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| 1 | 肌萎缩性侧索硬化蛋白激活小胶质细胞NLRP3炎性小体显示文摘小胶质细胞NLRP3炎性小体激活正在成为神经退行性变过程中神经炎症的关键因素。诸如β-淀粉样蛋白和α-突触核蛋白之类的致病性蛋白质聚集体触发小胶质NLRP3激活,从而导致半胱天冬酶-1激活和IL-1β的分泌。在小鼠肌萎缩性侧索硬化症(ALS)的SOD1G93A模型中,半胱天冬酶-1和IL-1β均促进疾病进展,提示小胶质NLRP3在该进程中发挥作用。然而先前的研究表明,SOD1G93A小鼠小胶质细胞不表达NLRP3,SOD1G93A蛋白在小胶质细胞中产生独立于NLRP3的IL-1β。本研究论证了使用Nlrp3-GFP基因敲入小鼠,在SOD1G93A小鼠中小胶质细胞表达NLRP3。本研究显示聚集和可溶性SOD1G93A均可激活小鼠原代小胶质细胞中的炎性小体,导致半胱天冬酶-1和IL-1β裂解,ASC斑点形成以及呈剂量和时间依赖性的IL-1β分泌。重要的是,SOD1G93A无法从缺乏Nlrp3的小胶质细胞或者用特异性NLRP3抑制剂MCC950预处理的小胶质细胞中诱导IL-1β分泌,从而证实NLRP3是介导SOD1诱导的小胶质细胞IL-1β分泌的关键炎症小体复合物。在TDP-43Q331K ALS小鼠模型中也观察到小胶质NLRP3上调,TDP-43野生型和突变蛋白亦可以NLRP3依赖性的方式激活小胶质炎性小体。从机制上讲,本研究确定了活性氧簇和ATP的生成是SOD1G93A介导的NLRP3激活所需的关键事件。总之,本研究的数据表明ALS小胶质细胞表达NLRP3,而病理ALS蛋白激活小胶质NLRP3炎性小体。因此,NLRP3抑制可能是阻止小胶质细胞神经炎症和ALS疾病进展的潜在治疗方法。 | Vandana Deora John D Lee Eduardo AAlbornoz Luke McAlary Cyril J Jagaraj Avril A B Robertson Julie D Atkin Matthew A Cooper Kate Schroder Justin J Yerbury Richard Gordon Trent MWoodruff 杜一星(编译) | 2020 | 神经损伤与功能重建2020，15，9： | 13 |
| 2 | 2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents显示文摘In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC_(50) values of 9.2 and 21.8 mmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme. | Erin Marie Kirwen Tarun Batra Chandrabose Karthikeyan Girdhar Singh Deora Vandana Rathore Chaitanya Mulakayala Naveen Mulakayala Amy Catherine Nusbaum Joel Chen Haneen Amawi Kyle Mc Intosh Sahabjada Neelam Shivnath Deepak Chowarsia Nisha Sharma Md Arshad Piyush Trivedi Amit KTiwari | 2017 | Acta Pharmaceutica Sinica B2017，7，1： | 3 |
| 3 | Effect of gossypol on hepatic and serum γ-glutamyhransferase activity in rats 显示文摘 | Deoras DP Young CP Dalvi RR | 1997 | Vrterinary Res Commynicat1997，21，5： | 1 |
| 4 | Design, synthesis and bio- logical evaluation of novel arylidinemalononitrile deriv- atives as non - carboxylic inhibitors of protein tyrosine phosphatase 1B 显示文摘 | Girdhar Singh Deora Chandrabose Karthikeyan Hari Narayana Moorthy N S | 2013 | Med Chem Res2013，22，： | 1 |
| 5 | Autoantibodiesagainst the fibrinolytic receptor, annexin 2 , in antiphospholipid syn-drome显示文摘 | Cesarman-Maus G Rios-Luna NP Deora AB ei al | 2006 | Blood2006，107，43： | 1 |
| 6 | Annexin Ⅱ regulates fibrin homeostasis and neo-angiogenesis in vivo 显示文摘 | Ling Q Jacovina AT Deora A | 2004 | J Clin Invest2004，113，1： | 1 |
| 7 | The endothelial cell annexin A2 system and vascular fibrinnlysis 显示文摘 | Dassah M Deora AB He K | 2009 | Gen Physiol Biophys2009，，28： | 1 |
| 8 | Agent-based forma- tion of virtual organizations显示文摘 | Dang V D Nguyen T D Deora V | 2004 | International Journal of Knowledge Based Systems2004，17，24： | 1 |
| 9 | Bilateral pedicled nasol- abial flaps for the anterior alveolus mandibular defect : a review 显示文摘 | Deora SS Nanjappa M Kumaraswamy SV | 2010 | J Maxillofac Oral Surg2010，9，4： | 1 |
| 10 | An ICAM-1 like cell adhesion moleculer is responsible for CD34 positive haemopoietic stem cells adhesion tobone marrow stroma 显示文摘 | Rao SGA Chitnis VS Deora A | 1996 | Cell Biol Inv1996，20，： | 1 |
| 11 | Expectation-based quality of service assessment显示文摘 | Deora V Shao Jianhua Gray W A | 2006 | International Journal on Digital Libraries2006，6，3： | 1 |
| 12 | Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia显示文摘 | Deora AA Philp N Hu J | 2005 | Proc Natl Acad Sci U S A2005，102，16： | 1 |
| 13 | Annexin II is a key regula- tor of fibrin homeostasis and neoangiogenesis in vivo 显示文摘 | Ling Q Jacovina AT Deora AB et 81 | 2004 | J Clin Ino vest2004，113，1： | 1 |
| 14 | Reverse transcriptase-mediated tropism switching in Bordetella bacteriophage 显示文摘 | Liu M S Deora R Doulatov S R Gingery M Eiserling F A Preston A Maskell D J Simons R W Cotter P A Parkhill J | 2002 | Science2002，295，5562： | 1 |
| 15 | Application of deep belief networks for natural language understanding显示文摘 | SARIKAYA R HINTON G E DEORAS A | 2014 | IEEE/ACM transactions on audio speech and language processing2014，22，4： | 1 |
| 16 | An annexin 2 phosphorylation switch mediates pll-dependent translocation of annexin 2 to the cell surface显示文摘 | Deora AB Kreitzer G Jacovina AT | 2004 | The Journal of Biological Chemistry2004，279，43： | 1 |
| 17 | Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo显示文摘 | Ling Q Jacovina AT Deora A | 2004 | J Clin Invest2004，113，1： | 1 |
| 18 | Balloon-assisted tracking of guide catheter dealing with radial artery perforation and subclavian loop during percutaneous coronary intervention by transradial approach显示文摘 | Deora S Shah S Patel T | 2013 | Int J Cardiol2013，，13： | 1 |
| 19 | Annexin li Medi- ates Plasminogen-l)ependent Matrix Invasion by Human Monocytes: Enhanced Expression hy Macrophages 显示文摘 | Brownstein C Deora A B Jacovina A T | 2004 | Blood2004，103，： | 1 |
| 20 | Clonal propagation of zizyphus sepecies though tissue ctdtoure显示文摘 | RATHORE T S SINGH R P DEORA N S | 1992 | Scientia Horticulturae1992，51，： | 1 |
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