{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:01:42Z","timestamp":1784563302433,"version":"3.55.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["0001"],"award-info":[{"award-number":["0001"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["CNPq #306533\/2023-5"],"award-info":[{"award-number":["CNPq #306533\/2023-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["#RGPIN 2020-06119"],"award-info":[{"award-number":["#RGPIN 2020-06119"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centros de Pesquisa, Inova\u00e7\u00e3o e Difus\u00e3o, Funda\u00e7\u00e3o Amaz\u00f4nia Paraense de Amparo \u00e0 Pesquisa","award":["FAPESP #2013\/07276-1"],"award-info":[{"award-number":["FAPESP #2013\/07276-1"]}]},{"name":"Centros de Pesquisa, Inova\u00e7\u00e3o e Difus\u00e3o, Funda\u00e7\u00e3o Amaz\u00f4nia Paraense de Amparo \u00e0 Pesquisa","award":["FAPESP #2020\/16227-8"],"award-info":[{"award-number":["FAPESP #2020\/16227-8"]}]},{"name":"Centros de Pesquisa, Inova\u00e7\u00e3o e Difus\u00e3o, Funda\u00e7\u00e3o Amaz\u00f4nia Paraense de Amparo \u00e0 Pesquisa","award":["FAPESP #2022\/12059-9"],"award-info":[{"award-number":["FAPESP #2022\/12059-9"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["#MOP-106657"],"award-info":[{"award-number":["#MOP-106657"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["#PJT-159760"],"award-info":[{"award-number":["#PJT-159760"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    Oral candidiasis is primarily caused by\n                    <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                    ; however, bacteria such as\n                    <jats:italic toggle=\"yes\">Streptococcus mutans<\/jats:italic>\n                    can also coexist and cooperate within the same biofilm. This study evaluated the combined effects of Histatin 3 (His3) and Histatin 5 (His5) with antimicrobial photodynamic therapy (aPDT) using a 3-dimensional oral epithelium model infected with mixed biofilms of\n                    <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                    (polyene-resistant strains) and\n                    <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                    . The tissues, divided into groups (His3 + aPDT, His5+aPDT, His3, His5, or aPDT), were first treated with the salivary proteins His3 or His5 (2 h, 37 \u00b0C, 60 rpm\/min) followed by infection with mixed biofilms. After 24 h of biofilm formation, aPDT was applied (PDZ: 200 mg\/L; LED light: 660 nm with 50 J\/cm\u00b2) using intermittent irradiation cycles (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 9\/group). Biofilm viability (CFU\/mL), total proteins (intracellular and extracellular), and proteomic analysis were performed. Biocompatibility and tissue invasion were also assessed by MTT assays and histological analysis, respectively. His3+aPDT and His5+aPDT reduced mixed biofilm viability by 67% (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.0038) and 65% (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.0062), respectively. His3 and His5 alone promoted a 35% to 45% (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.018;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 00.24) reduction, while aPDT alone reduced by 50% to 55% (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.022;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.037). Combined treatments enhanced efficacy by ~30% compared with individual treatments. Histological evaluation also confirmed reduced biofilm penetration and hyphal formation, particularly with His5+aPDT. Proteomic analysis of the proteins from\n                    <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                    revealed the downregulation of structural and transport proteins, which can likely weaken the biofilm. The combination of His3 and His5 with aPDT enhances antimicrobial efficacy against resistant multispecies biofilms while maintaining biocompatibility. By reducing biofilm viability and compromising proteins, this approach provides a promising alternative for treating oral candidiasis associated with polyene-resistant\n                    <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                    species.\n                  <\/jats:p>","DOI":"10.1177\/00220345251392876","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T04:38:32Z","timestamp":1766119112000},"page":"1089-1098","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Histatin\u2013Photodynamic Therapy for Polyene-Resistant Biofilms in a 3D Model"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-9715","authenticated-orcid":false,"given":"L.M.","family":"Dias","sequence":"first","affiliation":[{"name":"College of Dentistry, University of Saskatchewan, Saskatoon, SK, Canada"},{"name":"Laboratory of Applied Microbiology Department of Dental Materials and Prosthodontics, Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho,\u201d Faculdade de Odontologia de Araraquara, Araraquara, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-1994","authenticated-orcid":false,"given":"A.C.","family":"Pavarina","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Microbiology Department of Dental Materials and Prosthodontics, Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho,\u201d Faculdade de Odontologia de Araraquara, Araraquara, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-3658","authenticated-orcid":false,"given":"W.L.","family":"Siqueira","sequence":"additional","affiliation":[{"name":"College of Dentistry, University of Saskatchewan, Saskatoon, SK, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"crossref","unstructured":"Alfei S Schito GC Schito AM Zuccari G. 2024. 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Principal component analysis: a method for determining the essential dynamics of proteins. Methods Mol Biol. 1084:193\u2013226. https:\/\/doi.org\/10.1007\/978-1-62703-658-0_11","DOI":"10.1007\/978-1-62703-658-0_11"},{"key":"e_1_3_3_6_1","doi-asserted-by":"crossref","unstructured":"De Ryck T et al. 2014. Development of an oral mucosa model to study host-microbiome interactions during wound healing. Appl Microbiol Biotechnol. 98(15):6831\u20136846. https:\/\/doi.org\/10.1007\/s00253-014-5841-1","DOI":"10.1007\/s00253-014-5841-1"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063226"},{"key":"e_1_3_3_8_1","doi-asserted-by":"crossref","unstructured":"Dias LM Paul P Pavarina AC Siqueira WL. 2025. Salivary proteins-enhanced antimicrobial photodynamic therapy: overcoming three distinct cultures of resistant mixed biofilms. J Dent. 157:105778. https:\/\/doi.org\/10.1016\/j.jdent.2025.105778","DOI":"10.1016\/j.jdent.2025.105778"},{"key":"e_1_3_3_9_1","doi-asserted-by":"crossref","unstructured":"Enjalbert B Nantel A Whiteway M. 2003. Stress-induced gene expression in Candida albicans: absence of a general stress response. Mol Biol Cell. 14(4):1460\u20131467. https:\/\/doi.org\/10.1091\/mbc.e02-08-0546","DOI":"10.1091\/mbc.e02-08-0546"},{"key":"e_1_3_3_10_1","doi-asserted-by":"crossref","unstructured":"Flemming H-C Neu TR Wozniak DJ. 2007. The EPS matrix: the \u201chouse of biofilm cells\u201d. J Bacteriol. 189(22):7945\u20137947. https:\/\/doi.org\/10.1128\/JB.00858-07","DOI":"10.1128\/JB.00858-07"},{"key":"e_1_3_3_11_1","doi-asserted-by":"crossref","unstructured":"Fusco-Almeida AM et al. 2023. Alternative non-mammalian animal and cellular methods for the study of host\u2013fungal interactions. 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Lactobacillus casei reduces the extracellular matrix components of fluconazole-susceptible Candida albicans biofilms. Biofouling. 37(9\u201310):1006\u20131021. https:\/\/doi.org\/10.1080\/08927014.2021.2001645","DOI":"10.1080\/08927014.2021.2001645"},{"key":"e_1_3_3_30_1","doi-asserted-by":"crossref","unstructured":"Panariello BHD Klein MI Mima EGDO Pavarina AC. 2018. Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms. J Oral Microbiol. 10(1):1476644. https:\/\/doi.org\/10.1080\/20002297.2018.1476644","DOI":"10.1080\/20002297.2018.1476644"},{"key":"e_1_3_3_31_1","doi-asserted-by":"crossref","unstructured":"Patel M. 2022. Oral cavity and Candida albicans: colonisation to the development of infection. Pathogens. 11(3):335. https:\/\/doi.org\/10.3390\/pathogens11030335","DOI":"10.3390\/pathogens11030335"},{"key":"e_1_3_3_32_1","doi-asserted-by":"crossref","unstructured":"Petrovic S et al. 2022. 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