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BAM15 attenuated sepsis as indicated by survival, organ histology (kidneys and livers), spleen apoptosis (activated caspase 3), brain injury (SHIRPA score, serum s100\u03b2, serum miR370-3p, brain miR370-3p, brain TNF-\u03b1, and apoptosis), systemic inflammation (cytokines, cell-free DNA, endotoxemia, and bacteremia), and blood\u2013brain barrier (BBB) damage (Evan\u2019s blue dye and the presence of green fluorescent E. coli in brain after an oral administration). In parallel, brain miR arrays demonstrated miR370-3p at 24 h but not 120 h post-CLP, which was correlated with metabolic pathways. Either lipopolysaccharide (LPS) or TNF-\u03b1 upregulated miR370-3p in PC12 (neuron cells). An activation by sepsis factors (LPS, TNF-\u03b1, or miR370-3p transfection) damaged mitochondria (fluorescent color staining) and reduced cell ATP, possibly through profound mitochondrial activity (extracellular flux analysis) that was attenuated by BAM15. In bone-marrow-derived macrophages, LPS caused mitochondrial injury, decreased cell ATP, enhanced glycolysis activity (extracellular flux analysis), and induced pro-inflammatory macrophages (iNOS and IL-1\u03b2) which were neutralized by BAM15. In conclusion, BAM15 attenuated sepsis through decreased mitochondrial damage, reduced neuronal miR370-3p upregulation, and induced anti-inflammatory macrophages. BAM15 is proposed to be used as an adjuvant therapy against sepsis hyperinflammation.<\/jats:p>","DOI":"10.3390\/ijms23105445","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T08:37:02Z","timestamp":1652431022000},"page":"5445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Sepsis Encephalopathy Is Partly Mediated by miR370-3p-Induced Mitochondrial Injury but Attenuated by BAM15 in Cecal Ligation and Puncture Sepsis Male Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Pratsanee","family":"Hiengrach","sequence":"first","affiliation":[{"name":"Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peerapat","family":"Visitchanakun","sequence":"additional","affiliation":[{"name":"Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pakteema","family":"Tongchairawewat","sequence":"additional","affiliation":[{"name":"Chulalongkorn University International Medical Program, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ponphisudti","family":"Tangsirisatian","sequence":"additional","affiliation":[{"name":"Chulalongkorn University International Medical Program, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thitiphat","family":"Jungteerapanich","sequence":"additional","affiliation":[{"name":"Chulalongkorn University International Medical Program, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1392-4061","authenticated-orcid":false,"given":"Patcharee","family":"Ritprajak","sequence":"additional","affiliation":[{"name":"Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhammika Leshan","family":"Wannigama","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Stewardship Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-6916","authenticated-orcid":false,"given":"Pattarin","family":"Tangtanatakul","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Immunology and Immune-Mediated Disease, Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[{"name":"Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Nephrology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1007\/s10620-019-05581-y","article-title":"Gut Leakage of Fungal-Derived Inflammatory Mediators: Part of a Gut-Liver-Kidney Axis in Bacterial Sepsis","volume":"64","author":"Amornphimoltham","year":"2019","journal-title":"Dig. 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