{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:06:19Z","timestamp":1781845579231,"version":"3.54.5"},"reference-count":140,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Periodontitis is a general term for diseases characterised by inflammatory destruction of tooth-supporting tissues, gradual destruction of the marginal periodontal ligament and resorption of alveolar bone. Early-onset periodontitis is due to disturbed neutrophil extracellular trap (NET) formation and clearance. Indeed, mutations that inactivate the cysteine proteases cathepsin C result in the massive periodontal damage seen in patients with deficient NET formation. In contrast, exaggerated NET formation due to polymorphonuclear neutrophil (PMN) hyper-responsiveness drives the pathology of late-onset periodontitis by damaging and ulcerating the gingival epithelium and retarding epithelial healing. Despite the gingival regeneration, periodontitis progression ends with almost complete loss of the periodontal ligament and subsequent tooth loss. Thus, NETs help to maintain periodontal health, and their dysregulation, either insufficiency or surplus, causes heavy periodontal pathology and edentulism.<\/jats:p>","DOI":"10.3390\/cells9122614","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T21:37:42Z","timestamp":1607377062000},"page":"2614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["NETs Are Double-Edged Swords with the Potential to Aggravate or Resolve Periodontal Inflammation"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1249-0161","authenticated-orcid":false,"given":"Ljubomir","family":"Vitkov","sequence":"first","affiliation":[{"name":"Department of Biosciences, Vascular &amp; Exercise Biology Unit, University of Salzburg, 5020 Salzburg, Austria"},{"name":"Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1218-1913","authenticated-orcid":false,"given":"Bernd","family":"Minnich","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Vascular &amp; Exercise Biology Unit, University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-9370","authenticated-orcid":false,"given":"Jasmin","family":"Knopf","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU) and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Schauer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU) and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hannig","sequence":"additional","affiliation":[{"name":"Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-2484","authenticated-orcid":false,"given":"Martin","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU) and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads to neutrophil extracellular traps","volume":"176","author":"Fuchs","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Urban, C.F., Ermert, D., Schmid, M., Abu-Abed, U., Goosmann, C., Nacken, W., Brinkmann, V., Jungblut, P.R., and Zychlinsky, A. (2009). Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000639"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.4049\/jimmunol.1201719","article-title":"Neutrophil Extracellular Traps: Double-Edged Swords of Innate Immunity","volume":"189","author":"Kaplan","year":"2012","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1128\/IAI.00096-14","article-title":"NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis","volume":"82","author":"Grimm","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1073\/pnas.1414055112","article-title":"SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx","volume":"112","author":"Douda","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1136\/annrheumdis-2018-213223","article-title":"Cleaved N-terminal histone tails distinguish between NADPH oxidase (NOX)-dependent and NOX-independent pathways of neutrophil extracellular trap formation","volume":"77","author":"Pieterse","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.201006052","article-title":"Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps","volume":"191","author":"Papayannopoulos","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20100239","article-title":"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps","volume":"207","author":"Li","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/jth.13239","article-title":"Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis","volume":"14","author":"Martinod","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3389\/fcimb.2018.00184","article-title":"Entamoeba histolytica Trophozoites Induce a Rapid Non-classical NETosis Mechanism Independent of NOX2-Derived Reactive Oxygen Species and PAD4 Activity","volume":"8","author":"Fonseca","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.4049\/jimmunol.1202388","article-title":"Neutrophil Extracellular Trap\u2013Associated Protein Activation of the NLRP3 Inflammasome Is Enhanced in Lupus Macrophages","volume":"190","author":"Kahlenberg","year":"2013","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/nm.4027","article-title":"Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease","volume":"22","author":"Lood","year":"2016","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.immuni.2019.07.002","article-title":"Neutrophil Extracellular Traps Initiate Gallstone Formation","volume":"51","author":"Boeltz","year":"2019","journal-title":"Immunity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10973","DOI":"10.1038\/ncomms10973","article-title":"Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis","volume":"7","author":"Leppkes","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Schapher, M., Koch, M., Weidner, D., Scholz, M., Wirtz, S., Mahajan, A., Herrmann, I., Singh, J., Knopf, J., and Leppkes, M. (2020). Neutrophil Extracellular Traps Promote the Development and Growth of Human Salivary Stones. Cells, 9.","DOI":"10.3390\/cells9092139"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1096\/fj.201800752R","article-title":"Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases","volume":"33","author":"Hahn","year":"2018","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nm.3547","article-title":"Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines","volume":"20","author":"Schauer","year":"2014","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.3389\/fimmu.2019.02176","article-title":"Aggregated NETs Sequester and Detoxify Extracellular Histones","volume":"10","author":"Knopf","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/prd.12021","article-title":"Role of genetic factors in the pathogenesis of aggressive periodontitis","volume":"65","author":"Vieira","year":"2014","journal-title":"Periodontology 2000"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1902\/jop.2006.050124","article-title":"Description of Two New Cathepsin C Gene Mutations in Patients With Papillon-Lef\u00e8vre Syndrome","volume":"77","author":"Wani","year":"2006","journal-title":"J. Periodontol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1007\/s10875-011-9572-0","article-title":"Mutations in the ELANE Gene are Associated with Development of Periodontitis in Patients with Severe Congenital Neutropenia","volume":"31","author":"Ye","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.1111\/jcpe.12942","article-title":"Classification and diagnosis of aggressive periodontitis","volume":"45","author":"Fine","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1902\/jop.2003.74.2.219","article-title":"Constitutionally Hyperreactive Neutrophils in Periodontitis","volume":"74","author":"Fredriksson","year":"2003","journal-title":"J. Periodontol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1600-051X.2005.00883.x","article-title":"Hyper-reactive mononuclear cells and neutrophils in chronic periodontitis","volume":"33","author":"Gustafsson","year":"2006","journal-title":"J. Clin. Periodontol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1902\/jop.2007.070107","article-title":"A Hyperactive Neutrophil Phenotype in Patients With Refractory Periodontitis","volume":"78","author":"Johnstone","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1177\/1753425915589387","article-title":"Peripheral blood neutrophil cytokine hyper-reactivity in chronic periodontitis","volume":"21","author":"Ling","year":"2015","journal-title":"Innate Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1365-2249.2006.03276.x","article-title":"Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis: Neutrophil hyperactivity and reactivity in chronic periodontitis","volume":"147","author":"Matthews","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/prd.12232","article-title":"Genetics of periodontitis: Discovery, biology, and clinical impact","volume":"78","author":"Schaefer","year":"2018","journal-title":"Periodontology 2000"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/prd.12227","article-title":"Periodontal complications with age","volume":"78","author":"Persson","year":"2018","journal-title":"Periodontology 2000"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1034\/j.1600-0757.2003.03104.x","article-title":"Gingival crevice fluid flow","volume":"31","author":"Goodson","year":"2003","journal-title":"Periodontology 2000"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/j.1600-0765.2008.01175.x","article-title":"Extracellular neutrophil traps in periodontitis","volume":"44","author":"Vitkov","year":"2009","journal-title":"J. Periodontal Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3109\/01913120903419989","article-title":"Neutrophil Fate in Gingival Crevicular Fluid","volume":"34","author":"Vitkov","year":"2010","journal-title":"Ultrastruct. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1600-051X.1982.tb02108.x","article-title":"Patterns of progression and regression of advanced destructive periodontal disease","volume":"9","author":"Goodson","year":"1982","journal-title":"J. Clin. Periodontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1600-051X.1983.tb01278.x","article-title":"Comparison of different data analyses for detecting changes in attachment level","volume":"10","author":"Haffajee","year":"1983","journal-title":"J. Clin. Periodontol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1600-051X.1984.tb01305.x","article-title":"New concepts of destructive periodontal disease","volume":"11","author":"Socransky","year":"1984","journal-title":"J. Clin. Periodontol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/prd.12297","article-title":"The role of inflammation and genetics in periodontal disease","volume":"83","author":"Loos","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/prd.12181","article-title":"Revisiting the Page & Schroeder model: The good, the bad and the unknowns in the periodontal host response 40 years later","volume":"75","author":"Hajishengallis","year":"2017","journal-title":"Periodontology 2000"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/JLB.1RU0818-310R","article-title":"Macrophage immunomodulation in chronic osteolytic diseases\u2014The case of periodontitis","volume":"105","author":"Sima","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41467-018-03147-6","article-title":"Host defense against oral microbiota by bone-damaging T cells","volume":"9","author":"Tsukasaki","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41577-019-0178-8","article-title":"Osteoimmunology: Evolving concepts in bone\u2013immune interactions in health and disease","volume":"19","author":"Tsukasaki","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/prd.12190","article-title":"Chronic periodontitis and implant dentistry","volume":"74","author":"Smith","year":"2017","journal-title":"Periodontology 2000"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/prd.12148","article-title":"Host modulation therapy with anti-inflammatory agents","volume":"76","author":"Preshaw","year":"2017","journal-title":"Periodontology 2000"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s40496-018-0202-2","article-title":"Age and Periodontal Health\u2014Immunological View","volume":"5","author":"Ebersole","year":"2018","journal-title":"Curr. Oral. Health Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/prd.12192","article-title":"Dental geriatrics and periodontitis","volume":"74","author":"Persson","year":"2017","journal-title":"Periodontology 2000"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.4049\/jimmunol.182.2.1138","article-title":"Increased Reactivity of Dendritic Cells from Aged Subjects to Self-Antigen, the Human DNA","volume":"182","author":"Agrawal","year":"2009","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/mi.2014.64","article-title":"Retinoic acid primes human dendritic cells to induce gut-homing, IL-10-producing regulatory T cells","volume":"8","author":"Bakdash","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1084\/jem.20070590","article-title":"A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism","volume":"204","author":"Coombes","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.0105-2896.2009.00874.x","article-title":"Development and functional specialization of CD103+dendritic cells","volume":"234","author":"Bernhardt","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.18632\/aging.100973","article-title":"Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age","volume":"8","author":"Agrawal","year":"2016","journal-title":"Aging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/mi.2014.28","article-title":"Dendritic cells from aged subjects contribute to chronic airway inflammation by activating bronchial epithelial cells under steady state","volume":"7","author":"Prakash","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"896","DOI":"10.3389\/fimmu.2017.00896","article-title":"Role of Dendritic Cells in Inflammation and Loss of Tolerance in the Elderly","volume":"8","author":"Agrawal","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5304","DOI":"10.3402\/jom.v3i0.5304","article-title":"Review of osteoimmunology and the host response in endodontic and periodontal lesions","volume":"3","author":"Graves","year":"2011","journal-title":"J. Oral Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.smim.2016.02.002","article-title":"Immune and regulatory functions of neutrophils in inflammatory bone loss","volume":"28","author":"Hajishengallis","year":"2016","journal-title":"Semin. Immunol."},{"key":"ref_55","first-page":"160","article-title":"Paradigm Shift in the Pharmacological Management of Periodontal Diseases","volume":"Volume 15","author":"Kinane","year":"2011","journal-title":"Frontiers of Oral Biology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1080\/08916934.2018.1527907","article-title":"Periodontal sources of citrullinated antigens and TLR agonists related to RA","volume":"51","author":"Vitkov","year":"2018","journal-title":"Autoimmunity"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.3389\/fimmu.2017.01404","article-title":"Janus-Faced Neutrophil Extracellular Traps in Periodontitis","volume":"8","author":"Vitkov","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1046\/j.1440-1746.1999.01807.x","article-title":"Increased mucosal production of granulocyte colony-stimulating factor is related to a delay in neutrophil apoptosis in Inflammatory Bowel disease","volume":"14","author":"Ina","year":"1999","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/sj.cdd.4401110","article-title":"Downregulation of caspases and Fas ligand expression, and increased lifespan of neutrophils after transmigration across intestinal epithelium","volume":"10","author":"Rostagno","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lakschevitz, F.S., Aboodi, G.M., and Glogauer, M. (2013). Oral Neutrophil Transcriptome Changes Result in a Pro-Survival Phenotype in Periodontal Diseases. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068983"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/01913120590916832","article-title":"Surface Morphology of Pocket Epithelium","volume":"29","author":"Vitkov","year":"2005","journal-title":"Ultrastruct. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1042\/CBI20090019","article-title":"Expression and localization of cystic fibrosis transmembrane conductance regulator in human gingiva","volume":"34","author":"Ajonuma","year":"2010","journal-title":"Cell Biol. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/jlb.55.3.343","article-title":"Identification and characterization of human neutrophil carbonic anhydrase","volume":"55","author":"Campbell","year":"1994","journal-title":"J. Leukoc. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1432-0436.1993.tb00647.x","article-title":"Expression from the proximal promoter of the carbonic anhydrase 1 gene as a marker for differentiation in colon epithelia","volume":"53","author":"Sowden","year":"1993","journal-title":"Differentiation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s10266-017-0302-9","article-title":"The prominent proteins expressed in healthy gingiva: A pilot exploratory tissue proteomics study","volume":"106","author":"Yaprak","year":"2018","journal-title":"Odontology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12953-015-0089-y","article-title":"Analysis of protein expression in periodontal pocket tissue: A preliminary study","volume":"13","author":"Monari","year":"2015","journal-title":"Proteome Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1600-051X.2011.01805.x","article-title":"Novel protein identification methods for biomarker discovery via a proteomic analysis of periodontally healthy and diseased gingival crevicular fluid samples","volume":"39","author":"Baliban","year":"2012","journal-title":"J. Clin. Periodontol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Tsuchida, S., Satoh, M., Takiwaki, M., and Nomura, F. (2018). Current Status of Proteomic Technologies for Discovering and Identifying Gingival Crevicular Fluid Biomarkers for Periodontal Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010086"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1600-0765.1985.tb00408.x","article-title":"The pH of human crevicular fluid measured by a new microanalytical technique","volume":"20","author":"Bickel","year":"1985","journal-title":"J. Periodontal Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1177\/00220345850640100801","article-title":"Acid-base properties of human gingival crevicular fluid","volume":"64","author":"Bickel","year":"1985","journal-title":"J. Dent. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0003-9969(91)90091-8","article-title":"The pH of gingival crevices and periodontal pockets in children, teenagers and adults","volume":"36","author":"Eggert","year":"1991","journal-title":"Arch. Oral Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41581-019-0163-2","article-title":"Extracellular DNA traps in inflammation, injury and healing","volume":"15","author":"Daniel","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.jcf.2018.11.007","article-title":"Dental and periodontal manifestations in patients with cystic fibrosis\u2014A systematic review","volume":"18","author":"Cofta","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"154987","DOI":"10.1016\/j.cyto.2020.154987","article-title":"Levels of pro- and anti-inflammatory cytokines in cystic fibrosis patients with or without gingivitis","volume":"127","author":"Duruel","year":"2020","journal-title":"Cytokine"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"235","DOI":"10.26444\/aaem\/106087","article-title":"Periodontal condition and periodontal risk assessment in adult patients with cystic fibrosis","volume":"27","year":"2020","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1034\/j.1600-0765.2003.00677.x","article-title":"Gingival crevicular fluid collagenase-2 (MMP-8) test stick for chair-side monitoring of periodontitis","volume":"38","author":"Stenman","year":"2003","journal-title":"J. Periodontal Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1902\/jop.2005.76.6.951","article-title":"Aberrant Neutrophil Reactions in Periodontitis","volume":"76","author":"Figueredo","year":"2005","journal-title":"J. Periodontol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/prd.12101","article-title":"Analysis of matrix metalloproteinases, especially MMP-8, in gingival crevicular fluid, mouthrinse and saliva for monitoring periodontal diseases","volume":"70","author":"Sorsa","year":"2015","journal-title":"Periodontology 2000"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"eaao4227","DOI":"10.1126\/science.aao4227","article-title":"Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice","volume":"361","author":"Albrengues","year":"2018","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Saffarzadeh, M., Juenemann, C., Queisser, M.A., Lochnit, G., Barreto, G., Galuska, S.P., Lohmeyer, J., and Preissner, K.T. (2012). Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032366"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1034\/j.1600-051x.2000.027005313.x","article-title":"Increased amounts of laminin in GCF from untreated patients with periodontitis","volume":"27","author":"Figueredo","year":"2000","journal-title":"J. Clin. Periodontol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1902\/jop.2004.75.10.1387","article-title":"Effectiveness of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid laminin-5 gamma2 chain levels in chronic periodontitis","volume":"75","author":"Emingil","year":"2004","journal-title":"J. Periodontol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1600-051X.2006.00933.x","article-title":"Gingival crevicular fluid laminin-5 gamma2-chain levels in periodontal disease","volume":"33","author":"Emingil","year":"2006","journal-title":"J. Clin. Periodontol."},{"key":"ref_84","unstructured":"(1978). Epidemiology, Etiology, and Prevention of Periodontal Diseases: Report of a WHO Scientific Group, WHO."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/prd.12153","article-title":"The periodontal pocket: Pathogenesis, histopathology and consequences","volume":"76","author":"Bosshardt","year":"2018","journal-title":"Periodontology 2000"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/1348-0421.12672","article-title":"Aggregatibacter actinomycetemcomitans induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin-dependent neutrophil lysis","volume":"63","author":"Hiyoshi","year":"2019","journal-title":"Microbiol. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/jre.12370","article-title":"The histopathological comparison on the destruction of the periodontal tissue between normal junctional epithelium and long junctional epithelium","volume":"52","author":"Noguchi","year":"2016","journal-title":"J. Periodontal Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.4049\/jimmunol.1502353","article-title":"IgA Complexes in Plasma and Synovial Fluid of Patients with Rheumatoid Arthritis Induce Neutrophil Extracellular Traps via FcalphaRI","volume":"197","author":"Aleyd","year":"2016","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.4049\/jimmunol.1400478","article-title":"Immobilized immune complexes induce neutrophil extracellular trap release by human neutrophil granulocytes via FcgammaRIIIB and Mac-1","volume":"193","author":"Behnen","year":"2014","journal-title":"J. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/j.1600-0765.2012.01486.x","article-title":"Topical application of lipopolysaccharide into gingival sulcus promotes periodontal destruction in rats immunized with lipopolysaccharide","volume":"47","author":"Yoshinaga","year":"2012","journal-title":"J. Periodontal Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1600-0528.1989.tb00626.x","article-title":"Cigarette smoking as risk factor in chronic periodontal disease","volume":"17","author":"Bergstrom","year":"1989","journal-title":"Community Dent. Oral Epidemiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1600-051X.2008.01223.x","article-title":"Smoking-attributable periodontal disease in the Australian adult population","volume":"35","author":"Do","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1902\/jop.1993.64.1.16","article-title":"Evidence for Cigarette Smoking as a Major Risk Factor for Periodontitis","volume":"64","author":"Haber","year":"1993","journal-title":"J. Periodontol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1600-0765.2009.01233.x","article-title":"Relationship of smoking and smoking cessation with oral health status in Japanese men","volume":"45","author":"Yanagisawa","year":"2010","journal-title":"J. Periodontal Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1136\/thoraxjnl-2016-209887","article-title":"Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells","volume":"72","author":"Qiu","year":"2017","journal-title":"Thorax"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1165\/ajrcmb.22.2.3809","article-title":"Acute Cigarette Smoke\u2013Induced Connective Tissue Breakdown Is Mediated by Neutrophils and Prevented by \u03b1 1-Antitrypsin","volume":"22","author":"Dhami","year":"2000","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1902\/jop.1979.50.4s.11","article-title":"Bone Loss of Edentulous Alveolar Ridges","volume":"50","author":"Atwood","year":"1979","journal-title":"J. Periodontol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/j.1600-051X.2005.00642.x","article-title":"Dimensional ridge alterations following tooth extraction. An experimental study in the dog","volume":"32","author":"Lindhe","year":"2005","journal-title":"J. Clin. Periodontol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1600-0765.2005.00799.x","article-title":"Application of periodontal ligament cell sheet for periodontal regeneration: A pilot study in beagle dogs","volume":"40","author":"Akizuki","year":"2005","journal-title":"J. Periodontal Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1111\/j.1600-051X.2008.01326.x","article-title":"Periodontal ligament cell sheet promotes periodontal regeneration in athymic rats","volume":"35","author":"Flores","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1089\/biores.2015.0043","article-title":"Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model","volume":"5","author":"Tsumanuma","year":"2016","journal-title":"BioResearch Open Access"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1600-0757.1995.tb00035.x","article-title":"Clinical evaluation of periodontal diseases","volume":"7","author":"Armitage","year":"1995","journal-title":"Periodontology 2000"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1136\/thx.33.2.235","article-title":"Pus, deoxyribonucleic acid, and sputum viscosity","volume":"33","author":"Picot","year":"1978","journal-title":"Thorax"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"9188","DOI":"10.1073\/pnas.87.23.9188","article-title":"Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum","volume":"87","author":"Shak","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1600-051X.1981.tb00887.x","article-title":"Therapeutic considerations in the management of a periodontal abscess with an intrabony defect","volume":"8","author":"Kareha","year":"1981","journal-title":"J. Clin. Periodontol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/prd.12022","article-title":"Acute periodontal lesions","volume":"65","author":"Herrera","year":"2014","journal-title":"Periodontology 2000"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1902\/jop.1979.50.7.350","article-title":"The Predominant Cultivable Microbiota of the Periodontal Abscess","volume":"50","author":"Newman","year":"1979","journal-title":"J. Periodontol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/eos.12182","article-title":"Interindividual variation, correlations, and sex-related differences in the salivary biochemistry of young healthy adults","volume":"123","author":"Prodan","year":"2015","journal-title":"Eur. J. Oral Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/MAJ.0000000000000443","article-title":"Role of Saliva in Esophageal Defense: Implications in Patients With Nonerosive Reflux Disease","volume":"349","author":"Yandrapu","year":"2015","journal-title":"Am. J. Med. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1007\/s10620-014-3099-1","article-title":"Salivary Bicarbonate as a Major Factor in the Prevention of Upper Esophageal Mucosal Injury in Gastroesophageal Reflux Disease","volume":"59","author":"Skoczylas","year":"2014","journal-title":"Dig. Dis. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1182\/blood-2015-04-641142","article-title":"A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa","volume":"126","author":"Mohanty","year":"2015","journal-title":"Blood"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"eaap8798","DOI":"10.1126\/scitranslmed.aap8798","article-title":"Transcriptional signature primes human oral mucosa for rapid wound healing","volume":"10","author":"Uchiyama","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/prd.12114","article-title":"Scaling and root planing vs. conservative surgery in the treatment of chronic periodontitis","volume":"71","author":"Deas","year":"2016","journal-title":"Periodontology 2000"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1161\/CIRCULATIONAHA.107.758524","article-title":"Bacteremia associated with toothbrushing and dental extraction","volume":"117","author":"Lockhart","year":"2008","journal-title":"Circulation"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1600-051X.2008.01372.x","article-title":"Bacteraemia due to dental flossing","volume":"36","author":"Crasta","year":"2009","journal-title":"J. Clin. Periodontol."},{"key":"ref_116","first-page":"213","article-title":"Periodontal health status and bacteraemia from daily oral activities: Systematic review\/meta-analysis","volume":"39","author":"Diz","year":"2011","journal-title":"J. Clin. Periodontol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00402-013-1910-7","article-title":"The effect of gentamicin in irrigating solutions on articular infection prophylaxis during arthroscopic ACL reconstruction","volume":"134","author":"Yazdi","year":"2014","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1161\/01.ATV.0000155018.67835.1a","article-title":"Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis","volume":"25","author":"Kozarov","year":"2005","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1111\/odi.12364","article-title":"Oral bacteria in placental tissues: Increased molecular detection in pregnant periodontitis patients","volume":"21","author":"Blanc","year":"2015","journal-title":"Oral Dis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/nm.3887","article-title":"Diabetes primes neutrophils to undergo NETosis, which impairs wound healing","volume":"21","author":"Wong","year":"2015","journal-title":"Nat. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1177\/1753425919889392","article-title":"Periodontal therapy increases neutrophil extracellular trap degradation","volume":"26","author":"Moonen","year":"2019","journal-title":"Innate Immun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/prd.12298","article-title":"Diabetes as a risk factor for periodontal disease\u2014Plausible mechanisms","volume":"83","author":"Polak","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/prd.12270","article-title":"Diabetes as a potential risk for periodontitis: Association studies","volume":"83","author":"Genco","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1034\/j.1600-051X.2003.00350.x","article-title":"Delayed neutrophil apoptosis in chronic periodontitis patients","volume":"30","author":"Gamonal","year":"2003","journal-title":"J. Clin. Periodontol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"6912","DOI":"10.4049\/jimmunol.178.11.6912","article-title":"Altered Innate Immune Functioning of Dendritic Cells in Elderly Humans: A Role of Phosphoinositide 3-Kinase-Signaling Pathway","volume":"178","author":"Agrawal","year":"2007","journal-title":"J. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1177\/154405910708600806","article-title":"Neutrophil Hyper-responsiveness in Periodontitis","volume":"86","author":"Matthews","year":"2007","journal-title":"J. Dent. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1902\/jop.1982.53.11.659","article-title":"Progressive Replacement of Epithelial Attachment by a Connective Tissue Junction after Experimental Periodontal Surgery in Rats","volume":"53","author":"Listgarten","year":"1982","journal-title":"J. Periodontol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/prd.12003","article-title":"Regenerative periodontal therapy: 30 years of lessons learned and unlearned","volume":"62","author":"Susin","year":"2013","journal-title":"Periodontology 2000"},{"key":"ref_129","first-page":"236","article-title":"Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death","volume":"569","author":"Braster","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/jre.12487","article-title":"Characterization of hyperbranched core-multishell nanocarriers as an innovative drug delivery system for the application at the oral mucosa","volume":"53","author":"Jager","year":"2017","journal-title":"J. Periodontal Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12182","article-title":"The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system","volume":"260","author":"Pelaseyed","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.chom.2019.02.007","article-title":"Neutrophil Extracellular Traps Confine Pseudomonas aeruginosa Ocular Biofilms and Restrict Brain Invasion","volume":"25","author":"Thanabalasuriar","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fimmu.2016.00424","article-title":"Neutrophil Extracellular Traps Form a Barrier between Necrotic and Viable Areas in Acute Abdominal Inflammation","volume":"7","author":"Bilyy","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_134","first-page":"E5856","article-title":"Nanoparticles size-dependently initiate self-limiting NETosis-driven inflammation","volume":"113","author":"Bilyy","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1752-7325.2000.tb04072.x","article-title":"Periodontal disease in American Indians and Alaska Natives","volume":"60","author":"Skrepcinski","year":"2000","journal-title":"J. Public Health Dent."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/prd.12235","article-title":"Periodontal complications of hyperglycemia\/diabetes mellitus: Epidemiologic complexity and clinical challenge","volume":"78","author":"Kocher","year":"2018","journal-title":"Periodontology 2000"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1038\/aps.2011.102","article-title":"Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms","volume":"32","author":"Li","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_138","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":"Sima","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12931-017-0689-4","article-title":"Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma","volume":"18","author":"Vargas","year":"2017","journal-title":"Respir. Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1124\/jpet.112.202879","article-title":"Regulation of Neutrophil Extracellular Trap Formation by Anti-Inflammatory Drugs","volume":"345","author":"Lapponi","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/12\/2614\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:41:56Z","timestamp":1760179316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/12\/2614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,5]]},"references-count":140,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["cells9122614"],"URL":"https:\/\/doi.org\/10.3390\/cells9122614","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,5]]}}}