Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrha...Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.展开更多
Azithromycin loaded fumaryl diketopiperazine(FDKP)dry powder inhalation was designed and prepared for the treatment of community-acquired pneumonia.The solubility of FDKP and stability of azithromycin solution was inv...Azithromycin loaded fumaryl diketopiperazine(FDKP)dry powder inhalation was designed and prepared for the treatment of community-acquired pneumonia.The solubility of FDKP and stability of azithromycin solution was investigated.Formulation of azithromycin loaded FDKP microparticle was investigated and optimized by the single factor experiment.High-pressure homogenization and spray drying conditions were also optimized to prepare the particles by spray drying azithromycin dissolved FDKP microparticle suspension at pH 4.5.The in vitro antibacterial efficiency and in vitro dispersion performance was also investigated to confirm the antibacterial efficiency,dispersion and deposition behavers.FDKP/azithromycin mass ratio(3:2)was the optimized formulation of azithromycin loaded FDKP microparticle with the maximal drug loading efficiency.High-pressure homogenization and spray drying conditions were also optimized.The in vitro antibacterial results indicated that only with the antibiotic concentration higher than mutant prevention concentration could totally inhibit the reproduction of bacteria.In vitro dispersion performance of azithromycin loaded FDKP microparticles(AZM@FDKP-MPs)also shows remarkable improvement of dispersion and deposition behavers of AZM.AZM@FDKP-MPs dry powder inhalation as a targeting delivery route has better potential for lung infection treatment.展开更多
This article deals with correlating two variables that have values that fall below the known limit of detection (LOD) of the measuring device;these values are known as non-detects (NDs). We use simulation to compare s...This article deals with correlating two variables that have values that fall below the known limit of detection (LOD) of the measuring device;these values are known as non-detects (NDs). We use simulation to compare several methods for estimating the association between two such variables. The most commonly used method, simple substitution, consists of replacing each ND with some representative value such as LOD/2. Spearman’s correlation, in which all NDs are assumed to be tied at some value just smaller than the LOD, is also used. We evaluate each method under several scenarios, including small to moderate sample size, moderate to large censoring proportions, extr</span><span style="font-family:Verdana;">eme imbalance in censoring proportions, and non-bivariate nor</span><span style="font-family:Verdana;">mal (BVN) data. In this article, we focus on the coverage probability of 95% confidence intervals obtained using each method. Confidence intervals using a maximum likelihood approach based on the assumption of BVN data have acceptable performance under most scenarios, even with non-BVN data. Intervals based on Spearman’s coefficient also perform well under many conditions. The methods are illustrated using real data taken from the biomarker literature.展开更多
基金the Liaoning Provincial Science and Technology Plan Project(2023-MSLH-178)the Project Fund of Liaoning Provincial Department of Education(LJKMZ20221315,L202025)+1 种基金the Special Fund of Liaoning Provincial Department of Science and Technology for Central Guidance of Local Science and Technology Development(2018416016)the Project Fund of Liaoning Provincial Department of Human Resources and Social Security"Millions of Talents Program"(2020921097).
文摘Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.
基金supported by the Ministry of Science and Technology of China(No.2017ZX09101001-005-003)the National Natural Science Foundation of China(Nos.81501579,81673364 and 81972892)+2 种基金the Natural Science Foundation of Jiangsu Province(No.BK20150702)the Science and Technology Development Fund of Nanjing Medical University(No.2016NJMU105)Project Fundedby the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.KYCX170674)。
文摘Azithromycin loaded fumaryl diketopiperazine(FDKP)dry powder inhalation was designed and prepared for the treatment of community-acquired pneumonia.The solubility of FDKP and stability of azithromycin solution was investigated.Formulation of azithromycin loaded FDKP microparticle was investigated and optimized by the single factor experiment.High-pressure homogenization and spray drying conditions were also optimized to prepare the particles by spray drying azithromycin dissolved FDKP microparticle suspension at pH 4.5.The in vitro antibacterial efficiency and in vitro dispersion performance was also investigated to confirm the antibacterial efficiency,dispersion and deposition behavers.FDKP/azithromycin mass ratio(3:2)was the optimized formulation of azithromycin loaded FDKP microparticle with the maximal drug loading efficiency.High-pressure homogenization and spray drying conditions were also optimized.The in vitro antibacterial results indicated that only with the antibiotic concentration higher than mutant prevention concentration could totally inhibit the reproduction of bacteria.In vitro dispersion performance of azithromycin loaded FDKP microparticles(AZM@FDKP-MPs)also shows remarkable improvement of dispersion and deposition behavers of AZM.AZM@FDKP-MPs dry powder inhalation as a targeting delivery route has better potential for lung infection treatment.
文摘This article deals with correlating two variables that have values that fall below the known limit of detection (LOD) of the measuring device;these values are known as non-detects (NDs). We use simulation to compare several methods for estimating the association between two such variables. The most commonly used method, simple substitution, consists of replacing each ND with some representative value such as LOD/2. Spearman’s correlation, in which all NDs are assumed to be tied at some value just smaller than the LOD, is also used. We evaluate each method under several scenarios, including small to moderate sample size, moderate to large censoring proportions, extr</span><span style="font-family:Verdana;">eme imbalance in censoring proportions, and non-bivariate nor</span><span style="font-family:Verdana;">mal (BVN) data. In this article, we focus on the coverage probability of 95% confidence intervals obtained using each method. Confidence intervals using a maximum likelihood approach based on the assumption of BVN data have acceptable performance under most scenarios, even with non-BVN data. Intervals based on Spearman’s coefficient also perform well under many conditions. The methods are illustrated using real data taken from the biomarker literature.