Platelets are indispensable for physiological hemostasis and pathological thrombus formation,and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation,often overlooked in current a...Platelets are indispensable for physiological hemostasis and pathological thrombus formation,and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation,often overlooked in current antiplatelet therapies.This study aims to elucidate how ginsenoside CK enhances hemodynamic circulation,alleviates stasis,and proposes therapeutic mechanisms.Inspired by the effects on improving microcirculatory disturbances in an acute soft tissue injury model,CK was identified as a PHD2 inhibitor,effectively suppressing platelet adhesion to collagen.It was proposed that targeting PHD2 regulates collagen hydroxylation modification,thereby influencing the formation of its three-dimensional structure,reducing the binding affinity between VWF and collagen,and ultimately suppressing thrombotic events.The efficacy of this mechanism was subsequently confirmed through a mouse DIC model,demonstrating the feasibility of CK in alleviating circulatory disorders.It is worth noting that when Phd2 was knocked down in mice's lungs,pulmonary embolism was significantly reduced.Additionally,PHD2 inhibitors approved for other diseases have exhibited similar anti-thrombotic effects.Moreover,when PHD2 inhibitors were combined with aspirin,they more effectively inhibited arterial thrombosis in rats.The findings offer valuable insights into potential targets for developing antiplatelet drugs or expanding therapeutic applications for existing PHD2 inhibitors in treating thrombotic diseases.展开更多
N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathoge...N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathogen infections.To identify negative regulators of NHP biosynthesis,we performed a forward genetic screen to search for mutants with elevated expression of the NHP biosynthesis gene FLAVIN-DEPENDENT MONOOXYGENASE 1(FMO1).Analysis of two constitutive expression of FMO1(cef)and one induced expression of FMO1(ief)mutants revealed that the AIPP3–PHD2–CPL2 protein complex,which is involved in the recognition of the histone modification H3K27me3 and transcriptional repression,contributes to the negative regulation of FMO1 expression and NHP biosynthesis.Our study suggests that epigenetic regulation plays a crucial role in controlling FMO1 expression and NHP levels in plants.展开更多
基金supported by National Natural Science Foundation of China,grant number:82274184.
文摘Platelets are indispensable for physiological hemostasis and pathological thrombus formation,and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation,often overlooked in current antiplatelet therapies.This study aims to elucidate how ginsenoside CK enhances hemodynamic circulation,alleviates stasis,and proposes therapeutic mechanisms.Inspired by the effects on improving microcirculatory disturbances in an acute soft tissue injury model,CK was identified as a PHD2 inhibitor,effectively suppressing platelet adhesion to collagen.It was proposed that targeting PHD2 regulates collagen hydroxylation modification,thereby influencing the formation of its three-dimensional structure,reducing the binding affinity between VWF and collagen,and ultimately suppressing thrombotic events.The efficacy of this mechanism was subsequently confirmed through a mouse DIC model,demonstrating the feasibility of CK in alleviating circulatory disorders.It is worth noting that when Phd2 was knocked down in mice's lungs,pulmonary embolism was significantly reduced.Additionally,PHD2 inhibitors approved for other diseases have exhibited similar anti-thrombotic effects.Moreover,when PHD2 inhibitors were combined with aspirin,they more effectively inhibited arterial thrombosis in rats.The findings offer valuable insights into potential targets for developing antiplatelet drugs or expanding therapeutic applications for existing PHD2 inhibitors in treating thrombotic diseases.
文摘N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathogen infections.To identify negative regulators of NHP biosynthesis,we performed a forward genetic screen to search for mutants with elevated expression of the NHP biosynthesis gene FLAVIN-DEPENDENT MONOOXYGENASE 1(FMO1).Analysis of two constitutive expression of FMO1(cef)and one induced expression of FMO1(ief)mutants revealed that the AIPP3–PHD2–CPL2 protein complex,which is involved in the recognition of the histone modification H3K27me3 and transcriptional repression,contributes to the negative regulation of FMO1 expression and NHP biosynthesis.Our study suggests that epigenetic regulation plays a crucial role in controlling FMO1 expression and NHP levels in plants.
