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Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting

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Acta Pharmaceutica Sinica B 2019年第5期9卷 960-972页

作者： wei Sun Zhaona Yang Heng Lin Ming Liu Chenxi Zhao Xueying hou Zhuowei Hu Bing Cuin State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College

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 *** 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.

关键词： Monoclonal antibody Antibody maturation Phage display Yeast surface display CDR grafting Antibody engineering

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Liposome-based anchoring and core-encapsulation for combinatorial cancer therapy

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Chinese Chemical Letters 2022年第9期33卷 4191-4196页

作者： Qingqing Xiao Xiaotong Li Chang Liu Yi Yang Yuqi hou Ying Wang Mengxiang Su wei He School of Pharmacy China Pharmaceutical UniversityNanjing 211198China

Downregulated pro-apoptotic protein in cancer cells compromises the chemotherapy by a cytotoxic ***,we report co-delivery of a pro-apoptotic protein,caspase 3(Cas 3),and cytotoxic agent,oridonin(ORD),for synergistic cancer treatment,using a method of liposome-based anchoring and core ***,ORD is modified with hyaluronic acid(HA)to improve its ***,the targeted co-delivery system is prepared by assembling the conjugate HA-ORD onto the Cas 3-loaded liposomes,which the surface HA can target the CD44 receptor on cancer *** vitro,the co-loaded liposomes(120 nm)are specifically taken up by 4T1 cells and endow a 1.5-fold increase of Cas *** intravenous injection into the tumor-bearing mice,the liposomes accumulate in the tumor with high efficacy and significantly inhibit tumor growth via promoting apoptosis and anti-proliferation of cancer ***,the co-delivery works synergistically by upregulating the activated Cas form,cleaved-Cas 3.

关键词： Liposomes Co-delivery Chemotherapy Pro-apoptotic protein Tumor targeting

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Electrochemical Chiral Recognizing Tryptophan Enantiomers Based on Chiral Metal-Organic Framework D-MOF

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Chemical Research in Chinese Universities 2023年第6期39卷 976-984页

作者： hou Huipeng TANG Shanshan WANG wei LIU Miao LIANG Axin XIE Bingteng YI Yue LUO Aiqin Key Laboratory of Molecular Medicine and Biotherapy School of Life ScienceBeijing Institute of TechnologyBeijing 100081P.R.China

In this work,an electrochemical chiral sensor of a nanowire-like chiral metal-organic framework/multiwalled carbon nanotube-chitosan/glassy carbon electrode(D-MOF/MWCNTs-CS/GCE)was proposed for the enantiorecognition of L/D-tryptophan(L/D-Trp).The asymmetrical spatial structure of D-MOF provides the feasibility for the enantiorecognition of Trp ***,differential pulse voltammetry(DPV)was carried out to be the detection method and the DPV peak potential difference(ΔEp)between L-Trp and D-Trp was referred as the index of the enantiorecognition *** parameters,such as mass ratios and drop-coated volume of MWCNTs-CS,drop-coated volume and concentration of D-MOF,pH and detection temperature of D-MOF/MWCNTs-CS/GCE were optimized for the largestΔEp *** the molecular dynamics(MD)simulation was used to elucidate the enantiorecognition ***,the proportions of D-Trp(D-Trp%)in Trp mixtures were detected in a good linear relationship with the DPV peak potentials(Ep),and the proposed electrochemical chiral sensor exhibited good reproducibility,stability and enantiorecognition ***,the proposed electrochemical chiral sensor(D-MOF/MWCNTs-CS/GCE)has a good application prospect in the fields of biomedicine,clinical diagnosis,chemical production,pharmaceuticals safety and so on.

关键词： Electrochemical chiral sensor Chiral metal-organic framework Multiwalled carbon nanotube-chitosan(MWCNTs-CS) D-MOF Tryptophan(Trp) Potential difference(ΔEp)

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Chemical and biological diversity of new natural products from marine sponges:a review(2009–2018)

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Marine Life Science & Technology 2022年第3期4卷 356-372页

作者： Li‑Li Hong Ya‑Fang Ding wei Zhang hou‑Wen Lin Research Center for Marine Drugs State Key Laboratoryof Oncogenes and Related GenesDepartment of PharmacyRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China School of Food and Pharmacy Zhejiang Ocean UniversityZhoushan 316000China Centre for Marine Bioproducts Development FlindersUniversityAdelaideSA 5042Australia

Marine sponges are productive sources of bioactive secondary metabolites with over 200 new compounds isolated each year,contributing 23%of approved marine drugs so *** review describes statistical research,structural diversity,and pharmacological activity of sponge derived new natural products from 2009 to *** 2762 new metabolites have been reported from 180 genera of sponges this decade,of which the main structural types are alkaloids and terpenoids,accounting for 50%of the *** than half of new molecules showed biological activities including cytotoxic,antibacterial,antifungal,antiviral,anti-inflammatory,antioxidant,enzyme inhibition,and antimalarial *** summarized in this review,macrolides and peptides had higher proportions of new bioactive compounds in new compounds than other chemical *** chemical class displayed cytotoxicity as the dominant *** were the major contributors to antibacterial,antifungal,and antioxidant activities while steroids were primarily responsible for pest resistance ***,terpenoids,and steroids displayed the most diverse biological *** statistic research of new compounds by published year,chemical class,sponge taxonomy,and biological activity are *** novelty and significant bioactivities of some representative compounds are *** sponges are rich sources of novel bioactive compounds and serve as animal hosts for microorganisms,highlighting the undisputed potential of sponges in the marine drugs research and development.

关键词： Marine sponges New compounds Bioactivity Marine natural products

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北京城区四家传统中医门诊患者复诊情况调查

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国际中医中药杂志 2012年第10期34卷 876-878页

作者：刘睿李宛珊王雪青侯艳微汪玉娇陶晓华北京中医药大学针灸推拿学院 100029

目的研究北京城区4家传统中医门诊患者复诊情况，并宣传复诊的重要性。方法于2010年4月至2011年3月在北京城区4家传统中医门诊随机选取120位初诊患者及380位复诊患者进行问卷调查，分析复诊率、影响复诊的相关因素及复诊原因。采用SPSS1... 详细信息

目的研究北京城区4家传统中医门诊患者复诊情况，并宣传复诊的重要性。方法于2010年4月至2011年3月在北京城区4家传统中医门诊随机选取120位初诊患者及380位复诊患者进行问卷调查，分析复诊率、影响复诊的相关因素及复诊原因。采用SPSS17．0软件进行统计学分析。结果在4所门诊中，复诊率最高为56．7％，总复诊率为47．0％；患者未复诊原因中，13．7％选择无疗效或疗效不显著，12．6％选择时间不允许，10．3％选择已经康复；在影响复诊的相关因素调查中，患者自判疗效的有无、医嘱是否要求复诊可能是影响患者选择复诊与否的相关因素；患者复诊原因中，73．0％的复诊者选择有疗效，35．9％选择医生医德高尚，32．0％选择医生嘱咐患者复诊。结论北京城区4家传统中医门诊的复渗率较低；无疗效或疗效不显著、时间不允许、已经康复是未复诊的前三位原因；患者自判疗效的有无和医嘱是否要求复诊与患者是否选择复诊相关；有疗效、医生医德高尚及医生嘱咐复诊是前三位复诊原因。

关键词：中医门诊复诊调查

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注射器种类对注射泵应用质量影响的试验研究

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中国医疗设备 2008年第4期23卷 25-26,24页

作者：侯艺威严汉民白玫张玉洁印剑锋刘志成首都医科大学宣武医院医学工程科北京100053 首都医科大学生物医学工程学院北京100069

目的:本研究旨在评估不同品牌注射器对注射泵应用质量的影响。方法:将贝朗8714843型注射泵分别与10ml贝朗、洁瑞、新津牌注射器和50ml贝朗、洁瑞、玉升牌注射器配合使用,检测其实际流速,对比结果。结果:使用10ml非贝朗注射器时,流量误... 详细信息

目的:本研究旨在评估不同品牌注射器对注射泵应用质量的影响。方法:将贝朗8714843型注射泵分别与10ml贝朗、洁瑞、新津牌注射器和50ml贝朗、洁瑞、玉升牌注射器配合使用,检测其实际流速,对比结果。结果:使用10ml非贝朗注射器时,流量误差严重超标,分别为7.30%和-14.14%。使用50ml非贝朗注射器时,准确度变化较小,平均误差分别为0.23%和-1.15%。结论:注射器种类对注射泵应用质量的影响不可忽视,在临床使用中应慎重选择。

关键词：注射泵注射器注射效果

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胃血管球瘤MSCT表现及临床特征分析

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中国临床医学影像杂志 2023年第11期34卷 791-794页

作者：唐永强柴娜刘松涛张瑜侯炜寰刘会佳空军军医大学西京医院放射科陕西西安710032

目的:探讨胃血管球瘤多层螺旋CT(MSCT)的表现特点。方法:回顾性分析经病理确诊的10例胃血管球瘤患者的临床、病理及CT表现,分析总结其CT影像特点。结果:6例病灶位于胃窦部,2例位于胃体小弯侧,1例位于胃体大弯侧,1例位于胃底-小弯侧。CT... 详细信息

目的:探讨胃血管球瘤多层螺旋CT(MSCT)的表现特点。方法:回顾性分析经病理确诊的10例胃血管球瘤患者的临床、病理及CT表现,分析总结其CT影像特点。结果:6例病灶位于胃窦部,2例位于胃体小弯侧,1例位于胃体大弯侧,1例位于胃底-小弯侧。CT平扫1例巨大恶性病灶表现为不均匀低密度,其余病灶均呈均匀等或略低密度。当病灶长径≤2 cm时,增强扫描动脉期病灶呈完全显著强化,静脉期强化程度减低;病灶长径>2 cm时,增强扫描病灶表现为渐进性强化;另外,当病灶长径>2 cm且伴有明显坏死、形态欠规则时,提示恶性胃血管球瘤可能。结论:胃血管球瘤的CT表现具有一定特征性,充分认识其特征性表现,有助于提升术前诊断准确率。

关键词：血管球瘤体层摄影术螺旋计算机

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In situ triggering antitumor efficacy of alcoholabuse drug disulfiram through Cu-based metalorganic framework nanoparticles

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Acta Pharmaceutica Sinica B 2021年第7期11卷 2016-2030页

作者： Lin hou Yanlong Liu wei Liu Mervat Balash Hongling Zhang Yi Zhang Huijuan Zhang Zhenzhong Zhang Biotherapy Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China School of Pharmacy School of Pharmaceutical SciencesZhengzhou UniversityKey Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou 450001China

Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo severely limited its application in cancer ***,we proposed an in situ DSF antitumor efficacy triggered system,taking advantages of Cu-based metal-organic framework(MOF).In detail,DSF was encapsulated into Cu-MOF nanoparticles(NPs)during its formation,and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and ***,DSF loaded Cu-MOF NPs maintained stability and integrity without Cu;leakage in blood circulation,thus showing excellent *** accumulating at tumor site,NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu;simultaneously in the hyaluronidase-enriched and acidic intracellular tumor *** profile lead to in situ chelation reaction between DSF and Cu;,generating toxic DSF/Cu complex against tumor *** in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs,which facilitated the tumor-specific chemotherapeutic effects of *** system provided a promising strategy for the application of DSF in tumor therapy.

关键词： Disulfiram Copper Metal-organic framework Hyaluronic acid Lysosomal escape DSF/Cu complex In situ Antitumor therapy

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奶山羊乳房炎灭活疫苗的制备及免疫效果检测

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动物医学进展 2014年第12期35卷 18-22页

作者：侯伟杰张立强高洋赵玄多赵燕清刘方高晶晖张淼涛陈德坤西北农林科技大学动物医学院陕西杨凌712100

为评估奶山羊乳房炎灭活疫苗的免疫效果,以大肠埃希菌、金黄色葡萄球菌、凝固酶阴性表皮葡萄球菌及产色葡萄球菌为材料,经甲醛37℃灭活,按照6∶1(V/V)与铝胶盐充分混匀,分别经腹股沟皮下、颈部皮下注射途径,免疫泌乳期奶山羊,免疫剂量均... 详细信息

为评估奶山羊乳房炎灭活疫苗的免疫效果,以大肠埃希菌、金黄色葡萄球菌、凝固酶阴性表皮葡萄球菌及产色葡萄球菌为材料,经甲醛37℃灭活,按照6∶1(V/V)与铝胶盐充分混匀,分别经腹股沟皮下、颈部皮下注射途径,免疫泌乳期奶山羊,免疫剂量均为2mL,共免疫2次,每次间隔14d。分别在免疫前及第1次免疫后10、24、60、180d采集血样和乳样,ELISA测定抗体效价,用快速诊断液检测隐性乳房炎,统计患病奶山羊的数量。结果显示,与对照组相比,两次免疫后血液及乳汁中针对大肠埃希菌、金黄色葡萄球菌、凝固酶阴性表皮葡萄球菌及产色葡萄球菌的抗体效价含量均显著增加(P<0.05),抗体维持时间长;颈部皮下免疫组免疫后180d,腹股沟皮下免疫组免疫后的60d,隐性乳房炎奶山羊数量均明显下降。结果表明,本研究制备的奶山羊乳房炎疫苗不仅能够刺激机体产生较好的体液免疫应答,而且还对隐性乳房炎有显著的治疗效果。

关键词：乳房炎灭活疫苗免疫抗体效价隐性乳房炎

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个性化设计单侧穿刺PKP治疗中上胸椎椎体压缩性骨折

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现代临床医学 2018年第5期44卷 327-329页

作者：宋偲茂熊小明万趸石华刚邓轩赓侯伟顾韬四川省骨科医院脊柱外科四川成都610041

目的:探讨参照术前个性化设计单侧入路经皮椎体后凸成形术(PKP)治疗骨质疏松性中上胸椎椎体压缩骨折的可行性、安全性和临床疗效。方法:回顾性研究骨质疏松性中上胸椎椎体压缩骨折行PKP手术54例患者,共95节椎体。术前行通过CT影像设计... 详细信息

目的:探讨参照术前个性化设计单侧入路经皮椎体后凸成形术(PKP)治疗骨质疏松性中上胸椎椎体压缩骨折的可行性、安全性和临床疗效。方法:回顾性研究骨质疏松性中上胸椎椎体压缩骨折行PKP手术54例患者,共95节椎体。术前行通过CT影像设计单侧穿刺入路行PKP术。按照VAS评分、Oswetry评分标准及影像学资料对患者疼痛、日常活动功能及Cobb角进行评估。结果:37例共63节椎体顺利完成手术并得到全程随访,平均随访时间24个月,术后疼痛症状缓解;无神经损伤、肺栓塞、感染等并发症。VAS评分及ODI值与术前比较有显著性差异(P <0. 05)。结论:术前个性化设计单侧入路经皮椎体后凸成形术治疗中上胸椎压缩性骨折可取得满意疗效,且具有穿刺准确性高、手术安全等优点。

关键词：中上胸椎压缩性骨折单侧入路个性化设计椎体后凸成形术

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