Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury（EBI）.In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,p...Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury（EBI）.In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia（DCI）,being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.展开更多
After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes ...After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.展开更多
Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,g...Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.展开更多
Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial ...Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.展开更多
CCN1/CYR61(cellular communication network factor 1/cysteine-rich protein 61)是CCN家族成员,是一种重要的分泌基质蛋白。它在胚胎发育过程中对心血管的发育起着至关重要的作用;同时,在生物体成年期,其对炎症反应、血管生成、损伤...CCN1/CYR61(cellular communication network factor 1/cysteine-rich protein 61)是CCN家族成员,是一种重要的分泌基质蛋白。它在胚胎发育过程中对心血管的发育起着至关重要的作用;同时,在生物体成年期,其对炎症反应、血管生成、损伤修复、骨形成及过度纤维化和肿瘤等相关生理、病理过程起着关键作用。本文对CCN1/CYR61在骨再生中的作用作了简要总结,包括其对骨髓间充质干细胞、软骨细胞、成骨细胞及破骨细胞等骨再生相关细胞的调控,以及骨生成过程中必不可少的炎症反应和血管生成等生物学过程。展开更多
原发性开角型青光眼(primary open angle glaucoma,POAG)是一种慢性、进行性的视神经病变,其发病机制尚不明确。而眼内敏感区域[如小梁网邻管组织、筛板(lamina cribrosa,LC)等]的细胞外基质代谢异常在其中起关键作用。富含半胱氨酸的...原发性开角型青光眼(primary open angle glaucoma,POAG)是一种慢性、进行性的视神经病变,其发病机制尚不明确。而眼内敏感区域[如小梁网邻管组织、筛板(lamina cribrosa,LC)等]的细胞外基质代谢异常在其中起关键作用。富含半胱氨酸的酸性分泌蛋白(secreted protein, acidic and rich in cysteine,SPARC)作为一种基质细胞蛋白在眼内广泛分布,具有沟通细胞与细胞外基质信号传递的作用。研究表明SPARC可通过多种途径参与并调控青光眼的发生发展过程,有望成为疾病治疗的新靶点。展开更多
基金supported by a Grant-in-Aid for Scientific Research from Novartis Pharmaceuticals to HS
文摘Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury（EBI）.In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia（DCI）,being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.
文摘After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.
基金funded by Taiju Life Social Welfare Foundation(to HS).
文摘Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.
基金supported by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science(grant number:17K10825)to HS
文摘Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.
文摘CCN1/CYR61(cellular communication network factor 1/cysteine-rich protein 61)是CCN家族成员,是一种重要的分泌基质蛋白。它在胚胎发育过程中对心血管的发育起着至关重要的作用;同时,在生物体成年期,其对炎症反应、血管生成、损伤修复、骨形成及过度纤维化和肿瘤等相关生理、病理过程起着关键作用。本文对CCN1/CYR61在骨再生中的作用作了简要总结,包括其对骨髓间充质干细胞、软骨细胞、成骨细胞及破骨细胞等骨再生相关细胞的调控,以及骨生成过程中必不可少的炎症反应和血管生成等生物学过程。
文摘原发性开角型青光眼(primary open angle glaucoma,POAG)是一种慢性、进行性的视神经病变,其发病机制尚不明确。而眼内敏感区域[如小梁网邻管组织、筛板(lamina cribrosa,LC)等]的细胞外基质代谢异常在其中起关键作用。富含半胱氨酸的酸性分泌蛋白(secreted protein, acidic and rich in cysteine,SPARC)作为一种基质细胞蛋白在眼内广泛分布,具有沟通细胞与细胞外基质信号传递的作用。研究表明SPARC可通过多种途径参与并调控青光眼的发生发展过程,有望成为疾病治疗的新靶点。
文摘基质细胞蛋白是细胞外基质(extracellular matrix,ECM)的非结构成分,可以调节细胞外基质和细胞间的相互作用。分泌型模块化钙结合蛋白-2(secreted modular calcium binding protein-2,SMOC-2)是一种基质细胞蛋白,属于富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine,SPARC)家族。SMOC-2可以通过细胞外钙(extracellular calcium-binding,EC)结构域与胶原蛋白、硫酸乙酰肝素聚糖和整合素等进行结合,参与多种信号通路,从而在不同的生物过程中发挥作用。研究证实,SMOC-2能够影响细胞周期,调节生长因子的血管生成作用,并介导细胞附着和迁移,在胚胎发育、组织纤维化和钙化、炎症反应以及肿瘤的发生发展等方面都具有重要意义。但SMOC-2与疾病关联的具体机制和更多生物学功能尚需进一步研究。
