{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:33:04Z","timestamp":1780392784557,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T00:00:00Z","timestamp":1495497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012537","name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","doi-asserted-by":"crossref","award":["R103-16"],"award-info":[{"award-number":["R103-16"]}],"id":[{"id":"10.13039\/501100012537","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2018,2]]},"abstract":"Abstract<\/jats:title>Aim<\/jats:title>To determine the expressions of hypoxia\u2010related [hypoxia\u2010inducible transcription factors (HIF<\/jats:styled-content>)\u20101\u03b1, BCL<\/jats:styled-content>2\/adenovirus E1B 19\u00a0kDa protein\u2010interacting protein 3 (BNIP<\/jats:styled-content>3) and phospho\u2010adenosine monophosphate activated protein kinase (pAMPK<\/jats:styled-content>)] and autophagy\u2010related [microtubule\u2010associated protein 1 light chain 3 (LC<\/jats:styled-content>3), beclin\u20101 (BECN<\/jats:styled-content>\u20101), autophagy\u2010related gene (Atg)5\u201312, and p62] proteins in human inflammatory periapical lesions.<\/jats:p><\/jats:sec>Methodology<\/jats:title>Fifteen samples of radicular cysts (RC<\/jats:styled-content>s) and 21 periapical granulomas (PG<\/jats:styled-content>s), combined with 17 healthy dental pulp tissues, were examined. Enzyme\u2010linked immunosorbent assay (ELISA<\/jats:styled-content>) was used to detect interleukin (IL<\/jats:styled-content>)\u20101\u03b2 cytokine; immunohistochemical (IHC<\/jats:styled-content>) and Western blot (WB<\/jats:styled-content>) analyses were employed to examine autophagy\u2010related and hypoxia\u2010related proteins. Transmission electron microscopy (TEM<\/jats:styled-content>) was used to explore the ultrastructural morphology of autophagy in periapical lesions. Nonparametric Kruskal\u2013Wallis tests and Mann\u2013Whitney U<\/jats:italic>\u2010tests were used for statistical analyses.<\/jats:p><\/jats:sec>Results<\/jats:title>ELISA<\/jats:styled-content> revealed a significantly higher (P\u00a0<\/jats:italic>< 0.001) IL<\/jats:styled-content>\u20101\u03b2 expression in periapical lesions than in normal pulp tissue. Immunoscores of IHC<\/jats:styled-content> expressions of pAMPK<\/jats:styled-content>, HIF<\/jats:styled-content>\u20101\u03b1, BNIP<\/jats:styled-content>3, BECN<\/jats:styled-content>\u20101 and Atg5\u201312 proteins in periapical lesions were significantly higher (P\u00a0<\/jats:italic><\u00a00.001) (except BECN<\/jats:styled-content>\u20101) than those in normal pulp tissue. The results of IHC<\/jats:styled-content> studies were largely compatible with those of WB<\/jats:styled-content> analyses, where significantly higher (P\u00a0<\/jats:italic><\u00a00.05) expressions of hypoxia\u2010related and autophagy\u2010related proteins (except BECN<\/jats:styled-content>\u20101, p62 and LC<\/jats:styled-content>3II<\/jats:styled-content> in WB<\/jats:styled-content> analyses) in periapical lesions were noted as compared to normal pulp tissue. Upon TEM<\/jats:styled-content>, ultrastructural double\u2010membrane autophagosomes and autolysosomes were observed in PG<\/jats:styled-content>s and RC<\/jats:styled-content>s.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Autophagy associated with hypoxia may play a potential causative role in the development and maintenance of inflamed periapical lesions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.12782","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T07:13:13Z","timestamp":1493104393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The roles of autophagy and hypoxia in human inflammatory periapical lesions"],"prefix":"10.1111","volume":"51","author":[{"given":"H. Y.","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Dentistry Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital Chia\u2010Yi Taiwan"},{"name":"School of Dentistry College of Dental Medicine Kaohsiung Medical University Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. C.","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Dentistry College of Dental Medicine Kaohsiung Medical University Kaohsiung Taiwan"},{"name":"Oral & Maxillofacial Imaging Center College of Dental Medicine Kaohsiung Medical University Kaohsiung Taiwan"},{"name":"Division of Oral Pathology & Maxillofacial Radiology Department of Dentistry Kaohsiung Medical University Hospital Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Dentistry Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. P.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Dentistry Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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