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| 1 | Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting显示文摘Monoclonal antibodies(m Abs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17 A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17 A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-h IL-17 A antibody. From a large na?ve phage-displayed library, we isolated the anti-IL-17 A m Ab 7 H9 that can neutralize the effects of recombinant human IL-17 A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. In vitro affinity optimization was then used to generate 8 D3 by using yeast-displayed random mutagenesis libraries.This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions(CDRs) of 8 D3 were further grafted onto the stable framework of the hu Fv 4 D5 to improve thermostability. The resulting hybrid antibody9 NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cellbased assays and in vivo analyses in mice indicated that the anti-IL-17 A antibody 9 NT/S efficiently inhibited the secretion of IL-17 A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17 A m Ab might be used as a potential best-in-class candidate for treating IL-17 A related diseases. | Wei Sun Zhaona Yang Heng Lin Ming Liu Chenxi Zhao Xueying Hou Zhuowei Hu Bing Cuin | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 4 |
| 2 | Scanning pattern of diffusion tensor tractography and an analysis of the morphology and function of spinal nerve roots显示文摘Radiculopathy,commonly induced by intervertebral disk bulging or protrusion,is presently diagnosed in accordance with clinical symptoms because there is no objective quantitative diagnostic criterion.Diffusion tensor magnetic resonance imaging and diffusion tensor tractography revealed the characterization of anisotropic diffusion and displayed the anatomic form of nerve root fibers This study included 18 cases with intervertebral disc degeneration-induced unilateral radiculopathy Magnetic resonance diffusion tensor imaging was creatively used to reveal the scanning pattern o fiber tracking of the spinal nerve root.A scoring system of nerve root morphology was used to quantitatively assess nerve root morphology and functional alteration after intervertebral disc degeneration.Results showed that after fiber tracking,compared with unaffected nerve root,fiber bundles gathered together and interrupted at the affected side.No significant alteration was detected in the number of fiber bundles,but the cross-sectional area of nerve root fibers was reduced These results suggest that diffusion tensor magnetic resonance imaging-based tractography can be used to quantitatively evaluate nerve root function according to the area and morphology of fiber bundles of nerve roots. | Xin Tian Huaijun Liu Zuojun Geng Hua Yang Guoshi Wang Jiping Yang Chunxia Wang Cuining Li Ying Li | 2013 | Neural Regeneration Research2013，8，33： | 2 |
| 3 | Enhancing intestinal drug solubilisation using lipid-based delivery systems 显示文摘 | PORTER C J H POUTON C W CUINE J F | 2008 | Adv Drug Deliver Rev2008，60，6： | 1 |
| 4 | Amino acids regulate salinity-induced potassium efflux in barley root epidermis 显示文摘 | Cuin T A Shabala S | 2007 | Planta2007，225，： | 1 |
| 5 | Exogenously supplied compatible solutes rap- idly ameliorate NaCl-induced potassium efflux from barely roots 显示文摘 | Cuin T A Shabala S | 2005 | Plant Cell Physiology2005，46，： | 1 |
| 6 | Compatible solutes reduce ROS-induced po- tassium efflux in Arabidopsis roots 显示文摘 | Cuin T A Shabala S | 2007 | Plant Cell and Environ- ment2007，30，： | 1 |
| 7 | Genome-wide transcriptome profiling of the early cadmium response of Arabidopsis roots and shoots显示文摘 | S. Herbette L. Taconnat V. Hugouvieux L. Piette M.-L.M. Magniette S. Cuine P. Auroy P. Richaud C. Forestier J. Bourguignon J.-P. Renou A. Vavasseur N. Leonhardt | 2006 | Biochimie2006，，11： | 1 |
| 8 | Competition between uptake of ammonium and potassium in barley and Arabidopsis roots : moleeular mechanisms and physiological eonsequenees 显示文摘 | Hoopen F T Cuin T A Pedas P | 2010 | Journal of Experimental Botany2010，61，9： | 1 |
| 9 | Potassium activities in cell compartments of salt-grown barley leaves显示文摘 | Cuin T A Miller A J Laurie S A | 2003 | Soc Experiment Biol2003，54，383： | 1 |
| 10 | Heavy metal accumulation by recombinant mammalian metallothionein within Escherichia coli protects against elevated metal exposure显示文摘 | Sandrine Sauge-Merle Catherine Lecomte-Pradines Patrick Carrier Stéphan Cuiné Michael DuBow | 2012 | Chemosphere2012，，8： | 1 |
| 11 | Arabidopsis protein kinase PKS5 inhibits the plasma membrane H+ -ATPase bypreventing interaction with 14-33protein显示文摘 | FUGLSANG A T GUO Y CUIN T A | 2007 | Plant Cell2007，19，5： | 1 |
| 12 | A root's ability to retain K: correlates with salt tolerance in wheat显示文摘 | Cuin T A Betts S A Chalmandrier R et d | 2008 | Journal of Experimental Botany2008，59，10： | 1 |
| 13 | Enhancing intestinal drug solubilisation using lipid-based delivery systems 显示文摘 | Porter CJH Pouton CW Cuine JF | 2008 | Adv Drug Deliv Rev2008，60，： | 1 |
| 14 | Root plasma membrane trans- porters controlling K+/Na+ homeosta- sis in salt stressed barley 显示文摘 | CHEN Z POTTOSIN II CUIN TA | 2007 | Plant Physiology2007，145，： | 1 |
| 15 | Enhancing intestinal drug solubilisation using lipid-based delivery systems 显示文摘 | Porter C J H Pouton C W Cuine J F | 2008 | Adv Drug Delivery Rev2008，60，6： | 1 |
| 16 | Salinity-induced ion flux patterns from the excised roots of Arabidopsis sos mutants显示文摘 | SHABALA L CUIN T A NEWMAN I A | | 0，，06： | 1 |
| 17 | Salinity-induced ion flux Patterns from the excised roots of Arabidopsis sos mutants显示文摘 | Shabala L Cuin T A Newman L | 2005 | Planta2005，222，： | 1 |
| 18 | Analysis of the proteins targeted by CDSP32, a plastidic thioredoxin participating in oxidative stress responses 显示文摘 | Rey P Cuine S Eymery F Gafin J Court M Jacquot JP Rouhier N Broin M | 2005 | Plant J2005，41，1： | 1 |
| 19 | Enhancing intestinal drug solubilisation using lipid-based delivery systems显示文摘 | Porter C J Pouton C W Cuine J F | 2008 | Adv Drug Deliv Rev2008，60，6： | 1 |
| 20 | Assessing the role of root plasma membrane and tonoplast Na+/H+ exchangers in salinity tolerance in wheat:in planta quantification methods显示文摘 | CUIN T A BOSE J STEFANO G | | 0，，06： | 1 |
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