Heparin has been considered to be a potentially useful ligand for low-density lipoprotein（LDL） detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LD...Heparin has been considered to be a potentially useful ligand for low-density lipoprotein（LDL） detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface（GS-Hep） was fabricated by a self-assembling method and hydrophobic-modified gold surfaces（GS-Hydro） was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy（AFM） and the quantity of heparin bound to gold surface was assayed by the toluidine blue（TB） colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance（SPR） technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.展开更多
Objective： To investigate binding and release of vascular endothelial growth factor （VEGF） and its effect on adhesion and proliferation of endothelial cells （ECs） in acellular fresh specimens of bovine pericardiu...Objective： To investigate binding and release of vascular endothelial growth factor （VEGF） and its effect on adhesion and proliferation of endothelial cells （ECs） in acellular fresh specimens of bovine pericardiums, which were modified by heparinization. Methods： Cross-linked aeellular fresh specimens of bovine perieardiums were heparinized by three methods： （1） heparinizcd N-（3-diinethylaminopropyl）-N＇-ethylcarbodiimide hydrochloride （EDC） treated acellular tissue samples; （2） heparinized poly（ethyleneimine） （PEI） treated acellular tissue samples; （3） heparinized EDC-PEI treated aeellular tissue samples. Controlled release of VEGF and its effect on adhesion and proliferation of ECs was evaluated. Results： In the present study, binding and release of VEGF had better performance in heparinized EDC-PEI treated group, compared with heparinized EDC-alone treated group and heparinized PEI -alone group. We could observe enhanced ability to adhesion and proliferation via modest moisture and effective controlled binding and release of VEGF. Conclusion： Binding of VEGF in heparinized EDC treated group was stable, while reiease of VEGF in heparinized treated group was adjusted freely. Interestingly, controlled binding and release of VEGF could exert beneficial effect on adhesion and proliferation of ECs in heparinized EDC-PEI treated group.展开更多
The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we att...The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-vip hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-vip hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.展开更多
In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can...In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can quickly activate the extrinsic coagulation pathway by triggering the tissue factor(TF)and lead to coagulation.This damage,along with a loss of anticoagulant properties through antithrombinⅢ(ATⅢ),TF pathway inhibitors,and the protein C system,can result in a hypercoagulable state and even thrombosis.Hypercoagulability is not only a common feature of many cancers but also an important factor promoting tumor development and metastasis,which corresponds to the TCM theory of“blood stasis leading to tumors.”The pharmacological effects of heparin and aspirin have similarities with TCM's“activating blood circulation and removing blood stasis”theory in improving blood circulation,treating related diseases,and their anti-inflammatory effects.展开更多
Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeuti...Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.展开更多
Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually s...Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually seen bruising around the injection site during subcutaneous LMWH treatment,the abdominal wall(AW)hematoma(AWH)was scarcely observed and reported.A previous study demonstrated the usual etiological risk of AWH involved anticoagulation therapy,chronic kidney disease,and trauma.^([1])Most of these cases had a favorable prognosis after conservative treatment.展开更多
BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with ...BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with the occurrence of VTE following gastrointestinal surgery and to implement appropriate prevention and treatment measures.AIM To assess the efficacy of perioperative anticoagulation for the prevention of postoperative VTE.METHODS This retrospective study enrolled 205 patients who underwent gastrointestinal surgery.In the observation group(n=101),prophylactic anticoagulation was administered via hypodermic injection of low-molecular-weight heparin during the perioperative period,whereas the control group(n=104)only received lowmolecular-weight heparin treatment postoperatively.Blood coagulation parameters and the incidence of VTE of the bilateral lower limbs pre-and post-surgery were compared between groups.Postoperative VTE was transformed into a dichotomous variable,and influencing factors were explored using multivariate logistic regression analyses.RESULTS On the 7th day postoperatively,the incidence of VTE of the bilateral lower limbs was significantly lower in the observation group than in the control group,as were the D-dimer levels(P<0.05).At 1 month postoperatively,the incidence of VTE was significantly lower in the observation group than in the control group(P<0.05).An age≥65 years,a body mass index≥24 kg/m^(2),and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.CONCLUSION The incidence of VTE in patients who underwent gastrointestinal surgery peaked within 1 week postoperatively.The findings confirmed perioperative anticoagulation can safely and effectively reduce the incidence of postoperative VTE.展开更多
Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investi...Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investigated first.Then,environmental analysis of it was made based on the PEST model.Results and Conclusion There is room for optimization of the relevant policies for the development of heparin industry in China.The use of heparin drugs and regulation should be further improved.In addition,the research and development ability of pharmaceutical enterprises should be enhanced,and the development strategy of heparin industry needs to be adjusted.展开更多
The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functiona...The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functionalized solution for introducing the OH- and groups, and then the heparin was immobilized on the active TiO2 films through the electrostatic self assembly technology. It is shown that the heparinized films are mainly composed of anatase and rutile with smooth and dense surface. In vitro blood compatibility was evaluated by haemolysis test, clotting time and platelet adhesion behavior tests. The results show that the haemocompatibility of the alloy could be significantly improved by surface heparinization.展开更多
The synthesis and characterization of amphiphilic copolymers of poly（dimethyl siloxane）(PDMS),poly（ethylene oxide）(PEO), and heparin（Hep） were investigated. These multiblock copolymers wereidentified using;H-NMR...The synthesis and characterization of amphiphilic copolymers of poly（dimethyl siloxane）(PDMS),poly（ethylene oxide）(PEO), and heparin（Hep） were investigated. These multiblock copolymers wereidentified using;H-NMR, FTIR, end group analysis, and sulfur elemental analysis. The multiblockcopolymers were characterized by using DSC and X-ray diffractometry. The glass transition temperature,crystalline melting characteristics, annealing effect, and cold crystallization of the block copolymers weredetermined by DSC. The crystallinity of the block copolymers was also determined by X-ray diffractionmethod.展开更多
Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea p...Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province of China(Nos.Y4110606 and Y1090649)the Opening Foundation of Zhejing Provincial Top Key Discipline,China(No.20110915)+1 种基金the Zhejiang Provincial Innovative Research Team,China(No.2009R50004)the Fresenius Medical Care of Deutschland GmbH’s Nephrocore Program,Germany
文摘Heparin has been considered to be a potentially useful ligand for low-density lipoprotein（LDL） detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface（GS-Hep） was fabricated by a self-assembling method and hydrophobic-modified gold surfaces（GS-Hydro） was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy（AFM） and the quantity of heparin bound to gold surface was assayed by the toluidine blue（TB） colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance（SPR） technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.
文摘Objective： To investigate binding and release of vascular endothelial growth factor （VEGF） and its effect on adhesion and proliferation of endothelial cells （ECs） in acellular fresh specimens of bovine pericardiums, which were modified by heparinization. Methods： Cross-linked aeellular fresh specimens of bovine perieardiums were heparinized by three methods： （1） heparinizcd N-（3-diinethylaminopropyl）-N＇-ethylcarbodiimide hydrochloride （EDC） treated acellular tissue samples; （2） heparinized poly（ethyleneimine） （PEI） treated acellular tissue samples; （3） heparinized EDC-PEI treated aeellular tissue samples. Controlled release of VEGF and its effect on adhesion and proliferation of ECs was evaluated. Results： In the present study, binding and release of VEGF had better performance in heparinized EDC-PEI treated group, compared with heparinized EDC-alone treated group and heparinized PEI -alone group. We could observe enhanced ability to adhesion and proliferation via modest moisture and effective controlled binding and release of VEGF. Conclusion： Binding of VEGF in heparinized EDC treated group was stable, while reiease of VEGF in heparinized treated group was adjusted freely. Interestingly, controlled binding and release of VEGF could exert beneficial effect on adhesion and proliferation of ECs in heparinized EDC-PEI treated group.
基金supported by the National Natu-ral Science Foundation of China (T2288101,31971266,82272152,22075087)Guangdong Basic and Applied Basic Research Foundation (2022A1515011925)the Key Research and Development Program of Guangzhou (202007020002).
文摘The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-vip hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-vip hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)Youth Guidance Project{Qian Kehe Foundation-[2024]Youth 307}。
文摘In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can quickly activate the extrinsic coagulation pathway by triggering the tissue factor(TF)and lead to coagulation.This damage,along with a loss of anticoagulant properties through antithrombinⅢ(ATⅢ),TF pathway inhibitors,and the protein C system,can result in a hypercoagulable state and even thrombosis.Hypercoagulability is not only a common feature of many cancers but also an important factor promoting tumor development and metastasis,which corresponds to the TCM theory of“blood stasis leading to tumors.”The pharmacological effects of heparin and aspirin have similarities with TCM's“activating blood circulation and removing blood stasis”theory in improving blood circulation,treating related diseases,and their anti-inflammatory effects.
基金supported by the Natural Science Foundation of Jiangsu Province(BE2021623,BK20220155)Natural Science Foundation of Jiangsu Province(BE2021623)+4 种基金National Natural Science Foundation of China(32001665,U1903205,32021005)the National Key Research and Development Program of China(2017YF0400303)the Key Scientific and Technological Research Projects in the Key Areas of the Xinjiang Production and Construction Corps(2018AB010)the Key Research and Development 303 Program of Ningxia(2020BFG02012)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.
文摘Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually seen bruising around the injection site during subcutaneous LMWH treatment,the abdominal wall(AW)hematoma(AWH)was scarcely observed and reported.A previous study demonstrated the usual etiological risk of AWH involved anticoagulation therapy,chronic kidney disease,and trauma.^([1])Most of these cases had a favorable prognosis after conservative treatment.
文摘BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with the occurrence of VTE following gastrointestinal surgery and to implement appropriate prevention and treatment measures.AIM To assess the efficacy of perioperative anticoagulation for the prevention of postoperative VTE.METHODS This retrospective study enrolled 205 patients who underwent gastrointestinal surgery.In the observation group(n=101),prophylactic anticoagulation was administered via hypodermic injection of low-molecular-weight heparin during the perioperative period,whereas the control group(n=104)only received lowmolecular-weight heparin treatment postoperatively.Blood coagulation parameters and the incidence of VTE of the bilateral lower limbs pre-and post-surgery were compared between groups.Postoperative VTE was transformed into a dichotomous variable,and influencing factors were explored using multivariate logistic regression analyses.RESULTS On the 7th day postoperatively,the incidence of VTE of the bilateral lower limbs was significantly lower in the observation group than in the control group,as were the D-dimer levels(P<0.05).At 1 month postoperatively,the incidence of VTE was significantly lower in the observation group than in the control group(P<0.05).An age≥65 years,a body mass index≥24 kg/m^(2),and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.CONCLUSION The incidence of VTE in patients who underwent gastrointestinal surgery peaked within 1 week postoperatively.The findings confirmed perioperative anticoagulation can safely and effectively reduce the incidence of postoperative VTE.
文摘Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investigated first.Then,environmental analysis of it was made based on the PEST model.Results and Conclusion There is room for optimization of the relevant policies for the development of heparin industry in China.The use of heparin drugs and regulation should be further improved.In addition,the research and development ability of pharmaceutical enterprises should be enhanced,and the development strategy of heparin industry needs to be adjusted.
基金Project (31100693/C100302) supported by the National Natural Science Foundation of ChinaProject (31011120049) supported by the Australia-China Special Fund, International Science Linkages Program co-supported by the Department of Innovation, Industry, Science and Research of Australia, and the Ministry of Science and Technology and National Science Foundation of China+1 种基金Project(2010ZDKG-96) supported by the Major Subject of "13115" Programs of Shaan’xi Province, ChinaProject (2012CB619102) supported by the National Basic Research Program of China
文摘The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functionalized solution for introducing the OH- and groups, and then the heparin was immobilized on the active TiO2 films through the electrostatic self assembly technology. It is shown that the heparinized films are mainly composed of anatase and rutile with smooth and dense surface. In vitro blood compatibility was evaluated by haemolysis test, clotting time and platelet adhesion behavior tests. The results show that the haemocompatibility of the alloy could be significantly improved by surface heparinization.
文摘The synthesis and characterization of amphiphilic copolymers of poly（dimethyl siloxane）(PDMS),poly（ethylene oxide）(PEO), and heparin（Hep） were investigated. These multiblock copolymers wereidentified using;H-NMR, FTIR, end group analysis, and sulfur elemental analysis. The multiblockcopolymers were characterized by using DSC and X-ray diffractometry. The glass transition temperature,crystalline melting characteristics, annealing effect, and cold crystallization of the block copolymers weredetermined by DSC. The crystallinity of the block copolymers was also determined by X-ray diffractionmethod.
文摘Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.
