<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/1563-0625-IIA-3388</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-3388</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title></article-title><trans-title-group xml:lang="en"><trans-title>IMMUNO-INFLAMMATORY ASSESSMENT OF TNF-Α, RANKL, AND CALPROTECTIN IN GINGIVAL CREVICULAR FLUID OF PERIODONTITIS PATIENTS WITH TYPE 1 DIABETES MELLITUS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8804-7302</contrib-id><name-alternatives><name name-style="western" xml:lang="en"><surname>Talib</surname><given-names>E. Q.</given-names></name></name-alternatives><bio xml:lang="en"><p>Assistant Lecturer in Department of Basic Sciences, College of Dentistry, </p></bio><email xlink:type="simple">ehab.q.t@aliraqia.edu.iq</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-9103-2365</contrib-id><name-alternatives><name name-style="western" xml:lang="en"><surname>Mohammed</surname><given-names>H. A.</given-names></name></name-alternatives><bio xml:lang="en"><p>Assistant Lecturer in Department of Clinical Laboratory Science, College of Pharmacy, Al-Nahrain University, Baghdad, Iraq. </p></bio><email xlink:type="simple">haneen.ahmed@nahrainuniv.edu.iq</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Department of Basic Sciences, College of Dentistry, Al-Iraqia University, Baghdad, Iraq.</institution><country>Ирак</country></aff><aff xml:lang="en"><institution>Department of Basic Sciences, College of Dentistry, Al-Iraqia University, Baghdad, Iraq</institution><country>Iraq</country></aff></aff-alternatives><aff xml:lang="en" id="aff-2"><institution>Department of Clinical Laboratory Science, College of Pharmacy, Al-Nahrain University, Baghdad, Iraq</institution><country>Iraq</country></aff><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>06</day><month>08</month><year>2026</year></pub-date><volume>0</volume><issue>0</issue><issue-title>Online First</issue-title><elocation-id>3388</elocation-id><permissions><copyright-statement>Copyright &amp;#x00A9; Talib E.Q., Mohammed H.A., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Talib E.Q., Mohammed H.A.</copyright-holder><copyright-holder xml:lang="en">Talib E.Q., Mohammed H.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.mimmun.ru/mimmun/article/view/3388">https://www.mimmun.ru/mimmun/article/view/3388</self-uri><trans-abstract xml:lang="en"><sec><title>Objectives</title><p>Objectives: This study aimed to evaluate the levels of tumor necrosis factor-alpha (TNF-α), receptor activator of nuclear factor-κB ligand (RANKL), and calprotectin in GCF, as well as serum C-reactive protein (CRP), in periodontitis patients with and without T1DM compared with periodontally healthy controls.</p></sec><sec><title>Materials and Methods</title><p>Materials and Methods: A total of 90 participants were enrolled and divided into three groups (n = 30 each): healthy controls, periodontitis patients without diabetes, and periodontitis patients with T1DM. Clinical periodontal parameters, including probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and bleeding on probing (BOP), were recorded. GCF samples were analyzed for TNF-α, RANKL, and calprotectin using ELISA, while serum CRP and HbA1c levels were measured using automated analyzers. Statistical comparisons were performed using ANOVA and post-hoc tests.</p></sec><sec><title>Results</title><p>Results: Periodontal clinical parameters were significantly worse in both periodontitis groups compared with controls (PD: 3.00 ± 0.00 vs. 4.53 ± 0.51 and 4.63 ± 0.49 mm; CAL: 2.00 ± 0.00 vs. 3.53 ± 0.51 and 3.63 ± 0.49 mm; p &lt; 0.0001). TNF-α levels were significantly elevated in periodontitis patients with T1DM (15.11 ± 2.98 pg/mL) and without diabetes (13.90 ± 2.91 pg/mL) compared with controls (8.72 ± 2.35 pg/mL; p = 0.000). RANKL levels were highest in the diabetic periodontitis group (314.98 ± 74.65 pg/mL) compared with controls (270.46 ± 35.89 pg/mL; p = 0.021). Calprotectin levels showed a significant increase in periodontitis patients with T1DM (0.285 ± 0.149 ng/mL) compared with controls (0.223 ± 0.018 ng/mL; p = 0.017). A strong positive correlation was observed between TNF-α and RANKL in both periodontitis groups (r = 0.812, p &lt; 0.001).</p></sec><sec><title>Conclusion</title><p>Conclusion: Periodontitis is associated with significant elevations in local inflammatory and bone-resorptive biomarkers, with T1DM further amplifying neutrophil-mediated inflammation and osteoclastogenic activity. GCF biomarkers, particularly TNF-α, RANKL, and calprotectin, may serve as valuable adjunctive tools for periodontal disease assessment in diabetic patients.</p></sec></trans-abstract><kwd-group xml:lang="en"><kwd>Periodontitis</kwd><kwd>Type 1 diabetes mellitus</kwd><kwd>Gingival crevicular fluid</kwd><kwd>Inflammatory biomarkers</kwd><kwd>Bone resorption.</kwd></kwd-group><funding-group><funding-statement xml:lang="en">None</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Ray RR. Periodontitis: An Oral Disease with Severe Consequences. Appl Biochem Biotechnol 2023;195:17–32. https://doi.org/10.1007/s12010-022-04127-9.</mixed-citation><mixed-citation xml:lang="en">Ray RR. Periodontitis: An Oral Disease with Severe Consequences. Appl Biochem Biotechnol 2023;195:17–32. https://doi.org/10.1007/s12010-022-04127-9.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Neupane SP, Virtej A, Myhren LE, Bull VH. Biomarkers common for inflammatory periodontal disease and depression: A systematic review. Brain Behav Immun Health 2022;21:100450. https://doi.org/10.1016/j.bbih.2022.100450.</mixed-citation><mixed-citation xml:lang="en">Neupane SP, Virtej A, Myhren LE, Bull VH. Biomarkers common for inflammatory periodontal disease and depression: A systematic review. Brain Behav Immun Health 2022;21:100450. https://doi.org/10.1016/j.bbih.2022.100450.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Salvi GE, Roccuzzo A, Imber J, Stähli A, Klinge B, Lang NP. Clinical periodontal diagnosis. Periodontol 2000 2023. https://doi.org/10.1111/prd.12487.</mixed-citation><mixed-citation xml:lang="en">Salvi GE, Roccuzzo A, Imber J, Stähli A, Klinge B, Lang NP. Clinical periodontal diagnosis. Periodontol 2000 2023. https://doi.org/10.1111/prd.12487.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Jacobs R, Fontenele RC, Lahoud P, Shujaat S, Bornstein MM. Radiographic diagnosis of periodontal diseases – Current evidence versus innovations. Periodontol 2000 2024;95:51–69. https://doi.org/10.1111/prd.12580.</mixed-citation><mixed-citation xml:lang="en">Jacobs R, Fontenele RC, Lahoud P, Shujaat S, Bornstein MM. Radiographic diagnosis of periodontal diseases – Current evidence versus innovations. Periodontol 2000 2024;95:51–69. https://doi.org/10.1111/prd.12580.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Talib EQ, Taha GI. Involvement of interlukin-17A (IL-17A) gene polymorphism and interlukin-23 (IL-23) level in the development of peri-implantitis. BDJ Open 2024;10:12. https://doi.org/10.1038/s41405-024-00193-9.</mixed-citation><mixed-citation xml:lang="en">Talib EQ, Taha GI. Involvement of interlukin-17A (IL-17A) gene polymorphism and interlukin-23 (IL-23) level in the development of peri-implantitis. BDJ Open 2024;10:12. https://doi.org/10.1038/s41405-024-00193-9.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Taha GI, Talib EQ, Abed FB, Hasan IA. A review of microbial pathogens and diagnostic techniques in children’s oral health. Sri Lanka Journal of Child Health 2024;53:355–9. https://doi.org/10.4038/sljch.v53i4.11043.</mixed-citation><mixed-citation xml:lang="en">Taha GI, Talib EQ, Abed FB, Hasan IA. A review of microbial pathogens and diagnostic techniques in children’s oral health. Sri Lanka Journal of Child Health 2024;53:355–9. https://doi.org/10.4038/sljch.v53i4.11043.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Bibi T, Khurshid Z, Rehman A, Imran E, Srivastava KC, Shrivastava D. Gingival Crevicular Fluid (GCF): A Diagnostic Tool for the Detection of Periodontal Health and Diseases. Molecules 2021;26:1208. https://doi.org/10.3390/molecules26051208.</mixed-citation><mixed-citation xml:lang="en">Bibi T, Khurshid Z, Rehman A, Imran E, Srivastava KC, Shrivastava D. Gingival Crevicular Fluid (GCF): A Diagnostic Tool for the Detection of Periodontal Health and Diseases. Molecules 2021;26:1208. https://doi.org/10.3390/molecules26051208.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Koppolu P, Durvasula S, Palaparthy R, Rao M, Sagar V, Reddy SK, Lingam S. Estimate of CRP and TNF-alpha level before and after periodontal therapy in cardiovascular disease patients. Pan African Medical Journal 2013;15. https://doi.org/10.11604/pamj.2013.15.92.2326.</mixed-citation><mixed-citation xml:lang="en">Koppolu P, Durvasula S, Palaparthy R, Rao M, Sagar V, Reddy SK, Lingam S. Estimate of CRP and TNF-alpha level before and after periodontal therapy in cardiovascular disease patients. Pan African Medical Journal 2013;15. https://doi.org/10.11604/pamj.2013.15.92.2326.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Vlachou S, Loumé A, Giannopoulou C, Papathanasiou E, Zekeridou A. Investigating the Interplay: Periodontal Disease and Type 1 Diabetes Mellitus—A Comprehensive Review of Clinical Studies. Int J Mol Sci 2024;25:7299. https://doi.org/10.3390/ijms25137299..</mixed-citation><mixed-citation xml:lang="en">Vlachou S, Loumé A, Giannopoulou C, Papathanasiou E, Zekeridou A. Investigating the Interplay: Periodontal Disease and Type 1 Diabetes Mellitus—A Comprehensive Review of Clinical Studies. Int J Mol Sci 2024;25:7299. https://doi.org/10.3390/ijms25137299.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Wang X, Bao W, Liu J, OuYang Y-Y, Wang D, Rong S, Xiao X, Shan Z-L, Zhang Y, Yao P, Liu L-G. Inflammatory Markers and Risk of Type 2 Diabetes. Diabetes Care 2013;36:166–75. https://doi.org/10.2337/dc12-0702.</mixed-citation><mixed-citation xml:lang="en">Wang X, Bao W, Liu J, OuYang Y-Y, Wang D, Rong S, Xiao X, Shan Z-L, Zhang Y, Yao P, Liu L-G. Inflammatory Markers and Risk of Type 2 Diabetes. Diabetes Care 2013;36:166–75. https://doi.org/10.2337/dc12-0702.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Pan X, Kaminga AC, Wen SW, Liu A. Chemokines in Prediabetes and Type 2 Diabetes: A Meta-Analysis. Front Immunol 2021;12. https://doi.org/10.3389/fimmu.2021.622438.</mixed-citation><mixed-citation xml:lang="en">Pan X, Kaminga AC, Wen SW, Liu A. Chemokines in Prediabetes and Type 2 Diabetes: A Meta-Analysis. Front Immunol 2021;12. https://doi.org/10.3389/fimmu.2021.622438.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Nazar Majeed Z, Philip K, Alabsi AM, Pushparajan S, Swaminathan D. Identification of Gingival Crevicular Fluid Sampling, Analytical Methods, and Oral Biomarkers for the Diagnosis and Monitoring of Periodontal Diseases: A Systematic Review. Dis Markers 2016;2016:1–23. https://doi.org/10.1155/2016/1804727.</mixed-citation><mixed-citation xml:lang="en">Nazar Majeed Z, Philip K, Alabsi AM, Pushparajan S, Swaminathan D. Identification of Gingival Crevicular Fluid Sampling, Analytical Methods, and Oral Biomarkers for the Diagnosis and Monitoring of Periodontal Diseases: A Systematic Review. Dis Markers 2016;2016:1–23. https://doi.org/10.1155/2016/1804727.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Sejersen K, Eriksson M, Larsson A. Calprotectin as a Biomarker for Infectious Diseases: A Comparative Review with Conventional Inflammatory Markers. Int J Mol Sci 2025;26:6476. https://doi.org/10.3390/ijms26136476.</mixed-citation><mixed-citation xml:lang="en">Sejersen K, Eriksson M, Larsson A. Calprotectin as a Biomarker for Infectious Diseases: A Comparative Review with Conventional Inflammatory Markers. Int J Mol Sci 2025;26:6476. https://doi.org/10.3390/ijms26136476.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Wei L, Liu M, Xiong H. Role of Calprotectin as a Biomarker in Periodontal Disease. Mediators Inflamm 2019;2019:1–10. https://doi.org/10.1155/2019/3515026.</mixed-citation><mixed-citation xml:lang="en">Wei L, Liu M, Xiong H. Role of Calprotectin as a Biomarker in Periodontal Disease. Mediators Inflamm 2019;2019:1–10. https://doi.org/10.1155/2019/3515026.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Sereti M, Roy M, Zekeridou A, Gastaldi G, Giannopoulou C. Gingival crevicular fluid biomarkers in type 1 diabetes mellitus: A case–control study. Clin Exp Dent Res 2021;7:170–8. https://doi.org/10.1111/j.1600-051X.2008.01283.x.</mixed-citation><mixed-citation xml:lang="en">Sereti M, Roy M, Zekeridou A, Gastaldi G, Giannopoulou C. Gingival crevicular fluid biomarkers in type 1 diabetes mellitus: A case–control study. Clin Exp Dent Res 2021;7:170–8. https://doi.org/10.1002/cre2.351.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Berglundh T, Armitage G, Araujo MG, Avila‐Ortiz G, Blanco J, Camargo PM, Chen S, Cochran D, Derks J, Figuero E, Hämmerle CHF, Heitz‐Mayfield LJA, Huynh‐Ba G, Iacono V, Koo K, Lambert F, McCauley L, Quirynen M, Renvert S, Salvi GE, Schwarz F, Tarnow D, Tomasi C, Wang H, Zitzmann N. Peri‐implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri‐Implant Diseases and Conditions. J Clin Periodontol 2018;45. https://doi.org/10.1111/jcpe.12957.</mixed-citation><mixed-citation xml:lang="en">Berglundh T, Armitage G, Araujo MG, Avila‐Ortiz G, Blanco J, Camargo PM, Chen S, Cochran D, Derks J, Figuero E, Hämmerle CHF, Heitz‐Mayfield LJA, Huynh‐Ba G, Iacono V, Koo K, Lambert F, McCauley L, Quirynen M, Renvert S, Salvi GE, Schwarz F, Tarnow D, Tomasi C, Wang H, Zitzmann N. Peri‐implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri‐Implant Diseases and Conditions. J Clin Periodontol 2018;45. https://doi.org/10.1111/jcpe.12957.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Renvert S, Persson GR, Pirih FQ, Camargo PM. Peri‐implant health, peri‐implant mucositis, and peri‐implantitis: Case definitions and diagnostic considerations. J Clin Periodontol 2018;45:S278–85. https://doi.org/10.1111/jcpe.12956</mixed-citation><mixed-citation xml:lang="en">Renvert S, Persson GR, Pirih FQ, Camargo PM. Peri‐implant health, peri‐implant mucositis, and peri‐implantitis: Case definitions and diagnostic considerations. J Clin Periodontol 2018;45:S278–85. https://doi.org/10.1111/jcpe.12956</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Silness J, Löe H. Periodontal Disease in Pregnancy II. Correlation Between Oral Hygiene and Periodontal Condition. Acta Odontol Scand 1964;22:121–35. https://doi.org/10.3109/00016356408993968.</mixed-citation><mixed-citation xml:lang="en">Silness J, Löe H. Periodontal Disease in Pregnancy II. Correlation Between Oral Hygiene and Periodontal Condition. Acta Odontol Scand 1964;22:121–35. https://doi.org/10.3109/00016356408993968.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Lindhe J, Meyle J. Peri‐implant diseases: Consensus Report of the Sixth European Workshop on Periodontology. J Clin Periodontol 2008;35:282–5. https://doi.org/10.1111/j.1600-051X.2008.01283.x.</mixed-citation><mixed-citation xml:lang="en">Lindhe J, Meyle J. Peri‐implant diseases: Consensus Report of the Sixth European Workshop on Periodontology. J Clin Periodontol 2008;35:282–5. https://doi.org/10.1111/j.1600-051X.2008.01283.x.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Ali MF, Taha GI. Gingival Crevicular Fluid Volume and Protein Concentration: A Biomarker Tool for Predicting Periodontal Diseases Progression and Severity. Natural and Life Sciences Communications 2024;23. https://doi.org/10.12982/NLSC.2024.055.</mixed-citation><mixed-citation xml:lang="en">Ali MF, Taha GI. Gingival Crevicular Fluid Volume and Protein Concentration: A Biomarker Tool for Predicting Periodontal Diseases Progression and Severity. Natural and Life Sciences Communications 2024;23. https://doi.org/10.12982/NLSC.2024.055.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Malekmahmoodi M, Shamsi M, Roozbahani N, Moradzadeh R. A randomized controlled trial of an educational intervention to promote oral and dental health of patients with type 2 diabetes mellitus. BMC Public Health 2020;20:287. https://doi.org/10.1186/s12889-020-8395-4.</mixed-citation><mixed-citation xml:lang="en">Malekmahmoodi M, Shamsi M, Roozbahani N, Moradzadeh R. A randomized controlled trial of an educational intervention to promote oral and dental health of patients with type 2 diabetes mellitus. BMC Public Health 2020;20:287. https://doi.org/10.1186/s12889-020-8395-4.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Mohan M, Jhingran R, Bains VK, Gupta V, Madan R, Rizvi I, Mani K. Impact of scaling and root planing on C-reactive protein levels in gingival crevicular fluid and serum in chronic periodontitis patients with or without diabetes mellitus. J Periodontal Implant Sci 2014;44:158. https://doi.org/10.5051/jpis.2014.44.4.158.</mixed-citation><mixed-citation xml:lang="en">Mohan M, Jhingran R, Bains VK, Gupta V, Madan R, Rizvi I, Mani K. Impact of scaling and root planing on C-reactive protein levels in gingival crevicular fluid and serum in chronic periodontitis patients with or without diabetes mellitus. J Periodontal Implant Sci 2014;44:158. https://doi.org/10.5051/jpis.2014.44.4.158.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Bastos AS, Graves DT, Loureiro AP de M, Rossa Júnior C, Abdalla DSP, Faulin T do ES, Olsen Câmara N, Andriankaja OM, Orrico SRP. Lipid Peroxidation Is Associated with the Severity of Periodontal Disease and Local Inflammatory Markers in Patients with Type 2 Diabetes. J Clin Endocrinol Metab 2012;97:E1353–62. https://doi.org/10.1210/jc.2011-3397.</mixed-citation><mixed-citation xml:lang="en">Bastos AS, Graves DT, Loureiro AP de M, Rossa Júnior C, Abdalla DSP, Faulin T do ES, Olsen Câmara N, Andriankaja OM, Orrico SRP. Lipid Peroxidation Is Associated with the Severity of Periodontal Disease and Local Inflammatory Markers in Patients with Type 2 Diabetes. J Clin Endocrinol Metab 2012;97:E1353–62. https://doi.org/10.1210/jc.2011-3397.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Almeida-Junior LA, de Carvalho MS, Almeida LKY, Silva-Sousa AC, Sousa-Neto MD, Silva RAB, Silva LAB, Paula-Silva FWG. TNF-α–TNFR1 Signaling Mediates Inflammation and Bone Resorption in Apical Periodontitis. J Endod 2023;49:1319-1328.e2. https://doi.org/10.1016/j.joen.2023.07.013.</mixed-citation><mixed-citation xml:lang="en">Almeida-Junior LA, de Carvalho MS, Almeida LKY, Silva-Sousa AC, Sousa-Neto MD, Silva RAB, Silva LAB, Paula-Silva FWG. TNF-α–TNFR1 Signaling Mediates Inflammation and Bone Resorption in Apical Periodontitis. J Endod 2023;49:1319-1328.e2. https://doi.org/10.1016/j.joen.2023.07.013.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">López-Valverde N, Quispe-López N, Blanco Rueda JA. Inflammation and immune response in the development of periodontal disease: a narrative review. Front Cell Infect Microbiol 2024;14. https://doi.org/10.3389/fcimb.2024.1493818.</mixed-citation><mixed-citation xml:lang="en">López-Valverde N, Quispe-López N, Blanco Rueda JA. Inflammation and immune response in the development of periodontal disease: a narrative review. Front Cell Infect Microbiol 2024;14. https://doi.org/10.3389/fcimb.2024.1493818.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Barutta F, Bellini S, Durazzo M, Gruden G. Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis. Biomedicines 2022;10:178. https://doi.org/10.3390/biomedicines10010178.</mixed-citation><mixed-citation xml:lang="en">Barutta F, Bellini S, Durazzo M, Gruden G. Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis. Biomedicines 2022;10:178. https://doi.org/10.3390/biomedicines10010178.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
