Objectives: Sickle cell disease (SCD) has a varied clinical and biological expression depending on the hemoglobin phenotype: SSFA<sub>2</sub>, SFA<sub>2</sub>, SAFA<sub>2</sub> and ...Objectives: Sickle cell disease (SCD) has a varied clinical and biological expression depending on the hemoglobin phenotype: SSFA<sub>2</sub>, SFA<sub>2</sub>, SAFA<sub>2</sub> and SC. Considering the antioxidant properties of the different haptoglobin phenotypes (Hp 1-1, Hp 2-1, Hp 2-2), it seemed relevant to know their influence on the morbidity of the different hemoglobin phenotype of SCD. Thus, the objective of this study was to identify associations between haptoglobin phenotype and morbidity of different SCD phenotypes. Methods: In a retrospective cross-sectional descriptive and analytical study, with a cohort of 170 black African carriers of hemoglobin S, in Ivory Coast, West Africa, hemoglobin and haptoglobin phenotypes were determined by electrophoretic methods. Results: The three major phenotypes of haptoglobin polymorphism were found in the SCD cohort: Hp 1-1 (24.1%), Hp 2-1 (56.5%), Hp 2-2 (19.4%). Vaso-occlusions were associated with haptoglobin phenotype Hp 1-1, (OR = 2.03;CI<sub>95%</sub> = [1.06 - 3.9];p Conclusions: Haptoglobin phenotype was associated to morbidity-adjusted hemoglobin phenotype. The study revealed a greater probability of a worse morbidity when the hemoglobin phenotype is homozygous. Unexpectedly, the worse morbidity is associated to Hp 1-1 haptoglobin phenotype, the most powerful antioxidant within the different haptoglobin phenotypes. Associations found were not systematic and need further studies to enlighten the determinism of SCD morbidity.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a chronic,relapsing inflammation of the digestive tract.Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD,their low sen...BACKGROUND Inflammatory bowel disease(IBD)is a chronic,relapsing inflammation of the digestive tract.Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD,their low sensitivity and high variability characteristics limit clinical efficacy.Thus,the establishment of better biomarkers is expected.Fucosylation is one of the most important glycosylation modifications of proteins.Fucosylated haptoglobin(Fuc-Hpt)is used as a biomarker for several cancers and inflammation-related diseases.We recently established a novel glycan monoclonal antibody(mAb),designated 10-7G,which recognizes Fuc-Hpt.We developed an enzyme-linked immunosorbent assay(ELISA)to measure serum levels of Fuc-Hpt(10-7G values).AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.METHODS This was a case control study.Intestinal tissues of IBD patients(n=10)were examined immunohistochemically using the 10-7G mAb.We determined 10-7G values using serum from patients with ulcerative colitis(UC,n=110),Crohn’s disease(n=45),acute enteritis(AE,n=11),and healthy volunteers(HVs)who exhibited normal(n=20)or high(n=79)C-reactive protein(CRP)levels at medical check-up.We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers.RESULTS In the immunohistochemical analysis,positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles.The 10-7G values were significantly higher in patients with IBD(P<0.001)and AE(P<0.05)compared with HVs.In addition,10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC,particularly the CRP level(rs=0.525,P=0.003)and clinical activity index score(rs=0.435,P=0.038).However,there was no correlation between 10-7G values and CRP in HVs with high CRP levels,suggesting that the 10-7G values is not the same as a general inflammation biomarker.ROC curve analysis showed that area under the curve(AUC)value of 10-7G values for the diagnosis of endoscopic remission was higher than other biomarkers(AUC value=0.699).CONCLUSION The serum 10-7G value is a novel biomarker for evaluating intestinal inflammation and endoscopic mucosal healing in UC.展开更多
Haptoglobin（Hp）基因多态性与疟疾发病风险存在关联，但各研究结果不一致．本meta分析旨在探讨Hp基因多态性与疟疾发病风险的关系．在Pubmed数据库中查询文献，将包含Hp基因型频率的病例对照研究文献纳入本研究中，并计算疟疾发生危...Haptoglobin（Hp）基因多态性与疟疾发病风险存在关联，但各研究结果不一致．本meta分析旨在探讨Hp基因多态性与疟疾发病风险的关系．在Pubmed数据库中查询文献，将包含Hp基因型频率的病例对照研究文献纳入本研究中，并计算疟疾发生危险性的优势比（Oddratio，OR）及其95％置信区间（confidence interval，CI）．最终查到符合要求的文献4篇，其中病例组1312例，对照组1018例．分析结果显示：在各遗传模式下Hp基因多态性与疟疾发病风险的相关性均不显著（加性模式：OR=1．882，95％CI：0．959～3．692，P=0．066；显性模式：OR=1．395，95％CI：0．733～2．656，P=0．311；隐性模型：OR=2．449，95％C／：0．921～6．508，P=0．073：共显性模型：（hp^1／hp^2 vs hp^2／hp^2）OR=0．951，95％CI：0．76～1．189，P=0．658；共显性模型（hp^1／hp^1 vs hp^2／hp^2）OR=2．336，95％CI：0．78～6．994，P=0．129）．并且Egger’s检验（P〉0．05）和Begg’S检验（P〉0．05）均显示不存在发表偏倚．综上所述，haptoglobin基因多态性对疟疾发病风险提高的影响可能并不大．展开更多
Haptoglobin(Hp)is an acidic glycoprotein,existing in the serum and other body fluids of human beings and a variety of mammals.Hp is produced in the liver,white adipose tissue,and the kidney.The genetic polymorphisms a...Haptoglobin(Hp)is an acidic glycoprotein,existing in the serum and other body fluids of human beings and a variety of mammals.Hp is produced in the liver,white adipose tissue,and the kidney.The genetic polymorphisms and different phenotypes of Hp have different biological functions.Hp has antibacterial,antioxidant,and angiogenic effects and is associated with multiple diseases including simple obesity,vascular complications of diabetes mellitus,nonalcoholic fatty liver disease,hypertension,blood diseases,autoimmune diseases,and malignant tumors.Hp also participates in many life activities,indicating the importance of Hp in further studies.Previously,we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials.However,the specific mechanism of Hp in patients with simple obesity is still unclear.The purpose of this article is to introduce recent research progress on Hp,emphasizing the relationship between Hp and the development of metabolic disease,which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.展开更多
Haptoglobin (Hp) is a hemoglobin (Hb) binding protein which plays an important role in neutralizing oxidation reactions stimulated by heme-derived iron. Differences in Hp types due to the polymorphic nature of the gen...Haptoglobin (Hp) is a hemoglobin (Hb) binding protein which plays an important role in neutralizing oxidation reactions stimulated by heme-derived iron. Differences in Hp types due to the polymorphic nature of the gene have led to the discovery that individuals carrying the Hp 2-2 genotype are at increased risk of developing vascular complications in the setting of diabetes. Preeclampsia is a pregnancy related disease that is thought to be caused by increases in oxidative stress. The role of Hp polymorphism is determining preeclampsia has been addressed by several clinical studies but the results have been contradictory. Larger longitudinal studies are needed to answer this important question.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
Octameric hemoglobins have been developed by the introduction of surface cysteines in either the alpha or beta chain. Originally designed as a blood substitute, we report here the structure and ligand binding function...Octameric hemoglobins have been developed by the introduction of surface cysteines in either the alpha or beta chain. Originally designed as a blood substitute, we report here the structure and ligand binding function;in addition the interaction with haptoglobin was studied. The recombinant Hbs (rHbs) with mutations alpha Asn78Cys or beta Gly83Cys spontaneously form octamers under conditions where the cysteines are oxidized. Oxygen binding curves and CO kinetic studies indicate a correct allosteric transition of the tetramers within the octamer. Crystallographic studies of the two rHbs show two disulfide bonds per octamer. Reducing agents may provoke dissociation to tetramers, but the octamers are stable when mixed with fresh human plasma, indicating that the reduction by plasma is slower than the oxidation by the dissolved oxygen, consistent with an enhanced stability. The octameric rHbs were also mixed with a solution of haptoglobin (Hp), which binds the dimers of Hb: there was little interaction for incubation times of 15 min;however, on longer timescales a complex was formed. Dynamic light scattering was used to follow the interaction of Hp with the alpha Asn78Cys octamer during 24 hours;a transition from a simple complex of 15 nm to a final size of 60 nm was observed. The results indicate a specific orientation of the αβ dimers may be of importance for the binding to haptoglobin.展开更多
Profiles of energy metabolites and haptoglobin (Hp) in dairy cows that are transitioned from conventional to organic management in various Alberta farms were compared with those of dairy cows managed conventionally at...Profiles of energy metabolites and haptoglobin (Hp) in dairy cows that are transitioned from conventional to organic management in various Alberta farms were compared with those of dairy cows managed conventionally at the University of Alberta dairy farm. Blood samples were collected during the following periods: Dry, 0 - 30, 30 - 60, and 60 - 90 days in milk (DIM, n = 7 cows). Concentrations of metabolites were evaluated by enzymatic colorimetric methods. Concentrations of Hp were determined by bovine ELISA kits. Data were analyzed by the mixed procedures of SAS. Concentrations of NEFA and BHBA in blood were elevated (P < 0.001) 0 to 30 d, intermediate 30 to 60, and 60 to 90 d, and lower in the dry period. In addition, BHBA was higher (P < 0.0001) at all stages of lactation in conventional than organic cows (e.g. 1289.4 ± 88.6 vs. 883.6 ± 47.5 μmol/L in conventional and organic cows at 0 - 30 d, respectively). Serum concentrations of cholesterol increased with increasing DIM and returned to nadir levels during dry period and was higher (P < 0.0001) in conventional than organic cows. Low glucose concentrations were observed 0 to 30 d, levels were intermediate 30 to 60 and 60 to 90 d, and peaked during the dry period (P < 0.54) between conventional and organic cows. Lactate did not (P < 0.24) vary with DIM or day × farm type but was higher (P < 0.0001) in organic cows than in conventional cows. Serum concentrations of Hp were elevated during dry period;reached peak levels 0 to 30 d and decreased gradually with increasing days postpartum and were much higher at all periods in conventional than organic cows. Overall, concentrations of Hp were 528.1 ± 45.2 μg/mL in conventional cows vs. 261.1 ± 16.9 μg/mL in organic cows (P < 0.0001). Taken together, these data indicate that metabolic changes associated with initiation of lactation are preceded by an acute phase response in dairy cows, and that cows in organic systems seem to be healthier than cows under conventional systems. These differences might be due to differences in nutritional management in the two systems.展开更多
Introduction: The physiological status of a subject and the pathophysiology in some diseases might be under the influence of haptoglobin phenotype. The objective of this work was to determine the relationship between ...Introduction: The physiological status of a subject and the pathophysiology in some diseases might be under the influence of haptoglobin phenotype. The objective of this work was to determine the relationship between mortality from HIV/AIDS infection and haptoglobin phenotype in a black population in Côte d’Ivoire. Methods: The study was conducted from a retrospective panel of 933 sera/plasma from the previous workup of the ANRS 12136 TEMPRANO trial at month 0 of patients in deferred-ART arms. For each subject, we determined the serum haptoglobin concentration, haptoglobin phenotype, and other variables from patient files from the TEMPRANO trial database. Statistical tests used were Chi-2, Fischer, and Kruskal-Wallis tests for non-gaussian distribution. We used the Kaplan-Meier method for survival analysis. Results: The distributions of the haptoglobin phenotypes were 32.3% for Hp 1-1, 39.5% for Hp 2-1 and 27.2% for Hp 2-2. The blood haptoglobin concentration seemed to be associated with haptoglobin phenotypes (p-value > 5%). The survival rate at M30 and for an extended follow-up up to 6 years was independent of haptoglobin phenotype (p-value > 5%). Besides, the haptoglobin phenotypes do not appear to be associated with CD4+ T-cell count and with hemoglobin concentration. Conclusion: Haptoglobin phenotype seems to not impact the mortality of HIV/AIDS infection. However, given the antioxidant and immunomodulatory properties of some haptoglobin phenotypes, it would be relevant to seek out possible confounding factors indirectly associated with haptoglobin phenotypes and clinical or biological infection variables.展开更多
Objective: To analyze haptoglobin polymorphism, plasma haptoglobin concentration, and ABO blood groups associated with leprosy. Methods: Blood groups were determined using monoclonal anti-A and anti-B. Haptoglobin was...Objective: To analyze haptoglobin polymorphism, plasma haptoglobin concentration, and ABO blood groups associated with leprosy. Methods: Blood groups were determined using monoclonal anti-A and anti-B. Haptoglobin was genotyped by PCR;plasma haptoglobin concentration was measured by ELISA. Data were analyzed by SPSS version 21 and P-values ≤ 0.05 were considered as statistically significant. Results: ABO blood groups in leprosy patients were found to have no significant difference compared to controls and the general population (P > 0.05). The data showed a lower frequency of Hp1-1 (14.6%) and higher frequency of Hp2-2 (25.6%) in leprosy patients compared to healthy controls (23.1% and 19.8%, respectively), without significant association (P = 0.315). The mean of haptoglobin concentration was higher in leprosy patients [(1.32 ± 0.70) mg/mL] than in healthy controls [(1.17 ± 0.67) mg/mL] (P = 0.160). The mean (1.44 mg/mL) and median (1.37 mg/mL) values of haptoglobin concentration were significantly higher in male leprosy patients than in male healthy controls (1.11 mg/mL and 1.11 mg/mL, respectively) (P= 0.018). Independent sample t-test and One-way ANOVA analysis also indicated significant mean elevation of Hp along leprosy spectrum and bacterial index (P < 0.05). Conclusions: In conclusion, the study revealed absence of influence of Hp polymorphism and ABO blood groups on leprosy occurrence;however, plasma haptoglobin concentration elevates in leprosy patients and is significantly associated with leprosy spectrum and bacterial loads in patients.展开更多
To study the genetic features(characteristics)of haptoglobin gene,four different age groups of Fujian Han people were investigated.The phenotypes of the hap-toglobin of four different groups were analyzed by using pol...To study the genetic features(characteristics)of haptoglobin gene,four different age groups of Fujian Han people were investigated.The phenotypes of the hap-toglobin of four different groups were analyzed by using polyacrylamide gel electrophoresis.The frequency of Hp^(1) in the population of Fujian Han nationality accounted for 0.340,among which children,youths,middle aged and elder groups were 0.307,0.338,0.363 and 0.383,respect-ively.The Hp^(0-0)phenotype frequency was 0.026 in which the four age groups accounted for 0.032,0.046,0.014 and 0.014,respectively.The frequency of Hp^(1)gene is rising with increasing age.The frequency of Hp^(0-0)phenotype is highest in the middle aged group and then tends to drop with increasing age.展开更多
Objective:To investigate the regulatory effects of Shenfu Injection(SFI,参附注射液) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure(CHF).Methods:Forty-five healthy Wista...Objective:To investigate the regulatory effects of Shenfu Injection(SFI,参附注射液) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure(CHF).Methods:Forty-five healthy Wistar rats were randomized into three groups:sham,heart failure(model) and SFI group.The CHF was induced by left coronary artery ligation.Seven days after the surgical operation,animals in the sham group and the model group received saline(6.2 mL/kg/d),while animals in the SFI group received SFI(6.2 mL/kg·d) intraperitoneally.Four weeks later,cardiac hemodynamic parameters were measured via the carotid route.The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrixassisted laser desorption/ionization time-of-flight mass spectrometer(MALDI-TOF MS).Results:Recording of hemodynamic parameters showed that left ventricular systolic pressure(LVSP),maximum rate of left ventricular pressure(+dp/dt_(max)) rise,and maximum rate of left ventricular pressure(-dp/dt_(max)) decrease,while the left ventricular end diastolic pressure(LVEDP) rose in the model group compared to those in the sham group(P<0.05).The results of the MALDI-TOF MS indicated that haptoglobin(HP),pentraxin 3(PTX3) and alpha-1-antitrypsin were up-regulated,while serum albumin and 40 S ribosomal protein were down-regulated in the model group(P<0.05).Compared with the model group,LVSP,+dp/dt_(max)and-dp/dt_(max) were higher,while LVEDP was lower in the SFI group(P<0.05).Expression levels of HP and PTX3 were lower than in the model group(P<0.05).Conclusion:SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF.The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure,and they could also be the serum protein targets of SFI.展开更多
文摘Objectives: Sickle cell disease (SCD) has a varied clinical and biological expression depending on the hemoglobin phenotype: SSFA<sub>2</sub>, SFA<sub>2</sub>, SAFA<sub>2</sub> and SC. Considering the antioxidant properties of the different haptoglobin phenotypes (Hp 1-1, Hp 2-1, Hp 2-2), it seemed relevant to know their influence on the morbidity of the different hemoglobin phenotype of SCD. Thus, the objective of this study was to identify associations between haptoglobin phenotype and morbidity of different SCD phenotypes. Methods: In a retrospective cross-sectional descriptive and analytical study, with a cohort of 170 black African carriers of hemoglobin S, in Ivory Coast, West Africa, hemoglobin and haptoglobin phenotypes were determined by electrophoretic methods. Results: The three major phenotypes of haptoglobin polymorphism were found in the SCD cohort: Hp 1-1 (24.1%), Hp 2-1 (56.5%), Hp 2-2 (19.4%). Vaso-occlusions were associated with haptoglobin phenotype Hp 1-1, (OR = 2.03;CI<sub>95%</sub> = [1.06 - 3.9];p Conclusions: Haptoglobin phenotype was associated to morbidity-adjusted hemoglobin phenotype. The study revealed a greater probability of a worse morbidity when the hemoglobin phenotype is homozygous. Unexpectedly, the worse morbidity is associated to Hp 1-1 haptoglobin phenotype, the most powerful antioxidant within the different haptoglobin phenotypes. Associations found were not systematic and need further studies to enlighten the determinism of SCD morbidity.
基金Ministry of Education,Culture,Sports,Science and Technology of Japan,No.19H03562FUJIFILM Wako Pure Chemical Corporation,No.J770701626.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a chronic,relapsing inflammation of the digestive tract.Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD,their low sensitivity and high variability characteristics limit clinical efficacy.Thus,the establishment of better biomarkers is expected.Fucosylation is one of the most important glycosylation modifications of proteins.Fucosylated haptoglobin(Fuc-Hpt)is used as a biomarker for several cancers and inflammation-related diseases.We recently established a novel glycan monoclonal antibody(mAb),designated 10-7G,which recognizes Fuc-Hpt.We developed an enzyme-linked immunosorbent assay(ELISA)to measure serum levels of Fuc-Hpt(10-7G values).AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.METHODS This was a case control study.Intestinal tissues of IBD patients(n=10)were examined immunohistochemically using the 10-7G mAb.We determined 10-7G values using serum from patients with ulcerative colitis(UC,n=110),Crohn’s disease(n=45),acute enteritis(AE,n=11),and healthy volunteers(HVs)who exhibited normal(n=20)or high(n=79)C-reactive protein(CRP)levels at medical check-up.We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers.RESULTS In the immunohistochemical analysis,positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles.The 10-7G values were significantly higher in patients with IBD(P<0.001)and AE(P<0.05)compared with HVs.In addition,10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC,particularly the CRP level(rs=0.525,P=0.003)and clinical activity index score(rs=0.435,P=0.038).However,there was no correlation between 10-7G values and CRP in HVs with high CRP levels,suggesting that the 10-7G values is not the same as a general inflammation biomarker.ROC curve analysis showed that area under the curve(AUC)value of 10-7G values for the diagnosis of endoscopic remission was higher than other biomarkers(AUC value=0.699).CONCLUSION The serum 10-7G value is a novel biomarker for evaluating intestinal inflammation and endoscopic mucosal healing in UC.
基金supported by the National Science Foundation of China(No.81101547,30960152,31170735)the Planned Science and Technology Project of Yunnan Province(2009CA012,2011DH011)
文摘Haptoglobin（Hp）基因多态性与疟疾发病风险存在关联，但各研究结果不一致．本meta分析旨在探讨Hp基因多态性与疟疾发病风险的关系．在Pubmed数据库中查询文献，将包含Hp基因型频率的病例对照研究文献纳入本研究中，并计算疟疾发生危险性的优势比（Oddratio，OR）及其95％置信区间（confidence interval，CI）．最终查到符合要求的文献4篇，其中病例组1312例，对照组1018例．分析结果显示：在各遗传模式下Hp基因多态性与疟疾发病风险的相关性均不显著（加性模式：OR=1．882，95％CI：0．959～3．692，P=0．066；显性模式：OR=1．395，95％CI：0．733～2．656，P=0．311；隐性模型：OR=2．449，95％C／：0．921～6．508，P=0．073：共显性模型：（hp^1／hp^2 vs hp^2／hp^2）OR=0．951，95％CI：0．76～1．189，P=0．658；共显性模型（hp^1／hp^1 vs hp^2／hp^2）OR=2．336，95％CI：0．78～6．994，P=0．129）．并且Egger’s检验（P〉0．05）和Begg’S检验（P〉0．05）均显示不存在发表偏倚．综上所述，haptoglobin基因多态性对疟疾发病风险提高的影响可能并不大．
基金Shanghai Three-year Action Plan for Accelerating the Development of Traditional Chinese Medicine,No.ZY(2018-2020)-FWTX-6005Clinical Research Plan of SHDC,No.SHDC12017X16.
文摘Haptoglobin(Hp)is an acidic glycoprotein,existing in the serum and other body fluids of human beings and a variety of mammals.Hp is produced in the liver,white adipose tissue,and the kidney.The genetic polymorphisms and different phenotypes of Hp have different biological functions.Hp has antibacterial,antioxidant,and angiogenic effects and is associated with multiple diseases including simple obesity,vascular complications of diabetes mellitus,nonalcoholic fatty liver disease,hypertension,blood diseases,autoimmune diseases,and malignant tumors.Hp also participates in many life activities,indicating the importance of Hp in further studies.Previously,we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials.However,the specific mechanism of Hp in patients with simple obesity is still unclear.The purpose of this article is to introduce recent research progress on Hp,emphasizing the relationship between Hp and the development of metabolic disease,which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.
文摘Haptoglobin (Hp) is a hemoglobin (Hb) binding protein which plays an important role in neutralizing oxidation reactions stimulated by heme-derived iron. Differences in Hp types due to the polymorphic nature of the gene have led to the discovery that individuals carrying the Hp 2-2 genotype are at increased risk of developing vascular complications in the setting of diabetes. Preeclampsia is a pregnancy related disease that is thought to be caused by increases in oxidative stress. The role of Hp polymorphism is determining preeclampsia has been addressed by several clinical studies but the results have been contradictory. Larger longitudinal studies are needed to answer this important question.
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.
文摘Octameric hemoglobins have been developed by the introduction of surface cysteines in either the alpha or beta chain. Originally designed as a blood substitute, we report here the structure and ligand binding function;in addition the interaction with haptoglobin was studied. The recombinant Hbs (rHbs) with mutations alpha Asn78Cys or beta Gly83Cys spontaneously form octamers under conditions where the cysteines are oxidized. Oxygen binding curves and CO kinetic studies indicate a correct allosteric transition of the tetramers within the octamer. Crystallographic studies of the two rHbs show two disulfide bonds per octamer. Reducing agents may provoke dissociation to tetramers, but the octamers are stable when mixed with fresh human plasma, indicating that the reduction by plasma is slower than the oxidation by the dissolved oxygen, consistent with an enhanced stability. The octameric rHbs were also mixed with a solution of haptoglobin (Hp), which binds the dimers of Hb: there was little interaction for incubation times of 15 min;however, on longer timescales a complex was formed. Dynamic light scattering was used to follow the interaction of Hp with the alpha Asn78Cys octamer during 24 hours;a transition from a simple complex of 15 nm to a final size of 60 nm was observed. The results indicate a specific orientation of the αβ dimers may be of importance for the binding to haptoglobin.
文摘Profiles of energy metabolites and haptoglobin (Hp) in dairy cows that are transitioned from conventional to organic management in various Alberta farms were compared with those of dairy cows managed conventionally at the University of Alberta dairy farm. Blood samples were collected during the following periods: Dry, 0 - 30, 30 - 60, and 60 - 90 days in milk (DIM, n = 7 cows). Concentrations of metabolites were evaluated by enzymatic colorimetric methods. Concentrations of Hp were determined by bovine ELISA kits. Data were analyzed by the mixed procedures of SAS. Concentrations of NEFA and BHBA in blood were elevated (P < 0.001) 0 to 30 d, intermediate 30 to 60, and 60 to 90 d, and lower in the dry period. In addition, BHBA was higher (P < 0.0001) at all stages of lactation in conventional than organic cows (e.g. 1289.4 ± 88.6 vs. 883.6 ± 47.5 μmol/L in conventional and organic cows at 0 - 30 d, respectively). Serum concentrations of cholesterol increased with increasing DIM and returned to nadir levels during dry period and was higher (P < 0.0001) in conventional than organic cows. Low glucose concentrations were observed 0 to 30 d, levels were intermediate 30 to 60 and 60 to 90 d, and peaked during the dry period (P < 0.54) between conventional and organic cows. Lactate did not (P < 0.24) vary with DIM or day × farm type but was higher (P < 0.0001) in organic cows than in conventional cows. Serum concentrations of Hp were elevated during dry period;reached peak levels 0 to 30 d and decreased gradually with increasing days postpartum and were much higher at all periods in conventional than organic cows. Overall, concentrations of Hp were 528.1 ± 45.2 μg/mL in conventional cows vs. 261.1 ± 16.9 μg/mL in organic cows (P < 0.0001). Taken together, these data indicate that metabolic changes associated with initiation of lactation are preceded by an acute phase response in dairy cows, and that cows in organic systems seem to be healthier than cows under conventional systems. These differences might be due to differences in nutritional management in the two systems.
文摘Introduction: The physiological status of a subject and the pathophysiology in some diseases might be under the influence of haptoglobin phenotype. The objective of this work was to determine the relationship between mortality from HIV/AIDS infection and haptoglobin phenotype in a black population in Côte d’Ivoire. Methods: The study was conducted from a retrospective panel of 933 sera/plasma from the previous workup of the ANRS 12136 TEMPRANO trial at month 0 of patients in deferred-ART arms. For each subject, we determined the serum haptoglobin concentration, haptoglobin phenotype, and other variables from patient files from the TEMPRANO trial database. Statistical tests used were Chi-2, Fischer, and Kruskal-Wallis tests for non-gaussian distribution. We used the Kaplan-Meier method for survival analysis. Results: The distributions of the haptoglobin phenotypes were 32.3% for Hp 1-1, 39.5% for Hp 2-1 and 27.2% for Hp 2-2. The blood haptoglobin concentration seemed to be associated with haptoglobin phenotypes (p-value > 5%). The survival rate at M30 and for an extended follow-up up to 6 years was independent of haptoglobin phenotype (p-value > 5%). Besides, the haptoglobin phenotypes do not appear to be associated with CD4+ T-cell count and with hemoglobin concentration. Conclusion: Haptoglobin phenotype seems to not impact the mortality of HIV/AIDS infection. However, given the antioxidant and immunomodulatory properties of some haptoglobin phenotypes, it would be relevant to seek out possible confounding factors indirectly associated with haptoglobin phenotypes and clinical or biological infection variables.
文摘Objective: To analyze haptoglobin polymorphism, plasma haptoglobin concentration, and ABO blood groups associated with leprosy. Methods: Blood groups were determined using monoclonal anti-A and anti-B. Haptoglobin was genotyped by PCR;plasma haptoglobin concentration was measured by ELISA. Data were analyzed by SPSS version 21 and P-values ≤ 0.05 were considered as statistically significant. Results: ABO blood groups in leprosy patients were found to have no significant difference compared to controls and the general population (P > 0.05). The data showed a lower frequency of Hp1-1 (14.6%) and higher frequency of Hp2-2 (25.6%) in leprosy patients compared to healthy controls (23.1% and 19.8%, respectively), without significant association (P = 0.315). The mean of haptoglobin concentration was higher in leprosy patients [(1.32 ± 0.70) mg/mL] than in healthy controls [(1.17 ± 0.67) mg/mL] (P = 0.160). The mean (1.44 mg/mL) and median (1.37 mg/mL) values of haptoglobin concentration were significantly higher in male leprosy patients than in male healthy controls (1.11 mg/mL and 1.11 mg/mL, respectively) (P= 0.018). Independent sample t-test and One-way ANOVA analysis also indicated significant mean elevation of Hp along leprosy spectrum and bacterial index (P < 0.05). Conclusions: In conclusion, the study revealed absence of influence of Hp polymorphism and ABO blood groups on leprosy occurrence;however, plasma haptoglobin concentration elevates in leprosy patients and is significantly associated with leprosy spectrum and bacterial loads in patients.
基金This project was supported by the Science Foundation of Fujian Medical University(FJGXT04033).
文摘To study the genetic features(characteristics)of haptoglobin gene,four different age groups of Fujian Han people were investigated.The phenotypes of the hap-toglobin of four different groups were analyzed by using polyacrylamide gel electrophoresis.The frequency of Hp^(1) in the population of Fujian Han nationality accounted for 0.340,among which children,youths,middle aged and elder groups were 0.307,0.338,0.363 and 0.383,respect-ively.The Hp^(0-0)phenotype frequency was 0.026 in which the four age groups accounted for 0.032,0.046,0.014 and 0.014,respectively.The frequency of Hp^(1)gene is rising with increasing age.The frequency of Hp^(0-0)phenotype is highest in the middle aged group and then tends to drop with increasing age.
基金Supported by the Science and Technology Fund of the Beijing Bureau of Traditional Chinese Medicine(No.JJ2001-37)the National Nature Science Foundation of China(No.81173367)
文摘Objective:To investigate the regulatory effects of Shenfu Injection(SFI,参附注射液) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure(CHF).Methods:Forty-five healthy Wistar rats were randomized into three groups:sham,heart failure(model) and SFI group.The CHF was induced by left coronary artery ligation.Seven days after the surgical operation,animals in the sham group and the model group received saline(6.2 mL/kg/d),while animals in the SFI group received SFI(6.2 mL/kg·d) intraperitoneally.Four weeks later,cardiac hemodynamic parameters were measured via the carotid route.The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrixassisted laser desorption/ionization time-of-flight mass spectrometer(MALDI-TOF MS).Results:Recording of hemodynamic parameters showed that left ventricular systolic pressure(LVSP),maximum rate of left ventricular pressure(+dp/dt_(max)) rise,and maximum rate of left ventricular pressure(-dp/dt_(max)) decrease,while the left ventricular end diastolic pressure(LVEDP) rose in the model group compared to those in the sham group(P<0.05).The results of the MALDI-TOF MS indicated that haptoglobin(HP),pentraxin 3(PTX3) and alpha-1-antitrypsin were up-regulated,while serum albumin and 40 S ribosomal protein were down-regulated in the model group(P<0.05).Compared with the model group,LVSP,+dp/dt_(max)and-dp/dt_(max) were higher,while LVEDP was lower in the SFI group(P<0.05).Expression levels of HP and PTX3 were lower than in the model group(P<0.05).Conclusion:SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF.The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure,and they could also be the serum protein targets of SFI.
