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Curcumin exhibits potent anti\u2010inflammatory properties but has poor solubility and rapid plasma clearance. To overcome these physiochemical limitations and uncover the full therapeutic potential of curcumin in lung inflammation, in this study we utilized a novel water\u2010soluble curcumin formulation (CDC) and delivered it directly into the lungs of C57BL\/6 mice inoculated with a lethal dose of\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    (\n                    <jats:italic>KP<\/jats:italic>\n                    ). Administration of CDC led to a significant reduction in mortality, in bacterial presence within blood and lungs, as well as in lung injury, inflammation, and oxidative stress. The expression of\n                    <jats:italic>Klebsiella<\/jats:italic>\n                    hemolysin gene; TNF\u2010\u03b1; IFN\u2010\u03b2; nucleotide\u2010binding domain, leucine\u2010rich\u2010containing family, pyrin domain\u2010containing\u20103; hypoxia\u2010inducible factor 1\/2\u03b1; and NF\u2010\u03baB were also decreased following CDC treatment, suggesting modulation of the inflammasome complex and hypoxia signaling pathways as an underlying mechanism by which CDC reduces the severity of pneumonia. On a cellular level, CDC led to diminished cell death, improved viability, and protection of human lung epithelial cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Overall, our studies demonstrate that CDC administration improves cell survival and reduces injury, inflammation, and mortality in a murine model of lethal gram\u2010negative pneumonia. CDC, therefore, has promising anti\u2010inflammatory potential in pneumonia and likely other inflammatory lung diseases, demonstrating the importance of optimizing the physicochemical properties of active natural products to optimize their clinical application.\u2014Zhang, B., Swamy, S., Balijepalli, S., Panicker, S., Mooliyil, J., Sherman, M. A., Parkkinen, J., Raghavendran, K., Suresh, M. V. Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia. FASEB J. 33, 13294\u201313309 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901047rr","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T20:17:46Z","timestamp":1568751466000},"page":"13294-13309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia"],"prefix":"10.1096","volume":"33","author":[{"given":"Boya","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Surgery University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Swamy","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Balijepalli","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sreehari","family":"Panicker","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jashitha","family":"Mooliyil","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's National Medical Center Washington, DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaakko","family":"Parkkinen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishnan","family":"Raghavendran","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madathilparambil V.","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-200108000-00003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.121.6.1972"},{"key":"e_1_2_8_4_1","first-page":"1742","article-title":"Mortality trends of acute respiratory distress syndrome in the United States from 1999 to 2013","volume":"13","author":"Cochi S. 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