Avian influenza has caused enormous economic losses to poultry industry. To develop kits for rapid diagnosis of avian influenza virus (AIV) H9 subtype, 8-week-old Balb/c mice were administered with pcDNA3.1 ( + )...Avian influenza has caused enormous economic losses to poultry industry. To develop kits for rapid diagnosis of avian influenza virus (AIV) H9 subtype, 8-week-old Balb/c mice were administered with pcDNA3.1 ( + ) carrying hemagglutinin (HA) gene of AIV H9 subtype. After cell fusion, one positive hybridoma cell strain was screened out by hemagglutination inhibition assay ( HI ), and another positive hybddoma call strain was screened out by ELISA. After subcloning 3 times, the two cell strains could still secret antibodies against the HA of AIV H9 subtype. The mono- clonal antibodies did not react with Newcastle disease virus, AIV H5 subtype and duck adenovirus A. Their subtypes were IgG2b with kappa light chain. These two hybridoma cell strains may play an important role in rapid diagnosis and early-warning surveillance of AIV H9 subtype.展开更多
目的分析前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)单克隆抗体的全球研究现状、热点及前沿,为我国相关科研工作的开展及临床合理用药提供参考。方法检索2011年1月—2022年2月Web of Science数据...目的分析前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)单克隆抗体的全球研究现状、热点及前沿,为我国相关科研工作的开展及临床合理用药提供参考。方法检索2011年1月—2022年2月Web of Science数据库中收录的PCSK9单克隆抗体相关研究文献,通过可视化文献分析软件(CiteSpace)对纳入研究的文献进行分析。结果共纳入文献723篇,年发文量呈总体上升趋势,发文量排名前3位的国家分别为美国、法国和英国,发文量最多的机构是赛诺菲公司,文献篇均被引最高的机构是布莱根妇女医院;研究的热点内容主要有PCSK9单克隆抗体对高胆固醇血症、不耐受他汀类药物的患者、心血管高风险患者、联合他汀类药物降脂治疗的有效性和安全性;近两年研究的前沿为PCSK9单克隆抗体在急性冠脉综合征患者中的应用以及降低脂蛋白(a)水平后的临床获益。结论PCSK9单克隆抗体降血脂的有效性和安全性已经过大量研究证实,但仍缺乏对其经济性及在特殊人群中的应用研究,未来研究应重点关注。展开更多
Anri-idiotypic monoclonal antibody (Mab Ab2 ) by MAb COC166-9 against ovarian serous papillary adenocarcinoma was prepared. Hybridomas of Ab2 screened by sandwich ELISA and immunocompetitive inhibition tests were proc...Anri-idiotypic monoclonal antibody (Mab Ab2 ) by MAb COC166-9 against ovarian serous papillary adenocarcinoma was prepared. Hybridomas of Ab2 screened by sandwich ELISA and immunocompetitive inhibition tests were procured and named as 6B11 and 1H12. The number of their chromosomes were 93 and 91, and DNA analysis also proved the characteristics of hybridomas. These Ab2s could induce delayed type hypersensitivity (DTH), the cellular immune response. The results of the immune reaction of 6B11 with SKOV3 (ovarian carcinoma cell line) were similar to OC166-9 (Ag), the positive control, while 1H12 was weaker. Anti-and-idiotypic antibody (Ab3) was also raised by 6B11 and 1H12 respectively. They all showed positive immunohistochemical stainings with ovarian serous adenocarcinoma tissue sections and immunocytochemical stainings with SKOV3 cells as was shown by COC166-9. In the antibody dependent cell mediated cytotoxicity (ADCC) tests, they showed no differences against SKOV3 as compared with COC166-9. We anticipate that 6B11 and 1H12 may be used as vaccines against ovarian carcinoma and may provide a clue for its prevention and treatment.展开更多
冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的发病率及病死率居全球首位,而低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)的升高是CHD的主要危险因素,因此降低LDL-C水平可有效减少CHD的...冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的发病率及病死率居全球首位,而低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)的升高是CHD的主要危险因素,因此降低LDL-C水平可有效减少CHD的发病风险。临床上降脂药物如他汀类虽能够有效降低LDL-C水平,但仍有部分患者无法达到降脂目标或者无法耐受。前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)抑制剂作为新一代的降脂药物,越来越受到重视。其通过对PCSK9的抑制作用,增加低密度脂蛋白受体的循环利用,能够显著降低血清中LDL-C水平。目前PCSK9抑制剂已进入Ⅲ期临床试验,试验结果显示其具有良好的降脂效果和耐受性。该文就PCSK9抑制剂最新进展和面临的问题作一综述。展开更多
Carbohydrate antigen 19–9(CA19–9)with multi epitopes relatively high expresses on colorectal cancer(CRC)cells,making it an attractive target for developing radioimmunotherapy(RIT)for CRC.The lutetium-177(^(177)Lu)la...Carbohydrate antigen 19–9(CA19–9)with multi epitopes relatively high expresses on colorectal cancer(CRC)cells,making it an attractive target for developing radioimmunotherapy(RIT)for CRC.The lutetium-177(^(177)Lu)labeled monoclonal antibodies(mA bs)can selectively bind the corresponding antigens and release targeted cytotoxic radiation,which could induce cell apoptosis and reduce the drug-induced resistance.Here,a series of CA19–9 m Abs were labeled with zirconium-89(^(89)Zr),and one with high tumor uptake was screened via PET imaging,which has potential application for the diagnosis of CRC.Then the screened m Ab(C003)labeled with^(177)Lu was utilized for CA19–9 targeted RIT,which presents a significant suppression effect on the growth of colo205 xenografts than immunotherapy alone.Meanwhile,the side effects of ^(177)Lu-DOTA-C003 are limited according to the results of in vivo study.Both89Zr-DFO-C003for CRC immune-PET imaging and ^(177)Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.展开更多
Background:The new emerging avian influenza A H7N9 virus,causing severe human infection with a mortality rate of around 41%.This study aims to provide a novel treatment option for the prevention and control of H7N9.Me...Background:The new emerging avian influenza A H7N9 virus,causing severe human infection with a mortality rate of around 41%.This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods:H7 hemagglutinin(HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province,China.The human monoclonal antibodies(mAbs)were generated by amplification and cloning of these HA-specific B cells.First,all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay.Then,those mAbs,exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting(HAI)and microneutralizationin vitro assays.Finally,the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.Results:The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes,including H1N1 and H3N2.The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50(TCID_(50))of H7N9 virus(influenza A/Nanjing/1/2013)invitro,with neutralizing activity as low as 78 ng/mL.In addition,the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.Conclusion:The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.展开更多
基金funded by the National Key Technology R&D Program(2006BAK20A29)the Shenzhen Entry-Exit Inspection and Quarantine Project(sz2008102)
文摘Avian influenza has caused enormous economic losses to poultry industry. To develop kits for rapid diagnosis of avian influenza virus (AIV) H9 subtype, 8-week-old Balb/c mice were administered with pcDNA3.1 ( + ) carrying hemagglutinin (HA) gene of AIV H9 subtype. After cell fusion, one positive hybridoma cell strain was screened out by hemagglutination inhibition assay ( HI ), and another positive hybddoma call strain was screened out by ELISA. After subcloning 3 times, the two cell strains could still secret antibodies against the HA of AIV H9 subtype. The mono- clonal antibodies did not react with Newcastle disease virus, AIV H5 subtype and duck adenovirus A. Their subtypes were IgG2b with kappa light chain. These two hybridoma cell strains may play an important role in rapid diagnosis and early-warning surveillance of AIV H9 subtype.
文摘目的分析前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)单克隆抗体的全球研究现状、热点及前沿,为我国相关科研工作的开展及临床合理用药提供参考。方法检索2011年1月—2022年2月Web of Science数据库中收录的PCSK9单克隆抗体相关研究文献,通过可视化文献分析软件(CiteSpace)对纳入研究的文献进行分析。结果共纳入文献723篇,年发文量呈总体上升趋势,发文量排名前3位的国家分别为美国、法国和英国,发文量最多的机构是赛诺菲公司,文献篇均被引最高的机构是布莱根妇女医院;研究的热点内容主要有PCSK9单克隆抗体对高胆固醇血症、不耐受他汀类药物的患者、心血管高风险患者、联合他汀类药物降脂治疗的有效性和安全性;近两年研究的前沿为PCSK9单克隆抗体在急性冠脉综合征患者中的应用以及降低脂蛋白(a)水平后的临床获益。结论PCSK9单克隆抗体降血脂的有效性和安全性已经过大量研究证实,但仍缺乏对其经济性及在特殊人群中的应用研究,未来研究应重点关注。
文摘Anri-idiotypic monoclonal antibody (Mab Ab2 ) by MAb COC166-9 against ovarian serous papillary adenocarcinoma was prepared. Hybridomas of Ab2 screened by sandwich ELISA and immunocompetitive inhibition tests were procured and named as 6B11 and 1H12. The number of their chromosomes were 93 and 91, and DNA analysis also proved the characteristics of hybridomas. These Ab2s could induce delayed type hypersensitivity (DTH), the cellular immune response. The results of the immune reaction of 6B11 with SKOV3 (ovarian carcinoma cell line) were similar to OC166-9 (Ag), the positive control, while 1H12 was weaker. Anti-and-idiotypic antibody (Ab3) was also raised by 6B11 and 1H12 respectively. They all showed positive immunohistochemical stainings with ovarian serous adenocarcinoma tissue sections and immunocytochemical stainings with SKOV3 cells as was shown by COC166-9. In the antibody dependent cell mediated cytotoxicity (ADCC) tests, they showed no differences against SKOV3 as compared with COC166-9. We anticipate that 6B11 and 1H12 may be used as vaccines against ovarian carcinoma and may provide a clue for its prevention and treatment.
文摘冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)的发病率及病死率居全球首位,而低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)的升高是CHD的主要危险因素,因此降低LDL-C水平可有效减少CHD的发病风险。临床上降脂药物如他汀类虽能够有效降低LDL-C水平,但仍有部分患者无法达到降脂目标或者无法耐受。前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)抑制剂作为新一代的降脂药物,越来越受到重视。其通过对PCSK9的抑制作用,增加低密度脂蛋白受体的循环利用,能够显著降低血清中LDL-C水平。目前PCSK9抑制剂已进入Ⅲ期临床试验,试验结果显示其具有良好的降脂效果和耐受性。该文就PCSK9抑制剂最新进展和面临的问题作一综述。
基金supported by the National Natural Science Foundation of China(Nos.21976167,U20A20384)the CAEP Innovation and Development Foundation(No.CX20200003)+2 种基金Nuclear Energy Development Project of State Administration of Science,Technology and Industry for National Defense(No.20201192–1)Key R&D Project of Sichuan Science and Technology Program(No.2020YFS0030)the Central Guidance for Local Science and Technology Development Projects(No.202138–03)。
文摘Carbohydrate antigen 19–9(CA19–9)with multi epitopes relatively high expresses on colorectal cancer(CRC)cells,making it an attractive target for developing radioimmunotherapy(RIT)for CRC.The lutetium-177(^(177)Lu)labeled monoclonal antibodies(mA bs)can selectively bind the corresponding antigens and release targeted cytotoxic radiation,which could induce cell apoptosis and reduce the drug-induced resistance.Here,a series of CA19–9 m Abs were labeled with zirconium-89(^(89)Zr),and one with high tumor uptake was screened via PET imaging,which has potential application for the diagnosis of CRC.Then the screened m Ab(C003)labeled with^(177)Lu was utilized for CA19–9 targeted RIT,which presents a significant suppression effect on the growth of colo205 xenografts than immunotherapy alone.Meanwhile,the side effects of ^(177)Lu-DOTA-C003 are limited according to the results of in vivo study.Both89Zr-DFO-C003for CRC immune-PET imaging and ^(177)Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.
基金National Natural Science Foundation for Youth,China(No.81501793)。
文摘Background:The new emerging avian influenza A H7N9 virus,causing severe human infection with a mortality rate of around 41%.This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods:H7 hemagglutinin(HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province,China.The human monoclonal antibodies(mAbs)were generated by amplification and cloning of these HA-specific B cells.First,all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay.Then,those mAbs,exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting(HAI)and microneutralizationin vitro assays.Finally,the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.Results:The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes,including H1N1 and H3N2.The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50(TCID_(50))of H7N9 virus(influenza A/Nanjing/1/2013)invitro,with neutralizing activity as low as 78 ng/mL.In addition,the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.Conclusion:The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.