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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 | Toll-like receptor gene family and TIR-domin adapters in Danio rerio显示文摘 | Cyril J Laurent P Johanna C | 2004 | Molecular Immunology2004，40，： | 1 |
| 3 | The link between dietary fiber and human health显示文摘 | Cyril W K Amin E David J J | 2010 | Food Hydrocolloids2010，24，1： | 1 |
| 4 | Effect of plant sterols in combination with other choles-terol-lowering foods显示文摘 | David J A Jenkins Cyril W C Kendall Tri H Nguyen | 2008 | Metabolism Clinical and Experimental2008，57，1： | 1 |
| 5 | The link between dietary fiber and human health显示文摘 | Cyril W C Kendall Amin E David J A Jenkins | | 0，，01： | 1 |
| 6 | Changes in membrane polar lipid fatty aeids of seashore paspalum in response to low temperature exposure显示文摘 | Cyril J Powell G L Luncan R R | 2002 | Crop Sci2002，42，： | 1 |
| 7 | Changes in membrane polar lipid fatty acids of seashore paspalum in response to low temperature exposure显示文摘 | Cyril J Powell G L Luncan R R | 2002 | Crop Sci2002，42，： | 1 |
| 8 | Changes in membrane polar lipid fatty acids of seashore paspalum in response to low temperature exposure显示文摘 | Cyril J Powell G L Duncan R R | 2002 | Crop Science2002，42，： | 1 |
| 9 | Dietary fiber,the evolution of the human diet and coronary heart disease显示文摘 | David J A Jenkins Cyril W C Kendall Thomas PP Ransom | 1998 | Nutrition Research1998，18，4： | 1 |
| 10 | Changes in membrane polar lipid fatty acids of seashore paspalum in response to low temperature exposure显示文摘 | Cyril J Powell G L Duncan R R | 2002 | Crop Science2002，42，6： | 1 |
| 11 | Fast smooth-surface micro-finite element analysis of large-scale bone models 显示文摘 | Andreas J Wirth Cyril FIaig Thomas L Mueller | 2008 | Journal of Biomechanics2008，41，1： | 1 |
| 12 | Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds显示文摘To reflect human development,it is critical to create a substrate that can support long-term cell survival,differentiation,and maturation.Hydrogels are promising materials for 3D cultures.However,a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction.Herein,granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell(hiPSC)-derived neural networks.A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules.Cells and hydrogel granules were combined using a weaker secondary gelation step,forming self-supporting cell laden scaffolds.At three and seven days,granular scaffolds supported higher cell viability compared to bulk hydrogels,whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions(65.52±11.59μm)after seven days compared to bulk hydrogels(22.90±4.70μm).Long-term(three-month)cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold.This approach is significant as it provides a simple,rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures. | Chia-Chen Hsu Julian H.George Sharlayne Waller Cyril Besnard David A Nagel Eric J Hill Michael D.Coleman Alexander M.Korsunsky Zhanfeng Cui Hua Ye | 2022 | Bioactive Materials2022，7，3： | 1 |
| 13 | Changes in membrane polar lipid fatty acids of seashore paspalum in response to low temperature exposure 显示文摘 | CYRIL J POWELL G L DUNCAN R R | 2002 | Crop Sci2002，，42： | 1 |
| 14 | Hepatic overexpression of microsomal triglyeeride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein 显示文摘 | Tietge J F Ahmed Bakillah Cyrille Maugeais | 1999 | J Lipid Res1999，40，： | 1 |
| 15 | Synthesis and stereochemical studies of di and tetra 9,9' - spirobifluorene porphyrins: new building blocks for catalytic material显示文摘 | Cyril P Yann F Sandrine J et al | 2004 | tetrahedron2004，60，： | 1 |
| 16 | Opportunistic GP - based bowel cancer screening显示文摘 | Susan J Hamett S K Cyril Wong Gavin W Lackey | 2003 | MJA2003，178，2： | 1 |
| 17 | Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study显示文摘 | Joost Daemen Peter Wenaweser Keiichi Tsuchida Linda Abrecht Sophia Vaina Cyrill Morger Neville Kukreja Peter Jüni Georgios Sianos Gerrit Hellige Ron T van Domburg Otto M Hess Eric Boersma Bernhard Meier Stephan Windecker Patrick W Serruys | 2007 | The Lancet2007，，9562： | 1 |
| 18 | Management of primary hyperthyroidism: toward minimal access surgery显示文摘 | David Malinvaud Ga?l Potard Cyrille Fortun Alain Saraux Joseph André Jézéquel Rémi Marianowski | 2003 | Joint Bone Spine2003，，2： | 1 |
| 19 | Characteristics of Q-switched cladding-pumped Ytterbium-doped fiber lasers with different high-energy fiber designs显示文摘 | Renaud Cyril C Offerhaus H L Alvarez-Chavez J A | | 0，，： | 1 |
| 20 | Quality of Red BloodCeils Using Autotransfusion Devices: A Comparative Analysis显示文摘 | Cyril J Serrick Mary Scholz Arthur Melo | 2003 | JECT2003，35，： | 1 |
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