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
Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator（t PA） from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes t...Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator（t PA） from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density（PSD） that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^（2＋）/calmodulin-dependent protein kinase IIα（pCa MKIIα）,followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid（AMPA） receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate（NMDA） receptors and cyclin-dependent kinase 5（Cdk5）-induced phosphorylation of the protein phosphatase 1（PP1） at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.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
L-Palmitoylcarnitine(L-PC)is an important endogenous fatty acid metabolite.Its classical biological functions are involved in the regulations of membrane molecular dynamics and theβ-oxidation of fatty acids.Decreased...L-Palmitoylcarnitine(L-PC)is an important endogenous fatty acid metabolite.Its classical biological functions are involved in the regulations of membrane molecular dynamics and theβ-oxidation of fatty acids.Decreased plasma long-chain acylcarnitines showed the association of venous thrombosis,implying anticoagulant activity of the metabolites and inspiring us to investigate if and how L-PC,a long-chain acylcarnitine,takes part in coagulation.Here we show that L-PC exerted anti-coagulant effects by potentiating the enzymatic activities of plasmin and tissue plasminogen activator(tPA).L-PC directly interacts with plasmin and tPA with an equilibrium dissociation constant(KD)of 6.47×10^(-9)and 4.46×10^(-9)M,respectively,showing high affinities.In mouse model,L-PC administration significantly inhibited FeCl_(3)-induced arterial thrombosis.It also mitigated intracerebral thrombosis and inflammation in a transient middle cerebral artery occlusion(tMCAO)mouse model.L-PC induced little bleeding complications.The results show that L-PC has anti-thrombotic function by potentiating plasmin and tPA.展开更多
Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system.Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their h...Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system.Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life.Sclerotherapy has become the first-line therapy for venous system diseases.However,there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy,and improper operation will cause serious adverse consequences.Therefore,exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy.To solve the above problems,we proposed a new sclerotherapy strategy with a dual mechanism of“vascular damage and plasmin(PLA)system inhibition.”We intended to construct a novel cationic surfactant(AEOx-TA)by reacting tranexamic acid(TA),a parent structure,with fatty alcohol polyoxyethylene ether(AEOx)by ester bonds.AEOx-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus.Furthermore,AEOx-TA could be degraded by esterase and release the parent drug,TA,which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis.In addition,such surfactant-based sclerosants have foam-forming properties,and they can be blended with polyvinyl alcohol(PVA)to prepare a highly stable foam formulation(AEOx-TA/P),which can achieve a precise drug delivery and prolonged drug retention time,thereby improving drug efficacy and reducing the risk of ectopic embolism.Overall,the novel cationic surfactant AEOx-TA provides a new avenue to resolve the bottleneck:surfactant sclerosants’efficiency is relatively low in the current sclerotherapy.展开更多
Aberrant expression of annexin A2-SI00A10 heterotetramer （AIIt） associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia （APL）, but the mechanism is unclear. To faci...Aberrant expression of annexin A2-SI00A10 heterotetramer （AIIt） associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia （APL）, but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α （PML/RARα） fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5＇-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29 ± 0.13 fold higher than that by control pSG5 vector or wild-type RARer. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation （IRPG） in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid （ATRA） significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.展开更多
Objective: To study the changes of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) expressions and fibrinolysis molecular markers in patients with gastrointestinal cancer in order...Objective: To study the changes of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) expressions and fibrinolysis molecular markers in patients with gastrointestinal cancer in order to elucidate their clinical significance. Methods: The plasma levels of t-PA, u-PA, urokinase-type plasminogen activator receptor (u-PAR) and plasmin anti-plasmin complex (PAP) were measured by ELISA. t-PA and u-PA mRNAs were detected by Real-time RT-PCR. Results: The plasma levels of u-PA, u-PAR and PAP were elevated in gastrointestinal cancer patients, while u-PA was markedly elevated in patients with local infiltration, lymph node involvement or distal metastasis. U-PA mRNA was higher and t-PA was lower in gastrointestinal cancer compared to normal tissue. Conclusion: Hyperfibrinolysis is an important factor related with metastasis potential of gastrointestinal cancer. t-PA may be a character of well differentiated tissue.展开更多
目的探究超高温(ultra high temperature,UHT)乳生产过程中可能影响纤溶酶活性的关键因素。方法采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA),测定并分析从原料乳到UHT成品乳生产过程中多种因素对纤溶酶活性造成的影...目的探究超高温(ultra high temperature,UHT)乳生产过程中可能影响纤溶酶活性的关键因素。方法采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA),测定并分析从原料乳到UHT成品乳生产过程中多种因素对纤溶酶活性造成的影响。具体研究的影响因素包括牛患乳房炎程度、乳中体细胞数、接种疫苗、改变饲喂条件、离心处理、巴氏杀菌预热条件、微滤处理及UHT预热条件。结果在原料乳阶段,牛乳中纤溶酶活性高低与牛乳房炎的严重程度及乳中体细胞数呈现显著正相关,而与牛是否接种疫苗或是否改变饲料种类无显著相关性。在生产加工阶段,离心除菌会使得乳中纤溶酶活性略有上升;55℃相比于其他温度的巴氏杀菌预热处理能最有效地抑制纤溶酶活性上升;微滤可降低约10%的纤溶酶活性;不同UHT预热处理均会导致酶活性上升,其中90℃处理5 s的条件下,酶活性上升幅度较小,仅为1.52%。结论牧场端需对患乳房炎的奶牛进行重点控制,并关注体细胞数异常的牛乳。工艺端可采用合适的巴氏杀菌预热条件及UHT预热条件以抑制乳中纤溶酶活性上升,可引入微滤工艺以降低纤溶酶活性。本研究为抑制UHT乳中纤溶酶活性及该酶对成品乳造成不良影响的相关研究提供科学依据。展开更多
Plasmin is generally known as a promotor of inflammation.Recent advancement suggests that it has a complex role as immunity modulator.Pharmacological inhibition of plasmin production and activity has been proven to im...Plasmin is generally known as a promotor of inflammation.Recent advancement suggests that it has a complex role as immunity modulator.Pharmacological inhibition of plasmin production and activity has been proven to improve neurological outcomes in traumatic brain injury and subarachnoid hemorrhage,most probably by preventing re-bleeding.The immune-modulatory properties of antifibrinolytics,however,suggest that they probably have effects unrelated to fibrinolysis inhibition,which are currently not adequately harnessed.The present work aims to give an account of the existing data regarding antifibrinolytics as agents influencing neuroinflammation.Preclinical and clinical studies on the possible influence of antifibrinolytics on neuroinflammation are scarce.However,the emerging evidence suggests that inhibition of plasmin(ogen)activity can ameliorate neuroinflammation to some extent.This data demonstrate that plasmin(ogen)is not exclusively involved in fibrinolysis,but also has other substrates and can precipitate in inflammatory processes.Investigation on the role of plasmin as the factor for the development of neuroinflammation shows the significant potential of antifibrinolytics as pharmacotherapy of neuroinflammationm,which is worthy of further exploration.展开更多
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supported in part by National Institutes of Health Grants NS-079331(to MY)and NS-091201(to MY)
文摘Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator（t PA） from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density（PSD） that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^（2＋）/calmodulin-dependent protein kinase IIα（pCa MKIIα）,followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid（AMPA） receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate（NMDA） receptors and cyclin-dependent kinase 5（Cdk5）-induced phosphorylation of the protein phosphatase 1（PP1） at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.
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Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University(202101AC070461).
文摘L-Palmitoylcarnitine(L-PC)is an important endogenous fatty acid metabolite.Its classical biological functions are involved in the regulations of membrane molecular dynamics and theβ-oxidation of fatty acids.Decreased plasma long-chain acylcarnitines showed the association of venous thrombosis,implying anticoagulant activity of the metabolites and inspiring us to investigate if and how L-PC,a long-chain acylcarnitine,takes part in coagulation.Here we show that L-PC exerted anti-coagulant effects by potentiating the enzymatic activities of plasmin and tissue plasminogen activator(tPA).L-PC directly interacts with plasmin and tPA with an equilibrium dissociation constant(KD)of 6.47×10^(-9)and 4.46×10^(-9)M,respectively,showing high affinities.In mouse model,L-PC administration significantly inhibited FeCl_(3)-induced arterial thrombosis.It also mitigated intracerebral thrombosis and inflammation in a transient middle cerebral artery occlusion(tMCAO)mouse model.L-PC induced little bleeding complications.The results show that L-PC has anti-thrombotic function by potentiating plasmin and tPA.
基金supported by the Shenzhen Natural Science Foundation Project(JCYJ20240813113226035,China)Natural Science Foundation of Top Talent of SZTU(GDRC202305,China)Basic Scientific Research Funding of Education Department of Liaoning Province(JYTMS20231368,China).
文摘Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system.Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life.Sclerotherapy has become the first-line therapy for venous system diseases.However,there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy,and improper operation will cause serious adverse consequences.Therefore,exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy.To solve the above problems,we proposed a new sclerotherapy strategy with a dual mechanism of“vascular damage and plasmin(PLA)system inhibition.”We intended to construct a novel cationic surfactant(AEOx-TA)by reacting tranexamic acid(TA),a parent structure,with fatty alcohol polyoxyethylene ether(AEOx)by ester bonds.AEOx-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus.Furthermore,AEOx-TA could be degraded by esterase and release the parent drug,TA,which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis.In addition,such surfactant-based sclerosants have foam-forming properties,and they can be blended with polyvinyl alcohol(PVA)to prepare a highly stable foam formulation(AEOx-TA/P),which can achieve a precise drug delivery and prolonged drug retention time,thereby improving drug efficacy and reducing the risk of ectopic embolism.Overall,the novel cationic surfactant AEOx-TA provides a new avenue to resolve the bottleneck:surfactant sclerosants’efficiency is relatively low in the current sclerotherapy.
文摘Aberrant expression of annexin A2-SI00A10 heterotetramer （AIIt） associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia （APL）, but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α （PML/RARα） fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5＇-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29 ± 0.13 fold higher than that by control pSG5 vector or wild-type RARer. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation （IRPG） in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid （ATRA） significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.
文摘Objective: To study the changes of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) expressions and fibrinolysis molecular markers in patients with gastrointestinal cancer in order to elucidate their clinical significance. Methods: The plasma levels of t-PA, u-PA, urokinase-type plasminogen activator receptor (u-PAR) and plasmin anti-plasmin complex (PAP) were measured by ELISA. t-PA and u-PA mRNAs were detected by Real-time RT-PCR. Results: The plasma levels of u-PA, u-PAR and PAP were elevated in gastrointestinal cancer patients, while u-PA was markedly elevated in patients with local infiltration, lymph node involvement or distal metastasis. U-PA mRNA was higher and t-PA was lower in gastrointestinal cancer compared to normal tissue. Conclusion: Hyperfibrinolysis is an important factor related with metastasis potential of gastrointestinal cancer. t-PA may be a character of well differentiated tissue.
文摘目的通过高灵敏磁微粒化学发光法(magnetic particle chemiluminescence immunoassay,MCLIA)的原理建立一种检测纤溶酶-α2纤溶酶抑制剂复合物(plasmin-α2 plasmin inhibitor,PIC)的方法,并评价联合检测纤溶酶-α2纤溶酶抑制剂复合物(PIC)与凝血酶-抗凝血酶Ⅲ复合物(TAT)对血栓性疾病的诊断价值。方法实验选用迈瑞CL-6000i及Sysmex HISCL-800分析仪,通过共价交联法制备PIC磁珠包被抗体(100μg/mL)与碱性磷酸酶标记抗体,优化工作浓度分别为1.0mg/mL磁珠及1.0μg/mL标记物。采用夹心法原理,经两步孵育形成磁珠-抗原-酶标记物复合物,通过碱性磷酸酶催化底物发光实现定量检测。参考范围采用95%百分位数法确立。通过与希森美康试剂盒比对及ROC曲线分析(PIC联合TAT检测),验证该方法在血栓性疾病诊断中的临床效能。结果本法的定量限(LoQ)为0.05μg/mL。测定希森美康质控品与参考值相对偏差在±10.0%范围内。批内CV小于5.0%,批间CV小于10%。PIC试剂盒的正常参考范围<0.80μg/mL。联合检测PIC和TAT对脑梗死诊断的ROC曲线下面积(area under the curve,AUC)为0.8795%CI为0.81~0.93,灵敏度和特异性分别为77.2%和88.7%。结论成功建立了一种基于磁微粒化学发光免疫分析技术(MCLIA)的高灵敏度国产化PIC检测方法,该检测体系各项技术参数均符合临床应用标准,具备实际临床检测的应用价值。联合检测PIC和TAT对血栓性疾病具有较高的诊断效能。
文摘Plasmin is generally known as a promotor of inflammation.Recent advancement suggests that it has a complex role as immunity modulator.Pharmacological inhibition of plasmin production and activity has been proven to improve neurological outcomes in traumatic brain injury and subarachnoid hemorrhage,most probably by preventing re-bleeding.The immune-modulatory properties of antifibrinolytics,however,suggest that they probably have effects unrelated to fibrinolysis inhibition,which are currently not adequately harnessed.The present work aims to give an account of the existing data regarding antifibrinolytics as agents influencing neuroinflammation.Preclinical and clinical studies on the possible influence of antifibrinolytics on neuroinflammation are scarce.However,the emerging evidence suggests that inhibition of plasmin(ogen)activity can ameliorate neuroinflammation to some extent.This data demonstrate that plasmin(ogen)is not exclusively involved in fibrinolysis,but also has other substrates and can precipitate in inflammatory processes.Investigation on the role of plasmin as the factor for the development of neuroinflammation shows the significant potential of antifibrinolytics as pharmacotherapy of neuroinflammationm,which is worthy of further exploration.
