{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:08:27Z","timestamp":1791947307662,"version":"4.3.4"},"reference-count":82,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate M1 and M2 macrophage polarization in radicular cysts and periapical granulomas through an immunohistochemical analysis and the correlation between macrophage polarization and histopathological diagnosis, clinical characteristics and lesion volume using cone\u2010beam computed tomography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Periapical biopsies diagnosed as radicular cysts (<jats:italic>n<\/jats:italic>\u2009=\u200952) and periapical granulomas (<jats:italic>n<\/jats:italic>\u2009=\u200951) were analysed by immunohistochemical method. Teeth with periapical lesion with no history of root canal treatment (primary lesion) and lesions persistent to root canal treatment (persistent lesions) were included. Pathological diagnosis, patients' age, gender and clinical characteristics were obtained from treatment records. A cone\u2010beam computed tomographic periapical volume index (CBCTPAVI) score was assigned to each periapical lesion based on the volume of the lesion. Immuno\u2010expressions of CD68 and CD163 were quantified. The CD68\/CD163 ratio was adopted to represent M1 or M2 macrophage polarization. Mann\u2013Whitney <jats:italic>U<\/jats:italic> test was used to determine the different CD68\/CD163 ratio between groups of radicular cyst and periapical granuloma. Spearman's correlation test was performed to assess the correlation between the CD68\/CD163 ratio and lesion volume and CBCTPAVI score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Radicular cysts and periapical granulomas had CD68\/CD163 median of 2.05 (IQR\u2009=\u20091.33) and 1.26 (IQR\u2009=\u20090.81), respectively. A significantly higher CD68\/CD163 ratio was observed in radicular cysts (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). In contrast, periapical granulomas had significantly lower median of CD68\/CD163 ratio. Larger lesions had a higher median of CD68\/CD163 ratio, while smaller lesions had lower median of CD68\/CD163 ratio (<jats:italic>p<\/jats:italic>\u2009=\u2009.007, <jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u2009.262). CD68\/CD163 ratio was significantly correlated with the CBCTPAVI score in the overall periapical lesions (<jats:italic>p<\/jats:italic>\u2009=\u2009.002, <jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u2009.306). The higher CD68\/CD163 ratio in larger lesions indicated a higher degree of M1 polarization compared to smaller lesions. Regarding the pathological diagnosis, there was a significant positive correlation between CBCTPAVI score and CD68\/CD163 ratio in periapical granulomas (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001, <jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u2009.453), whereas the negative correlation was observed for radicular cysts (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001, <jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u2009\u2212.471).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Periapical granulomas are characterized by a M2\u2010dominant macrophage polarization, while radicular cysts have significantly higher M1 macrophages. The higher degree of M1 macrophage polarization was significantly correlated with larger volume and higher CBCTPAVI scores of overall periapical lesion and periapical granuloma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.14138","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T14:14:35Z","timestamp":1725286475000},"page":"1829-1847","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Macrophage polarization in human periapical lesions in relation to histopathological diagnosis, clinical features and lesion volume: An ex\u00a0vivo study"],"prefix":"10.1111","volume":"57","author":[{"given":"Supanant","family":"Visarnta","sequence":"first","affiliation":[{"name":"Section of Endodontics, Department of Operative Dentistry, Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-1540","authenticated-orcid":false,"given":"Chootima","family":"Ratisoontorn","sequence":"additional","affiliation":[{"name":"Section of Endodontics, Department of Operative Dentistry, Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchana","family":"Panichuttra","sequence":"additional","affiliation":[{"name":"Section of Endodontics, Department of Operative Dentistry, Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phonkit","family":"Sinpitaksakul","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soranun","family":"Chantarangsu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittipong","family":"Dhanuthai","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Anesthesiologists ASo. (2020)Statement on ASA physical status classification system. Available from:https:\/\/www.asahq.org\/standards\u2010and\u2010practice\u2010parameters\/statement\u2010on\u2010asa\u2010physical\u2010status\u2010classification\u2010system"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061801"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2015.08.036"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13257"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2010.11.014"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2021.04.027"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2013.09.037"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2007.11.024"},{"key":"e_1_2_11_10_1","first-page":"637","article-title":"The macrophage switch in obesity development","volume":"6","author":"Castoldi A.","year":"2015","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jds.2018.12.002"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00421"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2012.11.054"},{"key":"e_1_2_11_14_1","volume-title":"ENDODONTICS: colleagues for excellence","author":"Endodontic Diagnosis","year":"2013"},{"key":"e_1_2_11_15_1","unstructured":"Endodontists AAo. (2017)Treatment options for the compromised tooth: a decision guide. Available from:https:\/\/www.aae.org\/specialty\/clinical\u2010resources\/treatment\u2010planning\/treatment\u2010options\u2010guide\/"},{"key":"e_1_2_11_16_1","unstructured":"Endodontists AAo. (2020)Glossary of endodontic terms. Available from:https:\/\/www.aae.org\/specialty\/clinical\u2010resources\/glossary\u2010endodontic\u2010terms\/"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/tdj.tdj_36_18"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2008.08.013"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1995.tb01170.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1590\/1807-3107bor-2019.vol33.0047"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.13568"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-1546.2002.10105.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0099-2399(86)80278-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2008.00469.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-020-03556-2"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13156"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071545"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.11.001"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-062117-121224"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01512"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-013-9381-6"},{"issue":"2","key":"e_1_2_11_32_1","first-page":"54","article-title":"Endodontic periapical lesion: An overview on the etiology, diagnosis and current treatment modalities","volume":"5","author":"Karamifar K.","year":"2020","journal-title":"European Endodontic Journal"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcm.2016.02.012"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00419"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2014.2374"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199807000-00003"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq431"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.654559"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2007.02.006"},{"issue":"2","key":"e_1_2_11_40_1","first-page":"3044","article-title":"Macrophage functional phenotype can be consecutively and reversibly shifted to adapt to microenvironmental changes","volume":"8","author":"Liu H.","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tripleo.2006.01.001"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29881"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4133"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2666"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.12703\/P6-13"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.2741\/2692"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2013.10.036"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2019.10.007"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-9657.2000.016001001.x"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12102999"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034339"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13542"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1177\/154411130401500604"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0099-2399(07)80201-9"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2591.2006.01099.x"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(84)90267-6"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2591.2007.01323.x"},{"issue":"1","key":"e_1_2_11_58_1","first-page":"15","article-title":"Interleukin\u20101 beta stimulates bone resorption and inhibits bone formation in\u00a0vivo","volume":"10","author":"Nguyen L.","year":"1991","journal-title":"Lymphokine and Cytokine Research"},{"issue":"3","key":"e_1_2_11_59_1","first-page":"759","article-title":"Immunohistochemical assessment of localization and frequency of micrometastases in lymph nodes of colorectal cancer","volume":"8","author":"Noura S.","year":"2002","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8148272"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11071394"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2015.10.003"},{"issue":"2","key":"e_1_2_11_63_1","first-page":"86","article-title":"Role of interleukin\u20101 in pathogenesis of radicular cyst","volume":"22","author":"Qureshi W.","year":"2010","journal-title":"Journal of Ayub Medical College, Abbottabad"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1079-2104(96)80156-9"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tripleo.2005.03.038"},{"key":"e_1_2_11_66_1","unstructured":"Roda R.S.(2017)Nonsurgical retreatment: Clinical decision making. Available from:https:\/\/www.aae.org\/specialty\/newsletter\/nonsurgical\u2010retreatment\u2010clinical\u2010decision\u2010making\/"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2591.2001.00396.x"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.949102"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820139.2013.822766"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1177\/10454411980090040701"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.778078"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2009.00863.x"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-020-03324-2"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0099-2399(06)80503-0"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RU1018-378RR"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2485959"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2019.06.014"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-017-2123-1"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.10.034"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2016.160081"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173090"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12983"}],"container-title":["International Endodontic Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iej.14138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T05:18:39Z","timestamp":1735967919000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iej.14138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,2]]},"references-count":82,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/iej.14138"],"URL":"https:\/\/doi.org\/10.1111\/iej.14138","archive":["Portico"],"relation":{},"ISSN":["0143-2885","1365-2591"],"issn-type":[{"value":"0143-2885","type":"print"},{"value":"1365-2591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,2]]},"assertion":[{"value":"2023-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}