{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:58:51Z","timestamp":1785329931390,"version":"3.55.0"},"reference-count":149,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82530028"],"award-info":[{"award-number":["82530028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82220108018"],"award-info":[{"award-number":["82220108018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270981"],"award-info":[{"award-number":["82270981"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571092"],"award-info":[{"award-number":["82571092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Periodontology 2000"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite successful reduction of bacterial load and clinical inflammation following periodontal therapy, high recurrence rates indicate that prior infections induce lasting host alterations, maintaining latent disease susceptibility<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This review elucidates the biological basis of periodontal recalcitrance through innate immune memory (trained immunity), examining durable functional reprogramming at both local and systemic levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We comprehensively searched PubMed\/MEDLINE and Scopus databases for peer\u2010reviewed literature published primarily within the last decade (up to 2026). The search strategy utilized combinations of terms including \u201cperiodontitis\u201d, \u201ctrained immunity\u201d, \u201cepigenetic reprogramming\u201d, \u201cbone marrow axis\u201d, and \u201cclonal hematopoiesis\u201d. Mechanistic, multi\u2010omics, and clinical data were evaluated and synthesized, focusing on local resident cell reprogramming, ectopic lymphoid organogenesis, the periodontium\u2010bone marrow axis, and clonal hematopoiesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Current evidence supports the existence of a multi\u2010level immunological imprint. Locally, gingival fibroblasts and resident immune cells acquire stable epigenetic modifications and undergo glycolytic shifts. These changes lower their activation thresholds, generating a hyper\u2010responsive microenvironment sustained by Tertiary Lymphoid Structures. Systemically, periodontal inflammation transmits endocrine signals (IL\u20101\u03b2, type I interferons) to hematopoietic stem and progenitor cells. This central adaptation biases myeloid differentiation and establishes heritable epigenetic priming, accelerating the output of hyper\u2010reactive neutrophils. Additionally, age\u2010related Clonal Hematopoiesis of Indeterminate Potential (CHIP) amplifies this inflammatory dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Periodontitis recurrence is fundamentally driven by maladaptive immunological memory. This persistent state is encoded via epigenetic and metabolic reprogramming within local tissues and central hematopoietic niches, exacerbating destruction upon microbial restimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance<\/jats:title>\n                    <jats:p>Achieving true biological resolution in periodontitis requires a paradigm shift from solely controlling the biofilm to incorporating targeted host\u2010modulatory therapies that resolve these maladaptive epigenetic and metabolic adaptations<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/prd.70069","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:01:27Z","timestamp":1785326487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The immunological imprint of recurrent periodontitis: From local tissue memory to central trained immunity"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-9522","authenticated-orcid":false,"given":"Qin","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangyuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keer","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3290-3418","authenticated-orcid":false,"given":"Richard J.","family":"Miron","sequence":"additional","affiliation":[{"name":"Department of Periodontology University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-5477","authenticated-orcid":false,"given":"Anton","family":"Sculean","sequence":"additional","affiliation":[{"name":"Department of Periodontology University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-5291","authenticated-orcid":false,"given":"Yufeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"Kinane DF","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/prd.12362","article-title":"Microbial signatures of health, gingivitis, and periodontitis","volume":"86","author":"Abusleme L","year":"2021","journal-title":"Periodontol"},{"key":"e_1_2_12_4_1","first-page":"559","article-title":"Unveiling the causal roles of the Oral microbiome\u2010host metabolism\u2010inflammation Axis in periodontitis: a Mendelian randomisation study","volume":"23","author":"Zhao Z","year":"2025","journal-title":"Oral Health Prev Dent"},{"issue":"1","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12903-024-04898-z","article-title":"Guided biofilm therapy versus conventional protocol\u2010clinical outcomes in non\u2010surgical periodontal therapy","volume":"24","author":"Cyris M","year":"2024","journal-title":"BMC Oral Health"},{"issue":"22","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/jcpe.13236","article-title":"Adjunctive laser or antimicrobial photodynamic therapy to non\u2010surgical mechanical instrumentation in patients with untreated periodontitis: a systematic review and meta\u2010analysis","volume":"47","author":"Salvi GE","year":"2020","journal-title":"J Clin Periodontol"},{"issue":"10","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1002\/JPER.20-0839","article-title":"A re\u2010evaluation of scaling and root planing","volume":"92","author":"Cobb CM","year":"2021","journal-title":"J Periodontol"},{"issue":"24","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/jcpe.13553","article-title":"Recurrence and progression of periodontitis and methods of management in long\u2010term care: a systematic review and meta\u2010analysis","volume":"49","author":"Leow NM","year":"2022","journal-title":"J Clin Periodontol"},{"issue":"6","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/jcpe.13627","article-title":"Modified minimally invasive surgical technique in human intrabony defects with or without regenerative materials\u201010\u2010year follow\u2010up of a randomized clinical trial: tooth retention, periodontitis recurrence, and costs","volume":"49","author":"Cortellini P","year":"2022","journal-title":"J Clin Periodontol"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.70015"},{"key":"e_1_2_12_11_1","first-page":"159","article-title":"HA2\u2010FimA DNA Vaccine Treats Experimental Periodontitis","volume":"22","author":"Zhang H","year":"2024","journal-title":"Oral Health Prev Dent"},{"issue":"1","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-88803-6","article-title":"Transcriptomic phases of periodontitis lesions using the nonhuman primate model","volume":"11","author":"Ebersole JL","year":"2021","journal-title":"Sci Rep"},{"issue":"22","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/jcpe.13253","article-title":"Endpoints of active periodontal therapy","volume":"47","author":"Loos BG","year":"2020","journal-title":"J Clin Periodontol"},{"issue":"1","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/prd.12581","article-title":"Realizing the clinical utility of saliva for monitoring oral diseases","volume":"95","author":"Ebersole JL","year":"2024","journal-title":"Periodontol"},{"issue":"6","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/idj.12630","article-title":"Current concepts in the Management of Periodontitis","volume":"71","author":"Kwon T","year":"2021","journal-title":"Int Dent J"},{"issue":"20","key":"e_1_2_12_16_1","first-page":"S162","article-title":"Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and Peri\u2010implant diseases and conditions","volume":"45","author":"Papapanou PN","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"1","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/prd.12629","article-title":"Serum cytokines in periodontal diseases","volume":"98","author":"Ahmad P","year":"2025","journal-title":"Periodontol"},{"issue":"5","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","DOI":"10.1128\/msystems.00683-23","article-title":"Dysbiosis of oral microbiome persists after dental treatment\u2010induced remission of periodontal disease and dental caries","volume":"8","author":"Yama K","year":"2023","journal-title":"mSystems"},{"issue":"1","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.1038\/s41598-022-09192-y","article-title":"Microbial differences between active and remission peri\u2010implantitis","volume":"12","author":"Hashimoto Y","year":"2022","journal-title":"Sci Rep"},{"issue":"8","key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1177\/0022034521995157","article-title":"Host modulation and treatment of periodontal disease","volume":"100","author":"Balta MG","year":"2021","journal-title":"J Dent Res"},{"key":"e_1_2_12_21_1","doi-asserted-by":"crossref","DOI":"10.3389\/froh.2023.1288722","article-title":"Immunomodulation of periodontitis with SPMs","volume":"4","author":"Sahni V","year":"2023","journal-title":"Front Oral Health"},{"key":"e_1_2_12_22_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2023.108453","article-title":"Resolution of inflammation in oral diseases","volume":"247","author":"Eltay EG","year":"2023","journal-title":"Pharmacol Ther"},{"issue":"1","key":"e_1_2_12_23_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/prd.12317","article-title":"Understanding resolution of inflammation in periodontal diseases: is chronic inflammatory periodontitis a failure to resolve?","volume":"82","author":"Van Dyke TE","year":"2020","journal-title":"Periodontol"},{"issue":"9","key":"e_1_2_12_24_1","first-page":"4283","article-title":"Resolution of inflammation in periodontitis: a review","volume":"11","author":"Huang J","year":"2018","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12562"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12361"},{"issue":"47","key":"e_1_2_12_27_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202400882","article-title":"Outer membrane vesicles derived from Fusobacterium nucleatum trigger periodontitis through host Overimmunity","volume":"11","author":"Zhang L","year":"2024","journal-title":"Adv Sci (Weinh)"},{"issue":"3","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/JLB.4MR0421-756R","article-title":"Intersection between macrophages and periodontal pathogens in periodontitis","volume":"110","author":"Wang W","year":"2021","journal-title":"J Leukoc Biol"},{"issue":"1","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41368-024-00332-w","article-title":"The impact of aging on neutrophil functions and the contribution to periodontitis","volume":"17","author":"Wang Z","year":"2025","journal-title":"Int J Oral Sci"},{"issue":"1","key":"e_1_2_12_30_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012821","article-title":"Gingipains protect Porphyromonas gingivalis from macrophage\u2010mediated phagocytic clearance","volume":"21","author":"Widziolek M","year":"2025","journal-title":"PLoS Pathog"},{"issue":"6","key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/jre.12779","article-title":"The presence of neutrophils causes RANKL expression in periodontal tissue, giving rise to osteoclast formation","volume":"55","author":"Kim AR","year":"2020","journal-title":"J Periodontal Res"},{"issue":"1","key":"e_1_2_12_32_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0227757","article-title":"Impact of periodontal treatment on the RANKL\/OPG ratio in crevicular fluid","volume":"15","author":"Lopez Roldan A","year":"2020","journal-title":"PLoS One"},{"issue":"12","key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1177\/0022034510376402","article-title":"Destructive and protective roles of cytokines in periodontitis: a re\u2010appraisal from host defense and tissue destruction viewpoints","volume":"89","author":"Garlet GP","year":"2010","journal-title":"J Dent Res"},{"issue":"1","key":"e_1_2_12_34_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-024-02049-8","article-title":"Periodontopathogen\u2010related cell autophagy\u2010a double\u2010edged sword","volume":"48","author":"Ma L","year":"2025","journal-title":"Inflammation"},{"issue":"1","key":"e_1_2_12_35_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1177\/00220345251360752","article-title":"Periodontitis leads to systemic bone loss through neutrophil reprogramming","volume":"105","author":"Martin K","year":"2026","journal-title":"J Dent Res"},{"issue":"11","key":"e_1_2_12_36_1","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1111\/jre.13372","article-title":"Porphyromonas gingivalis\u2010lipopolysaccharide induced gingival fibroblasts trained immunity sustains inflammation in periodontitis","volume":"60","author":"Liu J","year":"2025","journal-title":"J Periodontal Res"},{"issue":"8","key":"e_1_2_12_37_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1902\/jop.1998.69.8.899","article-title":"Increased presence of interleukin\u20106 (IL\u20106) and IL\u20108 secreting fibroblast subpopulations in adult periodontitis","volume":"69","author":"Dongari\u2010Bagtzoglou A","year":"1998","journal-title":"J Periodontol"},{"issue":"2","key":"e_1_2_12_38_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1046\/j.1365-2249.2002.01753.x","article-title":"A type 2 response in lipopolysaccharide (LPS)\u2010stimulated whole blood cell cultures from periodontitis patients","volume":"127","author":"Fokkema SJ","year":"2002","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_12_39_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cyto.2020.155361","article-title":"Polymorphisms in the interleukin genes and chronic periodontitis: a field synopsis and revaluation by Bayesian approaches","volume":"138","author":"Da Silva FRP","year":"2021","journal-title":"Cytokine"},{"issue":"4","key":"e_1_2_12_40_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.11607\/jomi.10615","article-title":"Analysis of the association of IL\u20101A, IL\u20101B, and IL\u20101RN genetic polymorphisms with Peri\u2010implantitis in a Portuguese population","volume":"39","author":"Cardoso JM","year":"2024","journal-title":"Int J Oral Maxillofac Implants"},{"issue":"5","key":"e_1_2_12_41_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/00220345231151921","article-title":"The role of gingival fibroblasts in the pathogenesis of periodontitis","volume":"102","author":"Wielento A","year":"2023","journal-title":"J Dent Res"},{"issue":"1","key":"e_1_2_12_42_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s13148-021-01190-7","article-title":"Epigenetic adaptations of the masticatory mucosa to periodontal inflammation","volume":"13","author":"Richter GM","year":"2021","journal-title":"Clin Epigenetics"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62810"},{"issue":"5","key":"e_1_2_12_44_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1177\/0022034516686745","article-title":"Direct gingival fibroblast\/osteoblast Transdifferentiation via epigenetics","volume":"96","author":"Cho Y","year":"2017","journal-title":"J Dent Res"},{"issue":"7","key":"e_1_2_12_45_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41577-025-01132-x","article-title":"Trained immunity in chronic inflammatory diseases and cancer","volume":"25","author":"Hajishengallis G","year":"2025","journal-title":"Nat Rev Immunol"},{"issue":"13","key":"e_1_2_12_46_1","doi-asserted-by":"crossref","first-page":"15772","DOI":"10.18632\/oncotarget.7513","article-title":"Pre\u2010neoplastic epigenetic disruption of transcriptional enhancers in chronic inflammation","volume":"7","author":"Planello AC","year":"2016","journal-title":"Oncotarget"},{"issue":"7","key":"e_1_2_12_47_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202409398","article-title":"Senescent fibroblasts drive FAP\/OLN imbalance through mTOR signaling to exacerbate inflammation and bone resorption in periodontitis","volume":"12","author":"Yin C","year":"2025","journal-title":"Adv Sci (Weinh)"},{"issue":"12","key":"e_1_2_12_48_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1042\/CS20240036","article-title":"Galectin\u20103 inhibition alleviated LPS\u2010induced periodontal inflammation in gingival fibroblasts and experimental periodontitis mice","volume":"138","author":"Wenjing S","year":"2024","journal-title":"Clin Sci (Lond)"},{"issue":"9","key":"e_1_2_12_49_1","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1111\/jcpe.13841","article-title":"Inhibition of gingival fibroblast necroptosis mediated by RIPK3\/MLKL attenuates periodontitis","volume":"50","author":"Zhang K","year":"2023","journal-title":"J Clin Periodontol"},{"issue":"1","key":"e_1_2_12_50_1","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1186\/s12967-025-06925-1","article-title":"Multi\u2010omics data reveal that SAA1\u2009+\u2009fibroblasts exacerbate periodontitis by regulating macrophage inflammation and chemotaxis","volume":"23","author":"Li L","year":"2025","journal-title":"J Transl Med"},{"issue":"1","key":"e_1_2_12_51_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12903-023-02807-4","article-title":"Hexokinase 2\u2010mediated glycolysis supports inflammatory responses to Porphyromonas gingivalis in gingival fibroblasts","volume":"23","author":"Su W","year":"2023","journal-title":"BMC Oral Health"},{"issue":"7","key":"e_1_2_12_52_1","doi-asserted-by":"crossref","DOI":"10.3390\/antiox13070817","article-title":"Ganoderma Microsporum immunomodulatory protein alleviates Inflammaging and oxidative stress in diabetes\u2010associated periodontitis via Nrf2 signaling activation: an in\u00a0vitro study","volume":"13","author":"Su NY","year":"2024","journal-title":"Antioxidants (Basel)"},{"issue":"5","key":"e_1_2_12_53_1","doi-asserted-by":"crossref","DOI":"10.3892\/etm.2021.9861","article-title":"Hyperresponsiveness of human gingival fibroblasts from patients with aggressive periodontitis against bacterial lipopolysaccharide","volume":"21","author":"Li X","year":"2021","journal-title":"Exp Ther Med"},{"issue":"5","key":"e_1_2_12_54_1","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1007\/s10753-016-0421-4","article-title":"Healthy and inflamed gingival fibroblasts differ in their inflammatory response to Porphyromonas gingivalis lipopolysaccharide","volume":"39","author":"Kang W","year":"2016","journal-title":"Inflammation"},{"issue":"33","key":"e_1_2_12_55_1","doi-asserted-by":"crossref","first-page":"22139","DOI":"10.1021\/acsnano.4c05475","article-title":"Targeted reprogramming of pathogenic fibroblast genes at the 3'\u2010untranslated regions by DNA Nanorobots for periodontitis","volume":"18","author":"Zhang J","year":"2024","journal-title":"ACS Nano"},{"issue":"15","key":"e_1_2_12_56_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202520717","article-title":"Matrix Stiffness Governs Fibroblasts' Regulation of Gingival Immune Homeostasis","volume":"38","author":"Makkar H","year":"2026","journal-title":"Adv Mater"},{"key":"e_1_2_12_57_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2019.00270","article-title":"Role of fibroblast populations in periodontal wound healing and tissue remodeling","volume":"10","author":"Smith PC","year":"2019","journal-title":"Front Physiol"},{"issue":"4","key":"e_1_2_12_58_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/jre.13003","article-title":"Characterization of junctional structures in the gingival epithelium as barriers against bacterial invasion","volume":"57","author":"Ko YK","year":"2022","journal-title":"J Periodontal Res"},{"issue":"7677","key":"e_1_2_12_59_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nature24271","article-title":"Inflammatory memory sensitizes skin epithelial stem cells to tissue damage","volume":"550","author":"Naik S","year":"2017","journal-title":"Nature"},{"issue":"6","key":"e_1_2_12_60_1","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1007\/s12015-024-10734-2","article-title":"Immediate but temporal response: the role of distal epithelial cells in wound healing","volume":"20","author":"Thompson T","year":"2024","journal-title":"Stem Cell Rev Rep"},{"key":"e_1_2_12_61_1","doi-asserted-by":"crossref","DOI":"10.3389\/fdmed.2022.815810","article-title":"Periodontal wound healing and regeneration: insights for engineering new therapeutic approaches","volume":"3","author":"Fraser D","year":"2022","journal-title":"Front Dent Med"},{"issue":"11","key":"e_1_2_12_62_1","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/JPER.18-0692","article-title":"Effect of smoking on the DNA methylation pattern of the SOCS1 promoter in epithelial cells from the saliva of patients with chronic periodontitis","volume":"90","author":"De JHMC","year":"2019","journal-title":"J Periodontol"},{"issue":"9","key":"e_1_2_12_63_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1600-051X.2009.01446.x","article-title":"DNA methylation status of the IL8 gene promoter in oral cells of smokers and non\u2010smokers with chronic periodontitis","volume":"36","author":"Oliveira NF","year":"2009","journal-title":"J Clin Periodontol"},{"key":"e_1_2_12_64_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13148-017-0381-z","article-title":"Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study","volume":"9","author":"Cho YD","year":"2017","journal-title":"Clin Epigenetics"},{"issue":"1","key":"e_1_2_12_65_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41368-025-00385-5","article-title":"Single\u2010cell spatial atlas of smoking\u2010induced changes in human gingival tissues","volume":"17","author":"Zhang Y","year":"2025","journal-title":"Int J Oral Sci"},{"issue":"5","key":"e_1_2_12_66_1","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1111\/jre.13030","article-title":"Cellular expression of epigenetic markers and oxidative stress in periodontitis lesions of smokers and non\u2010smokers","volume":"57","author":"Dionigi C","year":"2022","journal-title":"J Periodontal Res"},{"key":"e_1_2_12_67_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.00933","article-title":"BET Bromodomain inhibitors suppress inflammatory activation of gingival fibroblasts and epithelial cells from periodontitis patients","volume":"10","author":"Maksylewicz A","year":"2019","journal-title":"Front Immunol"},{"issue":"7","key":"e_1_2_12_68_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1177\/0022034514534261","article-title":"BET inhibitor JQ1 blocks inflammation and bone destruction","volume":"93","author":"Meng S","year":"2014","journal-title":"J Dent Res"},{"issue":"1","key":"e_1_2_12_69_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/prd.12421","article-title":"Maladaptive trained immunity and clonal hematopoiesis as potential mechanistic links between periodontitis and inflammatory comorbidities","volume":"89","author":"Hajishengallis G","year":"2022","journal-title":"Periodontol"},{"issue":"14","key":"e_1_2_12_70_1","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1016\/j.cell.2024.05.003","article-title":"Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss","volume":"187","author":"Wang H","year":"2024","journal-title":"Cell"},{"key":"e_1_2_12_71_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cej.2024.158338","article-title":"Circular RNA\u2010chimeric CeO2 nanoplatform maintains protective autophagy in macrophages for periodontitis","volume":"503","author":"Han Y","year":"2025","journal-title":"Chem Eng J"},{"key":"e_1_2_12_72_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.763334","article-title":"Polarized macrophages in periodontitis: characteristics, function, and molecular signaling","volume":"12","author":"Sun X","year":"2021","journal-title":"Front Immunol"},{"key":"e_1_2_12_73_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.106549","article-title":"Resident memory macrophages and trained innate immunity at barrier tissues","volume":"14","author":"Kang A","year":"2025","journal-title":"elife"},{"issue":"2","key":"e_1_2_12_74_1","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202101198R","article-title":"Decoding the role of macrophages in periodontitis and type 2 diabetes using single\u2010cell RNA\u2010sequencing","volume":"36","author":"Agrafioti P","year":"2022","journal-title":"FASEB J"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.70156"},{"key":"e_1_2_12_76_1","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.14871","article-title":"The imbalance of liver resident macrophages polarization promotes chronic autoimmune hepatitis development in mice","volume":"11","author":"Chi G","year":"2023","journal-title":"PeerJ"},{"issue":"2","key":"e_1_2_12_77_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s43018-025-00909-2","article-title":"Linking macrophage metabolism to function in the tumor microenvironment","volume":"6","author":"Jin R","year":"2025","journal-title":"Nat Cancer"},{"issue":"1","key":"e_1_2_12_78_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41368-023-00270-z","article-title":"Tim4 deficiency reduces CD301b(+) macrophage and aggravates periodontitis bone loss","volume":"16","author":"Wang Z","year":"2024","journal-title":"Int J Oral Sci"},{"issue":"1","key":"e_1_2_12_79_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41368-023-00225-4","article-title":"CD301b(+) macrophage: the new booster for activating bone regeneration in periodontitis treatment","volume":"15","author":"Wang C","year":"2023","journal-title":"Int J Oral Sci"},{"key":"e_1_2_12_80_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.00330","article-title":"Disruption of monocyte and macrophage homeostasis in periodontitis","volume":"11","author":"Almubarak A","year":"2020","journal-title":"Front Immunol"},{"issue":"2","key":"e_1_2_12_81_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/jre.12709","article-title":"Resident memory T cells: possible players in periodontal disease recurrence","volume":"55","author":"Deli F","year":"2020","journal-title":"J Periodontal Res"},{"issue":"9","key":"e_1_2_12_82_1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/JPER.17-0674","article-title":"Memory T cell subsets in healthy gingiva and periodontitis tissues","volume":"89","author":"Mahanonda R","year":"2018","journal-title":"J Periodontol"},{"issue":"3","key":"e_1_2_12_83_1","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.mucimm.2025.02.003","article-title":"Triggering mouth\u2010resident antiviral CD8(+) T cells potentiates experimental periodontitis","volume":"18","author":"Saavedra FM","year":"2025","journal-title":"Mucosal Immunol"},{"key":"e_1_2_12_84_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.intimp.2018.07.003","article-title":"Switched memory B cells promote alveolar bone damage during periodontitis: an adoptive transfer experiment","volume":"62","author":"Han Y","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8020340"},{"issue":"3","key":"e_1_2_12_86_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4049\/jimmunol.1600540","article-title":"Human memory B cells in healthy gingiva, gingivitis, and periodontitis","volume":"197","author":"Mahanonda R","year":"2016","journal-title":"J Immunol"},{"issue":"5","key":"e_1_2_12_87_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s12275-012-2030-8","article-title":"Possible translocation of periodontal pathogens into the lymph nodes draining the oral cavity","volume":"50","author":"Amodini Rajakaruna G","year":"2012","journal-title":"J Microbiol"},{"issue":"5","key":"e_1_2_12_88_1","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1136\/gutjnl-2015-309897","article-title":"Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response","volume":"66","author":"Blasco\u2010Baque V","year":"2017","journal-title":"Gut"},{"issue":"15","key":"e_1_2_12_89_1","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.1016\/j.cell.2021.05.013","article-title":"Human oral mucosa cell atlas reveals a stromal\u2010neutrophil axis regulating tissue immunity","volume":"184","author":"Williams DW","year":"2021","journal-title":"Cell"},{"issue":"3","key":"e_1_2_12_90_1","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.7150\/thno.65694","article-title":"Single\u2010cell RNA landscape of the osteoimmunology microenvironment in periodontitis","volume":"12","author":"Chen Y","year":"2022","journal-title":"Theranostics"},{"issue":"2","key":"e_1_2_12_91_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0192986","article-title":"B cell subset distribution is altered in patients with severe periodontitis","volume":"13","author":"Demoersman J","year":"2018","journal-title":"PLoS One"},{"key":"e_1_2_12_92_1","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/615486","article-title":"Mechanisms of bone resorption in periodontitis","volume":"2015","author":"Hienz SA","year":"2015","journal-title":"J Immunol Res"},{"issue":"9","key":"e_1_2_12_93_1","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.joen.2023.06.006","article-title":"Tertiary lymphoid structures are related to inflammatory progression and bone loss in human apical periodontitis","volume":"49","author":"Liu J","year":"2023","journal-title":"J Endodont"},{"issue":"1","key":"e_1_2_12_94_1","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.1038\/s41467-024-49037-y","article-title":"Single\u2010cell and spatially resolved interactomics of tooth\u2010associated keratinocytes in periodontitis","volume":"15","author":"Easter QT","year":"2024","journal-title":"Nat Commun"},{"issue":"7","key":"e_1_2_12_95_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41577-020-00488-6","article-title":"Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities","volume":"21","author":"Hajishengallis G","year":"2021","journal-title":"Nat Rev Immunol"},{"issue":"684","key":"e_1_2_12_96_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abq8476","article-title":"Oral mucosal breaks trigger anti\u2010citrullinated bacterial and human protein antibody responses in rheumatoid arthritis","volume":"15","author":"Brewer RC","year":"2023","journal-title":"Sci Transl Med"},{"key":"e_1_2_12_97_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1681037","article-title":"Periodontopathic bacteria in rheumatoid arthritis pathogenesis: bridging clinical associations to molecular mechanisms","volume":"16","author":"Guo X","year":"2025","journal-title":"Front Immunol"},{"key":"e_1_2_12_98_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01108","article-title":"Infectious triggers in periodontitis and the gut in rheumatoid arthritis (RA): a complex story about association and causality","volume":"11","author":"Moller B","year":"2020","journal-title":"Front Immunol"},{"key":"e_1_2_12_99_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.exphem.2024.104215","article-title":"Forged in the fire: lasting impacts of inflammation on hematopoietic progenitors","volume":"134","author":"Cao R","year":"2024","journal-title":"Exp Hematol"},{"key":"e_1_2_12_100_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.106610","article-title":"Hematopoietic stem and progenitor cells as a reservoir for trained immunity","volume":"14","author":"Tran BT","year":"2025","journal-title":"elife"},{"issue":"13","key":"e_1_2_12_101_1","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.7150\/thno.110859","article-title":"IFN\u2010I\u2010mediated neutropoiesis bias drives neutrophil priming and inflammatory comorbidities","volume":"15","author":"Li Y","year":"2025","journal-title":"Theranostics"},{"issue":"6","key":"e_1_2_12_102_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.immuni.2006.04.008","article-title":"Toll\u2010like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment","volume":"24","author":"Nagai Y","year":"2006","journal-title":"Immunity"},{"issue":"6","key":"e_1_2_12_103_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.stemcr.2016.05.002","article-title":"Sepsis induces hematopoietic stem cell exhaustion and Myelosuppression through distinct Contributions of TRIF and MYD88","volume":"6","author":"Zhang H","year":"2016","journal-title":"Stem Cell Reports"},{"issue":"9","key":"e_1_2_12_104_1","first-page":"2343","article-title":"Simultaneous inhibition of Sirtuin 3 and cholesterol homeostasis targets acute myeloid leukemia stem cells by perturbing fatty acid beta\u2010oxidation and inducing lipotoxicity","volume":"108","author":"O'brien C","year":"2023","journal-title":"Haematologica"},{"issue":"8","key":"e_1_2_12_105_1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1158\/2159-8290.CD-18-1474","article-title":"Aging human hematopoietic stem cells manifest profound epigenetic reprogramming of enhancers that may predispose to leukemia","volume":"9","author":"Adelman ER","year":"2019","journal-title":"Cancer Discov"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1002\/jper.70040"},{"issue":"1","key":"e_1_2_12_107_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.identj.2021.07.006","article-title":"Is there a causal link between periodontitis and cardiovascular disease? A concise review of recent findings","volume":"72","author":"Febbraio M","year":"2022","journal-title":"Int Dent J"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2025.288827"},{"issue":"1","key":"e_1_2_12_109_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-87040-5","article-title":"Association between clonal hematopoiesis and periodontitis: a two\u2010sample mendelian randomization study","volume":"15","author":"Qiu F","year":"2025","journal-title":"Sci Rep"},{"issue":"11","key":"e_1_2_12_110_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25116115","article-title":"The bloody crossroads: interactions between periodontitis and hematologic diseases","volume":"25","author":"Lobacz M","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"1","key":"e_1_2_12_111_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s10529-012-0992-6","article-title":"Analysis of histone deacetylase inhibitor\u2010induced responses in human periodontal ligament fibroblasts","volume":"35","author":"Kim T","year":"2013","journal-title":"Biotechnol Lett"},{"issue":"6","key":"e_1_2_12_112_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/j.1600-0765.2011.01392.x","article-title":"Histone deacetylase inhibitors and periodontal bone loss","volume":"46","author":"Cantley MD","year":"2011","journal-title":"J Periodontal Res"},{"issue":"12","key":"e_1_2_12_113_1","doi-asserted-by":"crossref","first-page":"9691","DOI":"10.1002\/jcp.29780","article-title":"Epigenetic modifier trichostatin a enhanced osteogenic differentiation of mesenchymal stem cells by inhibiting NF\u2010kappaB (p65) DNA binding and promoted periodontal repair in rats","volume":"235","author":"Li Q","year":"2020","journal-title":"J Cell Physiol"},{"issue":"2","key":"e_1_2_12_114_1","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202504201R","article-title":"Butyrate alleviates diabetic periodontitis by suppressing macrophage M1 polarization and PANoptosis\u2010like cell death","volume":"40","author":"Yang W","year":"2026","journal-title":"FASEB J"},{"issue":"1","key":"e_1_2_12_115_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s13148-020-00982-7","article-title":"Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential","volume":"12","author":"Jurdzinski KT","year":"2020","journal-title":"Clin Epigenetics"},{"key":"e_1_2_12_116_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26072853"},{"issue":"6","key":"e_1_2_12_117_1","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1016\/j.apsb.2023.02.007","article-title":"Targeting histone deacetylases for cancer therapy: trends and challenges","volume":"13","author":"Liang T","year":"2023","journal-title":"Acta Pharm Sin B"},{"issue":"2","key":"e_1_2_12_118_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3109\/10717544.2014.935531","article-title":"Advanced drug delivery approaches against periodontitis","volume":"23","author":"Joshi D","year":"2016","journal-title":"Drug Deliv"},{"key":"e_1_2_12_119_1","first-page":"33","article-title":"Wisdom across interfaces: adhesion mechanism and application potential of wet\u2010adhesive hydrogel in periodontal tissue","volume":"56","author":"Duan Q","year":"2026","journal-title":"Bioact Mater"},{"issue":"1","key":"e_1_2_12_120_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12903-023-03512-y","article-title":"Efficacy of curcumin gel as an adjunct to scaling and root planing on salivary procalcitonin level in the treatment of patients with chronic periodontitis: a randomized controlled clinical trial","volume":"23","author":"Abdel\u2010Fatah R","year":"2023","journal-title":"BMC Oral Health"},{"issue":"2","key":"e_1_2_12_121_1","article-title":"A systematic review and meta\u2010analysis on the efficacy of locally delivered adjunctive curcumin (Curcuma longa L.) in the treatment of periodontitis","volume":"11","author":"Wendorff\u2010Tobolla LM","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_12_122_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2017.01682","article-title":"Emerging concepts in the resolution of periodontal inflammation: a role for Resolvin E1","volume":"8","author":"Balta MG","year":"2017","journal-title":"Front Immunol"},{"key":"e_1_2_12_123_1","doi-asserted-by":"crossref","DOI":"10.3389\/froh.2023.1217088","article-title":"Roles of specialized pro\u2010resolving mediators and omega\u20103 polyunsaturated fatty acids in periodontal inflammation and impact on oral microbiota","volume":"4","author":"Lee CT","year":"2023","journal-title":"Front Oral Health"},{"key":"e_1_2_12_124_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mam.2017.04.006","article-title":"Pro\u2010resolving mediators in the regulation of periodontal disease","volume":"58","author":"Van Dyke TE","year":"2017","journal-title":"Mol Asp Med"},{"key":"e_1_2_12_125_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.704163","article-title":"Safety and preliminary efficacy of a novel host\u2010modulatory therapy for reducing gingival inflammation","volume":"12","author":"Hasturk H","year":"2021","journal-title":"Front Immunol"},{"key":"e_1_2_12_126_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1469077","article-title":"Crosstalk between periodontitis and cardiovascular risk","volume":"15","author":"Schulze\u2010Spate U","year":"2024","journal-title":"Front Immunol"},{"issue":"11","key":"e_1_2_12_127_1","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1177\/0022034520933533","article-title":"Targeting NLRP3 Inflammasome reduces age\u2010related experimental alveolar bone loss","volume":"99","author":"Zang Y","year":"2020","journal-title":"J Dent Res"},{"key":"e_1_2_12_128_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2147\/JIR.S449661","article-title":"Updates on the role of periodontitis\u2010related epigenetics, inflammation, Oral microbiome, and treatment in cardiovascular risk","volume":"17","author":"Men B","year":"2024","journal-title":"J Inflamm Res"},{"issue":"12","key":"e_1_2_12_129_1","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory therapy with Canakinumab for atherosclerotic disease","volume":"377","author":"Ridker PM","year":"2017","journal-title":"N Engl J Med"},{"issue":"10118","key":"e_1_2_12_130_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(17)32814-3","article-title":"Relationship of C\u2010reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial","volume":"391","author":"Ridker PM","year":"2018","journal-title":"Lancet"},{"issue":"1","key":"e_1_2_12_131_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cell.2017.11.025","article-title":"Metabolic induction of trained immunity through the mevalonate pathway","volume":"172","author":"Bekkering S","year":"2018","journal-title":"Cell"},{"issue":"1","key":"e_1_2_12_132_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1186\/s12967-023-04456-1","article-title":"Repurposing metformin for periodontal disease management as a form of oral\u2010systemic preventive medicine","volume":"21","author":"Neves VCM","year":"2023","journal-title":"J Transl Med"},{"issue":"10","key":"e_1_2_12_133_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1902\/jop.2017.150096","article-title":"Efficacy of 1% metformin gel in patients with moderate and severe chronic periodontitis: a randomized controlled clinical trial","volume":"88","author":"Pradeep AR","year":"2017","journal-title":"J Periodontol"},{"issue":"6","key":"e_1_2_12_134_1","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1007\/s00784-018-2666-9","article-title":"Effect of adjuvant use of metformin on periodontal treatment: a systematic review and meta\u2010analysis","volume":"23","author":"Nicolini AC","year":"2019","journal-title":"Clin Oral Investig"},{"key":"e_1_2_12_135_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.70020"},{"issue":"6","key":"e_1_2_12_136_1","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.cell.2017.07.032","article-title":"Restoration of TET2 function blocks aberrant self\u2010renewal and leukemia progression","volume":"170","author":"Cimmino L","year":"2017","journal-title":"Cell"},{"issue":"1","key":"e_1_2_12_137_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/prd.12586","article-title":"Artificial intelligence and personalized diagnostics in periodontology: a narrative review","volume":"95","author":"Pitchika V","year":"2024","journal-title":"Periodontol"},{"issue":"2","key":"e_1_2_12_138_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/jre.13104","article-title":"Salivary histone deacetylase in periodontal disease: a cross\u2010sectional pilot study","volume":"58","author":"Liaw A","year":"2023","journal-title":"J Periodontal Res"},{"issue":"6","key":"e_1_2_12_139_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s40291-025-00799-1","article-title":"Salivary biomarkers in periodontal disease: revolutionizing early detection and precision dentistry","volume":"29","author":"Alavi SE","year":"2025","journal-title":"Mol Diagn Ther"},{"issue":"1","key":"e_1_2_12_140_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/jcpe.14061","article-title":"Gingival Crevicular fluid biomarkers during periodontitis progression and after periodontal treatment","volume":"52","author":"Teles F","year":"2025","journal-title":"J Clin Periodontol"},{"issue":"5","key":"e_1_2_12_141_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1111\/jre.12575","article-title":"High\u2010throughput proteomic analysis of candidate biomarker changes in gingival crevicular fluid after treatment of chronic periodontitis","volume":"53","author":"Guzman YA","year":"2018","journal-title":"J Periodontal Res"},{"issue":"1","key":"e_1_2_12_142_1","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1182\/hematology.2025000766","article-title":"Demystifying the diagnosis and management of ICUS, CHIP, and CCUS","volume":"2025","author":"Xie Z","year":"2025","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"1","key":"e_1_2_12_143_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-24475-w","article-title":"Prospective characterization of clonal hematopoiesis and its clinical associations in elderly patients","volume":"15","author":"Moyen TB","year":"2025","journal-title":"Sci Rep"},{"issue":"12","key":"e_1_2_12_144_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2025.114073","article-title":"Distinct immune landscapes between murine and human periodontitis","volume":"28","author":"Zhao Y","year":"2025","journal-title":"iScience"},{"issue":"1","key":"e_1_2_12_145_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s13577-023-00995-3","article-title":"Passaging of gingival fibroblasts from periodontally healthy and diseased sites upregulates osteogenesis\u2010related genes","volume":"37","author":"Karlis GD","year":"2024","journal-title":"Hum Cell"},{"issue":"1","key":"e_1_2_12_146_1","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-021-02116-y","article-title":"DNA methylation changes during long\u2010term in\u00a0vitro cell culture are caused by epigenetic drift","volume":"4","author":"Franzen J","year":"2021","journal-title":"Commun Biol"},{"key":"e_1_2_12_147_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1129577","article-title":"Transmission of stimulus\u2010induced epigenetic changes through cell division is coupled to continuous transcription factor activity","volume":"14","author":"Sun S","year":"2023","journal-title":"Front Immunol"},{"issue":"10","key":"e_1_2_12_148_1","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1111\/jcpe.14203","article-title":"KAT6A promotes macrophage inflammation and periodontitis","volume":"52","author":"Huang SJ","year":"2025","journal-title":"J Clin Periodontol"},{"issue":"10","key":"e_1_2_12_149_1","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/j.cell.2022.03.043","article-title":"Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities","volume":"185","author":"Li X","year":"2022","journal-title":"Cell"},{"issue":"1","key":"e_1_2_12_150_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/jcpe.13389","article-title":"Peripheral T helper cell profiles during management of periodontitis","volume":"48","author":"Medara N","year":"2021","journal-title":"J Clin Periodontol"}],"container-title":["Periodontology 2000"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/prd.70069","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/prd.70069","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/prd.70069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:01:46Z","timestamp":1785326506000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/prd.70069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":149,"alternative-id":["10.1111\/prd.70069"],"URL":"https:\/\/doi.org\/10.1111\/prd.70069","archive":["Portico"],"relation":{},"ISSN":["0906-6713","1600-0757"],"issn-type":[{"value":"0906-6713","type":"print"},{"value":"1600-0757","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"assertion":[{"value":"2026-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"prd.70069"}}