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• W3022417993 endingPage "105598" @default.
• W3022417993 startingPage "105598" @default.
• W3022417993 abstract "There is growing public awareness regarding the health effects of indoor nanoscale particulate matter (INPM) since people spend the majority of their time indoors. INPM could have a direct entry route into the brain via the axons of the olfactory nerve and migrating across the blood-brain barrier (BBB). Using animals to explore this possibility is not a reliable method to fully demonstrate human physiological responses. We, therefore, set out to develop a human 3D functional blood-brain barrier model to examine the potential effects of INPM on the cerebral nervous system.Human astrocytes were co-cultured and human umbilical vein endothelial cells in 3D within a microfluidic chip to simulate the micro-complex physiological structure of the human BBB. This 3D human organotypic model has then been made to investigate any INPM-induced BBB dysfunction linked to potential cellular responses.A 3D human functional blood-brain barrier was constructed in this study. We observed the translocation of INPM across the blood-brain barrier. The 3D human organotypic chip initially reflected damage to the nervous system with abnormal astrocyte proliferation and a decline in cell viability. We also looked at the behavior of oxidative stress-related biomarkers (ROS, GSH-Px, and MDA). INPM was implicated in aggravating inflammation via reactive oxygen species (ROS). The Keap1-Nrf2-ARE pathway is a key mechanism in cellular resistance to oxidative stress by mediating and activating a variety of antioxidant and detoxification enzymes. Following ROS accumulation, INPM induced abnormal expression of nuclear transcription factor Nrf2. This behavior disturbed the expression of, γ-glutamate synthase (γ-GCS) and heme oxygenase (HO-1), which further exacerbated the imbalance of the antioxidant system.This functional 3D human organotypic chip effectively mimics the physiological response of the human BBB. The chip provides a micro-complex structure to simulate the internal environment of the human blood-brain barrier, and partially simulates the physiological responses of the BBB to INPM exposure. Based on this model, INPM was shown to affect the blood-brain barrier biofunction by disrupting the Keap1-Nrf2-ARE pathways." @default.
• W3022417993 created "2020-05-13" @default.
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• W3022417993 date "2020-10-01" @default.
• W3022417993 modified "2023-10-13" @default.
• W3022417993 title "Study of the neurotoxicity of indoor airborne nanoparticles based on a 3D human blood-brain barrier chip" @default.
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• W3022417993 doi "https://doi.org/10.1016/j.envint.2020.105598" @default.
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