{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T17:15:43Z","timestamp":1781370943110,"version":"3.54.1"},"reference-count":94,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,2]],"date-time":"2023-07-02T00:00:00Z","timestamp":1688256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Cleft palate is one of the most common and well-studied congenital anomalies; however, the role of protective tissue factors in its pathophysiology is still debated. The aim of our study was to evaluate interleukin and antimicrobial peptide appearance and distribution in cleft palate. Eight soft palate samples were obtained during veloplasty procedures. Immunohistochemical staining was applied to detect HBD-2-, HBD-3-, HBD-4-, LL-37-, IL-10-, and CD-163-positive cells via light microscopy. For statistical evaluation, the Mann\u2013Whitney U test and Spearman\u2019s rank correlation coefficient were used. A significant difference between study groups was observed for HBD-2 and IL-10 in epithelial and connective tissue as well as HBD-4 in connective tissue. The number of HBD-3-positive cells was moderate in the patients, and few were observed in the controls. The number of LL-37-positive cells varied from a moderate amount to a numerous amount in both study groups, whilst CD-163 marked a moderate number of positive cells in patients, and a few-to-moderate amount was observed in the controls. Numerous correlations between studied factors were revealed in cleft tissues. The increase in antimicrobial peptides HBD-2 and HBD-4 and anti-inflammatory cytokine IL-10 suggested a wide compensatory elevation of the local immune system against cleft-raised tissue changes. The correlations between the studied factors (HBD-2, HBD-3, HBD-4, LL-37, and IL-10) proved the synergistic involvement of common local defense factors in postnatal cleft palate morphopathogenesis.<\/jats:p>","DOI":"10.3390\/children10071162","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:34:08Z","timestamp":1688344448000},"page":"1162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antimicrobial Peptides and Interleukins in Cleft Soft Palate"],"prefix":"10.3390","volume":"10","author":[{"given":"Arina","family":"De\u0146isova","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda Boulevard 9, LV-1010 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-4666","authenticated-orcid":false,"given":"M\u0101ra","family":"Pilmane","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda Boulevard 9, LV-1010 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0816-6446","authenticated-orcid":false,"given":"Dzintra","family":"Ka\u017eoka","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda Boulevard 9, LV-1010 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,2]]},"reference":[{"key":"ref_1","first-page":"S11","article-title":"Global Birth Prevalence of Orofacial Clefts: A Systematic Review","volume":"98","author":"Panamonta","year":"2015","journal-title":"J. Med. Assoc. Thai."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.4103\/jfmpc.jfmpc_472_20","article-title":"Cleft of lip and palate: A review","volume":"9","author":"Vyas","year":"2020","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1597\/05-177","article-title":"Neonatal care of infants with cleft lip and\/or palate: Feeding orientation and evolution of weight gain in a nonspecialized Brazilian hospital","volume":"44","author":"Magna","year":"2007","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_4","first-page":"139","article-title":"Caries Experience and Periodontal Status in Children and Adolescents with Cleft Lip and Palate","volume":"39","author":"Veiga","year":"2017","journal-title":"Pediatr. Dent."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1177\/10556656211028494","article-title":"Factors Associated with Psychological Adjustment in Adults With Cleft Lip and\/or Palate: Findings From a National Survey in the United Kingdom","volume":"59","author":"Costa","year":"2022","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrg2933","article-title":"Cleft lip and palate: Understanding genetic and environmental influences","volume":"12","author":"Dixon","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.4103\/0970-0358.57187","article-title":"Syndromes and anomalies associated with cleft","volume":"42","author":"Venkatesh","year":"2009","journal-title":"Indian J. Plast. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1093\/hmg\/ddn121","article-title":"Variation in WNT genes is associated with non-syndromic cleft lip with or without cleft palate","volume":"17","author":"Chiquet","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0722.2011.00938.x","article-title":"Genotype and haplotype analysis of WNT genes in non-syndromic cleft lip with or without cleft palate","volume":"120","author":"Mostowska","year":"2012","journal-title":"Eur. J. Oral Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, L., Wang, H., Yang, L., Zhao, M., Guo, Y., Bovet, P., and Xi, B. (2022). Maternal cigarette smoking before or during pregnancy increases the risk of birth congenital anomalies: A population-based retrospective cohort study of 12 million mother-infant pairs. BMC Med., 20.","DOI":"10.1186\/s12916-021-02196-x"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s10654-016-0171-5","article-title":"Maternal alcohol binge-drinking in the first trimester and the risk of orofacial clefts in offspring: A large population-based pooling study","volume":"31","author":"DeRoo","year":"2016","journal-title":"Eur. J. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.annepidem.2015.05.003","article-title":"Parental age and the risk of isolated cleft lip: A registry-based study","volume":"25","author":"Berg","year":"2015","journal-title":"Ann. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1128\/IAI.67.6.2740-2745.1999","article-title":"Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands","volume":"67","author":"Mathews","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1369\/0022155416656940","article-title":"Labial Salivary Glands in Infants: Histochemical Analysis of Cytoskeletal and Antimicrobial Proteins","volume":"64","author":"Stoeckelhuber","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12971-015-0029-8","article-title":"Effects of whole cigarette smoke on human beta defensins expression and secretion by oral mucosal epithelial cells","volume":"13","author":"Wang","year":"2015","journal-title":"Tob. Induc. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.archoralbio.2016.01.012","article-title":"The expression of human \u03b2-defensins (hBD-1, hBD-2, hBD-3, hBD-4) in gingival epithelia","volume":"66","author":"Li","year":"2016","journal-title":"Arch. Oral Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1365-2249.2006.03200.x","article-title":"Innate immune peptide LL-37 displays distinct expression pattern from beta-defensins in inflamed gingival tissue","volume":"146","author":"Hosokawa","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1038\/s41598-017-01661-z","article-title":"CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma","volume":"7","author":"Kubota","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1044249","DOI":"10.3389\/fimmu.2022.1044249","article-title":"Orofacial clefts lead to increased pro-inflammatory cytokine levels on neonatal oral mucosa","volume":"13","author":"Seidel","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Casaroto, A.R., da Silva, R.A., Salmeron, S., Rezende, M.L.R., Dion\u00edsio, T.J., Santos, C.F.D., Pinke, K.H., Klingbeil, M.F.G., Salom\u00e3o, P.A., and Lopes, M.M.R. (2019). Candida albicans-Cell Interactions Activate Innate Immune Defense in Human Palate Epithelial Primary Cells via Nitric Oxide (NO) and \u03b2-Defensin 2 (hBD-2). Cells, 8.","DOI":"10.3390\/cells8070707"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cie\u015blik, M., Bagi\u0144ska, N., G\u00f3rski, A., and Jo\u0144czyk-Matysiak, E. (2021). Human \u03b2-Defensin 2 and Its Postulated Role in Modulation of the Immune Response. Cells, 10.","DOI":"10.3390\/cells10112991"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.peptides.2012.09.013","article-title":"Enhanced expression of human \u03b2-defensin 2 in peripheral lungs of patients with chronic obstructive pulmonary disease","volume":"38","author":"Liao","year":"2012","journal-title":"Peptides"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/hel.12000","article-title":"Differential expression of human beta defensin 2 and 3 in gastric mucosa of Helicobacter pylori-infected individuals","volume":"18","author":"Bauer","year":"2013","journal-title":"Helicobacter"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/sj.jid.5700599","article-title":"Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines","volume":"127","author":"Niyonsaba","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.bjoms.2011.07.006","article-title":"Quantitative comparison of the expression of antimicrobial peptides in the oral mucosa and extraoral skin","volume":"50","author":"Kesting","year":"2012","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_26","first-page":"103","article-title":"Expression of gene proteins, interleukins and \u03b2-defensin in cleft-affected tissue","volume":"19","author":"Jankovska","year":"2017","journal-title":"Stomatologija"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5793","DOI":"10.3748\/wjg.v12.i36.5793","article-title":"Human beta-defensin-3 induction in H. pylori-infected gastric mucosal tissues","volume":"12","author":"Kawauchi","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1183\/09031936.06.00105904","article-title":"Identification of hBD-3 in respiratory tract and serum: The increase in pneumonia","volume":"27","author":"Ishimoto","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_29","first-page":"6157491","article-title":"The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes","volume":"2017","author":"Bayer","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/eji.200636379","article-title":"Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability","volume":"37","author":"Chen","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/jid.2012.319","article-title":"Human beta-defensin 3 induces maturation of human langerhans cell-like dendritic cells: An antimicrobial peptide that functions as an endogenous adjuvant","volume":"133","author":"Ferris","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/eji.201646799","article-title":"Human \u03b2-defensin 3 increases the TLR9-dependent response to bacterial DNA","volume":"47","author":"McGlasson","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"712781","DOI":"10.3389\/fimmu.2021.712781","article-title":"The Antimicrobial Peptide Human \u03b2-Defensin-3 Accelerates Wound Healing by Promoting Angiogenesis, Cell Migration, and Proliferation Through the FGFR\/JAK2\/STAT3 Signaling Pathway","volume":"12","author":"Takahashi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1034\/j.1600-0722.2002.11186.x","article-title":"The novel human beta-defensin-3 is widely expressed in oral tissues","volume":"110","author":"Dunsche","year":"2002","journal-title":"Eur. J. Oral Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.molimm.2017.08.012","article-title":"Human \u03b2-defensin 3 inhibits periodontitis development by suppressing inflammatory responses in macrophages","volume":"91","author":"Cui","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"349","DOI":"10.18388\/pb.2016_36","article-title":"Human \u03b2-defensin 4\u2014Defensin without the \u201ctwist\u201d. Ludzka \u03b2-defenzyna 4\u2014Defenzyna bez \u201c\u015bruby\u201d","volume":"62","author":"Prahl","year":"2016","journal-title":"Postep. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1096\/fj.00-0865fje","article-title":"Human beta-defensin 4: A novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity","volume":"15","author":"Krause","year":"2001","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/1465-9921-6-130","article-title":"Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection","volume":"6","author":"Yanagi","year":"2005","journal-title":"Respir. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.3389\/fphys.2020.01077","article-title":"Potential Application of Human \u03b2-Defensin 4 in Dental Pulp Repair","volume":"11","author":"Zhai","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105205","DOI":"10.1016\/j.micpath.2021.105205","article-title":"Human beta-defensins 2 and 4 are dysregulated in patients with coronavirus disease 19","volume":"160","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1128\/IAI.01218-07","article-title":"Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells","volume":"76","author":"Carranza","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"645898","DOI":"10.1155\/2009\/645898","article-title":"The effect of calcipotriol on the expression of human beta defensin-2 and LL-37 in cultured human keratinocytes","volume":"2009","author":"Kim","year":"2009","journal-title":"Clin. Dev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17356","DOI":"10.1038\/s41598-020-74401-5","article-title":"The structure of the antimicrobial human cathelicidin LL-37 shows oligomerization and channel formation in the presence of membrane mimics","volume":"10","author":"Bonetti","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1189\/jlb.0513304","article-title":"Antimicrobial peptide LL-37 promotes bacterial phagocytosis by human macrophages","volume":"95","author":"Wan","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1159\/000171533","article-title":"Host defence peptide LL-37 induces IL-6 expression in human bronchial epithelial cells by activation of the NF-kappaB signaling pathway","volume":"1","author":"Pistolic","year":"2009","journal-title":"J. Innate Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1161\/ATVBAHA.113.301851","article-title":"Cathelicidin LL-37 induces angiogenesis via PGE2-EP3 signaling in endothelial cells, in vivo inhibition by aspirin","volume":"33","author":"Salvado","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.peptides.2011.06.005","article-title":"Wound healing activity of the human antimicrobial peptide LL37","volume":"32","author":"Ramos","year":"2011","journal-title":"Peptides"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1515\/bc.2010.057","article-title":"The role of salivary histatin and the human cathelicidin LL-37 in wound healing and innate immunity","volume":"391","author":"Oudhoff","year":"2010","journal-title":"Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.7150\/thno.30726","article-title":"Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt\/\u03b2-catenin signaling","volume":"9","author":"Ji","year":"2019","journal-title":"Theranostics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102301","DOI":"10.1016\/j.anaerobe.2020.102301","article-title":"Inhibitory effect of LL-37 and human lactoferricin on growth and biofilm formation of anaerobes associated with oral diseases","volume":"67","author":"Wuersching","year":"2021","journal-title":"Anaerobe"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.archoralbio.2012.01.008","article-title":"Salivary concentration of the antimicrobial peptide LL-37 in children","volume":"57","author":"Davidopoulou","year":"2012","journal-title":"Arch. Oral Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8209","DOI":"10.1007\/s13277-015-4687-1","article-title":"Interleukin 10-expressing B cells inhibit tumor-infiltrating T cell function and correlate with T cell Tim-3 expression in renal cell carcinoma","volume":"37","author":"Cai","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/s41598-018-38125-x","article-title":"IL-10 produced by macrophages regulates epithelial integrity in the small intestine","volume":"9","author":"Morhardt","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000365417","article-title":"Human intestinal epithelial cells express interleukin-10 through Toll-like receptor 4-mediated epithelial-macrophage crosstalk","volume":"7","author":"Hyun","year":"2015","journal-title":"J. Innate Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7551","DOI":"10.4049\/jimmunol.177.11.7551","article-title":"Macrophages and Myeloid Dendritic Cells, but Not Plasmacytoid Dendritic Cells, Produce IL-10 in Response to MyD88- and TRIF-Dependent TLR Signals, and TLR-Independent Signals","volume":"177","author":"Boonstra","year":"2006","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1002\/eji.201343822","article-title":"Autocrine IL-10 promotes human B-cell differentiation into IgM- or IgG-secreting plasmablasts","volume":"44","author":"Heine","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1177\/154405910308200810","article-title":"Differential injury responses in oral mucosal and cutaneous wounds","volume":"82","author":"Szpaderska","year":"2003","journal-title":"J. Dent. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3390\/pediatric14040050","article-title":"Evaluation of the Multiple Tissue Factors in the Cartilage of Primary and Secondary Rhinoplasty in Cleft Lip and Palate Patients","volume":"14","author":"Buile","year":"2022","journal-title":"Pediatr. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pilmane, M., Jain, N., Jain, S., Akota, I., and Kroi\u010da, J. (2021). Quantification of Cytokines in Lip Tissue from Infants Affected by Congenital Cleft Lip and Palate. Children, 8.","DOI":"10.3390\/children8020140"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/jlb.67.1.97","article-title":"Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli","volume":"67","author":"Buechler","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Skytthe, M.K., Graversen, J.H., and Moestrup, S.K. (2020). Targeting of CD163+ Macrophages in Inflammatory and Malignant Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155497"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/07853890410033171","article-title":"CD163: A regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response","volume":"36","author":"Moestrup","year":"2004","journal-title":"Ann. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Goida, J., and Pilmane, M. (2021). Characterization of Macrophages and TNF-\u03b1 in Cleft Affected Lip Tissue. Cosmetics, 8.","DOI":"10.3390\/cosmetics8020042"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1093\/ajcp\/75.6.816","article-title":"The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics","volume":"75","author":"Hsu","year":"1981","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1177\/27.8.90074","article-title":"The use of avidin-biotin interaction in immunoenzymatic techniques","volume":"27","author":"Guesdon","year":"1979","journal-title":"J. Histochem. Cytochem."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pilmane, M., Sidhoma, E., Akota, I., and Kazoka, D. (2019). Characterization of Cytokines and Proliferation Marker Ki67 in Cleft Affected Lip Tissue. Medicina, 55.","DOI":"10.3390\/medicina55090518"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e1211","DOI":"10.1002\/cnr2.1211","article-title":"Evidence-based statistical analysis and methods in biomedical research (SAMBR) checklists according to design features","volume":"3","author":"Dwivedi","year":"2020","journal-title":"Cancer Rep."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Liu, L., Zhang, Q., Lin, J., Ma, L., Zhou, Z., He, X., Jia, Y., and Chen, F. (2016). Investigating Oral Microbiome Profiles in Children with Cleft Lip and Palate for Prognosis of Alveolar Bone Grafting. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155683"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/ipd.12934","article-title":"Association between oral clefts and periodontal clinical measures: A meta-analysis","volume":"32","author":"Marzouk","year":"2022","journal-title":"Int. J. Paediatr. Dent."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/oxfordjournals.jncimonographs.a003443","article-title":"Biology of oral mucosa and esophagus","volume":"29","author":"Squier","year":"2001","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Umehara, Y., Takahashi, M., Yue, H., Trujillo-Paez, J.V., Peng, G., Nguyen, H.L.T., Okumura, K., Ogawa, H., and Niyonsaba, F. (2022). The Antimicrobial Peptides Human \u03b2-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158800"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1167\/iovs.05-1360","article-title":"Defensins HNP1 and HBD2 stimulation of wound-associated responses in human conjunctival fibroblasts","volume":"47","author":"Li","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1084\/jem.174.5.1209","article-title":"Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes","volume":"174","author":"Abrams","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1084\/jem.174.4.915","article-title":"Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression","volume":"174","author":"Haanen","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0003-9969(99)00120-X","article-title":"Suppression of interleukin-10 release from human periodontal ligament cells by interleukin-1beta in vitro","volume":"45","author":"Deschner","year":"2000","journal-title":"Arch. Oral. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e12816","DOI":"10.1111\/sji.12816","article-title":"Local IL-10 level as a predictive factor in generalized aggressive periodontitis treatment response","volume":"90","author":"Taiete","year":"2019","journal-title":"Scand. J. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1006\/bbrc.1999.1381","article-title":"IL-10 inhibits Porphyromonas gingivalis LPS-stimulated human gingival fibroblasts production of IL-6","volume":"263","author":"Wang","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1365-2362.2008.02071.x","article-title":"Expression of beta-defensin 4 is increased in human gastritis","volume":"39","author":"Otte","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1590\/S0102-86502014001700008","article-title":"Human beta defensin-4 and keratinocyte growth factor gene expression in cultured keratinocyte and fibroblasts of burned patients","volume":"29","author":"Noronha","year":"2014","journal-title":"Acta Cir. Bras."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.4049\/jimmunol.175.3.1776","article-title":"The human beta-defensins (-1, -2, -3, -4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes","volume":"175","author":"Niyonsaba","year":"2005","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.4049\/jimmunol.0900712","article-title":"Antimicrobial peptides human beta-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cells","volume":"184","author":"Niyonsaba","year":"2010","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/j.0022-202X.2004.23234.x","article-title":"Differential gene induction of human beta-defensins (hBD-1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid","volume":"123","author":"Harder","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1189\/jlb.0111004","article-title":"Human \u03b2-defensin-2 enhances IFN-\u03b3 and IL-10 production and suppresses IL-17 production in T cells","volume":"89","author":"Kanda","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1128\/IAI.00936-15","article-title":"LL-37 immunomodulatory activity during Mycobacterium tuberculosis infection in macrophages","volume":"83","author":"Hancock","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1309\/QHD6YFN81KQXUUH6","article-title":"CD163: A specific marker of macrophages in paraffin-embedded tissue samples","volume":"122","author":"Lau","year":"2004","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ma, S., Zhao, Y., Liu, X., Zhang, A.S., Zhang, H., Hu, G., and Sun, X.F. (2022). CD163 as a Potential Biomarker in Colorectal Cancer for Tumor Microenvironment and Cancer Prognosis: A Swedish Study from Tissue Microarrays to Big Data Analyses. Cancers, 14.","DOI":"10.3390\/cancers14246166"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.2337\/db11-1635","article-title":"Adoptive transfer of immunomodulatory M2 macrophages prevents type 1 diabetes in NOD mice","volume":"61","author":"Parsa","year":"2012","journal-title":"Diabetes"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1189\/jlb.0105015","article-title":"Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation","volume":"79","author":"Verreck","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/bjd.12419","article-title":"Human \u03b2-defensin-2 as a marker for disease severity and skin barrier properties in atopic dermatitis","volume":"169","author":"Clausen","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Jansen, P.A., Rodijk-Olthuis, D., Hollox, E.J., Kamsteeg, M., Tjabringa, G.S., de Jongh, G.J., van Vlijmen-Willems, I.M., Bergboer, J.G., van Rossum, M.M., and de Jong, E.M. (2009). Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004725"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.acthis.2012.02.001","article-title":"\u03b2-Defensin-4 (HBD-4) is expressed in chondrocytes derived from normal and osteoarthritic cartilage encapsulated in PEGDA scaffold","volume":"114","author":"Musumeci","year":"2012","journal-title":"Acta Histochem."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Reiser, S.C., Tellermann, J., Akota, I., and Pilmane, M. (2021). Profiling and Characterization of Localized Cytokine Response in Congenital Cleft Affected Lip Tissue. Life, 11.","DOI":"10.3390\/life11060556"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.regpep.2006.03.008","article-title":"Oxytocin is expressed throughout the human gastrointestinal tract","volume":"135","author":"Ohlsson","year":"2006","journal-title":"Regul. Pept."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/alcalc\/36.3.213","article-title":"Neuropeptides in the duodenal mucosa of chronic alcoholic heavy drinkers","volume":"36","author":"Hauge","year":"2001","journal-title":"Alcohol Alcohol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/7\/1162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:04:55Z","timestamp":1760126695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/7\/1162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,2]]},"references-count":94,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["children10071162"],"URL":"https:\/\/doi.org\/10.3390\/children10071162","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,2]]}}}