{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:14:05Z","timestamp":1794366845123,"version":"4.9.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T00:00:00Z","timestamp":1488844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T00:00:00Z","timestamp":1488844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recently, a serial of studies have demonstrated that lipid mediators derived from Omega-3 fatty acid docosahexaenoic acid have pro-resolving or anti-inflammatory effects in many inflammatory diseases. Here, we sought to evaluate whether Protectin DX (PDX, an isomer of Protecin D1), a newly identified lipid mediator, could protect mice against sepsis and explore the underling mechanism. Animal model of sepsis was established by cecum ligation and puncture (CLP). We found that PDX increased overall survival rate within eight days and attenuated multiple organ injury in septic mice. In addition, PDX reduced pro-inflammatory cytokines and bacterial load 24\u2009h after CLP. Moreover, PDX promoted phagocytosis of peritoneal macrophages and increased the percentage of M2 macrophages in peritoneum of septic mice.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , M2 macrophage markers (Arg1 and Ym1) and its transcriptional regulator (peroxisome proliferator-activated receptor-\u03b3, PPAR-\u03b3) were upregulated in Raw264.7 macrophages challenged with PDX. GW9662 (a PPAR-\u03b3 inhibitor) and PPAR-\u03b3 siRNA abrogated the induction of Arg1 and Ym1 by PDX in Raw264.7 cells. Taken together, our results suggest that PDX is able to promote M2 polarization, enhance phagocytosis activity of macrophage and accelerate resolution of inflammation, finally leading to increased survival rate of septic mice.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-00103-0","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T10:14:56Z","timestamp":1488363296000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype"],"prefix":"10.1038","volume":"7","author":[{"given":"Haifa","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amro Fayez","family":"Abdelgawad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanglong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,7]]},"reference":[{"key":"103_CR1","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1097\/CCM.0b013e31827e83af","volume":"41","author":"RP Dellinger","year":"2013","unstructured":"Dellinger, R. P. et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Critical care medicine 41, 580\u2013637 (2013).","journal-title":"Critical care medicine"},{"key":"103_CR2","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/S2213-2600(14)70061-X","volume":"2","author":"JL Vincent","year":"2014","unstructured":"Vincent, J. L. et al. Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit. The Lancet. Respiratory medicine 2, 380\u2013386 (2014).","journal-title":"The Lancet. Respiratory medicine"},{"key":"103_CR3","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/S0140-6736(12)61815-7","volume":"381","author":"JL Vincent","year":"2013","unstructured":"Vincent, J. L., Opal, S. M., Marshall, J. C. & Tracey, K. J. Sepsis definitions: time for change. Lancet 381, 774\u2013775 (2013).","journal-title":"Lancet"},{"key":"103_CR4","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1038\/nature05877","volume":"447","author":"JM Schwab","year":"2007","unstructured":"Schwab, J. M., Chiang, N., Arita, M. & Serhan, C. N. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447, 869\u2013874 (2007).","journal-title":"Nature"},{"key":"103_CR5","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1038\/nature08541","volume":"461","author":"M Spite","year":"2009","unstructured":"Spite, M. et al. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature 461, 1287\u20131291 (2009).","journal-title":"Nature"},{"key":"103_CR6","doi-asserted-by":"publisher","first-page":"3539","DOI":"10.1111\/bph.12714","volume":"171","author":"J Gong","year":"2014","unstructured":"Gong, J. et al. Maresin 1 mitigates LPS-induced acute lung injury in mice. British journal of pharmacology 171, 3539\u20133550 (2014).","journal-title":"British journal of pharmacology"},{"key":"103_CR7","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3760\/cma.j.issn.0366-6999.20133348","volume":"127","author":"Y Shang","year":"2014","unstructured":"Shang, Y. & Yao, S. Pro-resolution of inflammation: a potential strategy for treatment of acute lung injury\/acute respiratory distress syndrome. Chinese medical journal 127, 801\u2013802 (2014).","journal-title":"Chinese medical journal"},{"key":"103_CR8","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.plefa.2012.04.001","volume":"88","author":"M Lagarde","year":"2013","unstructured":"Lagarde, M., Calzada, C., Guichardant, M. & Vericel, E. Dose-effect and metabolism of docosahexaenoic acid: pathophysiological relevance in blood platelets. Prostaglandins, leukotrienes, and essential fatty acids 88, 49\u201352 (2013).","journal-title":"Prostaglandins, leukotrienes, and essential fatty acids"},{"key":"103_CR9","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1194\/jlr.M035139","volume":"54","author":"M Liu","year":"2013","unstructured":"Liu, M. et al. Characterization and biological effects of di-hydroxylated compounds deriving from the lipoxygenation of ALA. Journal of lipid research 54, 2083\u20132094 (2013).","journal-title":"Journal of lipid research"},{"key":"103_CR10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s11745-013-3863-6","volume":"49","author":"M Liu","year":"2014","unstructured":"Liu, M. et al. Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities. Lipids 49, 49\u201357 (2014).","journal-title":"Lipids"},{"key":"103_CR11","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/nm.3549","volume":"20","author":"PJ White","year":"2014","unstructured":"White, P. J. et al. Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis. Nature medicine 20, 664\u2013669 (2014).","journal-title":"Nature medicine"},{"key":"103_CR12","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.4049\/jimmunol.176.3.1848","volume":"176","author":"CN Serhan","year":"2006","unstructured":"Serhan, C. N. et al. Anti-inflammatory actions of neuroprotectin D1\/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. Journal of immunology 176, 1848\u20131859 (2006).","journal-title":"Journal of immunology"},{"key":"103_CR13","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/nri3088","volume":"11","author":"T Lawrence","year":"2011","unstructured":"Lawrence, T. & Natoli, G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nature reviews. Immunology 11, 750\u2013761 (2011).","journal-title":"Nature reviews. Immunology"},{"key":"103_CR14","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nri3073","volume":"11","author":"PJ Murray","year":"2011","unstructured":"Murray, P. J. & Wynn, T. A. Protective and pathogenic functions of macrophage subsets. Nature reviews. Immunology 11, 723\u2013737 (2011).","journal-title":"Nature reviews. Immunology"},{"key":"103_CR15","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/nri2448","volume":"8","author":"DM Mosser","year":"2008","unstructured":"Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nature reviews. Immunology 8, 958\u2013969 (2008).","journal-title":"Nature reviews. Immunology"},{"key":"103_CR16","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1146\/annurev.immunol.021908.132532","volume":"27","author":"FO Martinez","year":"2009","unstructured":"Martinez, F. O., Helming, L. & Gordon, S. Alternative activation of macrophages: an immunologic functional perspective. Annual review of immunology 27, 451\u2013483 (2009).","journal-title":"Annual review of immunology"},{"key":"103_CR17","doi-asserted-by":"publisher","first-page":"520","DOI":"10.7150\/ijbs.8879","volume":"10","author":"YC Liu","year":"2014","unstructured":"Liu, Y. C., Zou, X. B., Chai, Y. F. & Yao, Y. M. Macrophage polarization in inflammatory diseases. International journal of biological sciences 10, 520\u2013529 (2014).","journal-title":"International journal of biological sciences"},{"key":"103_CR18","doi-asserted-by":"publisher","first-page":"5408","DOI":"10.4049\/jimmunol.1100225","volume":"187","author":"E Titos","year":"2011","unstructured":"Titos, E. et al. Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. Journal of immunology 187, 5408\u20135418 (2011).","journal-title":"Journal of immunology"},{"key":"103_CR19","doi-asserted-by":"publisher","first-page":"4288","DOI":"10.4049\/jimmunol.1202743","volume":"191","author":"R Marcon","year":"2013","unstructured":"Marcon, R. et al. Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis. Journal of immunology 191, 4288\u20134298 (2013).","journal-title":"Journal of immunology"},{"key":"103_CR20","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.metabol.2015.01.017","volume":"64","author":"PJ White","year":"2015","unstructured":"White, P. J. et al. Transgenic omega-3 PUFA enrichment alters morphology and gene expression profile in adipose tissue of obese mice: Potential role for protectins. Metabolism: clinical and experimental 64, 666\u2013676 (2015).","journal-title":"Metabolism: clinical and experimental"},{"key":"103_CR21","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/nature05894","volume":"447","author":"JI Odegaard","year":"2007","unstructured":"Odegaard, J. I. et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447, 1116\u20131120 (2007).","journal-title":"Nature"},{"key":"103_CR22","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.1073\/pnas.0915000107","volume":"107","author":"EE Ghosn","year":"2010","unstructured":"Ghosn, E. E. et al. Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proceedings of the National Academy of Sciences of the United States of America 107, 2568\u20132573 (2010).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"103_CR23","doi-asserted-by":"publisher","first-page":"e85834","DOI":"10.1371\/journal.pone.0085834","volume":"9","author":"J Ni Gabhann","year":"2014","unstructured":"Ni Gabhann, J. et al. Btk regulates macrophage polarization in response to lipopolysaccharide. PloS one 9, e85834 (2014).","journal-title":"PloS one"},{"key":"103_CR24","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1001\/jama.2011.1829","volume":"306","author":"JS Boomer","year":"2011","unstructured":"Boomer, J. S. et al. Immunosuppression in patients who die of sepsis and multiple organ failure. Jama 306, 2594\u20132605 (2011).","journal-title":"Jama"},{"key":"103_CR25","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature01326","volume":"420","author":"J Cohen","year":"2002","unstructured":"Cohen, J. The immunopathogenesis of sepsis. Nature 420, 885\u2013891 (2002).","journal-title":"Nature"},{"key":"103_CR26","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1097\/01.CCM.0000282072.56245.91","volume":"35","author":"E Abraham","year":"2007","unstructured":"Abraham, E. & Singer, M. Mechanisms of sepsis-induced organ dysfunction. Critical care medicine 35, 2408\u20132416 (2007).","journal-title":"Critical care medicine"},{"key":"103_CR27","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nature12034","volume":"496","author":"TA Wynn","year":"2013","unstructured":"Wynn, T. A., Chawla, A. & Pollard, J. W. Macrophage biology in development, homeostasis and disease. Nature 496, 445\u2013455 (2013).","journal-title":"Nature"},{"key":"103_CR28","doi-asserted-by":"publisher","first-page":"275","DOI":"10.14348\/molcells.2014.2374","volume":"37","author":"AC Labonte","year":"2014","unstructured":"Labonte, A. C., Tosello-Trampont, A. C. & Hahn, Y. S. The role of macrophage polarization in infectious and inflammatory diseases. Molecules and cells 37, 275\u2013285 (2014).","journal-title":"Molecules and cells"},{"key":"103_CR29","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1097\/SHK.0000000000000434","volume":"44","author":"J Gong","year":"2015","unstructured":"Gong, J. et al. Maresin 1 Prevents Lipopolysaccharide-Induced Neutrophil Survival and Accelerates Resolution of Acute Lung Injury. Shock 44, 371\u2013380 (2015).","journal-title":"Shock"},{"key":"103_CR30","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1097\/SHK.0000000000000446","volume":"44","author":"Y Wang","year":"2015","unstructured":"Wang, Y. et al. Maresin 1 Inhibits Epithelial-to-Mesenchymal Transition in Vitro and Attenuates Bleomycin Induced Lung Fibrosis in Vivo. Shock 44, 496\u2013502 (2015).","journal-title":"Shock"},{"key":"103_CR31","doi-asserted-by":"publisher","first-page":"C1058","DOI":"10.1152\/ajpcell.00270.2014","volume":"307","author":"S Hong","year":"2014","unstructured":"Hong, S. et al. Neuroprotectin\/protectin D1: endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes. American journal of physiology. Cell physiology 307, C1058\u20131067 (2014).","journal-title":"American journal of physiology. Cell physiology"},{"key":"103_CR32","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.cell.2013.02.027","volume":"153","author":"M Morita","year":"2013","unstructured":"Morita, M. et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell 153, 112\u2013125 (2013).","journal-title":"Cell"},{"key":"103_CR33","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1097\/SHK.0b013e31822798c1","volume":"36","author":"J Walker","year":"2011","unstructured":"Walker, J. et al. Lipoxin a4 increases survival by decreasing systemic inflammation and bacterial load in sepsis. Shock 36, 410\u2013416 (2011).","journal-title":"Shock"},{"key":"103_CR34","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1096\/fj.11-201442","volume":"26","author":"CN Serhan","year":"2012","unstructured":"Serhan, C. N. et al. Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 26, 1755\u20131765 (2012).","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"103_CR35","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1186\/s12967-015-0642-6","volume":"13","author":"D Ti","year":"2015","unstructured":"Ti, D. et al. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. Journal of translational medicine 13, 308 (2015).","journal-title":"Journal of translational medicine"},{"key":"103_CR36","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20081880","volume":"206","author":"CN Serhan","year":"2009","unstructured":"Serhan, C. N. et al. Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. The Journal of experimental medicine 206, 15\u201323 (2009).","journal-title":"The Journal of experimental medicine"},{"key":"103_CR37","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.immuni.2007.11.014","volume":"27","author":"EY Chung","year":"2007","unstructured":"Chung, E. Y. et al. Interleukin-10 expression in macrophages during phagocytosis of apoptotic cells is mediated by homeodomain proteins Pbx1 and Prep-1. Immunity 27, 952\u2013964 (2007).","journal-title":"Immunity"},{"key":"103_CR38","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1097\/SHK.0000000000000104","volume":"41","author":"H Li","year":"2014","unstructured":"Li, H. et al. BML-111, a lipoxin receptor agonist, attenuates ventilator-induced lung injury in rats. Shock 41, 311\u2013316 (2014).","journal-title":"Shock"},{"key":"103_CR39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/nri978","volume":"3","author":"S Gordon","year":"2003","unstructured":"Gordon, S. Alternative activation of macrophages. Nature reviews. Immunology 3, 23\u201335 (2003).","journal-title":"Nature reviews. Immunology"},{"key":"103_CR40","doi-asserted-by":"publisher","first-page":"4312","DOI":"10.1073\/pnas.94.9.4312","volume":"94","author":"BM Forman","year":"1997","unstructured":"Forman, B. M., Chen, J. & Evans, R. M. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proceedings of the National Academy of Sciences of the United States of America 94, 4312\u20134317 (1997).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"103_CR41","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1182\/blood-2010-07-295246","volume":"117","author":"O Klimchenko","year":"2011","unstructured":"Klimchenko, O. et al. Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions. Blood 117, 3065\u20133075 (2011).","journal-title":"Blood"},{"key":"103_CR42","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ydbio.2007.05.027","volume":"308","author":"F. Rae","year":"2007","unstructured":"Rae, F., Woods, K., Sasmono, T., Campanale, N., Taylor, D., Ovchinnikov, D. A., Grimmond, S. M., Hume, D. A., Ricardo, S. D. & Little, M. H. Characterisation and trophic functions of murine embryonic macrophages based upon the use of a Csf1r-EGFP transgene reporter. Dev Biol. 308, 15 (2007).","journal-title":"Dev Biol."},{"key":"103_CR43","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1002\/eji.201242765","volume":"43","author":"P Georgiev","year":"2013","unstructured":"Georgiev, P. et al. Genetic deletion of the HIF-1alpha isoform I.1 in T cells enhances antibacterial immunity and improves survival in a murine peritonitis model. European journal of immunology 43, 655\u2013666 (2013).","journal-title":"European journal of immunology"},{"key":"103_CR44","first-page":"13","volume":"10","author":"J Ikeda","year":"2015","unstructured":"Ikeda, J. Ichiki, T., Takahara, Y., Kojima, H., Sankoda, C., Kitamoto, S., Tokunou, T. & Sunagawa, K. PPAR\u03b3 Agonists Attenuate Palmitate-Induced ER Stress through Up-Regulation of SCD-1 in Macrophages. PLoS One. 10, 13 (2015).","journal-title":"PLoS One."},{"key":"103_CR45","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nprot.2008.214","volume":"4","author":"D Rittirsch","year":"2009","unstructured":"Rittirsch, D., Huber-Lang, M. S., Flierl, M. A. & Ward, P. A. Immunodesign of experimental sepsis by cecal ligation and puncture. Nature protocols 4, 31\u201336 (2009).","journal-title":"Nature protocols"},{"key":"103_CR46","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1378\/chest.11-0539","volume":"140","author":"KY Yang","year":"2011","unstructured":"Yang, K. Y. et al. IV delivery of induced pluripotent stem cells attenuates endotoxin-induced acute lung injury in mice. Chest 140, 1243\u20131253 (2011).","journal-title":"Chest"},{"key":"103_CR47","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.surg.2013.04.003","volume":"154","author":"T Zhao","year":"2013","unstructured":"Zhao, T. et al. Novel pharmacologic treatment attenuates septic shock and improves long-term survival. Surgery 154, 206\u2013213 (2013).","journal-title":"Surgery"},{"key":"103_CR48","doi-asserted-by":"publisher","first-page":"11822","DOI":"10.1038\/srep11822","volume":"5","author":"C Yu","year":"2015","unstructured":"Yu, C., Qi, D., Sun, J. F., Li, P. & Fan, H. Y. Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-kappaB activities. Scientific reports 5, 11822 (2015).","journal-title":"Scientific reports"},{"key":"103_CR49","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1007\/s00018-010-0609-y","volume":"68","author":"G Lopez-Castejon","year":"2011","unstructured":"Lopez-Castejon, G., Baroja-Mazo, A. & Pelegrin, P. Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules. Cellular and molecular life sciences: CMLS 68, 3095\u20133107 (2011).","journal-title":"Cellular and molecular life sciences: CMLS"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00103-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00103-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00103-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T18:24:22Z","timestamp":1750011862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00103-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,7]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["103"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-00103-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,7]]},"assertion":[{"value":"4 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"99"}}