Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,...Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.展开更多
Endothelin-1/endothelin A receptor(ET-1/ETAR)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver fibros...Endothelin-1/endothelin A receptor(ET-1/ETAR)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver fibrosis.Inactivating HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist(ERA)represents a promising therapeutic approach for liver fibrosis.Unfortunately,small-molecule ERAs possess limited clinical potential due to poor bioavailability,short half-life,and rapid renal clearance.To improve the clinical applicability,we conjugated ERA to superparamagnetic iron-oxide nanoparticles(SPIONs)and investigated the therapeutic efficacy of ERA and ERA-SPIONs in vitro and in vivo and analyzed liver uptake by in vivo and ex vivo magnetic resonance imaging(MRI),HSCs-specific localization,and ET-1/ETAR-pathway antagonism in vivo.In murine and human liver fibrosis/cirrhosis,we observed overexpression of ET-1 and ETAR that correlated with HSC activation,and HSC-specific localization of ETAR.ERA and successfully synthesized ERA-SPIONs demonstrated significant attenuation in TGFβ-induced HSC activation,ECM production,migration,and contractility.In an acute CCl4-induced liver fibrosis mouse model,ERA-SPIONs exhibited higher liver uptake,HSC-specific localization,and ET-1/ETAR pathway antagonism.This resulted in significantly reduced liver-to-body weight ratio,plasma ALT levels,andα-SMA and collagen-I expression,indicating attenuation of liver fibrosis.In conclusion,our study demonstrates that the delivery of ERA using SPIONs enhances the therapeutic efficacy of ERA in vivo.This approach holds promise as a theranostic strategy for the MRI-based diagnosis and treatment of liver fibrosis.展开更多
In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volum...In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.展开更多
基金National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences(NCRC2020013)CAMS Innovation Fund for Medical Sciences(2020-I2M-C&T-B-049)。
文摘Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.
文摘Endothelin-1/endothelin A receptor(ET-1/ETAR)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver fibrosis.Inactivating HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist(ERA)represents a promising therapeutic approach for liver fibrosis.Unfortunately,small-molecule ERAs possess limited clinical potential due to poor bioavailability,short half-life,and rapid renal clearance.To improve the clinical applicability,we conjugated ERA to superparamagnetic iron-oxide nanoparticles(SPIONs)and investigated the therapeutic efficacy of ERA and ERA-SPIONs in vitro and in vivo and analyzed liver uptake by in vivo and ex vivo magnetic resonance imaging(MRI),HSCs-specific localization,and ET-1/ETAR-pathway antagonism in vivo.In murine and human liver fibrosis/cirrhosis,we observed overexpression of ET-1 and ETAR that correlated with HSC activation,and HSC-specific localization of ETAR.ERA and successfully synthesized ERA-SPIONs demonstrated significant attenuation in TGFβ-induced HSC activation,ECM production,migration,and contractility.In an acute CCl4-induced liver fibrosis mouse model,ERA-SPIONs exhibited higher liver uptake,HSC-specific localization,and ET-1/ETAR pathway antagonism.This resulted in significantly reduced liver-to-body weight ratio,plasma ALT levels,andα-SMA and collagen-I expression,indicating attenuation of liver fibrosis.In conclusion,our study demonstrates that the delivery of ERA using SPIONs enhances the therapeutic efficacy of ERA in vivo.This approach holds promise as a theranostic strategy for the MRI-based diagnosis and treatment of liver fibrosis.
文摘In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.
