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
BACKGROUND: Many international studies have shown that plasminogen activator inhibitor-1 (PAl-l) 4G/5G promoter polymorphism does not increase the risk for cerebral infarction. OBJECTIVE: Using PCR methodology and...BACKGROUND: Many international studies have shown that plasminogen activator inhibitor-1 (PAl-l) 4G/5G promoter polymorphism does not increase the risk for cerebral infarction. OBJECTIVE: Using PCR methodology and agarose electrophoresis to detect PAI-1 4G/5G promoter polymorphism in patients with recurrent cerebral infarction in the North Jiangsu Province of China, and to compare results with healthy subjects and patients with first-occurrence cerebral infarction in the same region. DESIGN, TIME AND SETTING: Non-randomized, concurrent, control trial. A total of 122 cerebral infarction patients were admitted to Xuzhou Medical College Hospital's Department of Neurology and Xuzhou Central Hospital's Department of Neurology between July 2003 and August 2006. PARTICIPANTS: The patients consisted of 63 males and 59 females, aged (62 ± 10) years. They were divided into first-occurrence (n = 58) and recurrence (n = 64) groups. In addition, 50 healthy subjects that underwent physical examination in the outpatient department, including 26 males and 24 females, aged (60 ±12) years, were selected as controls. METHODS AND MAIN OUTCOME MEASURES: PAl-1 4G/5G promoter polymorphism was detected and analyzed using PCR methodology and agarose electrophoresis. RESULTS: Significant differences were determined in terms of genotypic frequency and allele frequency of PAI-1 4G/5G promoter polymorphism, in patients with first-occurrence or recurrent cerebral infarction, when compared with healthy subjects (P 〈 0.05). There was, however, no significant difference between the first-occurrence and recurrence groups (P 〉 0.05). CONCLUSION: PAl- 1 4G/5G promoter polymorphism is genetic risk factor for cerebral infarction in China. However, it may be associated with recurrence of cerebral infarction in patients from the North Jiangsu Province of China.展开更多
Objective: To observe the effect of different dosages of ligustrazine (LG) on the level of plasminogen activator inhibitor-1 (PAI-1) activity in patients with type 2 diabetes mellitus. Methods: Ninety cases of type 2 ...Objective: To observe the effect of different dosages of ligustrazine (LG) on the level of plasminogen activator inhibitor-1 (PAI-1) activity in patients with type 2 diabetes mellitus. Methods: Ninety cases of type 2 diabetes mellitus inpatients were selected, and randomly divided into LG small dosage group (SDG), LG large dosage group (LDG) and control group. The 120 mg LG, 400 mg LG and normal saline 250 ml were given through intravenous dripping respectively, once daily, 20 days as one treatment course. Before and after treatment, all the patients had their fasting blood taken for PAI-1 and tissue plasminogen activator (t-PA) assessment test to perform the comparative study. Results:Seventy-three out of the 90 patients completed the observation course, the PAI-1 activity of three groups after treatment all lowered compared with that before treatment, and the difference between groups was also significant (all P<0. 01). After treatment the PAI-1 level of SDG and LDG of LG were all markedly lowered (all P<0. 01), the LDG's lowering was more evident than that of SDG, and comparison between these two groups of patients showed significant difference (P<0. 01). Although in the control group there was some difference between before and after treatment, it was not so significant like the above-mentioned two groups (P = 0. 0140). No adverse reaction occurred in the 3 groups during the observation period. Conclusion:LG could safely and effectively lower type 2 diabetes mellitus patient's plasma PAI-1 activity level, and LDG of LG proved to be particularly effective.展开更多
Objective:To explore the relationship between serum plasminogen activator inhibitor(PAI-1)level and Type 2 Diabetes Mellitus(T2DM)accompanied by overweight or obesity by observing not only the changes of PAI-1 level i...Objective:To explore the relationship between serum plasminogen activator inhibitor(PAI-1)level and Type 2 Diabetes Mellitus(T2DM)accompanied by overweight or obesity by observing not only the changes of PAI-1 level in T2DM patients with overweight or obesity,but also glucose and lipid metabolism related indicators,the changes of the inflammatory cytokines secreted by adipocytes,and then making an analysis on the correlation to PAI-1.Methods:36 cases of healthy examinees were selected as normal control group(NC group),and the experimental group can be divided into T2DM group(54 cases),Overweight/Obesity group(35 cases)and T2DM+Overweight/Obesity group(48 cases).Glucose and lipid metabolism related indicators such as fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbA1c),fasting insulin(FINS),insulin resistance index(IR),body weight index(BMI)and inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α)and PAI-1 were observed and compared between groups,and then made an analysis to explore the correlation of these factors to PAI-1.Results:(1)Compared with NC group,the levels of FBG,HbA1c,FINS and IR were increased in T2DM group,and the difference was of statistical significance.However,there was no statistically significant difference in TG,TC,LDL-C and BMI between NC group and T2DM group;the levels of FINS,IR,TG,LDL-C,TC and BMI were elevated in Overweight/Obesity group,and the difference was of statistical significance.However,there was no statistically significant difference in FBG and HbA1c;the levels of FBG,HbA1c,FINS,IR,TG,LDL-C,TC and BMI were up-regulated in T2DM+Overweight/Obesity group,and the difference was of statistical significance.Compared with T2DM group,the levels of TG,TC,LDL-C and BMI were increased in Overweight/Obesity group,and the difference was of statistical significance,however,the levels of FBG,HbA1c,FINS and IR were decreased,and the difference was statistically significant;The levels of FINS,IR,TG,TC,LDL-C and BMI were elevated in T2DM+Overweight/Obesity group,and the difference was of statistical significance,however,there was no statistically significant difference in FBG and HbA1c.Compared with Overweight/Obesity group,the levels of FBG,FINS,IR,HbA1c and LDL-C were increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.However,the difference in TG,TC and BMI was not statistically significant.(2)Compared with NC group,the levels of IL-6,TNF-αand PAI-1 were increased in T2DM group,Overweight/Obesity group and T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with T2DM group,the levels of IL-6 and TNF-αwere elevated in Overweight/Obesity group,and the difference was of statistical significance,but there was no statistically significant difference in PAI-1;the levels of IL-6,TNF-αand PAI-1 were up-regulated in T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with Overweight/Obesity group,there was no statistically significant difference in IL-6 and TNF-αbetween T2DM+Overweight/Obesity group and Overweight/Obesity group,but the level of PAI-1 was increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.(3)Multivariate Logistic Regression Analysis showed that HbA1c,IR,TG,BMI,IL-6 and TNF-αwere independently associated with the level of PAI-1(all p<.05).Conclusions:(1)The level of PAI-1 is higher in type 2 diabetes mellitus patients with overweight or obesity than that in patients only with type 2 diabetes mellitus,and it is one of causes that result in vascular complications.(2)The increase in the level of PAI-1 is considered to be associated with IL-6 and TNF-αsecreted by adipocytes.展开更多
Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphism...Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.展开更多
Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effe...Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.展开更多
Background Cigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract (CSE) on fibrinolytic activity of human umb...Background Cigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract (CSE) on fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). Most recently, simvastatin has been marked in its effect on endothelial cells protection and anticoagulation. In this study, the effect of CSE on the expression of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-l(PAl-1) in HUVECs was addressed. The role of simvastatin in CSE-induced fibrinolytic activity changes was investigated as well. Methods The fourth to fifth generation of HUVECs were incubated respectively with 0, 5%, 10% and 20% CSE for 6 hours or exposed to 5% CSE for 0, 4, 6, 8, 12, 24 hours to determine the expression changes of t-PA and PAl-1 protein. Meanwhile, cells were also accordingly exposed either to 5% CSE alone or simvastatin pre-treated and 5% CSE for 24 hours to assess the role of simvastatin in CSE-induced t-PA and PAl-1 protein and mRNA expression in HUVECs. RT-PCR and ELISA techniques were used for detecting the t-PA or PAl-1 mRNA and protein. Results After 6-hour exposure to CSE, the expression levels of t-PA protein in 10% and 20% CSE-treated groups reduced significantly ((0.0365±0.0083) ng/ml, (0.0255±0.0087) ng/ml) when compared with that of control group ((0.0660±0.0120) ng/ml) (P 〈0.05). In contrast, the levels of PAl-1 protein in 5%, 10% and 20% CSE-treated groups increased remarkably ((13.3225±0.5680) ng/ml, (14.2675±1.5380) ng/ml, (14.4292±1.6230) ng/ml) when compared with that of control group ((8.5193_±0.7537)ng/ml) (P〈0.05). After stimulation with 5% CSE for 0, 4, 6, 8, 12, 24 hours, the levels of PAl-1 protein increased over time and reached the peak at 24 hours ((14.6400±1.0651) ng/ml), which was significantly higher than that of control group ((12.0656±0.6148) ng/ml) (P 〈0.05). Additionally, CSE could up-regulate PAl-1 expression at both the mRNA and the protein levels. The levels of PAl-1 mRNA and protein increased significantly in 5% CSE-treated group ((8.8030±0.4745) ng/ml, (1.8155±0.0412) ng/ml) compared with those of control groups ((5.0588±0.2315) ng/ml, (1.3030±0.0647) ng/ml) (P 〈0.01), and decreased after 2-hour simvastatin pre-treatment ((5.4875±0.3166) ng/ml, (1.3975-±0.0297) ng/ml) (P 〈0.01). No significant difference was found at the levels of t-PA protein and mRNA (P 〉0.05). Conclusions CSE inhibits the fibrinolytic activity of HUVECs in vitro. Simvastatin plays a protective role in CSE-induced fibrinolytic malfunction.展开更多
AIM: To determine the correlation between invasiveness, migration and prognosis in esophageal squamous cell carcinoma (ESCC) and expression of the B-cell-specific Moloney leukemia virus insert site 1 (Bmi-1) and plasm...AIM: To determine the correlation between invasiveness, migration and prognosis in esophageal squamous cell carcinoma (ESCC) and expression of the B-cell-specific Moloney leukemia virus insert site 1 (Bmi-1) and plasminogen activator inhibitor-1 (PAI-1).展开更多
C-reactive protein(CRP) is a biomarker of inflammation.Increased plasma levels of CRP are associated with an increased risk of myocardial infarction.However,the correlation between plasma CRP concentration and atheros...C-reactive protein(CRP) is a biomarker of inflammation.Increased plasma levels of CRP are associated with an increased risk of myocardial infarction.However,the correlation between plasma CRP concentration and atherosclerotic plaque burden is poor.Based on these observations,it has been hypothesized that CRP increases the risk of myocardial infarction by promoting thrombosis.This article reviews available data that link enhanced CRP expression to increased risk of thrombosis,with a focus on the effects of CRP on hemostasis,platelet function,and fibrinolysis.Overall,the available data support the hypothesis that CRP is an important mechanistic link between inflammation and throm bosis.展开更多
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
Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mech...Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mechanism of the protective action of rhein on endothelial cells. Methods A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFβ1 was determined by immunoprecipitation analysis and western blot. Results TGFβ1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFβ1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFβ1 in human endothelial cells. Conclusions Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.展开更多
glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARy) agonist, h...glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARy) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1 ) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting, respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARy antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). The ERK kinase inhibitor, U0126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the pbosphorylation of ERKI/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARy pathways. Our findings suggested pioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.展开更多
The neuroprotective effect of Zhutan Tongluo Tang is associated with the activities of the fibrinolytic system. Thus the present study was designed to investigate therapeutic effects of Zhutan Tongluo Tang on intracer...The neuroprotective effect of Zhutan Tongluo Tang is associated with the activities of the fibrinolytic system. Thus the present study was designed to investigate therapeutic effects of Zhutan Tongluo Tang on intracerebral hemorrhage in rats, induced by injecting collagenase into one side of the caudate nucleus. Fibrinolytic indices including tissue plasminogen activator, plasminogen activator inhibitor-1 and D-Dimer were determined. The results obtained demonstrated that Zhutan Tongluo Tang treatment could alleviate the neural and behavioral impairments of intracerebral hemorrhaging rats. Increased frequencies of placing their forelimb correctly and decreased frequencies of turning left were observed. Enzyme linked immunosorbent assay showed that Zhutan Tongluo Tang could significantly elevate the concentration of plasma tissue plasminogen activator and D-Dimer, while depress plasminogen activator inhibitor-1. Immunohistochemistry demonstrated increased levels of catalase and glutathione in whole brain rat tissue following intracerebral hemorrhage. In addition, elevated expression of Bcl-2 in various hippocampal regions was seen. These findings describe the ability of Zhutan Tongluo Tang to activate the fibrinolytic system, and suggests that antioxidant and apoptosis inhibitory mechanisms may be playing a crucial role in protecting against collagenase-induced intracerebral hemorrhage.展开更多
Objective: Plasminogen activator inhibitor-1 (PAI-1), one crucial component of the plasminogen activator system, is a major player in the pathogenesis of many vascular diseases as well as in cancer. High levels of ...Objective: Plasminogen activator inhibitor-1 (PAI-1), one crucial component of the plasminogen activator system, is a major player in the pathogenesis of many vascular diseases as well as in cancer. High levels of PAI-1 in breast cancer tissue are associated with poor prognosis. The aim of this study is to evaluate rigorously the potential of serum PAI-1 concentration functioning as a general screening test in diagnostic or prognostic assays. Methods: A protein-microarray-based sandwich fluorescence immunoassay (FIA) was developed to detect PAI-1 in serum. Several conditions of this microarray-based FIA were optimized to establish an efficacious method. Serum specimens of 84 healthy women and 285 women with breast cancer were analyzed using the optimized FIA microarray. Results: The median serum PAI-1 level of breast cancer patients was higher than that of healthy women (109.7 ng/ml vs. 63.4 ng/ml). Analysis of covariance revealed that PAI-1 levels of the two groups were significantly different (P0.001) when controlling for an age effect on PAI-1 levels. However, PAI-1 values in TNM stage I?IV patients respectively were not significantly different from each other. Conclusion: This microarray-based sandwich FIA holds potential for quantitative analysis of tumor markers such as PAI-1.展开更多
Plasminogen activator inhibitor 1 (PAI-1) is considered as the main physiological inhibitor of plasminogen activators in plasma which plays an important regulatory role in the control of the fibrinolytic activity in b...Plasminogen activator inhibitor 1 (PAI-1) is considered as the main physiological inhibitor of plasminogen activators in plasma which plays an important regulatory role in the control of the fibrinolytic activity in blood. The human PAI-1 gene is located at q21-22 region of chromosome 7. By using human PAI-1 cDNA (a gift from Dr. D. Ginsburg) as a probe, restriction fragment length polymorphisms (RFLPs) were studied with 8 different endonucleases in 35 unrelated Chinese individuals and the results showed as follows: (1) Taq Ⅰdetected allelic 2.7 kb and 1.8 kb fragments, with the frequencies of 0.96 and 0.04 respectively, 2.7 kb homozygote and 2.7 kb/1.8 kb heterozygote appeared with frequencies of 91% and 9%. (2) Sac Ⅰidentified an invariant 4.8kb band and a two-allele polymorphism with fragments of either 23 kb or 16 kb whose frequencies were 0.96 and 0.04. 23kb homozygote and 23kb/16kb heterozygote appeared with the frequencies of 91% and 9%. (3) HindⅢrevealed a single two-allele polymorphism with bands at either 25 kb or 14 kb, with the frequencies of 0.34 and 0.66, 25 kb homozygote, 25 kb/14 kb heterozygote and 14 kb homozygote appeared with the frequencies of 23%, 46% and 31% respectively. The restriction fragment with a size of 1.6kb for TaqⅠwas first reported in the present paper. No polymorphism was observed for EcoRI, BamHI, BglⅡ, PvuⅡand Pst Ⅰ. The RFLPs for PAI-1 gene may be served as important genetic markers for study of thrombotic and other PAI-1 related disorders.展开更多
Background:Plasminogen activator inhibitor-1(PAI-1)plays an important role in the pathophysiology of sepsis,but the exact mechanism remains debatable.In this study,we investigated the associations among the serum leve...Background:Plasminogen activator inhibitor-1(PAI-1)plays an important role in the pathophysiology of sepsis,but the exact mechanism remains debatable.In this study,we investigated the associations among the serum levels of PAI-1,the incidence of 4G/5G promoter PAI-1 gene polymorphisms,immunological indicators,and clinical outcomes in septic patients.Methods:A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study,with 28-day mortality as the primary outcome.The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms(SNPs)were examined.Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1,serum level of PAI-1,and 28-day mortality.Results:The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1(4G/4G and 4G/5G)(Odds ratio[OR]:2.49;95%confidence interval[CI]:1.09,5.68).Furthermore,a high serum level of PAI-1 strongly influenced 28-day mortality(OR 3.36;95%CI 1.51,7.49).The expression and activation of neutrophils(OR 0.96;95%CI 0.93,0.99),as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils(OR:1.00;95%CI:1.00,1.00),were both regulated by the genotype of PAI-1.Conclusions:Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1,which might contribute to mortality by affecting neutrophil activity.Thus,patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.展开更多
The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic.Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure.The pathoph...The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic.Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure.The pathophysiologic states of hypertension,including obesity,are regulated by the production of adipocytederived factors.Increased body mass index was closely linked to elevated blood pressure.Mostly the hypertensive subjects were obese as well as overweight.There are numerous adipokines,however,this review article only focuses on the major adipokines including chemerin,visfatin,retinol-binding protein 4,plasminogen activator inhibitor-1,monocyte chemotactic protein-1,omentin-1,lipocalin-2,vaspin,progranulin,complement c1q tumor necrosis factor-related protein,and nesfatin-1 role in the pathogenesis of hypertension.This review article concludes the significant association of major adipokines in the pathogenesis of hypertensives.New research should be focused on other newly reported adipokine roles in hypertensive subjects and the management of these adipokines in hypertensive subjects.The discovery of this information could result in the creation of antihypertensive medications,particularly those that focus on obesity-related hypertension.展开更多
随着糖皮质激素在临床的广泛应用,激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)成为非创伤性股骨头坏死( osteonecrosis of the femoral head,ONFH)的主要原因,约占非创伤性ONFH的2/3。长期接...随着糖皮质激素在临床的广泛应用,激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)成为非创伤性股骨头坏死( osteonecrosis of the femoral head,ONFH)的主要原因,约占非创伤性ONFH的2/3。长期接受糖皮质激素治疗或接受大剂量糖皮质激素冲击治疗的患者中,9%~40%可能会发生SONFH,同时伴有糖皮质激素诱导的骨质疏松。随着基因组学的发展,发现SONFH的发生与纤溶酶原激活物抑制物-1( plasminogen activator inhibitor-1,PAI-1)和三磷酸腺苷黏合转运体B1(adenosine triphosphate binding cassette B1,ABCB1)的基因多态性有一定联系[1-2]。现报道1例长期使用糖皮质激素致ONFH患者,进行基因分型检测,分析基因型对SONFH的影响机制及干预措施,为临床个体化、合理用药提供参考。展开更多
基金Sichuan Province Medical Research Project Plan(Project No.S21113)。
文摘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.
基金the Xuzhou Social Development Foundation of Jiangsu Province, No. 2006046
文摘BACKGROUND: Many international studies have shown that plasminogen activator inhibitor-1 (PAl-l) 4G/5G promoter polymorphism does not increase the risk for cerebral infarction. OBJECTIVE: Using PCR methodology and agarose electrophoresis to detect PAI-1 4G/5G promoter polymorphism in patients with recurrent cerebral infarction in the North Jiangsu Province of China, and to compare results with healthy subjects and patients with first-occurrence cerebral infarction in the same region. DESIGN, TIME AND SETTING: Non-randomized, concurrent, control trial. A total of 122 cerebral infarction patients were admitted to Xuzhou Medical College Hospital's Department of Neurology and Xuzhou Central Hospital's Department of Neurology between July 2003 and August 2006. PARTICIPANTS: The patients consisted of 63 males and 59 females, aged (62 ± 10) years. They were divided into first-occurrence (n = 58) and recurrence (n = 64) groups. In addition, 50 healthy subjects that underwent physical examination in the outpatient department, including 26 males and 24 females, aged (60 ±12) years, were selected as controls. METHODS AND MAIN OUTCOME MEASURES: PAl-1 4G/5G promoter polymorphism was detected and analyzed using PCR methodology and agarose electrophoresis. RESULTS: Significant differences were determined in terms of genotypic frequency and allele frequency of PAI-1 4G/5G promoter polymorphism, in patients with first-occurrence or recurrent cerebral infarction, when compared with healthy subjects (P 〈 0.05). There was, however, no significant difference between the first-occurrence and recurrence groups (P 〉 0.05). CONCLUSION: PAl- 1 4G/5G promoter polymorphism is genetic risk factor for cerebral infarction in China. However, it may be associated with recurrence of cerebral infarction in patients from the North Jiangsu Province of China.
文摘Objective: To observe the effect of different dosages of ligustrazine (LG) on the level of plasminogen activator inhibitor-1 (PAI-1) activity in patients with type 2 diabetes mellitus. Methods: Ninety cases of type 2 diabetes mellitus inpatients were selected, and randomly divided into LG small dosage group (SDG), LG large dosage group (LDG) and control group. The 120 mg LG, 400 mg LG and normal saline 250 ml were given through intravenous dripping respectively, once daily, 20 days as one treatment course. Before and after treatment, all the patients had their fasting blood taken for PAI-1 and tissue plasminogen activator (t-PA) assessment test to perform the comparative study. Results:Seventy-three out of the 90 patients completed the observation course, the PAI-1 activity of three groups after treatment all lowered compared with that before treatment, and the difference between groups was also significant (all P<0. 01). After treatment the PAI-1 level of SDG and LDG of LG were all markedly lowered (all P<0. 01), the LDG's lowering was more evident than that of SDG, and comparison between these two groups of patients showed significant difference (P<0. 01). Although in the control group there was some difference between before and after treatment, it was not so significant like the above-mentioned two groups (P = 0. 0140). No adverse reaction occurred in the 3 groups during the observation period. Conclusion:LG could safely and effectively lower type 2 diabetes mellitus patient's plasma PAI-1 activity level, and LDG of LG proved to be particularly effective.
文摘Objective:To explore the relationship between serum plasminogen activator inhibitor(PAI-1)level and Type 2 Diabetes Mellitus(T2DM)accompanied by overweight or obesity by observing not only the changes of PAI-1 level in T2DM patients with overweight or obesity,but also glucose and lipid metabolism related indicators,the changes of the inflammatory cytokines secreted by adipocytes,and then making an analysis on the correlation to PAI-1.Methods:36 cases of healthy examinees were selected as normal control group(NC group),and the experimental group can be divided into T2DM group(54 cases),Overweight/Obesity group(35 cases)and T2DM+Overweight/Obesity group(48 cases).Glucose and lipid metabolism related indicators such as fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbA1c),fasting insulin(FINS),insulin resistance index(IR),body weight index(BMI)and inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α)and PAI-1 were observed and compared between groups,and then made an analysis to explore the correlation of these factors to PAI-1.Results:(1)Compared with NC group,the levels of FBG,HbA1c,FINS and IR were increased in T2DM group,and the difference was of statistical significance.However,there was no statistically significant difference in TG,TC,LDL-C and BMI between NC group and T2DM group;the levels of FINS,IR,TG,LDL-C,TC and BMI were elevated in Overweight/Obesity group,and the difference was of statistical significance.However,there was no statistically significant difference in FBG and HbA1c;the levels of FBG,HbA1c,FINS,IR,TG,LDL-C,TC and BMI were up-regulated in T2DM+Overweight/Obesity group,and the difference was of statistical significance.Compared with T2DM group,the levels of TG,TC,LDL-C and BMI were increased in Overweight/Obesity group,and the difference was of statistical significance,however,the levels of FBG,HbA1c,FINS and IR were decreased,and the difference was statistically significant;The levels of FINS,IR,TG,TC,LDL-C and BMI were elevated in T2DM+Overweight/Obesity group,and the difference was of statistical significance,however,there was no statistically significant difference in FBG and HbA1c.Compared with Overweight/Obesity group,the levels of FBG,FINS,IR,HbA1c and LDL-C were increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.However,the difference in TG,TC and BMI was not statistically significant.(2)Compared with NC group,the levels of IL-6,TNF-αand PAI-1 were increased in T2DM group,Overweight/Obesity group and T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with T2DM group,the levels of IL-6 and TNF-αwere elevated in Overweight/Obesity group,and the difference was of statistical significance,but there was no statistically significant difference in PAI-1;the levels of IL-6,TNF-αand PAI-1 were up-regulated in T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with Overweight/Obesity group,there was no statistically significant difference in IL-6 and TNF-αbetween T2DM+Overweight/Obesity group and Overweight/Obesity group,but the level of PAI-1 was increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.(3)Multivariate Logistic Regression Analysis showed that HbA1c,IR,TG,BMI,IL-6 and TNF-αwere independently associated with the level of PAI-1(all p<.05).Conclusions:(1)The level of PAI-1 is higher in type 2 diabetes mellitus patients with overweight or obesity than that in patients only with type 2 diabetes mellitus,and it is one of causes that result in vascular complications.(2)The increase in the level of PAI-1 is considered to be associated with IL-6 and TNF-αsecreted by adipocytes.
基金supported by the General Project of Henan Natural Science Foundation(No.232300420034)the National Natural Science Foundation of China for the Youth(No.81600555)the General Project of China Postdoctoral Science Foundation(No.2018M640684)。
文摘Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.
基金ThisworkwassupportedbyagrantfromtheScienceandTechnologyFoundationofHubeiProvince (No 2 0 0 3AA3 0 1C14 )
文摘Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.
文摘Background Cigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract (CSE) on fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). Most recently, simvastatin has been marked in its effect on endothelial cells protection and anticoagulation. In this study, the effect of CSE on the expression of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-l(PAl-1) in HUVECs was addressed. The role of simvastatin in CSE-induced fibrinolytic activity changes was investigated as well. Methods The fourth to fifth generation of HUVECs were incubated respectively with 0, 5%, 10% and 20% CSE for 6 hours or exposed to 5% CSE for 0, 4, 6, 8, 12, 24 hours to determine the expression changes of t-PA and PAl-1 protein. Meanwhile, cells were also accordingly exposed either to 5% CSE alone or simvastatin pre-treated and 5% CSE for 24 hours to assess the role of simvastatin in CSE-induced t-PA and PAl-1 protein and mRNA expression in HUVECs. RT-PCR and ELISA techniques were used for detecting the t-PA or PAl-1 mRNA and protein. Results After 6-hour exposure to CSE, the expression levels of t-PA protein in 10% and 20% CSE-treated groups reduced significantly ((0.0365±0.0083) ng/ml, (0.0255±0.0087) ng/ml) when compared with that of control group ((0.0660±0.0120) ng/ml) (P 〈0.05). In contrast, the levels of PAl-1 protein in 5%, 10% and 20% CSE-treated groups increased remarkably ((13.3225±0.5680) ng/ml, (14.2675±1.5380) ng/ml, (14.4292±1.6230) ng/ml) when compared with that of control group ((8.5193_±0.7537)ng/ml) (P〈0.05). After stimulation with 5% CSE for 0, 4, 6, 8, 12, 24 hours, the levels of PAl-1 protein increased over time and reached the peak at 24 hours ((14.6400±1.0651) ng/ml), which was significantly higher than that of control group ((12.0656±0.6148) ng/ml) (P 〈0.05). Additionally, CSE could up-regulate PAl-1 expression at both the mRNA and the protein levels. The levels of PAl-1 mRNA and protein increased significantly in 5% CSE-treated group ((8.8030±0.4745) ng/ml, (1.8155±0.0412) ng/ml) compared with those of control groups ((5.0588±0.2315) ng/ml, (1.3030±0.0647) ng/ml) (P 〈0.01), and decreased after 2-hour simvastatin pre-treatment ((5.4875±0.3166) ng/ml, (1.3975-±0.0297) ng/ml) (P 〈0.01). No significant difference was found at the levels of t-PA protein and mRNA (P 〉0.05). Conclusions CSE inhibits the fibrinolytic activity of HUVECs in vitro. Simvastatin plays a protective role in CSE-induced fibrinolytic malfunction.
基金Supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region,No.2012211A035Graduate Research and Innovation Project of Xnjiang Uygur Autonomous Region,No.XJGRI2013076Research and Innovation Project of Xinjiang Medical University,No.XJC201314
文摘AIM: To determine the correlation between invasiveness, migration and prognosis in esophageal squamous cell carcinoma (ESCC) and expression of the B-cell-specific Moloney leukemia virus insert site 1 (Bmi-1) and plasminogen activator inhibitor-1 (PAI-1).
基金Supported by Merit Review Award from the Department of Veterans Affairs,research grants from the Missouri Life Sciences Research Board and NIH,No. HL57346
文摘C-reactive protein(CRP) is a biomarker of inflammation.Increased plasma levels of CRP are associated with an increased risk of myocardial infarction.However,the correlation between plasma CRP concentration and atherosclerotic plaque burden is poor.Based on these observations,it has been hypothesized that CRP increases the risk of myocardial infarction by promoting thrombosis.This article reviews available data that link enhanced CRP expression to increased risk of thrombosis,with a focus on the effects of CRP on hemostasis,platelet function,and fibrinolysis.Overall,the available data support the hypothesis that CRP is an important mechanistic link between inflammation and throm bosis.
基金This work was supported in part by National Institutes of Health Grant NS-NS091201(to MY)and VA MERIT Award IO1BX003441(to MY).
文摘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.
基金ThisstudywaspartlysupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 0 171191)
文摘Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mechanism of the protective action of rhein on endothelial cells. Methods A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFβ1 was determined by immunoprecipitation analysis and western blot. Results TGFβ1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFβ1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFβ1 in human endothelial cells. Conclusions Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.
基金supported by the National Science foundation of China(No.30070300)
文摘glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARy) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1 ) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting, respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARy antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). The ERK kinase inhibitor, U0126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the pbosphorylation of ERKI/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARy pathways. Our findings suggested pioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.
基金a grant by Wenzhou Science and Technology Bureau, No.Y20060700
文摘The neuroprotective effect of Zhutan Tongluo Tang is associated with the activities of the fibrinolytic system. Thus the present study was designed to investigate therapeutic effects of Zhutan Tongluo Tang on intracerebral hemorrhage in rats, induced by injecting collagenase into one side of the caudate nucleus. Fibrinolytic indices including tissue plasminogen activator, plasminogen activator inhibitor-1 and D-Dimer were determined. The results obtained demonstrated that Zhutan Tongluo Tang treatment could alleviate the neural and behavioral impairments of intracerebral hemorrhaging rats. Increased frequencies of placing their forelimb correctly and decreased frequencies of turning left were observed. Enzyme linked immunosorbent assay showed that Zhutan Tongluo Tang could significantly elevate the concentration of plasma tissue plasminogen activator and D-Dimer, while depress plasminogen activator inhibitor-1. Immunohistochemistry demonstrated increased levels of catalase and glutathione in whole brain rat tissue following intracerebral hemorrhage. In addition, elevated expression of Bcl-2 in various hippocampal regions was seen. These findings describe the ability of Zhutan Tongluo Tang to activate the fibrinolytic system, and suggests that antioxidant and apoptosis inhibitory mechanisms may be playing a crucial role in protecting against collagenase-induced intracerebral hemorrhage.
基金supported by the National "863" High Technology Project Found of China (No.2006AA02A402)
文摘Objective: Plasminogen activator inhibitor-1 (PAI-1), one crucial component of the plasminogen activator system, is a major player in the pathogenesis of many vascular diseases as well as in cancer. High levels of PAI-1 in breast cancer tissue are associated with poor prognosis. The aim of this study is to evaluate rigorously the potential of serum PAI-1 concentration functioning as a general screening test in diagnostic or prognostic assays. Methods: A protein-microarray-based sandwich fluorescence immunoassay (FIA) was developed to detect PAI-1 in serum. Several conditions of this microarray-based FIA were optimized to establish an efficacious method. Serum specimens of 84 healthy women and 285 women with breast cancer were analyzed using the optimized FIA microarray. Results: The median serum PAI-1 level of breast cancer patients was higher than that of healthy women (109.7 ng/ml vs. 63.4 ng/ml). Analysis of covariance revealed that PAI-1 levels of the two groups were significantly different (P0.001) when controlling for an age effect on PAI-1 levels. However, PAI-1 values in TNM stage I?IV patients respectively were not significantly different from each other. Conclusion: This microarray-based sandwich FIA holds potential for quantitative analysis of tumor markers such as PAI-1.
文摘Plasminogen activator inhibitor 1 (PAI-1) is considered as the main physiological inhibitor of plasminogen activators in plasma which plays an important regulatory role in the control of the fibrinolytic activity in blood. The human PAI-1 gene is located at q21-22 region of chromosome 7. By using human PAI-1 cDNA (a gift from Dr. D. Ginsburg) as a probe, restriction fragment length polymorphisms (RFLPs) were studied with 8 different endonucleases in 35 unrelated Chinese individuals and the results showed as follows: (1) Taq Ⅰdetected allelic 2.7 kb and 1.8 kb fragments, with the frequencies of 0.96 and 0.04 respectively, 2.7 kb homozygote and 2.7 kb/1.8 kb heterozygote appeared with frequencies of 91% and 9%. (2) Sac Ⅰidentified an invariant 4.8kb band and a two-allele polymorphism with fragments of either 23 kb or 16 kb whose frequencies were 0.96 and 0.04. 23kb homozygote and 23kb/16kb heterozygote appeared with the frequencies of 91% and 9%. (3) HindⅢrevealed a single two-allele polymorphism with bands at either 25 kb or 14 kb, with the frequencies of 0.34 and 0.66, 25 kb homozygote, 25 kb/14 kb heterozygote and 14 kb homozygote appeared with the frequencies of 23%, 46% and 31% respectively. The restriction fragment with a size of 1.6kb for TaqⅠwas first reported in the present paper. No polymorphism was observed for EcoRI, BamHI, BglⅡ, PvuⅡand Pst Ⅰ. The RFLPs for PAI-1 gene may be served as important genetic markers for study of thrombotic and other PAI-1 related disorders.
基金supported by grants from the National Natural Science Foundation of China(Nos.82172138 and 81873947)Special Medical Innovation Project of Shanghai Science and Technology Committee(No.21Y11902400)the Key Laboratory of Emergency and Trauma(Hainan Medical University),Ministry of Education(No.KLET-202016)
文摘Background:Plasminogen activator inhibitor-1(PAI-1)plays an important role in the pathophysiology of sepsis,but the exact mechanism remains debatable.In this study,we investigated the associations among the serum levels of PAI-1,the incidence of 4G/5G promoter PAI-1 gene polymorphisms,immunological indicators,and clinical outcomes in septic patients.Methods:A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study,with 28-day mortality as the primary outcome.The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms(SNPs)were examined.Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1,serum level of PAI-1,and 28-day mortality.Results:The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1(4G/4G and 4G/5G)(Odds ratio[OR]:2.49;95%confidence interval[CI]:1.09,5.68).Furthermore,a high serum level of PAI-1 strongly influenced 28-day mortality(OR 3.36;95%CI 1.51,7.49).The expression and activation of neutrophils(OR 0.96;95%CI 0.93,0.99),as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils(OR:1.00;95%CI:1.00,1.00),were both regulated by the genotype of PAI-1.Conclusions:Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1,which might contribute to mortality by affecting neutrophil activity.Thus,patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.
文摘The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic.Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure.The pathophysiologic states of hypertension,including obesity,are regulated by the production of adipocytederived factors.Increased body mass index was closely linked to elevated blood pressure.Mostly the hypertensive subjects were obese as well as overweight.There are numerous adipokines,however,this review article only focuses on the major adipokines including chemerin,visfatin,retinol-binding protein 4,plasminogen activator inhibitor-1,monocyte chemotactic protein-1,omentin-1,lipocalin-2,vaspin,progranulin,complement c1q tumor necrosis factor-related protein,and nesfatin-1 role in the pathogenesis of hypertension.This review article concludes the significant association of major adipokines in the pathogenesis of hypertensives.New research should be focused on other newly reported adipokine roles in hypertensive subjects and the management of these adipokines in hypertensive subjects.The discovery of this information could result in the creation of antihypertensive medications,particularly those that focus on obesity-related hypertension.
文摘随着糖皮质激素在临床的广泛应用,激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)成为非创伤性股骨头坏死( osteonecrosis of the femoral head,ONFH)的主要原因,约占非创伤性ONFH的2/3。长期接受糖皮质激素治疗或接受大剂量糖皮质激素冲击治疗的患者中,9%~40%可能会发生SONFH,同时伴有糖皮质激素诱导的骨质疏松。随着基因组学的发展,发现SONFH的发生与纤溶酶原激活物抑制物-1( plasminogen activator inhibitor-1,PAI-1)和三磷酸腺苷黏合转运体B1(adenosine triphosphate binding cassette B1,ABCB1)的基因多态性有一定联系[1-2]。现报道1例长期使用糖皮质激素致ONFH患者,进行基因分型检测,分析基因型对SONFH的影响机制及干预措施,为临床个体化、合理用药提供参考。