{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:35:24Z","timestamp":1781181324813,"version":"3.54.1"},"reference-count":66,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Research Support of State of S\u00e3o Paulo\u2014FAPESP","award":["2007\/08362-8"],"award-info":[{"award-number":["2007\/08362-8"]}]},{"name":"Foundation for Research Support of State of S\u00e3o Paulo\u2014FAPESP","award":["2009\/16233-9"],"award-info":[{"award-number":["2009\/16233-9"]}]},{"name":"Foundation for Research Support of State of S\u00e3o Paulo\u2014FAPESP","award":["2014\/16148-0"],"award-info":[{"award-number":["2014\/16148-0"]}]},{"name":"Foundation for Research Support of State of S\u00e3o Paulo\u2014FAPESP","award":["2015\/08678-1"],"award-info":[{"award-number":["2015\/08678-1"]}]},{"name":"Foundation for Research Support of State of S\u00e3o Paulo\u2014FAPESP","award":["2024\/153530"],"award-info":[{"award-number":["2024\/153530"]}]},{"DOI":"10.13039\/501100000106","name":"Saskatchewan Health Research Foundation","doi-asserted-by":"publisher","award":["Grant#5273"],"award-info":[{"award-number":["Grant#5273"]}],"id":[{"id":"10.13039\/501100000106","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["Grant#PJT-159760"],"award-info":[{"award-number":["Grant#PJT-159760"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["Grant#MOP-106657"],"award-info":[{"award-number":["Grant#MOP-106657"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["Grant# 2020\/06119"],"award-info":[{"award-number":["Grant# 2020\/06119"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["Grant#37442"],"award-info":[{"award-number":["Grant#37442"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human whole saliva contains informative proteins related to disease processes and is important for oral cavity homeostasis. The aim of this study was to investigate the global salivary proteomic profile, including functional enrichment analysis of individuals affected by combinations of poorly\/well-controlled type 2 diabetes mellitus (T2DM), dyslipidemia (DL), and periodontitis (P) for the identification of potential disease biomarkers. Biochemical and periodontal evaluations were performed on 150 subjects divided into five groups according to disease combinations. Unstimulated saliva was collected, and proteomic analysis was performed using Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS\/MS). Results were obtained by searching for the Homo sapiens database of the UniProt catalog using Proteome Discoverer 1.3. PANTHER GO-Slim (PANTHER version 19.0), and Cytoscape 3.10.1 (extensions Metascape) were used to access biological pathways. A total of 1762 proteins were identified in saliva samples. The proteomic profile of T2DM-DL-P groups (G1\u2014poorly controlled T2DM; G2\u2014well-controlled T2DM) were the most diverse and functionally enriched. In G1 and G3, the most abundant protein was TTN, with ENO-1 being highly enriched and associated with the aerobic glycolysis pathway and PFN1 associated with a pro-inflammatory environment. PFN1 was highly enriched in (G1) AKIRIN-2 (immune response), and in (G2) KMT2A (epigenetic regulation) and CALML3 (DNA metabolism and repair). For (G4), the highest abundant protein was RIMS-1, with VIRMA (cytoskeletal organization) being the most enriched. The global salivary proteomics analyses demonstrated significantly altered protein profiles in each group of different pathological combinations, providing new insights into their biology and identifying potential diagnostic and therapeutic candidates for these diseases of growing global concern.<\/jats:p>","DOI":"10.3390\/ijms262411778","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:17:07Z","timestamp":1764940627000},"page":"11778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Global Salivary Proteomic Profiling of Individuals with the Co-Occurrence of Type 2 Diabetes Mellitus, Dyslipidemia, and Periodontitis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-0268","authenticated-orcid":false,"given":"Raquel Mantuaneli","family":"Scarel-Caminaga","sequence":"first","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-2059","authenticated-orcid":false,"given":"Fran\u00e7ois Isnaldo Dias","family":"Caldeira","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-903, SP, Brazil"},{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-385, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-6072","authenticated-orcid":false,"given":"S\u00e2mia Cruz Tfaile","family":"Corbi","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-903, SP, Brazil"},{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-385, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-7385","authenticated-orcid":false,"given":"Diego Girotto","family":"Bussaneli","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-9066","authenticated-orcid":false,"given":"Alliny de Souza","family":"Bastos","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-385, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-8526","authenticated-orcid":false,"given":"Silvana Regina Perez","family":"Orrico","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP-S\u00e3o Paulo State University, Araraquara 14801-385, SP, Brazil"},{"name":"Advanced Research Center in Medicine, Union of the Colleges of the Great Lakes (UNILAGO), S\u00e3o Jos\u00e9 do Rio Preto 15030-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-5064","authenticated-orcid":false,"given":"Cristiane Ribeiro","family":"Salmon","sequence":"additional","affiliation":[{"name":"Dental Research Division, School of Dentistry, Paulista University, S\u00e3o Paulo 04026-002, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-3658","authenticated-orcid":false,"given":"Walter Luiz","family":"Siqueira","sequence":"additional","affiliation":[{"name":"College of Dentistry, University of Saskatchewan, Saskatoon, SK S7N 5E4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Matsuoka, M., Soria, S.A., Pires, J.R., Sant\u2019Ana, A.C.P., and Freire, M. (2025). Natural and induced immune responses in oral cavity and saliva. BMC Immunol., 26.","DOI":"10.1186\/s12865-025-00713-8"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Khurshid, Z., Zohaib, S., Najeeb, S., Zafar, M.S., Slowey, P.D., and Almas, K. (2016). Human saliva collection devices for proteomics: An update. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060846"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"140494","DOI":"10.1016\/j.bbapap.2020.140494","article-title":"Proteomic advances in salivary diagnostics","volume":"1868","author":"Pappa","year":"2020","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cca.2012.11.001","article-title":"Salivary proteomics in biomedical research","volume":"415","author":"Zhang","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1039\/c3mb70196d","article-title":"Salivary proteins associated with hyperglycemia in diabetes: A proteomic analysis","volume":"9","author":"Bencharit","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jia, S.Y., Zhang, Y.L., Sun, X.Y., Yuan, C., and Zheng, S.G. (2021). Impact of the glycemic level on the salivary proteome of middle-aged and elderly people with type 2 diabetes mellitus: An observational study. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.790091"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1194\/jlr.M500161-JLR200","article-title":"A proteomic study of the apolipoproteins in LDL subclasses in patients with the metabolic syndrome and type 2 diabetes","volume":"46","author":"Davidsson","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1074\/mcp.M600326-MCP200","article-title":"Compositional protein analysis of high density lipoproteins in hypercholesterolemia by shotgun LC-MS\/MS and probabilistic peptide scoring","volume":"6","author":"Heller","year":"2007","journal-title":"Mol. Cell Proteom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/jre.13357","article-title":"Salivary proteomics for detecting novel biomarkers of periodontitis: A systematic review","volume":"60","author":"Corana","year":"2025","journal-title":"J. Periodontal Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yadalam, P.K., Arumuganainar, D., Ronsivalle, V., Di Blasio, M., Badnjevic, A., Marrapodi, M.M., Cervino, G., and Minervini, G. (2024). Prediction of interactomic hub genes in PBMC cells in type 2 diabetes mellitus, dyslipidemia, and periodontitis. BMC Oral Health, 24.","DOI":"10.1186\/s12903-024-04041-y"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e033350","DOI":"10.1161\/JAHA.123.033350","article-title":"Saliva, plasma, and multifluid metabolomic signatures of periodontal disease, type 2 diabetes progression, and markers of glycemia and dyslipidemia among Puerto Rican adults with overweight and obesity","volume":"13","author":"Wang","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/jre.13033","article-title":"Relationship between periodontal status and dyslipidemia in patients with type 2 diabetic nephropathy and chronic periodontitis: A cross-sectional study","volume":"57","author":"Zhang","year":"2022","journal-title":"J. Periodontal Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yekani, M., Dastgir, M., Fattahi, S., Shahi, S., Maleki Dizaj, S., and Memar, M.Y. (2025). Microbiological and molecular aspects of periodontitis pathogenesis: An infection-induced inflammatory condition. Front. Cell Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1533658"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/jcpe.12808","article-title":"Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology","volume":"45","author":"Sanz","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.diabres.2011.11.017","article-title":"Lipid profile of people with diabetes mellitus type 2 and periodontal disease","volume":"96","author":"Nassar","year":"2012","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/sdi.12022","article-title":"Periodontal diseases and systemic inflammation","volume":"26","author":"Craig","year":"2013","journal-title":"Semin. Dial."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 2. Diagnosis and classification of diabetes: Standards of care in diabetes\u20132025. Diabetes Care, 48, S27\u2013S49.","DOI":"10.2337\/dc25-S002"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2174\/187152612801319302","article-title":"Inflammatory mechanisms and redox status in periodontal and cardiometabolic diseases: Effects of adjunctive nutritional antioxidants and statins","volume":"12","author":"Soory","year":"2012","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bitencourt, F.V., Nascimento, G.G., Costa, S.A., Orrico, S.R.P., Ribeiro, C.C.C., and Leite, F.R.M. (2023). The role of dyslipidemia in periodontitis. Nutrients, 15.","DOI":"10.3390\/nu15020300"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100763","DOI":"10.1016\/j.xcrm.2022.100763","article-title":"Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes, and normal tissues","volume":"3","author":"Diamanti","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s10096-010-1101-1","article-title":"C-reactive protein as a systemic marker of inflammation in periodontitis","volume":"30","author":"Pejcic","year":"2011","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, C.Z., Yuan, Y.H., Liu, H.H., Li, S.S., Zhang, B.W., Chen, W., An, Z.J., Chen, S.Y., Wu, Y.Z., and Han, B. (2020). Epidemiologic relationship between periodontitis and type 2 diabetes mellitus. BMC Oral Health, 20.","DOI":"10.1186\/s12903-020-01180-w"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/0022034514552491","article-title":"Global burden of severe periodontitis in 1990\u20132010: A systematic review and meta-regression","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/idh.12789","article-title":"The impact of different states of type 2 diabetes when stratified by baseline HbA1c on the periodontal outcomes of non-surgical periodontal treatment: A systematic review and network meta-analysis","volume":"22","author":"Kang","year":"2024","journal-title":"Int. J. Dent. Hyg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1016\/j.dsx.2019.07.003","article-title":"Systemic expression of genes related to inflammation and lipid metabolism in patients with dyslipidemia, type 2 diabetes mellitus and chronic periodontitis","volume":"13","author":"Nepomuceno","year":"2019","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.bpj.2009.05.037","article-title":"Modulation of titin-based stiffness by disulfide bonding in the cardiac titin N2-B unique sequence","volume":"97","author":"Grutzner","year":"2009","journal-title":"Biophys. J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Stroik, D., Gregorich, Z.R., Raza, F., Ge, Y., and Guo, W. (2024). Titin: Roles in cardiac function and diseases. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1385821"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1161\/CIRCRESAHA.117.312166","article-title":"Diabetes-induced cardiomyocyte passive stiffening is caused by impaired insulin-dependent titin modification and can be modulated by neuregulin-1","volume":"123","author":"Hopf","year":"2018","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s40618-024-02490-4","article-title":"Urinary titin as a biomarker of sarcopenia in diabetes: A propensity score matching analysis","volume":"48","author":"Takiguchi","year":"2025","journal-title":"J. Endocrinol. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1007\/s00018-020-03531-w","article-title":"Akirin proteins in development and disease: Critical roles and mechanisms of action","volume":"77","author":"Bosch","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1007\/s00125-022-05735-0","article-title":"Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease","volume":"65","author":"Sandholm","year":"2022","journal-title":"Diabetologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/BF00570890","article-title":"Purification and characterization of immunoglobulin production stimulating factor-II beta derived from Namalwa cells","volume":"10","author":"Sugahara","year":"1992","journal-title":"Cytotechnology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/ajh.10299","article-title":"Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-enolase","volume":"72","author":"Longstaff","year":"2003","journal-title":"Am. J. Hematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.2337\/db17-0194","article-title":"The histone methyltransferase MLL1 directs macrophage-mediated inflammation in wound healing and is altered in a murine model of obesity and type 2 diabetes","volume":"66","author":"Kimball","year":"2017","journal-title":"Diabetes"},{"key":"ref_35","first-page":"405","article-title":"Metformin suppresses gastric cancer progression through calmodulin-like protein 3 secreted from tumor-associated fibroblasts","volume":"41","author":"Chen","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1016\/j.celrep.2019.04.060","article-title":"PLEKHA4\/kramer attenuates Dishevelled ubiquitination to modulate Wnt and planar cell polarity signaling","volume":"27","author":"Batrouni","year":"2019","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1042\/bj3510019","article-title":"Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities","volume":"351","author":"Dowler","year":"2000","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00784-025-06171-1","article-title":"Salivary proteomic analysis in patients with type 2 diabetes mellitus and periodontitis","volume":"29","author":"Furukawa","year":"2025","journal-title":"Clin. Oral Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1107\/S0907444908008561","article-title":"Structure of human alpha-enolase (hENO1), a multifunctional glycolytic enzyme","volume":"64","author":"Kang","year":"2008","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1074\/mcp.RA118.000718","article-title":"Targeted proteomics guided by label-free quantitative proteome analysis in saliva reveal transition signatures from health to periodontal disease","volume":"17","author":"Bostanci","year":"2018","journal-title":"Mol. Cell Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/jcpe.13803","article-title":"Salivary annexin A1: A candidate biomarker for periodontitis","volume":"50","author":"Casarin","year":"2023","journal-title":"J. Clin. Periodontol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/jcpe.13630","article-title":"Discovery, validation, and diagnostic ability of multiple protein-based biomarkers in saliva and gingival crevicular fluid to distinguish between health and periodontal diseases","volume":"49","author":"Grant","year":"2022","journal-title":"J. Clin. Periodontol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/jcpe.12130","article-title":"Identification of periodontitis associated changes in the proteome of whole human saliva by mass spectrometric analysis","volume":"40","author":"Salazar","year":"2013","journal-title":"J. Clin. Periodontol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Caglayan, E., Romeo, G.R., Kappert, K., Odenthal, M., S\u00fcdkamp, M., Body, S.C., Shernan, S.K., Hackbusch, D., Vantler, M., and Kazlauskas, A. (2010). Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013608"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.2337\/db13-0050","article-title":"Profilin-1 haploinsufficiency protects against obesity-associated glucose intolerance and preserves adipose tissue immune homeostasis","volume":"62","author":"Romeo","year":"2013","journal-title":"Diabetes"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"159072","DOI":"10.1016\/j.bbalip.2021.159072","article-title":"The HDL Proteome Watch: Compilation of studies leads to new insights on HDL function","volume":"1867","author":"Davidson","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"363","DOI":"10.2478\/acph-2023-0034","article-title":"Rosuvastatin effects on the HDL proteome in hyperlipidemic patients","volume":"73","author":"Vavlukis","year":"2023","journal-title":"Acta Pharm."},{"key":"ref_48","first-page":"8112","article-title":"Evaluation of profilin 1 as a biomarker in myocardial infarction","volume":"24","author":"Paszek","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_49","unstructured":"(2025, October 12). GeneCards. RIMS1 Gene\u2014Regulating Synaptic Membrane Exocytosis 1. Available online: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=RIMS1."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41421-018-0019-0","article-title":"VIRMA mediates preferential m6A mRNA methylation in 3\u2032UTR and near stop codon and associates with alternative polyadenylation","volume":"4","author":"Yue","year":"2018","journal-title":"Cell Discov."},{"key":"ref_51","unstructured":"(2025, October 12). AHNAK Gene\u2014AHNAK Nucleoprotein. Available online: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=AHNAK."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100431","DOI":"10.1016\/j.jgeb.2024.100431","article-title":"Identification of key signaling pathways and novel computational drug target for oral cancer, metabolic disorders and periodontal disease","volume":"22","author":"Alam","year":"2024","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_53","first-page":"392","article-title":"A summary on the genetics of systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and Sjogren\u2019s syndrome","volume":"64","author":"Martin","year":"2023","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.identj.2024.07.1212","article-title":"Research trends in the comorbidity between periodontitis and neurodegenerative diseases","volume":"75","author":"Han","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_55","first-page":"35","article-title":"Periodontitis in Chediak\u2013Higashi syndrome: An altered immunoinflammatory response","volume":"3","author":"Reboucas","year":"2018","journal-title":"JDR Clin. Trans. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e20170561","DOI":"10.1590\/1678-7757-2017-0561","article-title":"Standardization of a protocol for shotgun proteomic analysis of saliva","volume":"26","author":"Ventura","year":"2018","journal-title":"J. Appl. Oral Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8145","DOI":"10.1038\/s41598-020-65042-9","article-title":"Circulating lymphocytes and monocytes transcriptomic analysis of patients with type 2 diabetes mellitus, dyslipidemia and periodontitis","volume":"10","author":"Corbi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"(2002). National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 106, 3143\u20133421.","DOI":"10.1161\/circ.106.25.3143"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"89","author":"Tonetti","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Carvalho, J.G., Leite Ade, L., Peres-Buzalaf, C., Salvato, F., Labate, C.A., Everett, E.T., Whitford, G.M., and Buzalaf, M.A. (2013). Renal proteome in mice with different susceptibilities to fluorosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053261"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1002\/pmic.200700017","article-title":"Diabetes-induced changes in the renal cortical proteome assessed with two-dimensional gel electrophoresis and mass spectrometry","volume":"7","author":"Tilton","year":"2007","journal-title":"Proteomics"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Siqueira, W.L., Bakkal, M., Xiao, Y., Sutton, J.N., and Mendes, F.M. (2012). Quantitative proteomic analysis of the effect of fluoride on the acquired enamel pellicle. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042204"},{"key":"ref_63","unstructured":"Ohm Robin, A., Nicolas, F., Bernard, H., Schoch Conrad, L., Horwitz Benjamin, A., Barry Kerrie, W., Condon Bradford, J., Copeland Alex, C., Braham, D., and Fabian, G. (2007). An interactive tool for comparing lists with Venn diagrams. BioinfoGP."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bader, G.D., and Hogue, C.W. (2003). An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform., 4.","DOI":"10.1186\/1471-2105-4-2"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11778\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T08:12:59Z","timestamp":1769674379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":66,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411778"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411778","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]}}}