Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
Embryonic stem （ES） cells are potent resources for cell therapy,and monoclonal antibodies （mAbs） against native cell surface markers of ES cells could be useful tools for therapeutic applications.Here,we report th...Embryonic stem （ES） cells are potent resources for cell therapy,and monoclonal antibodies （mAbs） against native cell surface markers of ES cells could be useful tools for therapeutic applications.Here,we report the development of a feasible approach,which could be used in mass production,for experimentally producing rabbit mAbs against native cell surface antigens on the cell surface.Two of the 14 mAbs,which were selected at random,could be bound to the cell surface antigens of mES cells.The immunocytochemistry （ICC） and Western blot results showed that mAb 39 recognises conformational epitopes.The target antigen of mAb 39 was then successfully purified using an improved immunoprecipitation approach in which mAb was bounded to intact mES cells before the cells were lysed.The LC-LTQ mass spectrum analysis showed that the target antigen of mAb 39 was Glut3.This result was further confirmed by Western blot using commercially available antibodies against Glut3.Further experiments showed that mAb 39 exhibited an antiproliferative effect on mES cells.We also found that Glut3 was differentially expressed among the mES cell population as detected by flow cytometry.展开更多
目的评价丝裂酶原活化蛋白激酶（mitogen—activated protein kinase，MAPK）信号转导通路中MAPK激酶1／2（MEKI／2）在骨关节炎发病过程中的作用。方法新西兰家兔30只，制作OA模型，随机分成3组，每组10只。从造模术后第4天开始，第1...目的评价丝裂酶原活化蛋白激酶（mitogen—activated protein kinase，MAPK）信号转导通路中MAPK激酶1／2（MEKI／2）在骨关节炎发病过程中的作用。方法新西兰家兔30只，制作OA模型，随机分成3组，每组10只。从造模术后第4天开始，第1组和第2组分别注射100μmol／L和40μmol／L的PD98059，第3组注射PBS液体作为安慰剂对照组，每周2次。另取10只家兔，正常关节内注射PBS液体作为正常对照组。8周后处死动物，进行股骨髁关节软骨退变的大体评分。用Western Blot印记杂交法测定软骨组织中ERK1／2以及磷酸化ERK1／2的表达。用实时定量PCR方法测定基质金属蛋白酶-1／13（MMp-1／13）的mRNA表达水平。结果与使用PBS的安慰剂对照组相比，使用PD98059的关节软骨破坏明显减轻。磷酸化的ERK1／2在100μmol／LPD98059干预组明显低于40μmol／L干预组和安慰剂对照组。而MMP-1／13的mRNA表达在不同浓度的干预组均低于安慰剂对照组。结论MAPK信号转导通路参与了骨关节炎关节软骨破坏的病理过程。MEK1／2选择性阻滞剂PD98059可以在关节炎动物活体内有效抑制关节炎软骨破坏的程度，该作用可能与其有效抑制ERK1／2的磷酸化激活有关。展开更多
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
基金supported by the National Key Scientific Research Program of China,the Ministry of Science and Technology of the People’s Republic of China (No 2007947804)
文摘Embryonic stem （ES） cells are potent resources for cell therapy,and monoclonal antibodies （mAbs） against native cell surface markers of ES cells could be useful tools for therapeutic applications.Here,we report the development of a feasible approach,which could be used in mass production,for experimentally producing rabbit mAbs against native cell surface antigens on the cell surface.Two of the 14 mAbs,which were selected at random,could be bound to the cell surface antigens of mES cells.The immunocytochemistry （ICC） and Western blot results showed that mAb 39 recognises conformational epitopes.The target antigen of mAb 39 was then successfully purified using an improved immunoprecipitation approach in which mAb was bounded to intact mES cells before the cells were lysed.The LC-LTQ mass spectrum analysis showed that the target antigen of mAb 39 was Glut3.This result was further confirmed by Western blot using commercially available antibodies against Glut3.Further experiments showed that mAb 39 exhibited an antiproliferative effect on mES cells.We also found that Glut3 was differentially expressed among the mES cell population as detected by flow cytometry.
文摘目的评价丝裂酶原活化蛋白激酶（mitogen—activated protein kinase，MAPK）信号转导通路中MAPK激酶1／2（MEKI／2）在骨关节炎发病过程中的作用。方法新西兰家兔30只，制作OA模型，随机分成3组，每组10只。从造模术后第4天开始，第1组和第2组分别注射100μmol／L和40μmol／L的PD98059，第3组注射PBS液体作为安慰剂对照组，每周2次。另取10只家兔，正常关节内注射PBS液体作为正常对照组。8周后处死动物，进行股骨髁关节软骨退变的大体评分。用Western Blot印记杂交法测定软骨组织中ERK1／2以及磷酸化ERK1／2的表达。用实时定量PCR方法测定基质金属蛋白酶-1／13（MMp-1／13）的mRNA表达水平。结果与使用PBS的安慰剂对照组相比，使用PD98059的关节软骨破坏明显减轻。磷酸化的ERK1／2在100μmol／LPD98059干预组明显低于40μmol／L干预组和安慰剂对照组。而MMP-1／13的mRNA表达在不同浓度的干预组均低于安慰剂对照组。结论MAPK信号转导通路参与了骨关节炎关节软骨破坏的病理过程。MEK1／2选择性阻滞剂PD98059可以在关节炎动物活体内有效抑制关节炎软骨破坏的程度，该作用可能与其有效抑制ERK1／2的磷酸化激活有关。
