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      IL-17A deletion reduces sevoflurane-induced neurocognitive impairment in neonatal mice by inhibiting NF-κB signaling pathway

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          ABSTRACT

          We investigated the role of IL-17A in sevoflurane-inducedneurocognitive impairment in neonatal mice. Seventy-two wild-type (WT) and 42 IL-17A knockout (KO) neonatal mice were randomly divided into WT ( n = 36), IL-17A −/− ( n = 6), sevoflurane (Sev, n = 36), and IL-17A −/− + sevoflurane (IL-17A −/− + Sev, n = 36) groups. The latter two groups were given 3% sevoflurane for 2 h per day on postnatal days (P) 6–8. Behavioral experiments were performed on P30–36. At P37, RNA sequencing and qRT-PCR of the hippocampus was performed, neurons were detected by Nissl staining, and neuropathological changes were evaluated by HE staining. NF-κB pathway-related proteins were evaluated by western blot and immunofluorescence analyses, IL-1β and IL-6 levels were assessed by ELISA. RNA sequencing identified 131 differentially expressed genes, highlighting several enriched biological processes (chemokine activity, immune response, extracellular region, extracellular space, inflammatory response) and signaling pathways (IL-17 signaling pathway, chemokine signaling pathway, cytokine–cytokine receptor interaction, ECM–receptor interaction and influenza A). Repeated sevoflurane exposures induced long-term cognitive impairment in WT mice. The cognitive impairment was comparatively less severe in IL-17A KO mice. In addition, the increased levels of NF-κB p65, iNOS, COX-2, IL-17A, IL-6 and IL-1β, reduced neuronal numbers and neuropathological changes were ameliorated in neonatal mice in the IL-17A −/− + Sev group compared with neonatal mice in Sev group. IL-17A deletion protects against long-term cognitive impairment induced by repeated sevoflurane exposure in neonatal mice. The underlying mechanism may relate to inhibiting NF-κB signaling pathway as well as the reducing neuroinflammation.

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          clusterProfiler: an R package for comparing biological themes among gene clusters.

          Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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            Complex heatmaps reveal patterns and correlations in multidimensional genomic data.

            Parallel heatmaps with carefully designed annotation graphics are powerful for efficient visualization of patterns and relationships among high dimensional genomic data. Here we present the ComplexHeatmap package that provides rich functionalities for customizing heatmaps, arranging multiple parallel heatmaps and including user-defined annotation graphics. We demonstrate the power of ComplexHeatmap to easily reveal patterns and correlations among multiple sources of information with four real-world datasets.
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              STRING v10: protein–protein interaction networks, integrated over the tree of life

              The many functional partnerships and interactions that occur between proteins are at the core of cellular processing and their systematic characterization helps to provide context in molecular systems biology. However, known and predicted interactions are scattered over multiple resources, and the available data exhibit notable differences in terms of quality and completeness. The STRING database (http://string-db.org) aims to provide a critical assessment and integration of protein–protein interactions, including direct (physical) as well as indirect (functional) associations. The new version 10.0 of STRING covers more than 2000 organisms, which has necessitated novel, scalable algorithms for transferring interaction information between organisms. For this purpose, we have introduced hierarchical and self-consistent orthology annotations for all interacting proteins, grouping the proteins into families at various levels of phylogenetic resolution. Further improvements in version 10.0 include a completely redesigned prediction pipeline for inferring protein–protein associations from co-expression data, an API interface for the R computing environment and improved statistical analysis for enrichment tests in user-provided networks.
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                Author and article information

                Journal
                Bioengineered
                Bioengineered
                Bioengineered
                Taylor & Francis
                2165-5979
                2165-5987
                26 June 2022
                2022
                26 June 2022
                : 13
                : 6
                : 14562-14577
                Affiliations
                [a ]Department of Anesthesiology, Hebei Children’s Hospital Affiliated to Hebei Medical University; , Shijiazhuang, Hebei, China
                [b ]Department of Anesthesiology, The Third Hospital of Hebei Medical University; , Shijiazhuang, Hebei, China
                [c ]Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
                [d ]NHC Key Laboratory of Intelligent Orthopaedic, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
                [e ]Department of Pathophysiology, Hebei Medical University, Shijiazhuang, Hebei, China
                [f ]Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
                Author notes
                CONTACT Qiujun Wang wangqiujunsy@ 123456163.com Department of Anesthesiology, The Third Hospital of Hebei Medical University; , No. 139 Ziqiang Road, Shijiazhuang City, Hebei Province, China
                [#]

                The two authors contributed equally to this study.

                Article
                2090608
                10.1080/21655979.2022.2090608
                9342424
                35758051
                eebd97fd-02b9-4dcd-b5f1-590acc3e7a7b
                © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 8, Tables: 2, References: 47, Pages: 16
                Categories
                Research Article
                Research Paper

                Biomedical engineering
                il-17a,sevoflurane,nf-κb signaling pathway,neuroinflammation,cognitive dysfunction

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