Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The suscep...Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.展开更多
It has been generally accepted that about 85％ of cancers are caused by chemical factors and the chemically induced carcinogenic process can be divided into two or three stages, i. e. initiation and promotion, or toge...It has been generally accepted that about 85％ of cancers are caused by chemical factors and the chemically induced carcinogenic process can be divided into two or three stages, i. e. initiation and promotion, or together with further progression. The initiation is usually considered to be an irreversible process, but it can be blocked to further progress to cancer. For this reason, searching of objective markers for identifying initiated cells has played an important role in defining the preneoplastic lesion. So far, a large number of studies have been carried out on this object, including biochemistry, histopathology, histochemistry, immunohistochemistry, etc., and nearly thirty histochemical and other phenotypic changes have been found associated with the putative preneoplastic liver展开更多
Just like in animals, the essence of fertilization process in plants is the fusion of male andfemale gametes. Although it is already possible, with the aid of cytological manipulation, toachieve in vitro fusion of iso...Just like in animals, the essence of fertilization process in plants is the fusion of male andfemale gametes. Although it is already possible, with the aid of cytological manipulation, toachieve in vitro fusion of isolated egg and sperm cell to form zygote, it remains to be solvedwhether the fusion of male and female gametes in nature is at random or there exists some kindof 'recognition'.展开更多
基金National Natural Scientific Foundation of ChinaGrant/Award Number:81972975+2 种基金National Human Diseases Animal Model Resource CenterNational Science Foundation for Young Scientists of ChinaGrant/Award Number:81703170。
文摘Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.
基金Project supported by the National Natural Science Foundation of China
文摘It has been generally accepted that about 85％ of cancers are caused by chemical factors and the chemically induced carcinogenic process can be divided into two or three stages, i. e. initiation and promotion, or together with further progression. The initiation is usually considered to be an irreversible process, but it can be blocked to further progress to cancer. For this reason, searching of objective markers for identifying initiated cells has played an important role in defining the preneoplastic lesion. So far, a large number of studies have been carried out on this object, including biochemistry, histopathology, histochemistry, immunohistochemistry, etc., and nearly thirty histochemical and other phenotypic changes have been found associated with the putative preneoplastic liver
基金Project supported by the National Natural Science Foundation of China.
文摘Just like in animals, the essence of fertilization process in plants is the fusion of male andfemale gametes. Although it is already possible, with the aid of cytological manipulation, toachieve in vitro fusion of isolated egg and sperm cell to form zygote, it remains to be solvedwhether the fusion of male and female gametes in nature is at random or there exists some kindof 'recognition'.
