{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:51:32Z","timestamp":1790506292353,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      The Gene Expression Omnibus (GEO) database, an international public repository of genomics data sets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An\n                      <jats:italic>ex vivo<\/jats:italic>\n                      pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t\u2010test or ANOVA with the level of significance set at\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      \u2264\u00a0.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pulpitis gene signatures were created using differential gene expression analysis at cutoff points\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a0.0001 and .000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel upregulated genes, chemokine (C\u2010C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a0.0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      &lt;\u00a0.001) and MMP9 (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      &lt;\u00a0.05) in the\n                      <jats:italic>ex vivo<\/jats:italic>\n                      pulpitis model, while dequalinium chloride reduced AQP9 (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      &lt;\u00a0.001) but had no significant effect on the other biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      AQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an\n                      <jats:italic>ex vivo<\/jats:italic>\n                      pulpitis model.\n                      <jats:italic>In vivo<\/jats:italic>\n                      testing of these licenced drugs is warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.13547","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T03:20:01Z","timestamp":1620530401000},"page":"1571-1580","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Identification and validation of novel biomarkers and therapeutics for pulpitis using connectivity mapping"],"prefix":"10.1111","volume":"54","author":[{"given":"Banan","family":"Al\u2010Natour","sequence":"first","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences Queen\u2019s University Belfast Belfast UK"},{"name":"Department of Oral Medicine and Oral Surgery Jordan University of Science and Technology Irbid Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robby","family":"Rankin","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences Queen\u2019s University Belfast Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"McKenna","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences Queen\u2019s University Belfast Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"McMillan","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences Queen\u2019s University Belfast Belfast 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