This study addresses the intractable“infectioninflammation-injury”vicious cycle in MRSA pneumonia therapy.We have designed a glycosylated mesoporous polydopamine nanoaerosols(MPDA/B@M),which achieves effective treat...This study addresses the intractable“infectioninflammation-injury”vicious cycle in MRSA pneumonia therapy.We have designed a glycosylated mesoporous polydopamine nanoaerosols(MPDA/B@M),which achieves effective treatment of MRSA infected pneumonia through multi mechanism synergistic effects.The aerosol encapsulates bufalin,an active component of traditional Chinese medicine,within MPDA carriers.Surface modification with mannose enables macrophage-targeted delivery.Upon inhalation,the aerosol accumulates efficiently in pulmonary lesions,directly killing pathogens via photothermal effects while releasing bufalin to suppress inflammation.Furthermore,MPDA/B@M scavenges excess reactive oxygen species(ROS)and upregulates heat shock protein 70(HSP70)expression,providing dual cell-protective and antiinflammatory effects.In vitro and in vivo studies demonstrate that MPDA/B@M nanoaerosols achieves 98.2%antibacterial efficacy against MRSA.In MRSA-infected murine pneumonia models,it significantly reduces pulmonary bacterial loads and reprograms macrophage phenotypes to modulate inflammatory responses.This integrated strategy synergizes targeted delivery,antibacterial action,oxidative stress modulation,and anti-inflammatory effects,offering an innovative solution for drug-resistant bacterial pneumonia.展开更多
The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed...The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.展开更多
基金supported by the National Natural Science Foundation of China(No.22173029)the Natural Science Foundation of Nantong Municipal Science and Technology Bureau(No.JC2024011)+2 种基金Excellent Young and Middle-aged Science and Technology Innovation Team Program of Universities in Hubei Province(No.T2024014)the Talent Introduction Project of Hubei Normal University(No.HS2023RC078)the Open Research Fund of Hubei Key Laboratory of Pollutant Analysis&Reuse Technology(No.PA230213).
文摘This study addresses the intractable“infectioninflammation-injury”vicious cycle in MRSA pneumonia therapy.We have designed a glycosylated mesoporous polydopamine nanoaerosols(MPDA/B@M),which achieves effective treatment of MRSA infected pneumonia through multi mechanism synergistic effects.The aerosol encapsulates bufalin,an active component of traditional Chinese medicine,within MPDA carriers.Surface modification with mannose enables macrophage-targeted delivery.Upon inhalation,the aerosol accumulates efficiently in pulmonary lesions,directly killing pathogens via photothermal effects while releasing bufalin to suppress inflammation.Furthermore,MPDA/B@M scavenges excess reactive oxygen species(ROS)and upregulates heat shock protein 70(HSP70)expression,providing dual cell-protective and antiinflammatory effects.In vitro and in vivo studies demonstrate that MPDA/B@M nanoaerosols achieves 98.2%antibacterial efficacy against MRSA.In MRSA-infected murine pneumonia models,it significantly reduces pulmonary bacterial loads and reprograms macrophage phenotypes to modulate inflammatory responses.This integrated strategy synergizes targeted delivery,antibacterial action,oxidative stress modulation,and anti-inflammatory effects,offering an innovative solution for drug-resistant bacterial pneumonia.
基金supported by the National Natural Science Foundation of China,Nos.91849115 and U1904207(to YX),81974211 and 82171247(to CS)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No.2020-PT310-01(to YX).
文摘The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.
