{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:45:03Z","timestamp":1792176303935,"version":"4.4.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T00:00:00Z","timestamp":1478476800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T00:00:00Z","timestamp":1478476800000},"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                    Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (\u2212)-naloxone, in infection-associated preterm birth. Treatment with (+)-naloxone prevented preterm delivery and alleviated fetal demise\n                    <jats:italic>in utero<\/jats:italic>\n                    elicited by i.p. LPS administration in late gestation. A similar effect with protection from preterm birth and perinatal death, and partial correction of reduced birth weight and postnatal mortality, was conferred by (+)-naloxone administration after intrauterine administration of heat-killed\n                    <jats:italic>E. coli<\/jats:italic>\n                    . Local induction by\n                    <jats:italic>E. coli<\/jats:italic>\n                    of inflammatory cytokine genes\n                    <jats:italic>Il1b<\/jats:italic>\n                    ,\n                    <jats:italic>Il6, Tnf<\/jats:italic>\n                    and\n                    <jats:italic>Il10<\/jats:italic>\n                    in fetal membranes was suppressed by (+)-naloxone, and cytokine expression in the placenta, and uterine myometrium and decidua, was also attenuated. These data demonstrate that inhibition of TLR4 signaling with the novel TLR4 antagonist (+)-naloxone can suppress the inflammatory cascade of preterm parturition, to prevent preterm birth and perinatal death. Further studies are warranted to investigate the utility of small molecule inhibition of TLR-driven inflammation as a component of strategies for fetal protection and delaying preterm birth in the clinical setting.\n                  <\/jats:p>","DOI":"10.1038\/srep36112","type":"journal-article","created":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T05:07:33Z","timestamp":1478495253000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth"],"prefix":"10.1038","volume":"6","author":[{"given":"Peck Yin","family":"Chin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla L.","family":"Dorian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Hutchinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenner C.","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan M.","family":"Moldenhauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,7]]},"reference":[{"key":"BFsrep36112_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(08)60074-4","volume":"371","author":"RL Goldenberg","year":"2008","unstructured":"Goldenberg, R. 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