Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Na...Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.展开更多
The physiological functions of endogenous amyloid-β(Aβ),which plays important role in the pathology of Alzheimer's disease(AD),have not been paid enough attention.Here,we review the multiple physiological effect...The physiological functions of endogenous amyloid-β(Aβ),which plays important role in the pathology of Alzheimer's disease(AD),have not been paid enough attention.Here,we review the multiple physiological effects of Aβ,particularly in regulating synaptic transmission,and the possible mechanisms,in order to decipher the real characters of Aβunder both physiological and pathological conditions.Some worthy studies have shown that the deprivation of endogenous Aβgives rise to synaptic dysfunction and cognitive deficiency,while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal hyperexcitability.In this review,we provide a new view for understanding the role of Aβin AD pathophysiology from the perspective of physiological meaning.展开更多
Many children show a lot of interest in playing with sand.I will discuss about the features that sand play as a loose part in children s imaginative play.Through online video observation,six features were found.These ...Many children show a lot of interest in playing with sand.I will discuss about the features that sand play as a loose part in children s imaginative play.Through online video observation,six features were found.These factors can be implemented into real design projects for children.Then some relevant questions such as gender and age about sand play will be discussed.展开更多
基金supported by the National Natural Science Foundation of China,No.82101327(to YY)President Foundation of Nanfang Hospital,Southern Medical University,No.2020A001(to WL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,Nos.2019A1515110150,2022A1515012362(both to YY)Guangzhou Science and Technology Project,No.202201020111(to YY).
文摘Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.
基金supported by grants from the Shanghai Municipal Science and Technology Major Project,the National Key Research and Development Program Foundation of China(2016YFC1306403)the National Natural Science Foundation of China(81870822,91332201,81901081,81600930,82171408,82171411)the Natural Science Foundation of Fujian Province(2020CXB049).
文摘The physiological functions of endogenous amyloid-β(Aβ),which plays important role in the pathology of Alzheimer's disease(AD),have not been paid enough attention.Here,we review the multiple physiological effects of Aβ,particularly in regulating synaptic transmission,and the possible mechanisms,in order to decipher the real characters of Aβunder both physiological and pathological conditions.Some worthy studies have shown that the deprivation of endogenous Aβgives rise to synaptic dysfunction and cognitive deficiency,while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal hyperexcitability.In this review,we provide a new view for understanding the role of Aβin AD pathophysiology from the perspective of physiological meaning.
文摘Many children show a lot of interest in playing with sand.I will discuss about the features that sand play as a loose part in children s imaginative play.Through online video observation,six features were found.These factors can be implemented into real design projects for children.Then some relevant questions such as gender and age about sand play will be discussed.
