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
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
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 RTPCR 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%; χ2 = 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%, χ2= 7.61, P＜0.05), Lauren's classification of diffuse/mixed types: 54.2%, intestinal type: 26.3%, χ2 = 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
Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer t...Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer therapy. Most current uPA inhibitors employ a highly basic group (either amidine or guanidine group) to target the S1 pocket of uPA active site, which leads to poor oral bioavailability. Here we study the possibility of using less basic 2-aminobenzothiazole (ABT) as S1 pocket binding group. We report the crystal structures of uPA complexes with ABT or 2-amino-benzothiazole-6-carboxylic acid ethyl ester (ABTCE). The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that ABTCE is a better inhibitor for uPA (Ki = 656 μM) than ABT (Ki = 5.03 mM). This work shows that 2-amniobenzothiazole can be used as P1 group which may have better oral bioavailability than the commonly used amidine or guanidine group. We also found the ethyl ester group occupies the characteristic oxyanion hole and contacts to uPA 37- and 60-loops. Such work provides structural information for further improvements of potency and selectivity of this new class of uPA inhibitor.展开更多
Objective To explore the role of urokinase-type plasminogen activator(uPA) inprecontact sperm-egg communication and fertility of mice in vitro.Methods Firstly, sperm chemotaxis (SC) induced by uPA was assayed by measu...Objective To explore the role of urokinase-type plasminogen activator(uPA) inprecontact sperm-egg communication and fertility of mice in vitro.Methods Firstly, sperm chemotaxis (SC) induced by uPA was assayed by measuringthe sperm densities in capillaries with a descending gradient or no gradient of uPArespectively. Secondly, the role of uPAR that exists in sperm plasma membrane in SCwas studied by examining the change of sperm density in capillary after incubatingspermatozoa with anti-uPAR antibody. Thirdly, SC induced by eggs, which had beentreated with uPA, PAI-1 and anti-uPAR beforehand respectively, was assayed to studythe role of uPA in PSEC. Lastly, the fertilization capability of spermatozoa treated withuPA was examined by counting the number of fertilized eggs.Results 1)The density of spermatozoa that migrated down the gradient of uPA intothe capillary was significantly lower than that into the capillary containing no-gradientuPA. 2) When uPAR of spermatozoa was inhibited by anti-uPAR antibody, the densityof spermatozoa that migrated into the capillary with ascending gradient of uPAdecreased correspondingly. 3) The density of spermatozoa attracted by eggs, whichwere treated with uPA beforehand, increased significantly than that of attracted bynon-treated eggs. On the contrary, the sperm density decreased correspondingly whenthe egg was treated with PAI-1. 4) The number of fertilized eggs increased significantlyafter the spermatozoa used here was treated with uPA beforehand.Conclusion uPA could induce SC of mice sperm in vitro through the uPAR on itsmembrane, enhance the capability of egg inducing SC, and promote spermatozoa tofertilize eggs. Thus, uPA may act as an attractant in PSEC, increase the chance encounterof spermatozoa and eggs, therefore, enhance the fertility success correspondingly.This study, in some degree, provides an evidence that uPA may be used as a newmedicine and diagnostic reagent for male infertility.展开更多
Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The differ...Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.展开更多
A missense C/T polymorphism in exon 6 (the NCBI rsID is rs2227564) of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer's disease risk. The present study analyz...A missense C/T polymorphism in exon 6 (the NCBI rsID is rs2227564) of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer's disease risk. The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer's disease by PCR-restriction fragment length polymorphism. Results showed that CC, CT and TT genotype distribution frequencies had significant differences between sporadic Alzheimer's disease patients and healthy controls. In-depth analysis of the association between urokinase-type plasminogen gene rs2227564 polymorphisms and sporadic Alzheimer's disease indicated that people with the C-positive genotype CC + CT were at a higher risk for developing sporadic Alzheimer's disease. These results support the contribution of the polymorphisms of rs2227564 in the urokinase-type plasminogen gene to the pathogenesis of sporadic Alzheimer's disease in the Han Chinese population.展开更多
Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease and plays a key role in several biological processes, including tissue remodeling, cell migration, and matrix degradation. The inhibitors of...Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease and plays a key role in several biological processes, including tissue remodeling, cell migration, and matrix degradation. The inhibitors of uPA have been shown to prevent the spread of metastasis and tumor growth, and accordingly uPA is widely recognized as a target for the treatment of cancer. In this work, we report the crystal structures of the complexes of uPA with its inhibitors: 4-(aminomethyl)-benzoic acid (AMBA) and 4-(aminomethyl-phenyl)-methanol (AMPM), both at a resolution of 2.35 . The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that AMBA is a better inhibitor for uPA (Ki = 2.68 mM) than AMPM (Ki = 13.99 mM). The structural study shows that the binding mode of inhibitor AMBA on uPA is similar to that of AMPM on uPA, both docked into the active site S1 pocket of uPA. Structural details of these complexes are provided to explain the difference of inhibitory constants.展开更多
The aim of this study is to investigate the che-motactic effect of urokinase-type plasminogen activator(uPA)on mouse spermatozoa.Capillary assays were applied to study the chemotactic activity of ascending and descend...The aim of this study is to investigate the che-motactic effect of urokinase-type plasminogen activator(uPA)on mouse spermatozoa.Capillary assays were applied to study the chemotactic activity of ascending and descending gradients of uPA.Firstly,the chemotactic effect of an ascending gradient of uPA on mouse sper-matozoa was observed by counting the number of sper-matozoa that migrated into the capillary after incubation with uPA for 5,10,20,and 30 min,respectively,com-pared with that after incubation with F10.Twenty min-utes was a suitable incubation time to obtain a plateau of sperm accumulation.Meanwhile,to confirm the specific effect of uPA on mouse sperm chemotaxis,uPA inhibitor(PAI-1)and anti-uPAR rabbit IgG were added to the test solution containing 20 U/mL uPA,respectively.To exclude the possibility that PAI-1 and anti-uPAR rabbit IgG may affect sperm accumulation nonspecifically,PAI-1 and anti-uPAR rabbit IgG were added to F10,respect-ively.It was found that the chemotactic effect of uPA was neutralized completely by PAI-1 and anti-uPAR rabbit IgG.PAI-1 and anti-uPAR rabbit IgG had no neutral-izing effect on the sperm chemotactic effect.Lastly,the sperm chemotaxis response to a descending gradient of uPA was also observed.Taken together,the results sug-gest that uPA can induce sperm chemotaxis in vitro by binding to its receptor on the sperm membrane and may act as a chemoattractant in precontacting sperm-egg com-munication thereby increasing the chance encounter of spermatozoa and eggs.展开更多
Two types of plasminogen activators, tissue type (tPA) and urokinase type(uPA),and a plasminogen activator inhibitor (PAI-1) have been identified in ovariangranulosa cells (GC) of both rat and rhesus monkey. Interacti...Two types of plasminogen activators, tissue type (tPA) and urokinase type(uPA),and a plasminogen activator inhibitor (PAI-1) have been identified in ovariangranulosa cells (GC) of both rat and rhesus monkey. Interaction and coordinated expression of tPA and PAI-1 in the same tissue cells are closely related with certain reproductive processes such as ovulation, spermatogenesis and endometrium cycle. In our previous studies on gonadotropin-induced ovulation in rhesus monkeys,we展开更多
To investigate the expression and clinical significance of urokinase type plasminogen activator (uPA) in human gliomas Methods mRNA and protein expressions of uPA were examined by Northern blot hybridization and immun...To investigate the expression and clinical significance of urokinase type plasminogen activator (uPA) in human gliomas Methods mRNA and protein expressions of uPA were examined by Northern blot hybridization and immunohistochemical method in 43 cases of gliomas and 5 cases of normal brain tissues and their relationship to clinical indexes was comprehensively analyzed Results All tissues expressed the 2 5*!kb transcript of uPA mRNA The uPA mRNA level in high-grade gliomas was considerably higher than that in low-grade gliomas and normal brain tissues ( P <0 01) Levels of uPA mRNA expression in tumor tissues with recurrence during 18 postoperative months and a survival period less than 3 years, were significantly higher than counterparts ( P <0 01) uPA mRNA expression was strongly correlated with the microvessel quantity (MVQ) in gliomas ( r =0 56, P <0 01) uPA protein was mainly distributed in tumor cells and endothelial cells of glioblastomas and anaplastic astrocytomas Conclusion Expression of uPA is associated with the malignant progression, invasion and angiogenesis of gliomas, and it may play a critical role in the recurrence and prognosis of展开更多
Objective: To study the expression and clinicalsignificance of urokinase-type plasminogen activator(uPA) in breast cancer. Methods: Applyingstreptavidin-biotin complex (SABC) immunohistochemical technique, expression ...Objective: To study the expression and clinicalsignificance of urokinase-type plasminogen activator(uPA) in breast cancer. Methods: Applyingstreptavidin-biotin complex (SABC) immunohistochemical technique, expression of uPA was studied in100 patients with primary breast canceL Results: Therewere 55 patients with high uPA expression, and 45 withlower expression. There was significant correlationbetween uPA expression and TNM stage, lymph nodestatus, and the tumor size. Neither age, menopausalstatus, nor ER status was significantly related with levelof uPA expression. The patients with high expression ofuPA had significantly shorter disease-free survival (DFS)and overall survival (OS) than did those with lowexpression of uPA. Univariate analysis showed that uPAas a prognostic factor was of similar magnitude tolymph node status and TNM stage, hut stronger thanthat of ER status and tumor size. UPA was anindependent prognostic factor affecting disease-freesurvival and overall survival. Collclusion: uPA appearsto be a strong and independent biologic marker forpredicting prognosis of breast cancer.展开更多
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
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
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
AIM:To 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 endothe...AIM:To 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.METHODS:A total of 36 vitreous samples were collected from 36 patients with PDR(PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS:The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group(P <0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression(P <0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR.VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.展开更多
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
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;−675 4G/5G and −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 −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 −844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was −675 4G/5G polymorphism (regression coefficient β = 4.6, P Conclusion: the present study identifies −675 4G/5G not −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
Tissue plasminogen activator(t PA)use in the treatment of ischemic stroke:t PA is a serine protease that catalyzes the breakdown of blood clots.Because of its thrombolytic properties,t PA is used to treat specific typ...Tissue plasminogen activator(t PA)use in the treatment of ischemic stroke:t PA is a serine protease that catalyzes the breakdown of blood clots.Because of its thrombolytic properties,t PA is used to treat specific types of stroke,including ischemia,but is contraindicated for treatment of hemorrhagic stroke or head trauma.Although a life saving and powerful‘clot buster’,t PA has a展开更多
文摘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.
基金Supported by National Natural Science Foundation of ChinaNo.81460114+5 种基金Natural Science Foundation of Guangxi Zhuang Autonomous RegionNo.1355005-3-2 and No.2012GXNSFAA053143Chinese Traditional Medicine Science Foundation of Guangxi Zhuang Autonomous RegionNo.GZPT1238Science Foundation of Guangxi Department of EducationNo.201203YB036 and No.2013LX031
文摘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.
文摘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 RTPCR 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%; χ2 = 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%, χ2= 7.61, P＜0.05), Lauren's classification of diffuse/mixed types: 54.2%, intestinal type: 26.3%, χ2 = 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.
基金Supported by FJIRSM (SZD08003)National Natural Science Foundation of China (30811130467, 30625011)+1 种基金Ministry of Science of Technology (2006AA02A313, 2007CB914304)Chinese Academy of Sciences (KSCX2-YW-R-082)
文摘Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer therapy. Most current uPA inhibitors employ a highly basic group (either amidine or guanidine group) to target the S1 pocket of uPA active site, which leads to poor oral bioavailability. Here we study the possibility of using less basic 2-aminobenzothiazole (ABT) as S1 pocket binding group. We report the crystal structures of uPA complexes with ABT or 2-amino-benzothiazole-6-carboxylic acid ethyl ester (ABTCE). The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that ABTCE is a better inhibitor for uPA (Ki = 656 μM) than ABT (Ki = 5.03 mM). This work shows that 2-amniobenzothiazole can be used as P1 group which may have better oral bioavailability than the commonly used amidine or guanidine group. We also found the ethyl ester group occupies the characteristic oxyanion hole and contacts to uPA 37- and 60-loops. Such work provides structural information for further improvements of potency and selectivity of this new class of uPA inhibitor.
基金This work is supported by a grant of the National "Tenth Five Years" Key Technologies R&D Programme,China(No.2004BA720A33-01).
文摘Objective To explore the role of urokinase-type plasminogen activator(uPA) inprecontact sperm-egg communication and fertility of mice in vitro.Methods Firstly, sperm chemotaxis (SC) induced by uPA was assayed by measuringthe sperm densities in capillaries with a descending gradient or no gradient of uPArespectively. Secondly, the role of uPAR that exists in sperm plasma membrane in SCwas studied by examining the change of sperm density in capillary after incubatingspermatozoa with anti-uPAR antibody. Thirdly, SC induced by eggs, which had beentreated with uPA, PAI-1 and anti-uPAR beforehand respectively, was assayed to studythe role of uPA in PSEC. Lastly, the fertilization capability of spermatozoa treated withuPA was examined by counting the number of fertilized eggs.Results 1)The density of spermatozoa that migrated down the gradient of uPA intothe capillary was significantly lower than that into the capillary containing no-gradientuPA. 2) When uPAR of spermatozoa was inhibited by anti-uPAR antibody, the densityof spermatozoa that migrated into the capillary with ascending gradient of uPAdecreased correspondingly. 3) The density of spermatozoa attracted by eggs, whichwere treated with uPA beforehand, increased significantly than that of attracted bynon-treated eggs. On the contrary, the sperm density decreased correspondingly whenthe egg was treated with PAI-1. 4) The number of fertilized eggs increased significantlyafter the spermatozoa used here was treated with uPA beforehand.Conclusion uPA could induce SC of mice sperm in vitro through the uPAR on itsmembrane, enhance the capability of egg inducing SC, and promote spermatozoa tofertilize eggs. Thus, uPA may act as an attractant in PSEC, increase the chance encounterof spermatozoa and eggs, therefore, enhance the fertility success correspondingly.This study, in some degree, provides an evidence that uPA may be used as a newmedicine and diagnostic reagent for male infertility.
文摘Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.
基金supported by the National Natural Science Foundation of China, No. 30470615
文摘A missense C/T polymorphism in exon 6 (the NCBI rsID is rs2227564) of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer's disease risk. The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer's disease by PCR-restriction fragment length polymorphism. Results showed that CC, CT and TT genotype distribution frequencies had significant differences between sporadic Alzheimer's disease patients and healthy controls. In-depth analysis of the association between urokinase-type plasminogen gene rs2227564 polymorphisms and sporadic Alzheimer's disease indicated that people with the C-positive genotype CC + CT were at a higher risk for developing sporadic Alzheimer's disease. These results support the contribution of the polymorphisms of rs2227564 in the urokinase-type plasminogen gene to the pathogenesis of sporadic Alzheimer's disease in the Han Chinese population.
基金Supported by the National Natural Science Foundation of China (30430190, 30625011)973 (2007CB914304)Young Talent Programme of Fujian Province (2007F3119)
文摘Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease and plays a key role in several biological processes, including tissue remodeling, cell migration, and matrix degradation. The inhibitors of uPA have been shown to prevent the spread of metastasis and tumor growth, and accordingly uPA is widely recognized as a target for the treatment of cancer. In this work, we report the crystal structures of the complexes of uPA with its inhibitors: 4-(aminomethyl)-benzoic acid (AMBA) and 4-(aminomethyl-phenyl)-methanol (AMPM), both at a resolution of 2.35 . The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that AMBA is a better inhibitor for uPA (Ki = 2.68 mM) than AMPM (Ki = 13.99 mM). The structural study shows that the binding mode of inhibitor AMBA on uPA is similar to that of AMPM on uPA, both docked into the active site S1 pocket of uPA. Structural details of these complexes are provided to explain the difference of inhibitory constants.
基金supported by grants from National“Tenth-Five Years”Key Technologies R&D Program,China(No.2004BA720A33-01).
文摘The aim of this study is to investigate the che-motactic effect of urokinase-type plasminogen activator(uPA)on mouse spermatozoa.Capillary assays were applied to study the chemotactic activity of ascending and descending gradients of uPA.Firstly,the chemotactic effect of an ascending gradient of uPA on mouse sper-matozoa was observed by counting the number of sper-matozoa that migrated into the capillary after incubation with uPA for 5,10,20,and 30 min,respectively,com-pared with that after incubation with F10.Twenty min-utes was a suitable incubation time to obtain a plateau of sperm accumulation.Meanwhile,to confirm the specific effect of uPA on mouse sperm chemotaxis,uPA inhibitor(PAI-1)and anti-uPAR rabbit IgG were added to the test solution containing 20 U/mL uPA,respectively.To exclude the possibility that PAI-1 and anti-uPAR rabbit IgG may affect sperm accumulation nonspecifically,PAI-1 and anti-uPAR rabbit IgG were added to F10,respect-ively.It was found that the chemotactic effect of uPA was neutralized completely by PAI-1 and anti-uPAR rabbit IgG.PAI-1 and anti-uPAR rabbit IgG had no neutral-izing effect on the sperm chemotactic effect.Lastly,the sperm chemotaxis response to a descending gradient of uPA was also observed.Taken together,the results sug-gest that uPA can induce sperm chemotaxis in vitro by binding to its receptor on the sperm membrane and may act as a chemoattractant in precontacting sperm-egg com-munication thereby increasing the chance encounter of spermatozoa and eggs.
基金Task Foroe for Post-ovulatory Method Special Programme of Research Development+1 种基金Research Training in Human Reproduction of the World Health OrganizationState Family Planning Commission
文摘Two types of plasminogen activators, tissue type (tPA) and urokinase type(uPA),and a plasminogen activator inhibitor (PAI-1) have been identified in ovariangranulosa cells (GC) of both rat and rhesus monkey. Interaction and coordinated expression of tPA and PAI-1 in the same tissue cells are closely related with certain reproductive processes such as ovulation, spermatogenesis and endometrium cycle. In our previous studies on gonadotropin-induced ovulation in rhesus monkeys,we
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 39970 75 2 )
文摘To investigate the expression and clinical significance of urokinase type plasminogen activator (uPA) in human gliomas Methods mRNA and protein expressions of uPA were examined by Northern blot hybridization and immunohistochemical method in 43 cases of gliomas and 5 cases of normal brain tissues and their relationship to clinical indexes was comprehensively analyzed Results All tissues expressed the 2 5*!kb transcript of uPA mRNA The uPA mRNA level in high-grade gliomas was considerably higher than that in low-grade gliomas and normal brain tissues ( P <0 01) Levels of uPA mRNA expression in tumor tissues with recurrence during 18 postoperative months and a survival period less than 3 years, were significantly higher than counterparts ( P <0 01) uPA mRNA expression was strongly correlated with the microvessel quantity (MVQ) in gliomas ( r =0 56, P <0 01) uPA protein was mainly distributed in tumor cells and endothelial cells of glioblastomas and anaplastic astrocytomas Conclusion Expression of uPA is associated with the malignant progression, invasion and angiogenesis of gliomas, and it may play a critical role in the recurrence and prognosis of
文摘Objective: To study the expression and clinicalsignificance of urokinase-type plasminogen activator(uPA) in breast cancer. Methods: Applyingstreptavidin-biotin complex (SABC) immunohistochemical technique, expression of uPA was studied in100 patients with primary breast canceL Results: Therewere 55 patients with high uPA expression, and 45 withlower expression. There was significant correlationbetween uPA expression and TNM stage, lymph nodestatus, and the tumor size. Neither age, menopausalstatus, nor ER status was significantly related with levelof uPA expression. The patients with high expression ofuPA had significantly shorter disease-free survival (DFS)and overall survival (OS) than did those with lowexpression of uPA. Univariate analysis showed that uPAas a prognostic factor was of similar magnitude tolymph node status and TNM stage, hut stronger thanthat of ER status and tumor size. UPA was anindependent prognostic factor affecting disease-freesurvival and overall survival. Collclusion: uPA appearsto be a strong and independent biologic marker forpredicting prognosis of breast cancer.
文摘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.
文摘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.
文摘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.
基金Supported by Natural Science Foundation of Ningxia(No.NZ10129)
文摘AIM:To 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.METHODS:A total of 36 vitreous samples were collected from 36 patients with PDR(PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS:The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group(P <0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression(P <0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR.VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.
基金supported by a grant from Shanghai Municipal Health Bureau(GWDTR201219)
文摘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.
文摘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;−675 4G/5G and −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 −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 −844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was −675 4G/5G polymorphism (regression coefficient β = 4.6, P Conclusion: the present study identifies −675 4G/5G not −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.
文摘Tissue plasminogen activator(t PA)use in the treatment of ischemic stroke:t PA is a serine protease that catalyzes the breakdown of blood clots.Because of its thrombolytic properties,t PA is used to treat specific types of stroke,including ischemia,but is contraindicated for treatment of hemorrhagic stroke or head trauma.Although a life saving and powerful‘clot buster’,t PA has a
