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Antibody Therapies Targeting Complex Membrane Proteins

Engineering 2021年第11期7卷 1541-1551页

作者： Georgina To’a Salazar Ziyi Huang Ningyan zhang xue-guang zhang Zhiqiang An Texas Therapeutics Institute Brown Foundation Institute of Molecular MedicineThe University of Texas Health Science Center at HoustonHoustonTX 77030USA Jiangsu Institute of Clinical Immunology The First Affiliated Hospital of Soochow UniversitySuzhou 215123China Jiangsu Key Laboratory of Clinical Immunology Soochow UniversitySuzhou 215123China Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology The First Affiliation Hospital of Soochow UniversitySuzhou 215123China State Key Laboratory of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China

In analyses of protein families that may serve as drug targets,membrane-associated G-protein-coupled receptors(GPCRs)dominate,followed by ion channels,transporters,and—to a lesser extent—membrane-bound ***,various challenges put such membrane proteins among key groups of underutilized opportunities for the application of therapeutic *** hold the promise of exquisite specificity,as they are able to target even specific conformations of a particular membrane protein,as well as adaptability through engineering into various antibody ***,the ease of raising and isolating specific,effective antibodies targeting membrane proteins depends on many *** particular,the generation of specific antibodies is easier when targeting larger,simpler,extracellular domains with greater uniqueness of amino acid *** rareness of such ideal conditions is illustrated by the limited number of approved biologics for targeting GPCRs and other complex membrane *** in developing antibodies to complex membrane proteins such as GPCRs,ion channels,transporters,and membrane-bound enzymes can be addressed by the design of the antigen,antibody-generation strategies,lead optimization technologies,and antibody modalities.A better understanding of the membrane proteins being targeted would facilitate mechanism-based drug *** review describes the advantages and challenges of targeting complex membrane proteins with antibodies and discusses the preparation of membrane protein antigens and antibody generation,illustrated by select examples of success.

关键词： Antibody therapy Complex membrane protein Ion channels Transporters Membrane-bound enzymes GPCRs Drug discovery

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Inhibited experimental corneal neovascularization by neutralizing anti-SDF-1α antibody

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International Journal of Ophthalmology(English edition) 2012年第1期5卷 7-12页

作者： Gao-Qin Liu, xue-guang zhang Department of Ophthalmology the First Affiliated Hospital of Soochow University Suzhou 215006 Jiangsu Province China Jiangsu Institute of Clinic Immunology the First Affiliated Hospital of Soochow University Suzhou 215006 Jiangsu Province China

AIM: To explore the effect of SDF-1α on the development of experimental corneal neovascularization (CRNV).METHODS: CRNV was induced by alkali injury in mice. The expression of SDF-1α and CXCR4 in burned corneas was examined by Flow Cytometry. Neutralizing anti-mouse SDF-1α antibody was locally administrated after alkali injury and the formation of CRNV 2 weeks after injury was assessed by Immunohistochemistry. The expression of VEGF and C-Kit in burned corneas was detected by ***: The number of CRNV peaks at 2 weeks after alkali injury. Compared to control group, SDF-1α neutralizing antibody treatment significantly decreased the number of CRNV. RT-PCR confirmed that SDF-1α neutralizing antibody treatment resulted in decreased intracorneal VEGF and C-Kit ***: SDF-1α neutralizing antibody treated mice exhibited impaired experimental CRNV through down regulated VEGF and C-Kit expression.

关键词： corneal neovascularization alkali injury chemokine

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Excessive Copper Induces the Production of Reactive Oxygen Species,which is Mediated by Phospholipase D, Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Antioxidant Systems

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Journal of Integrative Plant Biology 2008年第2期50卷 157-167页

作者： Zhong-Lian Yu Jin-guang zhang xue-Chen Wang Jia Chen State Key Laboratory of Plant Physiology and Biochemistry College of Biological Sciences China Agricultural University Beijing 100094 China

Tobacco BY-2 suspension cells were used to study the chemical damage and its associated mechanisms caused by Cu^2＋. Treatment with 100 μmol/L Cu^2＋ generated a large amount of HzOz and thiobarbituric acid-reactive substances （TBARS） in cells. Using phospholipase D （PLD） specific inhibitor （1-butanol） or phosphatidic acid （PA）, we demonstrated that PLD plays an important role in the generation of H2O2 and TBARS. Semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme activity assays with wild type and nicotinamide adenine dinucleotide phosphate （NADPH） oxidaseoverexpressing BY-2 cells revealed that PLD and PA are the key factors leading to NADPH oxidase activation, which is responsible for H2O2 and TBARS production induced by Cu^2＋. Moreover, the content of ascorbic acid （AsA）, an effective antioxidant, was sharply reduced in BY-2 cells exposed to excessive Cu^2＋. Furthermore, a significant downregulation of the enzymes of AsA biosynthesis and the antioxidant system was found. This evidence suggests that excessive Cu^2＋-elevated reactive oxygen species （ROS） production is caused by upregulated PLD that elevates the activity of NADPH oxidase and its collapsed antioxidant systems that scavenges ROS.

关键词： ascorbic acid Cu^2+ nicotinamide adenine dinucleotide phosphate oxidase phospholipase D reactive oxygen species.

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Development of setal patterns in embryonic and adult aphids of the Hormaphidinae （Hemiptera： Aphididae）

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Insect Science 2007年第4期14卷 339-350页

作者： LI-YUN JIANG GE-XIA QIA0 guang-xue zhang Institute of Zoology Chinese Academy of Sciences Graduate University of Chinese Academy of Sciences BeijingChina

The elementary traits and diversity of embryonic setal patterns of 31 species of 22 genera, in three tribes of Hormaphidinae are studied. The embryonic setal patterns to every species are provided. Based on the parsimony principle and the developmental principle, these patterns are analyzed in each tribe following the terminology of Richards （1965）. It is suggested that the setal patterns of abdominal tergites are the most important characters in embryonic and adult setal patterns. In conclusion, neoteny is a phylogenetic trend in the Hormaphidinae. Nipponaphidini and Hormaphidini have more typical neoteny in each genus and more diversity in different types of adult viviparous females than Cerataphidini, by showing more frequent and various protopatterns or mesopatterns.

关键词： Hemiptera Hormaphidinae embryo adult setal pattern development neo-teny

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Minimally invasive thalamic hematoma drainage can improve the six-month outcome of thalamic hemorrhage

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Journal of Geriatric Cardiology 2017年第4期14卷 266-273页

作者： Wen-Ming LIU xue-guang zhang Ze-Li zhang Gang LI Qi-Bing HUANG Department of Emergency Surgery Qilu Hospital of Shandong University and Brain Science Research Institute of Shandong University Jinan ShandongChina Department of Neurosurgery Liaocheng People's Hospital Liaocheng Shandong China Department of Neurosurgery Qilu Hospital of Shandong University and Brain Science Research Institute of Shandong University Jinan Shandong China

Objective To explore predictors of the 6-month clinical outcome ofthalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage （THD） could improve its prognosis. Methods A total of 54 patients with spontaneous thalamic hemorrhage were evaluated retrospectively. Clinical data, including demographics, stroke risk factors, neuroimaging variables, Glasgow Coma Score （GCS） on admission, surgical strategy, and outcome, were collected. Clinical outcome was assessed using a modified Rankin Scale, six months after onset. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of a poor outcome. Results Conservative treatnaent was performed for five patients （9.3%）, external ventricular drainage （EVD） for 20 patients （37.0%）, THD for four patients （7.4%）, and EVD combined with THD for 25 patients （46.3%）. At six months after onset, 21 （38.9%） patients achieved a favorable outcome, while 33 （61.1%） had a poor outcome. In the univariate analysis, predictors of poor 6-month outcome were lower GCS on admis- sion （P = 0.001）, larger hematoma volume （P 〈 0.001）, midline shift （P = 0.035）, acute hydrocephalus （P = 0.039）, and no THD （P = 0.037）. The independent predictors of poor outcome, according to the multivariate logistic regression analysis, were no THD and larger hematoma volume. Conclusions Minimally invasive THD, which removes most of the hematoma within a few days, with limited damage to perihematomal brain tissue, improved the 6-month outcome of thalamic hemorrhage. Thus, THD can be widely applied to treat patients with thalamic hemorrhage.

关键词： Hematoma volume Minimally invasive Outcome Predictor Thalamic hematoma drainage Thalamic hemorrhage

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Study of overthrust nappe structure and its geodynamic mechanism along the southeastern margin of Nansha Trough

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China Geology 2018年第4期1卷 459-465页

作者： guang-xue zhang Zhen Yang Li zhang Wei Yan Kun-sheng Qiang MLR Key Laboratory of Marine Mineral Resources Guangzhou Marine Geological SurveyGuangzhou 510075China Marine Petroleum and Gas geological Research Center (China Geological Survey) Guangzhou Marine Geological SurveyGuangzhou 510075China

On the basis of interpretation of comprehensive geophysical data and foreign data analysis,there existed a lot of overburden detachment shear thrust faults along the southeastern margin of Nansha Trough,which composed imbricated overthrust nappe ***-faulted nappe structure pattern is determined in this area,which consists of frontal fault zone,thrust fault-folded zone and root zone structures,and presents regularly zonation on *** detail description of the structural geometrical characteristics is given in shallow thrust fault zone,and the kinematical mechanism of thrust fault nappe structure is furtherly *** nappe structure in this area is resulted from island arc-continent collision and orogenic activities.

关键词： Overthrust Structure Geodynamic Mechanism Nansha Trough

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Significant contribution of carbonyls to atmospheric oxidation capacity(AOC)during the winter haze pollution over North China Plain

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Journal of Environmental Sciences 2024年第5期139卷 377-388页

作者： xue Yang Gen zhang guang Pan Guolan Fan Houyong zhang Xuan Ge Mingyue Du School of Municipal and Environmental Engineering Shandong Jianzhu UniversityJi’nan 250101China State Key Laboratory of Severe Weather&Key Laboratory of Atmospheric Chemistry of China Meteorological Administration Chinese Academy of Meteorological SciencesBeijing 100081China Shandong Jinan Ecological Environment Monitoring Center Ji’nan 250101China

Atmospheric carbonyl compounds play significant roles in the cycling of radicals and have exhibited surprisingly high levels in winter that were well correlated to particulate matter,for which the reason have not been clearly *** we measured carbonyl compounds and other trace gasses together with PM_(2.5)over urban Jinan in North China Plain during the *** higher carbonyl concentrations(average:14.63±4.21 ppbv)were found during wintertime haze pollution,about one to three-times relative to those on nonhaze days,with slight difference in chemical composition except formaldehyde(HCHO).HCHO(3.68 ppbv),acetone(3.17 ppbv),and acetaldehyde(CH_3CHO)(2.83 ppbv)were the three most abundant species,accounting for~75% of the total carbonylson both haze and non-haze *** from observational-based model(OBM)with atmospheric oxidation capacity(AOC)indicated that AOC significantly increased with the increasing carbonyls during the winter haze *** photolysis have supplied key oxidants such as RO_(2) and HO_(2),and thereby enhancing the formation of fine particles and secondary organic aerosols,elucidating the observed haze-carbonyls *** variation with carbonyls exhibiting peak values at early-noon and night highlighted the combined contribution of both secondary formation and primary diesel-fuel sources.1-butene was further confirmed to be the major precursor for *** study confirms the great contribution of carbonyls to AOC,and also suggests that reducing the emissions of carbonyls would be an effective way to mitigate haze pollution in urban area of the NCP region.

关键词： Carbonyls Haze Observation-based model Source apportionment Atmospheric oxidation capacity

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The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development

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Genes & Diseases 2024年第5期11卷 252-271页

作者： Qing Ma guang Chen Ying Li Zhenming Guo xue zhang NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Harbin Medical UniversityHarbinHeilongjiang 150000China Department of Urology The Fourth Hospital of Harbin Medical UniversityHarbinHeilongjiang 150000China Department of Child and Adolescent Health School of Public HealthHarbin Medical UniversityHarbinHeilongjiang 150000China Institute for Regenerative Medicine Shanghai East HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China

Malformations of cortical development(MCD)are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental *** kinds of MCD are caused by genetic *** is the common cause of intellectual disability and intractable *** rapid advances in imaging and sequencing technologies,the diagnostic rate of MCD has been increasing,and many potential genes causing MCD have been successively ***,the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted ***,in this review,we outline important events of cortical *** we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR ***,we briefly discuss the diagnostic methods,disease models,and therapeutic strategies for *** information will facilitate further research on *** the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

关键词： Epilepsy Gene mutation Genetics Malformations of cortical development PI3K/PTEN/AKT/mTOR pathway

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Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis

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World Journal of Gastroenterology 2006年第3期12卷 457-459页

作者： Chang-Ping Wu Jing-Ting Jiang Min Tan Yi-Bei Zhu Mei Ji Kuan-Feng Xu Jie-Min Zhao guang-Bo zhang xue-guang zhang The Third Affiliated Hospital of Suzhou University Changzhou213003 Jiangsu Province China Institute of Biotechnology Suzhou University KeyLaboratory of Clinical Immunology of Jiangsu Province Suzhou215007 Jiangsu Province China 不详

AIM:To investigate the expression of co-stimulatorymolecule B7-H3 in gastric carcinoma and adenomatissue as well as normal gastric tissue and to explore therelationship between B7-H3 expression and pathologicalfeatures and prognosis of gastric ***:B7-H3 expression was detected in 102samples of human gastric carcinoma and 10 samples ofgastric adenoma and 10 samples of normal gastric tissueby immunohistochemical *** betweenthe expression of B7-H3 and the patients'age,sex,gastric carcinoma locus,tumor size,tissue type,tumorinfiltration depth,differentiation degree,lymph nodemetastasis,and survival time was ***:B7-H3 was expressed in all gastric adenomasamples and in 58.8% samples of gastric carcinoma.B7-H3 expression in gastric carcinoma samples wasnot related with the patients'age,sex,lymph nodemetastasis,and tumor size(P>0.05),but with thesurvival time,infiltration depth of tumor and tissue ***:Detection of B7-H3 expression in gastriccarcinoma tissue is beneficial to the judgment of theprognosis of gastric carcinoma patients and the choice oftreatment.

关键词： B7-H3 expression Gastric carcinoma Gastricadenoma Prognosis

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Anti-apoptosis effects of vascular endothelial cadherin in experimental corneal neovascularization

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International Journal of Ophthalmology(English edition) 2015年第6期8卷 1083-1088页

作者： Gao-Qin Liu Hong-Ya Wu Jing Xu Meng-Jiao Wang Pei-Rong Lu xue-guang zhang Department of Ophthalmology the First Affiliated Hospital of Soochow University Jiangsu Clinical Immunology Institute the First Affiliated Hospital of Soochow University

AIMTo explore the effects and mechanism of vascular endothelial cadherin (VE-cadherin) on experimental corneal neovascularization (CRNV).METHODSMouse corneas were burned with sodium hydroxide to build a CRNV model. The burned corneas were locally administrated with anti-mouse VE-cadherin neutralizing antibody. Annexin V and cluster of differentiation 31 (CD31) double staining was used to measure vascular endothelial cell apoptosis with the use of flow cytometry (FCM). The protein expression of NADPH oxidase 2 (Nox2), caspase-3, and protein kinase C (PKC) in the burned corneas were examined by Western blot. Human retinal endothelial cell (HREC) proliferation was detected using a Cell Counting Kit 8 (CCK-8) assay in *** amount of CRNV peaked two weeks after the alkali burn. FCM confirmed that VE-cadherin neutralizing antibody treatment increased CD31 positive cell apoptosis. Western blot revealed that the intracorneal protein expression of Nox2 and caspase-3 were up-regulated, while PKC was down-regulated in the VE-cadherin neutralizing antibody administrated group. CCK-8 assay showed that VE-cadherin neutralizing antibody markedly inhibited HREC ***-cadherin exhibited an anti-apoptosis effect through enhanced PKC signaling and an enhanced cell proliferation pathway.

关键词： vascular endothelial cadherin neovascularization cornea chemokine

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