Objective Hydroquinone(HQ),one of the phenolic metabolites of benzene,is widely recognized as an important participant in benzene-induced hematotoxicity.However,there are few relevant proteomics in HQ-induced hematoto...Objective Hydroquinone(HQ),one of the phenolic metabolites of benzene,is widely recognized as an important participant in benzene-induced hematotoxicity.However,there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn’t been fully understood yet.Methods In this study,we treated K562 cells with 40μmol/L HQ for 72 h,examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring(PRM),and performed bioinformatics analysis to identify interaction networks.Results One hundred and eighty-seven upregulated differentially expressed proteins(DEPs)and 279 downregulated DEPs were identified in HQ-exposed K562 cells,which were involved in neutrophilmediated immunity,blood microparticle,and other GO terms,as well as the lysosome,metabolic,cell cycle,and cellular senescence-related pathways.Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways,we constructed the network of protein interactions and determined 6 DEPs(STAT1,STAT3,CASP3,KIT,STAT5B,and VEGFA)as main hub proteins with the most interactions,among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity.Conclusion Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.展开更多
Benzene is a classified as ahuman carcinogen that can cause myelodysplastic syndrome and acute myelogenousleukemia;.This compound is also a potent toxin suppressing the bone marrow.Accordingly,benzene causes serious h...Benzene is a classified as ahuman carcinogen that can cause myelodysplastic syndrome and acute myelogenousleukemia;.This compound is also a potent toxin suppressing the bone marrow.Accordingly,benzene causes serious hematological adverse effects,such as pancytopenia and aplastic展开更多
Salmonella typhi is a facultative intracellular pathogen that causes typhoid fever in humans. In the present study, the effect of Salmonella typhi infection on hematological indices and spleen histology in Wistar rats...Salmonella typhi is a facultative intracellular pathogen that causes typhoid fever in humans. In the present study, the effect of Salmonella typhi infection on hematological indices and spleen histology in Wistar rats was investigated and was followed by an evaluation of the ameliorative potential of the methanol leaf extract of Chromolaena odorata (MLECO) compared with ciprofloxacin treatment. The animals were divided into six groups: group 1 was normal control, group 2 was infected with Salmonella typhi without treatment (negative control), groups 3, 4 and 5 were Salmonella typhi infected and treated with 100 mg/kg, 200 mg/kg and 400 mg/kg of the extract respectively and group 6 was also Salmonella typhi infected and treated with 500 mg/70kg of ciprofloxacin. The animals were inoculated with a single infectious dose of Salmonella typhi bacteria and thereafter, treated with the extract and ciprofloxacin for a period of seventeen days, after the animals were confirmed infected. The rats were humanely sacrificed and blood samples taken for haematological investigations, and the spleen harvested and processed for histological examinations. Chromolaena odorata administration reversed the adverse hematotoxicity and histopathological changes in the spleen induced by?Salmonella typhi?infection.展开更多
Hematological toxicity （bone marrow suppression） is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 （Nrf2） is a pivotal coordinator of cellular defen...Hematological toxicity （bone marrow suppression） is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 （Nrf2） is a pivotal coordinator of cellular defensive responses against chemical insults in many tissues including bone marrow. In the present study, the effects of tert-butylhydroquinone （tBHQ） on the expression of Nrf2-regulated genes in peripheral blood cells and cyclophosphamide （CTX）-induced hematotoxicity in mice were investigated. CTX induced apoptosis of peripheral blood nucleated cells and leukopenia in mice, accompanied by mobilization of bone marrow hematopoietic cells, tBHQ treatment induced the expression of Nrf2-regulated genes such as heine oxygenase 1 （HO1） and glutamate-cysteine ligase catalytic subtmit （GCLC） in RAW264.7 mouse macrophage cells and peripheral blood cells both in vitro and in vivo. Interestingly, pretreatment with tBHQ alleviated CTX-induced mouse peripheral blood cell apoptosis and leukopenia in vivo, indicating possible involvement of Nrf2 in the protection against CTX-induced hematotoxicity. This study provides new information on the chemotherapy-induced hematotoxicity, and suggests Nrf2 could serve as a target for the development of chemoprotectants against hematotoxicity.展开更多
基金supported by the National Natural Science Foundation of China[Project No.81573192].
文摘Objective Hydroquinone(HQ),one of the phenolic metabolites of benzene,is widely recognized as an important participant in benzene-induced hematotoxicity.However,there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn’t been fully understood yet.Methods In this study,we treated K562 cells with 40μmol/L HQ for 72 h,examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring(PRM),and performed bioinformatics analysis to identify interaction networks.Results One hundred and eighty-seven upregulated differentially expressed proteins(DEPs)and 279 downregulated DEPs were identified in HQ-exposed K562 cells,which were involved in neutrophilmediated immunity,blood microparticle,and other GO terms,as well as the lysosome,metabolic,cell cycle,and cellular senescence-related pathways.Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways,we constructed the network of protein interactions and determined 6 DEPs(STAT1,STAT3,CASP3,KIT,STAT5B,and VEGFA)as main hub proteins with the most interactions,among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity.Conclusion Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.
基金supported by the Key Program of the National Natural Science Foundation of China [81730087]Jiangsu Provincial Youth Medical Talent program [QNRC2016536]+3 种基金Six Talent Peaks Project in Jiangsu Province [WSW-017]Jiangsu Province’s Outstanding Medical Academic Leader program [CXTDA2017029]Preventive Medicine Foundation of Jiangsu [Y2015049]Occupational Health Risk assessement and National Occupational Hygienic Standard Formulation [131031109000150003]
文摘Benzene is a classified as ahuman carcinogen that can cause myelodysplastic syndrome and acute myelogenousleukemia;.This compound is also a potent toxin suppressing the bone marrow.Accordingly,benzene causes serious hematological adverse effects,such as pancytopenia and aplastic
文摘Salmonella typhi is a facultative intracellular pathogen that causes typhoid fever in humans. In the present study, the effect of Salmonella typhi infection on hematological indices and spleen histology in Wistar rats was investigated and was followed by an evaluation of the ameliorative potential of the methanol leaf extract of Chromolaena odorata (MLECO) compared with ciprofloxacin treatment. The animals were divided into six groups: group 1 was normal control, group 2 was infected with Salmonella typhi without treatment (negative control), groups 3, 4 and 5 were Salmonella typhi infected and treated with 100 mg/kg, 200 mg/kg and 400 mg/kg of the extract respectively and group 6 was also Salmonella typhi infected and treated with 500 mg/70kg of ciprofloxacin. The animals were inoculated with a single infectious dose of Salmonella typhi bacteria and thereafter, treated with the extract and ciprofloxacin for a period of seventeen days, after the animals were confirmed infected. The rats were humanely sacrificed and blood samples taken for haematological investigations, and the spleen harvested and processed for histological examinations. Chromolaena odorata administration reversed the adverse hematotoxicity and histopathological changes in the spleen induced by?Salmonella typhi?infection.
基金National Natural Science Foundation(Grant No.81272468 and 21001011)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education
文摘Hematological toxicity （bone marrow suppression） is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 （Nrf2） is a pivotal coordinator of cellular defensive responses against chemical insults in many tissues including bone marrow. In the present study, the effects of tert-butylhydroquinone （tBHQ） on the expression of Nrf2-regulated genes in peripheral blood cells and cyclophosphamide （CTX）-induced hematotoxicity in mice were investigated. CTX induced apoptosis of peripheral blood nucleated cells and leukopenia in mice, accompanied by mobilization of bone marrow hematopoietic cells, tBHQ treatment induced the expression of Nrf2-regulated genes such as heine oxygenase 1 （HO1） and glutamate-cysteine ligase catalytic subtmit （GCLC） in RAW264.7 mouse macrophage cells and peripheral blood cells both in vitro and in vivo. Interestingly, pretreatment with tBHQ alleviated CTX-induced mouse peripheral blood cell apoptosis and leukopenia in vivo, indicating possible involvement of Nrf2 in the protection against CTX-induced hematotoxicity. This study provides new information on the chemotherapy-induced hematotoxicity, and suggests Nrf2 could serve as a target for the development of chemoprotectants against hematotoxicity.
