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. 2023 Jul 13;20:164. doi: 10.1186/s12974-023-02844-4

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Endothelial Il-1β damaged BBB in patient PBMC-humanized mice. A PCA showing a clear overall deference in the transcriptome between the patient group and the HC (healthy control) and Ctrl (medium control) group. B, C Volcano plot showing DEGs between groups (n = 3/group). D RT-qPCR validation of DEGs in B and C. E Bar chart of 20 summarized GOBP terms (adjusted p < 0.05) based on the commonly (between patient vs. HC and patient vs. NC) downregulated DEGs and interaction network of all significant GOBP terms. Nodes refer to GOBP terms with similar semantics as summarized terms in the same color. F Bar chart of 16 summarized GOBP terms (adjusted p < 0.05) based on the commonly upregulated DEGs and interaction network of all significant GOBP terms. G PPI network of common DEGs. H Western blot of IL-1β on total tissue lysates from whole brain (n = 3/group) and statistical analysis. I Immunofluorescence of P-Glycoprotein (brain microvascular endothelial cells, red) and Il-1β (green) in meninges (n = 3/group). Nuclei were counterstained with DAPI (blue). J Immunofluorescence of GFAP (astrocytes, red) and Il-1β (green) in meninges (n = 3/group). Nuclei were counterstained with DAPI (blue). K Relative changes in transendothelial electrical resistance (TEER) of in vitro BBB model with different treatments (n = 5/group). L FITC-dextran recovery of in vitro BBB model with different treatments (n = 5/group). M Western blot of Il-1β, Occludin, Claudin-1, ZO-1, and Claudin-5 on cell lysates from hCMEC/D3 cells with different treatments (n = 5/group). N Western blot of IL-1β, Occludin, Claudin-1, ZO-1, and Claudin-5 on cell lysates from hCMEC/D3 cells transfected with empty vector or Il-1β-overexpression plasmid (n = 3). O Western blot of Il-1β, Occludin, Claudin-1, ZO-1, and Claudin-5 on cell lysates from hCMEC/D3 cells transfected with medium, siRNA control (siNC), or Il1b siRNA (si1 and si2) (n = 3). **p < 0.01, one-way ANOVA with post hoc Tukey’s test