肿瘤是危害人类健康的重要杀手,大约5%~10%的肿瘤由遗传性肿瘤综合征引起。遗传性肿瘤包括孟德尔遗传模式的单基因遗传性肿瘤以及由多基因与环境互相作用的多基因遗传性肿瘤。遗传性肿瘤综合征中与妇科肿瘤相关的有:遗传性乳腺癌-卵巢...肿瘤是危害人类健康的重要杀手,大约5%~10%的肿瘤由遗传性肿瘤综合征引起。遗传性肿瘤包括孟德尔遗传模式的单基因遗传性肿瘤以及由多基因与环境互相作用的多基因遗传性肿瘤。遗传性肿瘤综合征中与妇科肿瘤相关的有:遗传性乳腺癌-卵巢癌综合征(hereditary breast and ovarian cancer,HBOC).展开更多
AIM： Microcirculatory dysfunction and free oxygen radicals are important factors in the pathogenesis of severe acute pancreatitis. Additional oxygen delivery might enhance lipid peroxidation but may also improve panc...AIM： Microcirculatory dysfunction and free oxygen radicals are important factors in the pathogenesis of severe acute pancreatitis. Additional oxygen delivery might enhance lipid peroxidation but may also improve pancreatic microcirculation. This study assesses the effect of free cellular bovine hemoglobin on the formation of oxygen radicals and microcirculation in a rodent model of severe acute pancreatitis. METHODS： Fifteen minutes after induction of acute pancreatitis Wistar rats received either 0.8 mL bovine hemoglobin （HBOC-200）, hydroxyethyl starch （HES） or 2.4 mL of normal saline to ensure normovolemic substitution. After 6 h of examination the pancreas was excised and rapidly processed for indirect measurement of lipid peroxidation products malondialdehyde （MDA） and reduced glutathione （GSH） in pancreatic tissue. RESULTS： The single application of HBOC-200 improved pancreatic microcirculation and reduced histopathological tissue damage significantly. Tissue concentration of MDA did not differ between the groups. Also no differences in GSH levels were detected.CONCLUSION： Though the single application of HBOC-200 and HES improve pancreatic microcirculation, no differences in lipid peroxidation products were detected. The beneficial effect of additional oxygen supply （HBOC-200） does not lead to enhanced lipid peroxidation.展开更多
One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) ...One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) takes care of the Hb physiologically leaked into the plasma-it binds Hb and makes it much less toxic while retaining the Hb’s high oxygen transporting capacity.We used Electron Paramagnetic Resonance(EPR) spectroscopy to show that the protein bound radical induced by H2O2 in Hb and Hp-Hb complex is formed on the same tyrosine residue(s),but,in the complex,the radical is found in a more hydrophobic environment and decays slower than in unbound Hb,thus mitigating its oxidative capacity.The data obtained in this study might set new directions in engineering blood substitutes for transfusion that would have the oxygen transporting efficiency typical of Hb,but which would be non-toxic.展开更多
Blood transfusions are regarded as the most well-known and frequently performed cell transplantations.Although current transfusion systems are sophisticated,they cannot be freed from the inherent difficulties that inc...Blood transfusions are regarded as the most well-known and frequently performed cell transplantations.Although current transfusion systems are sophisticated,they cannot be freed from the inherent difficulties that include infection,short shelf life,and blood type mismatching.Artificial oxygen carriers produced using hemoglobin(Hb)are designated as Hb-based oxygen carriers(HBOCs),which are anticipated for use as biomaterials that have potential to resolve issues of transfusion by a radical paradigm shift.Various HBOCs,nanometer-sized to micrometer-sized bioparticles having an oxygen-carrying function,are developed for use as substitutes for red blood cells(RBCs).This paper presents an overview of the classification of HBOCs with reference to their histories,preparations,structures,functions,and in vitro and in vivo properties.Additionally,we give a more detailed introduction of our academic studies of liposome encapsulated Hb,designated as Hb-vesicles(HbV),which mimic the physiologically important corpuscular structure of RBCs.This review outlines perennial efforts and approaches to mimic RBC functions through chemical,genetic,and encapsulation techniques.It will provide important insights into the eventual realization of an alternative for RBC transfusion.展开更多
文摘肿瘤是危害人类健康的重要杀手,大约5%~10%的肿瘤由遗传性肿瘤综合征引起。遗传性肿瘤包括孟德尔遗传模式的单基因遗传性肿瘤以及由多基因与环境互相作用的多基因遗传性肿瘤。遗传性肿瘤综合征中与妇科肿瘤相关的有:遗传性乳腺癌-卵巢癌综合征(hereditary breast and ovarian cancer,HBOC).
文摘AIM： Microcirculatory dysfunction and free oxygen radicals are important factors in the pathogenesis of severe acute pancreatitis. Additional oxygen delivery might enhance lipid peroxidation but may also improve pancreatic microcirculation. This study assesses the effect of free cellular bovine hemoglobin on the formation of oxygen radicals and microcirculation in a rodent model of severe acute pancreatitis. METHODS： Fifteen minutes after induction of acute pancreatitis Wistar rats received either 0.8 mL bovine hemoglobin （HBOC-200）, hydroxyethyl starch （HES） or 2.4 mL of normal saline to ensure normovolemic substitution. After 6 h of examination the pancreas was excised and rapidly processed for indirect measurement of lipid peroxidation products malondialdehyde （MDA） and reduced glutathione （GSH） in pancreatic tissue. RESULTS： The single application of HBOC-200 improved pancreatic microcirculation and reduced histopathological tissue damage significantly. Tissue concentration of MDA did not differ between the groups. Also no differences in GSH levels were detected.CONCLUSION： Though the single application of HBOC-200 and HES improve pancreatic microcirculation, no differences in lipid peroxidation products were detected. The beneficial effect of additional oxygen supply （HBOC-200） does not lead to enhanced lipid peroxidation.
基金supported by the Biomedical EPR Facility of the University of Essexgranted by the EPSRC funded UK National Service for Computational Chemistry Software(NSCCS,1996-2017)Imperial College London。
文摘One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) takes care of the Hb physiologically leaked into the plasma-it binds Hb and makes it much less toxic while retaining the Hb’s high oxygen transporting capacity.We used Electron Paramagnetic Resonance(EPR) spectroscopy to show that the protein bound radical induced by H2O2 in Hb and Hp-Hb complex is formed on the same tyrosine residue(s),but,in the complex,the radical is found in a more hydrophobic environment and decays slower than in unbound Hb,thus mitigating its oxidative capacity.The data obtained in this study might set new directions in engineering blood substitutes for transfusion that would have the oxygen transporting efficiency typical of Hb,but which would be non-toxic.
基金supporting to our research group with grants from the Japan Society for the Promotion of Science (JSPS)the Japan Agency for Medical Research and Development(AMED).
文摘Blood transfusions are regarded as the most well-known and frequently performed cell transplantations.Although current transfusion systems are sophisticated,they cannot be freed from the inherent difficulties that include infection,short shelf life,and blood type mismatching.Artificial oxygen carriers produced using hemoglobin(Hb)are designated as Hb-based oxygen carriers(HBOCs),which are anticipated for use as biomaterials that have potential to resolve issues of transfusion by a radical paradigm shift.Various HBOCs,nanometer-sized to micrometer-sized bioparticles having an oxygen-carrying function,are developed for use as substitutes for red blood cells(RBCs).This paper presents an overview of the classification of HBOCs with reference to their histories,preparations,structures,functions,and in vitro and in vivo properties.Additionally,we give a more detailed introduction of our academic studies of liposome encapsulated Hb,designated as Hb-vesicles(HbV),which mimic the physiologically important corpuscular structure of RBCs.This review outlines perennial efforts and approaches to mimic RBC functions through chemical,genetic,and encapsulation techniques.It will provide important insights into the eventual realization of an alternative for RBC transfusion.
