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
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.
文摘目的建立并优化大体积进样-离子色谱法(ion chromatography,IC)测定食品接触用塑料制品中高氯酸盐(ClO4-)迁移量的检测方法。方法选用水、3%乙酸(m:V)、4%乙酸(V:V)、10%乙醇(V:V)、20%乙醇(V:V)、50%乙醇(V:V)、95%乙醇(V:V)作为食品模拟物,以14.0 mmol/L无水碳酸钠和20%乙腈(体积分数)混合溶液作为流动相进行等度洗脱,进样量800μL,流速1.0 mL/min,采用Metrosep A Supp 4离子色谱柱(250 mm×4.0 mm,9.0μm)和Metrosep A Supp RP Guard保护柱(50 mm×4.0 mm,9.0μm),柱温30℃,以电导检测器进行测定,外标法定量。结果方法验证结果表明,该方法线性关系良好,标准工作曲线的线性相关系数大于0.995,方法检出限为0.15μg/kg,定量限为0.50μg/kg,加标回收率为83.2%~99.1%,精密度为2.7%~9.1%(n=6)。结论该方法可靠、方便、灵敏,分离效果好,适用于食品接触用塑料制品中高氯酸盐迁移量的检测。
