measurement and prediction of voltage flicker magnitude and frequency显示文摘 | Girgis A A Stephens J W Makram E B | 1995 | IEEE Trans on Power Delivery1995，10，3： | 1 |
| 9 | Stability and composition of terrestrially derived dissolved organic nitrogen in continental shelf surface waters 显示文摘 | GARDNER W S STEPHENS J A | 1978 | Marine Chemistry1978，6，4： | 1 |
| 10 | In situ investigation of the calcium-induced proteolytic and salting-in mechanisms causing tenderization in calcium-enhanced muscle显示文摘 | Lawrance T E Dikeman M E Stephens J W | 2003 | Meat Sci2003，66，： | 1 |
| 11 | Analysis of ammonia-oxidizing bacteria of the 13 subdivision of the class Pro- teobacteria in coastal sand dunes by denaturing gradient gel electro- pboresis and sequencing of PCR-amplified 16S ribosomal DNA frag- ments 显示文摘 | KOWALCHUK G A STEPHEN J R DE BOER W | 1997 | Appl Environ Microbiol1997，63，4： | 1 |
| 12 | Representation of skew in time-stepped two-dimensional finite-element models of electrical machines显示文摘 | Stephen W Timothy J F Alhertus FV | 1995 | IEEE Transactions on Industry Applications1995，31，5： | 1 |
| 13 | A cDNA encoding a cold-induced glycine-rich RNA binding protein from Prunus avium expressed in embryonic axes 显示文摘 | Stephen J R Dent K C Finch-Savage W E | 2003 | Gene2003，320，27： | 1 |
| 14 | Irrigation short rotation coppice with landfill leachate: Constraits to productivity due to chloride显示文摘 | STEPHENS W TYRRL S F TIBERGHIEN J E | 2000 | Bioresource Technology2000，75，： | 1 |
| 15 | An investigation of the kinetics of cellulose degradation under non - isothermal conditions 显示文摘 | Stephen W Bigger Scheid J | 1998 | Pol- ymer Degmiation and Stability1998，62，1： | 1 |
| 16 | Consequences of the Allee effect for behaviour, ecology and conservation显示文摘 | Stephens P A Sutherland W J | 1999 | Trends in Ecology and Evolution1999，14，： | 1 |
| 17 | Gradient projection for sparse reconstruction: application to compressed sensing and other inverse problems 显示文摘 | Figueiredo M T Nowak R D Stephen J W | 2007 | IEEE Journal of Selected Topics in Signal Processing2007，1，4： | 1 |
| 18 | Economic Impact of Antidiabetic Medications and Glycemic Control on Managed Care Organizations: A Review of the Literature显示文摘 | Stephens J M Botteman M F Hay J W | 2006 | Journal of Managed Care Pharmacy2006，12，2： | 1 |
| 19 | Coping style as a psychological resource of grateful people显示文摘 | Alex M W Stephen J Linley A P | 2007 | Journal of Social and Clinical Psychology2007，26，9： | 1 |
| 20 | Long-termexposure of plaque to zinc citrate 显示文摘 | Jones C L Stephen K W Ritchie J A | 1988 | Caries Res1988，22，2： | 1 |
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