Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mec...Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol(ISO)continuous stimulation-induced chronic heart failure(CHF)in mice,providing direct experimental evidence for further clinical applications.In vivo,continuous ISO infusion was administered to mice,and ventricular myocytes were utilized to explore LGZG's potential mechanism of action on theβ1-adrenergic receptor(β1-AR)/Gs/G protein-coupled receptor kinases(GRKs)/β-arrestin signaling deflection system in the heart.The findings reveal that LGZG significantly reduced the messenger ribonucleic acid(mRNA)expression of hypertrophy-related biomarkers[atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)]and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF.Furthermore,LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate(c AMP)/protein kinase A(PKA)signaling and downregulated the downstream transcriptional activity of c AMP-response element binding protein(CREB)and the expression of the coactivator CBP/P300.Notably,LGZG downregulated the expression ofβ-arrestin1 and GRK 2/3/5 while upregulating the expression ofβ1-AR andβ-arrestin2.These results suggest that LGZG inhibits Gs/c AMP/PKA signaling andβ-arrestin/GRK-mediated desensitization and internalization ofβ1-AR,potentially exerting cardioprotective effects through the synergistic regulation of theβ1-AR/Gs/GRKs/β-arrestin signaling deflection system via multiple pathways.展开更多
Cortical layer 2/3 plays a pivotal role in regulating perception and consciousness.However,the effects of anesthetic agents on the dynamic activity patterns in this layer remain poorly understood.This study examined h...Cortical layer 2/3 plays a pivotal role in regulating perception and consciousness.However,the effects of anesthetic agents on the dynamic activity patterns in this layer remain poorly understood.This study examined how neuronal activity in cortical layer 2/3 dynamically changes under anesthesia.Using high-resolution wide-field microscopy,we performed whole-brain synchronous imaging of layer 2/3 neuronal activity in mice.Using these recordings,we performed an unbiased segmentation of the awake,anesthesia,and recovery stages and classified neurons into three categories according to their activity features.Our findings revealed the characteristics of cortical dynamics under anesthesia,including a rebound effect during recovery and nonlinear changes in neuronal activity.We also confirmed the consistent and uniform characteristics of superficial cortical layer activity under anesthesia.These results increase the understanding of cortical dynamics and provide a theoretical basis for improving clinical monitoring techniques and protocols.展开更多
基金supported by the National Natural Science Foundation of China(No.82074054)Shanghai Municipal Commission of Health and Family Planning(No.ZY(2021-2023)-0208)+2 种基金Youth Program of the National Natural Science Foundation of China(No.81903831)Shanghai Municipality:Shanghai Chenguang Program(No.19CG48)Natural Science Foundation of Shanghai(No.24ZR1465900)。
文摘Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol(ISO)continuous stimulation-induced chronic heart failure(CHF)in mice,providing direct experimental evidence for further clinical applications.In vivo,continuous ISO infusion was administered to mice,and ventricular myocytes were utilized to explore LGZG's potential mechanism of action on theβ1-adrenergic receptor(β1-AR)/Gs/G protein-coupled receptor kinases(GRKs)/β-arrestin signaling deflection system in the heart.The findings reveal that LGZG significantly reduced the messenger ribonucleic acid(mRNA)expression of hypertrophy-related biomarkers[atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)]and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF.Furthermore,LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate(c AMP)/protein kinase A(PKA)signaling and downregulated the downstream transcriptional activity of c AMP-response element binding protein(CREB)and the expression of the coactivator CBP/P300.Notably,LGZG downregulated the expression ofβ-arrestin1 and GRK 2/3/5 while upregulating the expression ofβ1-AR andβ-arrestin2.These results suggest that LGZG inhibits Gs/c AMP/PKA signaling andβ-arrestin/GRK-mediated desensitization and internalization ofβ1-AR,potentially exerting cardioprotective effects through the synergistic regulation of theβ1-AR/Gs/GRKs/β-arrestin signaling deflection system via multiple pathways.
基金National Natural Science Foundation of China(82271213,82401504)。
文摘Cortical layer 2/3 plays a pivotal role in regulating perception and consciousness.However,the effects of anesthetic agents on the dynamic activity patterns in this layer remain poorly understood.This study examined how neuronal activity in cortical layer 2/3 dynamically changes under anesthesia.Using high-resolution wide-field microscopy,we performed whole-brain synchronous imaging of layer 2/3 neuronal activity in mice.Using these recordings,we performed an unbiased segmentation of the awake,anesthesia,and recovery stages and classified neurons into three categories according to their activity features.Our findings revealed the characteristics of cortical dynamics under anesthesia,including a rebound effect during recovery and nonlinear changes in neuronal activity.We also confirmed the consistent and uniform characteristics of superficial cortical layer activity under anesthesia.These results increase the understanding of cortical dynamics and provide a theoretical basis for improving clinical monitoring techniques and protocols.
