{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:39:09Z","timestamp":1793741949921,"version":"4.6.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Periodontal disease is among the sixth most common inflammatory diseases worldwide with high risk to promote complications from other inflammatory diseases including diabetes, cardiovascular disease and Alzheimer\u2019s Disease. Failure of active resolution of inflammation pathways is implicated in pathogenesis of periodontal diseases, including gingivitis. Lipoxin A4 (LXA4), a member of the specialized pro-resolving lipid mediators (SPMs) that drive resolution of inflammation\n                      <jats:italic>via<\/jats:italic>\n                      GPC-receptor mediated pathways, offered therapeutic advantages in preclinical models of periodontitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a randomized, placebo-controlled, parallel-group Phase 1 clinical trial to determine the safety and preliminary efficacy of an LXA4 analog in patients with gingival inflammation. One hundred twenty-seven (127) individuals were randomized to daily use of an oral rinse containing a LXA4 mimetic, methyl ester-benzo-lipoxin A4 (BLXA4), placebo rinse or a no-rinse control group for 28 days. Treatment emergent adverse events (TEAEs) were assessed for safety, the primary outcome. Secondary outcomes included the change in the level of gingival inflammation and periodontal pocket depth (PD). Serum SPMs were monitored using targeted lipid mediator lipidomics to assess potential systemic impact of BLXA4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The frequency of TEAEs was similar in BLXA4 and placebo-treated groups with no study-related SAEs. Once-daily rinsing with BLXA4 for 28-days resulted in a greater decrease in gingival inflammation compared to placebo rinse and no-rinse control groups (mean change: 0.26 GI unit\n                      <jats:italic>vs<\/jats:italic>\n                      0.21 and 0.17, respectively). PD reduction was also greater with BLXA4 oral rinse compared to placebo and no-rinse groups (mean reduction: 1.23 mm\n                      <jats:italic>vs<\/jats:italic>\n                      . 0.71 mm and 0.46 mm, respectively). Topical application of BLXA4 increased serum levels of SPMs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Treatment with BLXA4 reduces local inflammation, and increases abundance of pro-resolution molecules systemically, which may dampen inflammation that can mediate progression and course of inflammatory diseases beyond periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, identifier (NCT02342691).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2021.704163","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T10:01:47Z","timestamp":1631527307000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":81,"title":["Safety and Preliminary Efficacy of a Novel Host-Modulatory Therapy for Reducing Gingival Inflammation"],"prefix":"10.3389","volume":"12","author":[{"given":"Hatice","family":"Hasturk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Schulte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homa","family":"Sherzai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Floros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaryAnn","family":"Cugini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Jung","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Van Dyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601222R","article-title":"Treating Inflammation and Infection in the 21st Century: New Hints From Decoding Resolution Mediators and Mechanisms","volume":"31","author":"Serhan","year":"2017","journal-title":"FASEB J: Off Publ Fed Am Soc Exp Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2017.08.002","article-title":"New Pro-Resolving N-3 Mediators Bridge Resolution of Infectious Inflammation to Tissue Regeneration","volume":"64","author":"Serhan","year":"2018","journal-title":"Mol Aspects Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mam.2017.04.006","article-title":"Pro-Resolving Mediators in the Regulation of Periodontal Disease","volume":"58","author":"Van Dyke","year":"2017","journal-title":"Mol Aspects Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514552491","article-title":"Global Burden of Severe Periodontitis in 1990-2010: A Systematic Review and Meta-Regression","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J Dental Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514537828","article-title":"Global Burden of Severe Tooth Loss: A Systematic Review and Meta-Analysis","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J Dental Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.080279","article-title":"Inflammation and Periodontal Diseases: A Reappraisal","volume":"79","author":"Van Dyke","year":"2008","journal-title":"J Periodontol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1995.tb01793.x","article-title":"Crevicular Fluid Osteocalcin and Pyridinoline Cross-Linked Carboxyterminal Telopeptide of Type I Collagen (ICTP) as Markers of Rapid Bone Turnover in Periodontitis. 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