Hypoxic preconditioning(HPC) refers to exposure of organisms,systems,organs,tissues or cells to moderate hypoxia/ischemia that is able to result in a resistance to subsequent severe hypoxia/ischemia in tissues and cel...Hypoxic preconditioning(HPC) refers to exposure of organisms,systems,organs,tissues or cells to moderate hypoxia/ischemia that is able to result in a resistance to subsequent severe hypoxia/ischemia in tissues and cells.The effects exerted by HPC are well documented.The original local in situ(LiHPC) is now broadened to remote ectopic organs-tissues(ReHPC) and extended crossly to cross pluripotential HPC(CpHPC) induced by a variety of stresses other than hypoxia/ischemia,including cancer,for example.We developed a unique animal model of repetitive autohypoxia in adult mice,and studied systematically on the effects and mechanisms of HPC on the model in our laboratory since the early 1960 s.The tolerances to hypoxia and protection from injury increased significantly in this model.The adult mice behave like hypoxia-intolerant mammalian newborns and hypoxia-tolerant adult animals during their exposure to repetitive autohypoxia.The overall energy supply and demand decreased,the microorganization of the brain maintained and the spacial learning and memory ability improved but not impaired,the detrimental neurochemicals such as free radicals down-regulated and the beneficial neurochemicals such as adenosine(ADO) and antihypoxic gene(s)/factor(s)(AHGs/AHFs) up-regulated.Accordingly,we hypothesize that mechanisms for the tolerance / protective effects of HPC are fundamentally depending on energy saving and brain plasticity in particular.It is thought that these two major mechanisms are triggered by exposure to hypoxia/ischemia via oxygen sensing-transduction pathways and HIF-1 initiation cascades.We suggest that HPC is an intrinsic mechanism developed in biological evolution and is a novel potential strategy for fighting against hypoxia-ischemia and other stresses.Motivation of endogenous antihypoxic potential,activation of oxygen sensing- signal transduction systems and supplement of exogenous antihypoxic substances as well as development of HPC appliances and HPC medicines such as AHFs are encouraged based on our basic research on HPC.HPC may result in therapeutic augmentation of the endogenous cytoprotection in hypoxic-ischemic or suffering from other diseases' patients.Evolutionary consideration of HPC and clinical implications of HPC are both discussed to guide future research.The product of AHF is expected to be one of the most effective first aid medicines to rescue patients in critical condition.HPC is beginning to be used in surgery and is expected to be developed into a feasible adaptive medicine in the near future.展开更多
Background Runt-related transcription factor 1 （Runxl） plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runxl...Background Runt-related transcription factor 1 （Runxl） plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runxl will induce leukemia and how the change of Runxl expression level could affect BCR-ABL-induced leukemogenesis. In the present study, we aimed to analyze if abnormal expression of Runxl in BaF3 cells alone would induce teukemogenesis. And we also wanted to know if abnormal expression of Runxl in leukemic cells would affect leukemogenesis. Furthermore, we investigated whether overexpression or knock-down of Runxl in BaF3 cells would induce leukemogenesis. Methods Plasmids containing full-length Runxl cDNA were transduced into BaF3 cells and BaF3-P185wt cells （BCR-ABL transformed BaF3 cells） by electroporation. Plasmids containing a short hairpin RNA of Runxl were transduced into BaF3 cells and BaF3-P185wt cells by electroporation. Runxl expression level was quantified by Western blotting and quantitative real-time PCR. The effects of overexpression or knock-down of Runxl on proliferation, apoptosis and migration of cells were detected in vitro. Then, using MSCV-P185wt-EGFP as a control, we transplanted MSCV-P185wt-Runx1 cells or MSCV-P185wt-shRNA cells into Balb/c mice through tail vein and observed tumorgenesis of the different phenotypes. Results In vitro analysis revealed that overexpression of Runxl in P185wt cells could inhibit cell proliferation and slow down cell migration; while knock-down of Runxl could promote cell proliferation and speed up cell migration. In vivo analysis indicated that mice transplanted with MSCV-P185wt-Runx1 survived longer than controls. In contrast, mice transplanted with MSCV-P185wt-shRNA survived shorter than the control group. Gross pathological analysis revealed that the MSCV-P185wt-Runx1 group had less severe splenomegaly and hepatomegaly compared to the control group, and the MSCV-P185wt-shRNA group had more severe splenomegaly and hepatomegaly. No splenomegaly or hepatomegaly was detected in mice transplanted with MSCV-BaF3-Runxl cells or MSCV-BaF3-shRNA cells. Both the mice of MSCV-BaF3-Runxl group and MSCV-BaF3-shRNA group were healthy with no sign of leukemia for up to three months. Conclusions Overexpression or knock-down of Runxl gene in BaF3 cells alone could not induce leukemogenesis. However, in BaF3-P185wt cells, alteration of Runxl expression could affect BCR-ABL-induced proliferation and migration in vitro and leukemoaenesis in vivo.展开更多
文摘Hypoxic preconditioning(HPC) refers to exposure of organisms,systems,organs,tissues or cells to moderate hypoxia/ischemia that is able to result in a resistance to subsequent severe hypoxia/ischemia in tissues and cells.The effects exerted by HPC are well documented.The original local in situ(LiHPC) is now broadened to remote ectopic organs-tissues(ReHPC) and extended crossly to cross pluripotential HPC(CpHPC) induced by a variety of stresses other than hypoxia/ischemia,including cancer,for example.We developed a unique animal model of repetitive autohypoxia in adult mice,and studied systematically on the effects and mechanisms of HPC on the model in our laboratory since the early 1960 s.The tolerances to hypoxia and protection from injury increased significantly in this model.The adult mice behave like hypoxia-intolerant mammalian newborns and hypoxia-tolerant adult animals during their exposure to repetitive autohypoxia.The overall energy supply and demand decreased,the microorganization of the brain maintained and the spacial learning and memory ability improved but not impaired,the detrimental neurochemicals such as free radicals down-regulated and the beneficial neurochemicals such as adenosine(ADO) and antihypoxic gene(s)/factor(s)(AHGs/AHFs) up-regulated.Accordingly,we hypothesize that mechanisms for the tolerance / protective effects of HPC are fundamentally depending on energy saving and brain plasticity in particular.It is thought that these two major mechanisms are triggered by exposure to hypoxia/ischemia via oxygen sensing-transduction pathways and HIF-1 initiation cascades.We suggest that HPC is an intrinsic mechanism developed in biological evolution and is a novel potential strategy for fighting against hypoxia-ischemia and other stresses.Motivation of endogenous antihypoxic potential,activation of oxygen sensing- signal transduction systems and supplement of exogenous antihypoxic substances as well as development of HPC appliances and HPC medicines such as AHFs are encouraged based on our basic research on HPC.HPC may result in therapeutic augmentation of the endogenous cytoprotection in hypoxic-ischemic or suffering from other diseases' patients.Evolutionary consideration of HPC and clinical implications of HPC are both discussed to guide future research.The product of AHF is expected to be one of the most effective first aid medicines to rescue patients in critical condition.HPC is beginning to be used in surgery and is expected to be developed into a feasible adaptive medicine in the near future.
文摘Background Runt-related transcription factor 1 （Runxl） plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runxl will induce leukemia and how the change of Runxl expression level could affect BCR-ABL-induced leukemogenesis. In the present study, we aimed to analyze if abnormal expression of Runxl in BaF3 cells alone would induce teukemogenesis. And we also wanted to know if abnormal expression of Runxl in leukemic cells would affect leukemogenesis. Furthermore, we investigated whether overexpression or knock-down of Runxl in BaF3 cells would induce leukemogenesis. Methods Plasmids containing full-length Runxl cDNA were transduced into BaF3 cells and BaF3-P185wt cells （BCR-ABL transformed BaF3 cells） by electroporation. Plasmids containing a short hairpin RNA of Runxl were transduced into BaF3 cells and BaF3-P185wt cells by electroporation. Runxl expression level was quantified by Western blotting and quantitative real-time PCR. The effects of overexpression or knock-down of Runxl on proliferation, apoptosis and migration of cells were detected in vitro. Then, using MSCV-P185wt-EGFP as a control, we transplanted MSCV-P185wt-Runx1 cells or MSCV-P185wt-shRNA cells into Balb/c mice through tail vein and observed tumorgenesis of the different phenotypes. Results In vitro analysis revealed that overexpression of Runxl in P185wt cells could inhibit cell proliferation and slow down cell migration; while knock-down of Runxl could promote cell proliferation and speed up cell migration. In vivo analysis indicated that mice transplanted with MSCV-P185wt-Runx1 survived longer than controls. In contrast, mice transplanted with MSCV-P185wt-shRNA survived shorter than the control group. Gross pathological analysis revealed that the MSCV-P185wt-Runx1 group had less severe splenomegaly and hepatomegaly compared to the control group, and the MSCV-P185wt-shRNA group had more severe splenomegaly and hepatomegaly. No splenomegaly or hepatomegaly was detected in mice transplanted with MSCV-BaF3-Runxl cells or MSCV-BaF3-shRNA cells. Both the mice of MSCV-BaF3-Runxl group and MSCV-BaF3-shRNA group were healthy with no sign of leukemia for up to three months. Conclusions Overexpression or knock-down of Runxl gene in BaF3 cells alone could not induce leukemogenesis. However, in BaF3-P185wt cells, alteration of Runxl expression could affect BCR-ABL-induced proliferation and migration in vitro and leukemoaenesis in vivo.
