Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limite...Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.展开更多
Introduction: A correlation between AVPR1A promoter polymorphisms and prepulse inhibition (PPI) of startle reflexes has been described in healthy adults. Many children with nocturnal enuresis (NE) have a reduced PPI a...Introduction: A correlation between AVPR1A promoter polymorphisms and prepulse inhibition (PPI) of startle reflexes has been described in healthy adults. Many children with nocturnal enuresis (NE) have a reduced PPI and treatment with desamino arginine vasopressin (dDAVP), a ligand of the arginine vasopressin receptor 1A (AVPR1A), and both improve clanical symptoms and significantly increase PPI. Methods: In 17 children (median 9.1 years, range 6.4-17.3) with NE, promoter repeats within the RS1 and RS3 regions of AVPR1A were quantified and correlated to PPI (native and age-adjusted). Results: No direct correlation was found between the number of promoter repeats at RS1 and PPI (correlation coefficient—0.240, p = 0.346) or RS3 and PPI (correlation coefficient—0.0192, p = 0.936), with no change through age-adjustment of PPI. The different RS3 length subgroups did not show differences in PPI, nor did differentiation of NE according to clinical subtype or treatment response to dDAVP show differences in the number of promoter repeats. Conclusion: The missing reproducibility of the correlation between AVPR1A promoter polymorphisms and PPI in a group with wide range of PPI suggests a more complex interaction. Therefore, further investigations are needed to analyze this very plausible interaction. Conditions with a reduced PPI, such as enuresis, schizophrenia or autism, are particularly interesting for this research.展开更多
基金support from the Medical Discipline Construction Program of Shanghai Pudong New Area Health Commission(the Specialty Program)(Grant Number:PWZzb2022-21)The Academic Leaders Training Program of Shanghai Pudong New Area Health Commission(Grant Number:PWRd2022-14)+1 种基金The Scientific Research Program of Shanghai Pudong New Area Health Commission(the Achievement Transformation Program)(Grant Number:PW2023A-51)the Shanghai Pudong New Area Gongli Hospital Youth Fund Project(Grant Number:2020YQNJJ-16).
文摘Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.
文摘Introduction: A correlation between AVPR1A promoter polymorphisms and prepulse inhibition (PPI) of startle reflexes has been described in healthy adults. Many children with nocturnal enuresis (NE) have a reduced PPI and treatment with desamino arginine vasopressin (dDAVP), a ligand of the arginine vasopressin receptor 1A (AVPR1A), and both improve clanical symptoms and significantly increase PPI. Methods: In 17 children (median 9.1 years, range 6.4-17.3) with NE, promoter repeats within the RS1 and RS3 regions of AVPR1A were quantified and correlated to PPI (native and age-adjusted). Results: No direct correlation was found between the number of promoter repeats at RS1 and PPI (correlation coefficient—0.240, p = 0.346) or RS3 and PPI (correlation coefficient—0.0192, p = 0.936), with no change through age-adjustment of PPI. The different RS3 length subgroups did not show differences in PPI, nor did differentiation of NE according to clinical subtype or treatment response to dDAVP show differences in the number of promoter repeats. Conclusion: The missing reproducibility of the correlation between AVPR1A promoter polymorphisms and PPI in a group with wide range of PPI suggests a more complex interaction. Therefore, further investigations are needed to analyze this very plausible interaction. Conditions with a reduced PPI, such as enuresis, schizophrenia or autism, are particularly interesting for this research.