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Diagnostic Value of the Padua Score Combined with Thrombotic Biomarker Tissue Plasminogen Activator Inhibitor-1 (tPAI-1) Detection for the Risk of Deep Vein Thrombosis in Patients with Pulmonary Heart Disease
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作者 Xiaoyun Zhang Xinlong Xi +1 位作者 Wenming Bian Qiang Liu 《Journal of Clinical and Nursing Research》 2024年第8期137-144,共8页
This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with p... This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model. 展开更多
关键词 Padua prediction score Tissue plasminogen activator inhibitor-1(tPAI-1)detection Deep vein thrombosis(DVT) Pulmonary heart disease(cor pulmonale) Diagnostic accuracy
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THE INCREASE IN PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 EXPRESSION BY STIMULATION OF ACTIVATORS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS IN HUMAN ENDOTHELIAL CELLS 被引量:5
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作者 叶平 胡晓晖 赵亚力 《Chinese Medical Sciences Journal》 CAS CSCD 2002年第2期112-116,共5页
Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the pos... Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay. 展开更多
关键词 peroxisome proliferator-activate d receptors plasminogen activator inhibitor type-1 EXPRESSION endothelial cells
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Genetic and Metabolic Determinants of Plasminogen Activator Inhibitor 1 (PAI-1) in Tunisian Type 2 Diabetes Patients 被引量:2
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作者 Mohamed Moustapha Molka Chadhli-Chaieb +1 位作者 Touhami Mahjoub Larbi Chaieb 《Open Journal of Endocrine and Metabolic Diseases》 2017年第6期141-150,共10页
Background: PAI-1 (plasminogen activator inhibitor-1) is a powerful regulator of fibrinolysis and plasma level is high in type 2 diabetes and cardio-vascular disease, which is determined by genetic polymorphisms in PA... Background: PAI-1 (plasminogen activator inhibitor-1) is a powerful regulator of fibrinolysis and plasma level is high in type 2 diabetes and cardio-vascular disease, which is determined by genetic polymorphisms in PAI-1 gene and environmental factors. The aim of the study was to examine the determinants of plasma PAI-1 Ag level among type 2 diabetes patients. Methods: 491 Tunisian type 2 diabetes patients had clinical evaluation (weight, high, BMI, Waist Circumference), laboratory investigations including FBG Hb1Ac, cholesterol, triglyceride;HDL-cholesterol was done;plasma PAI-1 antigen level was done with ELISA;&minus;675 4G/5G and &minus;844 G/A polymorphisms of PAI-1 gene was done by PCR-ASA and PCR-RFLP respectively. Results: The mean age for our patients was 58.3 ± 10.5 years;sex-ratio = 0.92;mean PAI-1 level was 34.6 ± 21.3 ng/ml. We didn’t find correlation between PAI-1 level and BMI, but we have found significant correlation between PAI-1 and waist circumference (p = 0.032), most enhanced in men (P = 0.002), T2D patients who have FBG > 11 mmol/l had PAI-1 Ag level higher than those who have FBG P = 0.034), but no difference found between T2D with high Hb1Ac > 8% and those with Hb1Ac < 8%, significant correlation was seen between PAI-1 level and LDL-cholesterol (P = 0.05), high correlation between PAI-1 Ag level and &minus;675 4G/5G polymorphism genotype was seen, 4G/4G carriers had the highest PAI-1 level, 4G/5G had intermediary level and 5G/5G had the lowest level (P &minus;844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was &minus;675 4G/5G polymorphism (regression coefficient β = 4.6, P Conclusion: the present study identifies &minus;675 4G/5G not &minus;844 G/A polymorphism of PAI gene as the principal determinant of plasma PAI-1 level in Tunisian T2D patients, the android fat distribution, dyslipidemia and hyperglycemia play a modest role in this variation. 展开更多
关键词 plasminogen activATOR Inhibitor 1 POLYMORPHISM PCR Type 2 Diabetes MELLITUS metabOLIC Syndrome X
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THE EFFECT OF RADIX SALVIAE MILTIORRHIZAE ON THE INHIBITORY ACTIVITY OF VASCULAR SMOOTH MUSCLE CELLS TO THE PLASMINOGEN ACTIVATORS SECRETED BY ENDOTHELIAL CELLS
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作者 毛申兰 张彩英 +1 位作者 黄桂秋 王振义 《Medical Bulletin of Shanghai Jiaotong University》 CAS 1993年第1期37-42,共6页
Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial... Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial cells (EC-CM),the PA activities of the latter decreased significantly. Cocultivation of EC with SMC alsoresulted in a significant decrease (70.7%) of PA activities produced by EC. Sodiumdodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of SMC-CMfollowed by reverse fibrin autography demonstrated that the PA inhibitor had a molecularweight of 49000-62000. In this study we also investigated the effect of a Chinese herbalmedicine-Radix Salviae Miltiorrhizae (RSM) on the inhibitory activity of SMC. The re-sults showed that RSM significantly decreased the inhibitory activity of SMC against thePA secreted by EC. 展开更多
关键词 smooth muscle CELLS endothelial CELLS plasminogen activATOR plasminogen activATOR inhibitor RADIX Salviae Miltiorrhizae
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Human urokinase-type plasminogen activator gene-modifiedbone marrow-derived mesenchymal stem cells attenuateliver fibrosis in rats by down-regulating the Wnt signalingpathway 被引量:33
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作者 Zhi-Gang Ma Xiao-Dan Lv +9 位作者 Ling-Ling Zhan Lan Chen Qi-Yuan Zou Ji-Qiao Xiang Jiao-Li Qin Wei-Wei Zhang Zhao-Jing Zeng Hui Jin Hai-Xing Jiang Xiao-Ping Lv 《World Journal of Gastroenterology》 SCIE CAS 2016年第6期2092-2103,共12页
AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.M... AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway. 展开更多
关键词 bone marrow-derived mesenchymal STEMCELLS liver fibrosis UROKINASE plasminogen activator Wnt signaling PATHWAY
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Overexpression of hepatic plasminogen activator inhibitor type 1 mRNA in rabbits with fatty liver 被引量:8
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作者 Jian-Gao Fan~1 Liang-Hua Chen~2 Zheng-Jie Xu~1 Min-De Zeng~3 1 Department of Gastroenterology,Shanghai First People’s Hospital,Shanghai 200085,China2 Department of Cardiology,Shandong Provincial Hospital,Jinan 250021,China3 Shanghai Institute of Digestive Diseases,Shanghai 200080,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第5期710-712,共3页
INTRODUCTIONPlasminogen activator inhibitor type 1 ( PAI-I ), an approximately Mr 50000 glycoprotein, is the major physiological inhibitor of plasminogen activators. It is not only the priming factor for atheroscleros... INTRODUCTIONPlasminogen activator inhibitor type 1 ( PAI-I ), an approximately Mr 50000 glycoprotein, is the major physiological inhibitor of plasminogen activators. It is not only the priming factor for atherosclerosis and coronary thrombosis[1-3] , but also participates in the genesis of chronic hepatitis and liver fibrosis[4-11] . However, there has been no available report yet about the research of hepatic PAl-1 gene expression in hyperlipidemia and fatty liver. The present study aimed to explore the change of hepatic PAl-1 mRNA and its plasma activity by means of animal model. 展开更多
关键词 ANIMALS Fatty Liver Gene Expression HYPERLIPIDEMIA Liver Male plasminogen activator Inhibitor 1 RNA Messenger RABBITS
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Inhibiting endogenous tissue plasminogen activator enhanced neuronal apoptosis and axonal injury after traumatic brain injury 被引量:10
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作者 Jun-Jie Zhao Zun-Wei Liu +4 位作者 Bo Wang Ting-Qin Huang Dan Guo Yong-Lin Zhao Jin-Ning Song 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第4期667-675,共9页
Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumat... Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumatic brain injury was established by weight-drop method.The tissue plasminogen activator inhibitor neuroserpin(5μL,0.25 mg/mL)was injected into the lateral ventricle.Neurological function was assessed by neurological severity score.Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining.Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay.Apoptotic marker cleaved caspase-3,neuronal marker neurofilament light chain,astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining.Apoptotic cell types were detected by immunofluorescence double labeling.Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining.Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining.Expression of tissue plasminogen activator was increased at 6 hours,and peaked at 3 days after traumatic brain injury.Neuronal apoptosis and axonal injury were detected after traumatic brain injury.Moreover,neuroserpin enhanced neuronal apoptosis,neuronal injury and axonal injury,and activated microglia and astrocytes.Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury.Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury,and activates microglia and astrocytes.This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015. 展开更多
关键词 apoptosis ASTROCYTES AXONAL INJURY inflammation microglia nerve REGENERATION neural REGENERATION neuronal INJURY neurons NEUROSERPIN tissue plasminogen activator traumatic brain INJURY
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Intraclot Recombinant Tissue-type Plasminogen Activator Reduces Perihematomal Edema and Mortality in Patients with Spontaneous Intracerebral Hemorrhage 被引量:9
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作者 连立飞 许峰 +8 位作者 唐洲平 薛峥 梁奇明 胡琦 朱文浩 康慧聪 刘晓艳 王芙蓉 朱遂强 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第2期165-171,共7页
The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with ... The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (To). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From TI to T2, reduction in PHE volume was strongly associ- ated with the percentage of clot evacuation (p=0.34; P=-0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (p ranging from 0.39-0.56, P〈0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (p=0.24; P=0.12) or de- layed (T3) PHE volume (p=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mor- tality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed. 展开更多
关键词 intracerebral hemorrhage minimally invasive surgery clot aspiration perihematomaledema recombinant tissue-type plasminogen activator
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Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer 被引量:12
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作者 FengJi Yue-LiangChen En-YunJin Wei-LinWang Zi-LiYang You-MingLi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第21期3222-3226,共5页
AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric canc... AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer. METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RT-PCR and Northern blot respectively.Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA,uPA and uPA-R mRNA in tumor tissues (31%,41%,and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; X2=4.59,43.58, and 53.24 respectively, P<0.05,0.0001,and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis: 61.9%, no metastasis: 39.1%, X2= 7.61, P<0.05),Lauren's classification of diffuse/mixed types:54.2%,intestinal type: 26.3%,X2 = 4.25, P<0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, X2=5.72 and 6.40 respectively, P<0.05).Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P= 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer. 展开更多
关键词 Gastric cancer Matrix metalloproteinase-2 Urokinase-type plasminogen activator
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The plasminogen activating system in the pathogenesis of Alzheimer’s disease 被引量:3
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作者 Manuel Yepes 《Neural Regeneration Research》 SCIE CAS CSCD 2021年第10期1973-1977,共5页
Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s diseas... Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published to this date. 展开更多
关键词 Alzheimer’s disease amyloid precursor protein amyloidβ NEUROSERPIN PLASMIN plasminogen activating system plasminogen activator inhibitor-1 synapse tissue-type plasminogen activator urokinase-type plasminogen activator
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Therapeutic effect of recombinant tissue plasminogen activator on acute cerebral infarction at different times 被引量:20
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作者 Ming Liu Hai-rong Wang +4 位作者 Jia-fu Liu Hao-jun Li Shen-xing Chen Sha Shen Shu-ming Pan 《World Journal of Emergency Medicine》 CAS 2013年第3期205-209,共5页
BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A re... BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale(NIHSS) scores were statistically decreased in both groups(P>0.05) at 24 hours and 7 days after ACI.There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups(P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rtPA within 4.5 hours after the onset of this disease.Therefore,intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe. 展开更多
关键词 Acute cerebral infarction THROMBOLYSIS Recombinant tissue type plasminogen activator
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Recombinant Tissue Plasminogen Activator-conjugated Nanoparticles Effectively Targets Thrombolysis in a Rat Model of Middle Cerebral Artery Occlusion 被引量:3
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作者 Jun DENG Heng MEI +6 位作者 Wei SHI Zhi-qing PANG Bo ZHANG Yao GUO Hua-fang WANG Xin-guo JIANG Yu HU 《Current Medical Science》 SCIE CAS 2018年第3期427-435,共9页
The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a ... The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a fibrin-targeted nanoparticle (NP) drug delivery system for thrombosis combination therapy. We conjugated rtPA to poly(ethylene glycol)- poly(ε-caprolactone) (PEG-PCL) nanoparticles (rtPA-NP) and investigated its physicochemical characteristics such as particle size, zeta potential, enzyme activity of conjugated rtPA and its storage stability at 4℃. The thrombolytic activity of rtPA-NP was evaluated in vitro and in vivo as well as the half-life of rtPA-NP, the properties to fibrin targeting and its influences on systemic hemostasis in vivo. The results showed that rtPA-NP equivalent to 10% of a typical dose of rtPA could dissolve fibrin clots and were demonstrated to have a neuroprotective effect after focal cerebral ischemia as evidenced by decreased infarct volume and improved neurological deficit (P〈0.001). RtPA-NP did not influence the in vivo hemostasis or coagulation system. The half-life of conjugated rtPA was shown to be approximately 18 times longer than that of free rtPA. These experiments suggested that rtPA-conjugated PEG-PCL nanoparticles might be a promising fibrin-targeted delivery system for a combination treatment of thrombosis. 展开更多
关键词 recombinant tissue plasminogen activator THROMBOLYSIS NANOPARTICLES drug delivery system
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INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE 被引量:6
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作者 马水清 白春梅 边旭明 《Chinese Medical Sciences Journal》 CAS CSCD 2001年第3期169-171,共3页
Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type- I (PAI- I) in women with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pr... Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type- I (PAI- I) in women with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH,26 moderate PIH,22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA,PAI- I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method. Results. Circulating levels of TM, PAI- I and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups. Conclusion. TM and PAI- I may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH, which is very important in evaluating and following the development of PIH. 展开更多
关键词 pregnancy complication HYPERTENSION plasminogen activator inhibitor THROMBOMODULIN
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Urokinase-type plasminogen activator receptor as a predictor of poor outcome in patients with systemic inflammatory response syndrome 被引量:8
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作者 Xiao-ling Wu Ding Long +3 位作者 Li Yu Jun-hui Yang Yuan-chao Zhang Feng Geng 《World Journal of Emergency Medicine》 CAS 2013年第3期190-195,共6页
BACKGROUND:Urokinase-type plasminogen activator(uPA) and urokinase-type plasminogen activator receptor(uPAR) are known as important factors,which mediate a variety of functions in terms of vascular homeostasis,inflamm... BACKGROUND:Urokinase-type plasminogen activator(uPA) and urokinase-type plasminogen activator receptor(uPAR) are known as important factors,which mediate a variety of functions in terms of vascular homeostasis,inflammation and tissue repair.However,their role in systemic inflammatory response syndrome(SIRS) has been less well studied.This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are directly related to the patients with SIRS.We therefore analyzed their role and clinicopathological significance in patients with SIRS.METHODS:A case-control study was conducted with 85 patients who were divided into two groups according to the diagnostic criteria of SIRS:SIRS group(n=50) and non-SIRS group(/7=35).The SIRS group was divided into MODS group(n=26) and non-MODS group(n=24) by their severity,and survival group(n=35) and non-survival group(n=15) by their prognosis.Another 30 healthy adults served as normal controls.uPA and uPAR in plasma were detected by commercial enzyme-linked immunosorbent assay(ELISA) kits.RESULTS:The plasma level of uPA was lower in the SIRS group than in the non-SIRS group and controls(P<0.001 and P<0.001).It was lower in sepsis patients and the MODS group than in the non-sepsis patients and the non-MODS patients(all P<0.05).However,there was no difference in uPA level between survivors and non-survivors(P>0.05).The plasma level of uPAR increased in the SIRS group compared with the non-SIRS group and controls(P<0.001 and P<0.001).There was a significant elevation of uPAR in sepsis patients,MODS patients and non-survivors as compared with non-sepsis patients,non-MODS patients and survivors respectively(all P<0.05).Plasma uPAR levels were positively correlated with APACHE Ⅱ score(r=0.575,P<0.001) and SOFA score(r=0.349,P=0.013).AUCs for the prediction of SIRS mortality were 0.67 and 0.51,respectively,for uPA and uPAR.CONCLUSION:uPAR could be a predictor of poor outcome in patients with SIRS. 展开更多
关键词 Systemic inflammatory response syndrome Multiple organ dysfunction syndrome Urokinase-type plasminogen activator Urokinase-type plasminogen activator receptor
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Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy 被引量:2
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作者 Shu-Ling Wu Dong-Mei Zhan +1 位作者 Shu-Hong Xi Xiang-Lian He 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2014年第5期764-767,共4页
AIMTo investigate the role of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in proliferative diabetic retinopathy (PDR) and to discuss the correlations among t-PA, PAI and vascular endo... AIMTo investigate the role of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in proliferative diabetic retinopathy (PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor (VEGF) expressions. 展开更多
关键词 proliferative diabetic retinopathy vascular endothelial growth factor tissue plasminogen activator plasminogen activator inhibitor ANGIOGENESIS
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UROKINASE-TYPE PLASMINOGEN ACTIVATOR,ITS RECEPTOR AND INHIBITOR EXPRESSION IN HEPATOCELLULAR CARCINOMA RELATION TO CANCER INVASIVENESS AND PROGNOSIS 被引量:2
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作者 郑起 汤钊猷 +4 位作者 吴志全 施达仁 唐辉滨 朱运松 宋后燕 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1998年第4期36-39,共4页
Objective: To study the relevance of uPA, uPAR and PAI 1 to hepatocellular carcinoma (HCC) Methods: The expression at protein level of uPA, uPAR and PAI 1 was determined in 48 cases of HCC and 12 cases of benign ... Objective: To study the relevance of uPA, uPAR and PAI 1 to hepatocellular carcinoma (HCC) Methods: The expression at protein level of uPA, uPAR and PAI 1 was determined in 48 cases of HCC and 12 cases of benign tumors of liver (as control) by immunohistochemistry Results: When compared to cancer adjacent liver tissue and the control, positive rate of immune staining for uPA, uPAR and PAI 1 on cell membrane were significantly higher in HCC cells ( P <0 05) Positive staining of uPA and uPAR was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively ( P <0 01 and P <0 001) In 8 of 8 cases with cancer embolus, and in 6 of 6 cases with lymph node metastasis was the expression of positive uPAR Compared with 2 of 17 cases without recurrence, uPAR was positive in 15 of 17 recurrent cases ( P <0 01) In 36 cases who survived, 17 was positive uPAR and 15 positive PAI 1, while in 12 cases who died 2 years after surgery, 12 were positive for uPAR and 9 positive PAI 1, respectively ( P <0 01 and P <0 05) In 15 positive cases for all three parameters, 11 had cancer invasion and 7 died within 2 years, while in negative cases, 2 had invasion and none died within 2 years ( P <0 05) Conclusion: Expression of uPA, uPAR and PAI 1 is increased in HCC, uPA and uPAR may contribute significantly to HCC invasion and metastasis uPAR and PAI 1 are associated with poor prognosis of HCC 展开更多
关键词 CARCINOMA HEPATOCELLULAR plasminogen activators Neoplasm invasiveness Neoplasm metastasis Immunohistochemistry
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Studies on the Relationship between Urokinase Plasminogen Activator(uPA)and Human Sperm Motility 被引量:3
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作者 黄勋彬 夏文家 +3 位作者 熊承良 肖敦振 沈继云 周洁玲 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 1997年第4期213-217,共5页
To clarify the role of urokinase plasminogen activator(uPA) in the mechanisms of regulating sperm motility and the ability of fertilizing, we investigated the quantities and activities of uPA in human seminal Plasma a... To clarify the role of urokinase plasminogen activator(uPA) in the mechanisms of regulating sperm motility and the ability of fertilizing, we investigated the quantities and activities of uPA in human seminal Plasma and on the membrane of spermatozoa.Semens were harvested from 22 infertile patients with asthenospermia and 20 healthy fertile men according to WHO standards. To quantify the membrane-bound uPA in the samples, polyclonal antibodies against human urokinase were employed by means of a sandwich ELISA. The uPA activities in seminal plasma and on the surface of spermatozoa were determined using Agarose-Fibrine-Plate method and the experiment of immunological identification with polyclonal antibodies against urokinase. In lysates of spermatozoa, significantly lower levels of uPA(23. 1±7.35 mu/106 cells ) and uPA activity (5.13±3.85 mu/106 cells) were found in patient group as compared to healthy fertile men exhibiting normospermia (29. 89±9. 40 mu/105 cells and 10. 17±6. 18 mu/106 cells). In seminal plasma, uPA activity in patient group (2134±1581. 3 IU/L)was also found significantly lower than that of normal group (3365±1859. 5 IU/L). Positive correlations were observed between sperm motility and uPA quantities (r=0. 48, P<0. 005), as well as with uPA activities (r= 0. 45,P<0. 005).Thus, it is inferred that membrane associated uPA on human spermatozoa may be related directly to sperm motility and fertility. 展开更多
关键词 urokinase plasminogen activator sperm motility ASTHENOSPERMIA
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Gene expression changes of urokinase plasminogen activator and urokinase receptor in rat testes at postnatal stages 被引量:2
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作者 Dong-Hui Huang Hu Zhao +3 位作者 Yong-Hong Tian Hong-Gang Li Xiao-Fang Ding Cheng-Liang Xiong 《Asian Journal of Andrology》 SCIE CAS CSCD 2007年第5期679-683,共5页
Aim: To investigate the gene expression changes of urokinase plasminogen activator (uPA)/urokinase receptor (uPAR) in rat testes at postnatal stages and explore the effects of uPA/uPAR system on the rat spermatog... Aim: To investigate the gene expression changes of urokinase plasminogen activator (uPA)/urokinase receptor (uPAR) in rat testes at postnatal stages and explore the effects of uPA/uPAR system on the rat spermatogenesis. Methods: The mRNAs of uPA and uPAR in rat testes were measured by using real-time quantitative polymerase chain reaction (PCR) at postnatal days 0, 5, 10, 15, 21, 28, 35, 42, 49 and 56, respectively. Results: The tendencies of uPA and uPAR mRNA expression were similar at most postnatal stages except for Do. The expression of uPAR mRNA in rats testes was relatively higher than that of uPA at postnatal Do, and both were decreased until D21, increased obviously at postnatal D28, reached a peak at postnatal D35, then declined sharply at postnatal D42 and retained at a low level afterwards. Conclusion: The uPA/uPAR system may be strongly linked to spermiation and spermatogenesis via regulating germ cell migration and proliferation, as well as promoting the spermiation and detached residual bodies from the mature spermatids. 展开更多
关键词 RATS SPERMATOGENESIS urokinase plasminogen activator urokinase receptor quantitative polymerase chain reaction
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Activity of Ginkgo biloba Extract and Quercetin on Thrombomodulin Expression and Tissue-type Plasminogen Activator Secretion by Human Umbilical Vein Endothelial Cells 被引量:2
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作者 WEN-JUN LAN XIAO-XIANG ZHENG 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2006年第4期249-253,共5页
Objective In order to investigate the pharmacological properties of Ginkgo biloba extract (GBE) on improving blood circulation, the regulating action of GBE and quercetin (a main flavonoid ingredient in GBE) on th... Objective In order to investigate the pharmacological properties of Ginkgo biloba extract (GBE) on improving blood circulation, the regulating action of GBE and quercetin (a main flavonoid ingredient in GBE) on thrombomodulin (TM) expression and tissue-type plasminogen activator (t-PA) secretion was studied. Methods Using flow cytometer and gel image system respectively, we evaluated the TM expression and the t-PA secretion by human umbilical vein endothelial cells (HUVECs) in vitro. Results The increase of TM expression on HUVECs surface was induced by GBE rather than quercetin in a dose- and time-dependent manner. Both GBE and quercetin increased the t-PA release significantly. Conclusion The effect of GBE on improving blood circulation may be partly attributed to its promoting TM expression and t-PA secretion by endothelial ceils, and quercetin participated in the effect of GBE on t-PA secretion. However, the action of GBE on increasing TM expression needs further study. 展开更多
关键词 Ginkgo biloba extract QUERCETIN THROMBOMODULIN Tissue-type plasminogen activator
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Urokinase-type plasminogen activator promotes synaptic repair in the ischemic brain 被引量:5
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作者 ariel diaz manuel yepes 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第2期232-233,共2页
The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body's mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this ene... The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body's mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this energy is used to maintain synaptic activity, even a mild decrease in its supply to the brain has deleterious implications for synaptic function. 展开更多
关键词 Urokinase-type plasminogen activator promotes synaptic repair in the ischemic brain AR TSP OGD LRP
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