Pseudogene and fibrin peptide which has rapid evolve speed and good stability are used in this study to determine the divergence date among groups.Through calculating the evolutionary rate of hemoglobin α chain,γ ch...Pseudogene and fibrin peptide which has rapid evolve speed and good stability are used in this study to determine the divergence date among groups.Through calculating the evolutionary rate of hemoglobin α chain,γ chain in vertebrate（including birds and mammals）,it is concluded that the evolutionary rate of hemoglobin α chain,γ chain is not invariable.It shows different evolutionary rates in different periods,that is,faster in early evolution stage and relatively slow in later stage.展开更多
OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METH...OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.展开更多
Studies on the chaperone protein α-hemoglobin stabilizing protein （AHSP） reveal that abundant AHSP in erythroid cells en-hance the cells＇ tolerance to oxidative stress imposed by excess a-hemoglobin in pathologica...Studies on the chaperone protein α-hemoglobin stabilizing protein （AHSP） reveal that abundant AHSP in erythroid cells en-hance the cells＇ tolerance to oxidative stress imposed by excess a-hemoglobin in pathological conditions. However, the poten-tial intracellular modulation of AHSP expression itself in response to oxidative stress is still unknown. The present study ex-amined the effect and molecular mechanism of STAT3, an oxidative regulator, on the expression of AHSP. AHSP expression increased in K562 cells upon cytokine IL-6-induced STAT3 activation and decreased in STAT3 knock-down K562 cells. Reg-ulation of AHSP in oxidative circumstance was then examined in α-globin-overloaded K562 cells, and real-time PCR showed strengthened expression of both AHSP and STAT3. ChIP analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and upon α-globin overexpression. Dual luciferase reporter assays of the wildtype and mutated SB3 element, an IL-6RE site, in the AHSP promoter in K562 cells highlighted the direct regulatory ef-fect of STAT3 on AHSP gene. Finally, direct binding of STAT3 to SB3 site of AHSP promoter was confirmed with EMSA as-says. Our work reveals an adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway, and provides clues to the therapeutic strategy for AHSP enhancement.展开更多
基金Supported by Youth Foundation of Hunan Institution of Humanities,Science and Technology(2009QN08)Educational Reform Project of Hunan Institution of Humanities,Science and Technology(RKJGZ1013)~~
文摘Pseudogene and fibrin peptide which has rapid evolve speed and good stability are used in this study to determine the divergence date among groups.Through calculating the evolutionary rate of hemoglobin α chain,γ chain in vertebrate（including birds and mammals）,it is concluded that the evolutionary rate of hemoglobin α chain,γ chain is not invariable.It shows different evolutionary rates in different periods,that is,faster in early evolution stage and relatively slow in later stage.
文摘OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.
基金supported by the National Natural Science Foundation of China(31030026,31021091)the National Basic Research Program of China(2011CB965203,2011CB964803)
文摘Studies on the chaperone protein α-hemoglobin stabilizing protein （AHSP） reveal that abundant AHSP in erythroid cells en-hance the cells＇ tolerance to oxidative stress imposed by excess a-hemoglobin in pathological conditions. However, the poten-tial intracellular modulation of AHSP expression itself in response to oxidative stress is still unknown. The present study ex-amined the effect and molecular mechanism of STAT3, an oxidative regulator, on the expression of AHSP. AHSP expression increased in K562 cells upon cytokine IL-6-induced STAT3 activation and decreased in STAT3 knock-down K562 cells. Reg-ulation of AHSP in oxidative circumstance was then examined in α-globin-overloaded K562 cells, and real-time PCR showed strengthened expression of both AHSP and STAT3. ChIP analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and upon α-globin overexpression. Dual luciferase reporter assays of the wildtype and mutated SB3 element, an IL-6RE site, in the AHSP promoter in K562 cells highlighted the direct regulatory ef-fect of STAT3 on AHSP gene. Finally, direct binding of STAT3 to SB3 site of AHSP promoter was confirmed with EMSA as-says. Our work reveals an adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway, and provides clues to the therapeutic strategy for AHSP enhancement.
