{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:03:35Z","timestamp":1779915815840,"version":"3.53.1"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Dysregulated cytokine signaling is implicated in persistent inflammation and fibrosis in oral submucous fibrosis (OSMF) and has been reported in association with pathways observed in oral squamous cell carcinoma (OSCC). This study investigated cytokine associated inflammatory and fibrotic responses following treatment with a mucoadhesive buccal patch containing isotretinoin, bromelain, and limonene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The formulation was evaluated using lipopolysaccharide (LPS) induced acute inflammatory in vitro models and a carbon tetrachloride (CCl\n                      <jats:sub>\u2084<\/jats:sub>\n                      ) induced\n                      <jats:italic>in vivo<\/jats:italic>\n                      oral fibrotic model. Gene expression analysis was performed using qPCR to assess IL-6, TNF-\u03b1, MMP-2, IL-2, and TGF-\u03b2 expression. Protein expression of COX-2 and CK17 was also examined. Bromelain activity within the formulation was evaluated using collagen degradation assays under different concentrations and incubation periods. Histological analysis and functional assessment of mouth opening were conducted in vivo to evaluate fibrotic alterations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LPS stimulation induced upregulation of IL-6, TNF-\u03b1, and MMP-2, while treatment with the formulation was associated with reduced expression of these inflammatory markers. Altered IL-2 and TGF-\u03b2 expression suggested modulation of immune regulatory and fibrosis-associated pathways. The in vitro model represented an acute inflammatory epithelial response and did not fully recapitulate the fibrotic pathology of OSMF. Protein analysis demonstrated reduced COX-2 expression and alterations in CK17 levels, consistent with changes in inflammatory and epithelial responses. Bromelain retained enzymatic activity within the formulation and demonstrated concentration and time dependent collagen degradation. In vivo treatment showed reduced collagen-associated staining, improved tissue architecture, and changes in mouth opening, indicating attenuation of fibrotic progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide preliminary observations on cytokine-associated responses under inflammatory and fibrotic conditions relevant to OSMF. Further studies are required to define underlying mechanisms and evaluate translational applicability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1847576","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:10:19Z","timestamp":1779912619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of a multi-component mucoadhesive buccal patch: cytokine-associated inflammatory responses and tissue remodeling in experimental models"],"prefix":"10.3389","volume":"17","author":[{"given":"Rekha Rani","family":"Kokkanti","sequence":"first","affiliation":[{"name":"School of Biotechnology, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhiya","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandita","family":"Parida","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumyajit","family":"Biswas","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajraj Singh","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"Technology Business Incubator, KIIT University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratap Kumar","family":"Deheri","sequence":"additional","affiliation":[{"name":"School of Applied Sciences, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok Kumar","family":"Panda","sequence":"additional","affiliation":[{"name":"School of Applied Sciences, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abikshyeet","family":"Panda","sequence":"additional","affiliation":[{"name":"Kalinga Institute of Dental Science, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul Anand","family":"Bajoria","sequence":"additional","affiliation":[{"name":"Kalinga Institute of Dental Science, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Patnaik","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Kalinga Institute of Industrial Technology, (KIIT) Deemed to be University","place":["Bhubaneswar, Odisha, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.27843","article-title":"Detection of oral cancer and oral potentially Malignant disorders using artificial intelligence-based image analysis","volume":"46","author":"Kouketsu","year":"2024","journal-title":"Head Neck"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.825266","article-title":"Oral potentially Malignant disorders: Etiology, pathogenesis, and transformation into oral cancer","volume":"13","author":"Kumari","year":"2022","journal-title":"Front Pharmacol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering11030228","article-title":"State of the art in the diagnosis and assessment of oral Malignant and potentially Malignant disorders: Present insights and future outlook-an overview","volume":"11","author":"Menditti","year":"2024","journal-title":"Bioeng (Basel)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13704","article-title":"Oral potentially Malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer","volume":"27","author":"Warnakulasuriya","year":"2021","journal-title":"Oral Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2026.189582","article-title":"Cysteine proteases in oral potentially Malignant disorders: Molecular drivers, diagnostic signatures, and therapeutic opportunities","volume":"1181","author":"Biswas","year":"2026","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"102493","DOI":"10.1016\/j.mtla.2025.102493","article-title":"Mucoadhesive drug delivery system for oral submucous fibrosis in three dimensional multicellular and in vivo models: Novel approach towards translational therapeutics","volume":"42","author":"Sandhiya","year":"2025","journal-title":"Materialia"},{"key":"B8","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41392-024-01868-3","article-title":"Targeting cytokine and chemokine signaling pathways for cancer therapy","volume":"9","author":"Yi","year":"2024","journal-title":"Sig Transd Targ Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.136216","article-title":"Synergic effects of DL-limonene, R-limonene, and cisplatin on AKT, PI3K, and mTOR gene expression in MDA-MB-231 and 5637 cell lines","volume":"280","author":"Motie","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12885-021-08639-1","article-title":"Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis","volume":"21","author":"Chebet","year":"2021","journal-title":"BMC Cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj091","article-title":"Randomized phase III trial of low-dose isotretinoin for prevention of second primary tumors in stage I and II head and neck cancer patients","volume":"98","author":"Khuri","year":"2006","journal-title":"J Natl Cancer Inst"},{"key":"B12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.abd.2020.09.001","article-title":"Consensus on the use of oral isotretinoin in dermatology-Brazilian Society of Dermatology","volume":"95","author":"Bagatin","year":"2020","journal-title":"Bras Dermatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1358\/mf.2006.28.2.977843","article-title":"Evaluation of the clinical and histological effectiveness of isotretinoin in the therapy of oral leukoplakia: ten years of experience: is management still up to date and effective","volume":"28","author":"Scardina","year":"2006","journal-title":"Methods Find Exp Clin Pharmacol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/nu16132060","article-title":"Exploring the therapeutic potential of bromelain: Applications, benefits, and mechanisms","volume":"16","author":"Kansakar","year":"2024","journal-title":"Nutrients"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2024.02.005","article-title":"Areca nut-induced oral fibrosis - Reassessing the biology of oral submucous fibrosis","volume":"66","author":"Sharma","year":"2024","journal-title":"J Oral Biosci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2174\/1573394718666220421112750","article-title":"Anticancer mechanism of d-limonene: an updated review and therapeutic possibilities","volume":"18","author":"Mandal","year":"2022","journal-title":"Curr Cancer Ther Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7125","article-title":"Anticancer activity of limonene: A systematic review of target signaling pathways","volume":"35","author":"Ara\u00fajo\u2010Filho","year":"2021","journal-title":"Phytother Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13050728","article-title":"Development of mucoadhesive buccal film for rizatriptan: In vitro and In vivo evaluation","volume":"13","author":"Nair","year":"2021","journal-title":"Pharmaceutics"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.12991\/jrespharm.1634623","article-title":"Dissolution methods to discriminate In vitro dissolution of poor water soluble weak base drug using three strategies: Acid modification, solvent evaporation and gastroretentive: Ciprofloxacin HCl case","volume":"29","author":"Al Ameri","year":"2025","journal-title":"J Res Pharm"},{"key":"B20","article-title":"Overview on native cellulose and microcrystalline cellulose I structure studied by X-ray diffraction (WAXD): Comparison between measurement techniques","volume":"89","author":"Terinte","year":"2011","journal-title":"Lenzinger Berichte"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/polym14235146","article-title":"Characterization of an in vitro\/ex vivo mucoadhesiveness measurement method of PVA films","volume":"14","author":"Muller","year":"2022","journal-title":"Polymers"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.22159\/ajpcr.2018.v11i8.26126","article-title":"Formulation, In vitro and ex vivo characterization of mucoadhesive buccal tablets for antihypertensive drug","volume":"11","author":"Peddapalli","year":"2018","journal-title":"Asian J Pharm Clin Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.matchemphys.2024.129818","article-title":"Disintegration of fish-collagen by bromelain added in a mucoadhesive patch: An insight for achieving of therapeutic lead for oral submucous fibrosis","volume":"326","author":"Bajoria","year":"2024","journal-title":"Mater Chem Phys"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s40204-017-0077-7","article-title":"New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate","volume":"6","author":"Salehi","year":"2017","journal-title":"Prog Biomater"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2005.01217.x","article-title":"The distribution of oral mucosal pH values in healthy saliva secretors","volume":"12","author":"Aframian","year":"2006","journal-title":"Oral Dis"},{"key":"B26","article-title":"Formulation and characterization of orodispersible film containing diltiazem hydrochloride with taste masked effects","volume":"35","author":"Latif","year":"2022","journal-title":"Pak J Pharm Sci"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1029\/2009JD012864","article-title":"Appearance of strong absorbers and fluorophores in limonene\u2010O3 secondary organic aerosol due to NH4+\u2010mediated chemical aging over long time scales","volume":"115","author":"Bones","year":"2010","journal-title":"J Geophys Res Atmos"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/ma15228274","article-title":"Solubilization and thermodynamic analysis of isotretinoin in eleven different green solvents at different temperatures","volume":"15","author":"Shakeel","year":"2022","journal-title":"Mater (Basel)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.105736","article-title":"Hydroxypropyl methylcellulose: Physicochemical properties and ocular drug delivery formulations","volume":"159","author":"Tundisi","year":"2021","journal-title":"Eur J Pharm Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2017.12.007","article-title":"Optimization and evaluation of mucoadhesive buccal films loaded with resveratrol","volume":"44","author":"Ansari","year":"2018","journal-title":"J Drug Delivery Sci Technol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S394523","article-title":"Development, In vitro evaluation, and Iin vivo study of adhesive buccal films for the treatment of diabetic pediatrics via trans mucosal delivery of gliclazide","volume":"16","author":"Gaber","year":"2022","journal-title":"Drug Des Devel Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37257","article-title":"Fabrication of multifunctional mucoadhesive buccal patch for drug delivery applications","volume":"109","author":"Rohani Shirvan","year":"2021","journal-title":"J BioMed Mater Res A"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2024.102063","article-title":"Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation","volume":"32","author":"Alfaraj","year":"2024","journal-title":"Saudi Pharm J"},{"key":"B34","article-title":"Isotretinoin oral-mucosal formulations and methods for using same","volume-title":"US patent application 20210244656","author":"Tan","year":"2021"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.9734\/jpri\/2021\/v33i47A33017","article-title":"Formulation and characterization of modified release microspheres of Lornoxicam using okra gum as natural polymer and ethyl cellulose as synthetic polymer","author":"Saxena","year":"2021","journal-title":"J Pharm Res Int"},{"key":"B36","doi-asserted-by":"publisher","first-page":"214731","DOI":"10.1016\/j.bioadv.2026.214731","article-title":"In vitro and ex vivo evaluation of a papain-loaded mucoadhesive buccal patch with potential antifibrotic and anticancer activity","volume":"182","author":"Parida","year":"2026","journal-title":"Biomater Adv"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1177\/1559325820945164","article-title":"Improved transmucosal delivery of glimepiride via unidirectional release buccal film loaded with vitamin E TPGS-based nanocarrier","volume":"18","author":"Basahih","year":"2020","journal-title":"Dose-Response"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.09.053","article-title":"The role of biopolymer matrix films derived from carboxymethyl cellulose, sodium alginate and polyvinyl alcohol on the sustained transdermal release of diltiazem","volume":"107","author":"Anirudhan","year":"2018","journal-title":"Int J Biol Macromol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2023.105294","article-title":"Modification of the swelling behavior of a hydrophilic polymer as an approach to maintaining a constant gel layer thickness","volume":"92","author":"Bagde","year":"2024","journal-title":"J Drug Delivery Sci Technol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4155\/tde-2016-0026","article-title":"Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets","volume":"7","author":"Timmins","year":"2016","journal-title":"Ther Delivery"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s10924-020-01823-7","article-title":"Synthesis and characterization of poly (limonene) by photoinduced controlled radical polymerization","volume":"28","author":"De Oliveira","year":"2020","journal-title":"J Polym Environ"},{"key":"B42","doi-asserted-by":"publisher","first-page":"18031","DOI":"10.1038\/s41598-017-18271-4","article-title":"Bacterial nanocellulose loaded with bromelain: Assessment of antimicrobial, antioxidant and physical-chemical properties","volume":"7","author":"Ataide","year":"2017","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2015.08.014","article-title":"Hydrothermal conversion of biomass waste to activated carbon with high porosity: a review","volume":"273","author":"Jain","year":"2015","journal-title":"Chem Eng J"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1754-6834-3-10","article-title":"Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance","volume":"3","author":"Park","year":"2010","journal-title":"Biotechnol Biofuels"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27092752","article-title":"Characterization of natural anthocyanin indicator based on cellulose bio-composite film for monitoring the freshness of chicken tenderloin","volume":"27","author":"Boonsiriwit","year":"2022","journal-title":"Molecules"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.35041","article-title":"Development of mucoadhesive modified kappa\u2010carrageenan\/pectin patches for controlled delivery of drug in the buccal cavity","volume":"110","author":"Ozkahraman","year":"2022","journal-title":"J BioMed Mater Res B Appl Biomater"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2021.102991","article-title":"Evaluation of modified pectin\/alginate buccal patches with enhanced mucoadhesive properties for drug release systems: In-vitro and ex-vivo study","volume":"67","author":"Ozba\u015f","year":"2022","journal-title":"J Drug Delivery Sci Technol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtcomm.2024.111307","article-title":"Innovative anti-fibrotic strategy using a bromelain containing mucoadhesive patch for effective collagen breakdown and cytotoxicity in oral submucous fibrosis","volume":"42","author":"Bajoria","year":"2025","journal-title":"Mater Today Commun"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120451","article-title":"Thiolated cyclodextrins: Mucoadhesive and permeation enhancing excipients for ocular drug delivery","volume":"599","author":"Asim","year":"2021","journal-title":"Int J Pharm"},{"key":"B50","doi-asserted-by":"publisher","first-page":"239","DOI":"10.4103\/2277-9175.168606","article-title":"Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology","volume":"4","author":"Ikram","year":"2015","journal-title":"Adv BioMed Res"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2010.08.012","article-title":"Two phase partitioning and collagen hydrolysis of bromelain from pineapple peel Nang Lae cultivar","volume":"52","author":"Ketnawa","year":"2010","journal-title":"Biochem Eng J"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajoms.2020.04.001","article-title":"Retinoic acids in oral precancer: Utility and challenges","volume":"32","author":"Pandey","year":"2020","journal-title":"J Oral Maxillofac Surg Med Pathol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26463","article-title":"Topical oral cavity chemoprophylaxis using isotretinoin rinse: a 15\u2010year experience","volume":"127","author":"Kadakia","year":"2017","journal-title":"Laryngoscope"},{"key":"B54","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1186\/s12931-022-02270-9","article-title":"d-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro","volume":"23","author":"Zhu","year":"2022","journal-title":"Respir Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4103\/jmss.JMSS_42_18","article-title":"Bromelain inhibitory effect on colony formation: An In vitro study on Human AGS, PC3, and MCF7 cancer cells","volume":"9","author":"Raeisi","year":"2019","journal-title":"J Med Signal Sens"},{"key":"B56","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s12906-024-04453-x","article-title":"Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells","volume":"24","author":"Salim","year":"2024","journal-title":"BMC Complem Med Ther"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S155716","article-title":"d-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer","volume":"11","author":"Yu","year":"2018","journal-title":"OncoTarg Ther"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-007-0117-0","article-title":"Oral lichen planus treated with 13-cis-retinoic acid (isotretinoin): effects on the apoptotic process","volume":"11","author":"Piattelli","year":"2007","journal-title":"Clin Oral Investig"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179778","article-title":"TGF-\u03b2 signalling mediates the anti-inflammatory activity of enamel matrix derivative in vitro","volume":"23","author":"Panahipour","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.82579","article-title":"Chronic inflammation: A multidisciplinary analysis of shared pathways in autoimmune, infectious, and degenerative diseases","volume":"17","author":"Yacine","year":"2025","journal-title":"Cureus"},{"key":"B61","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3892\/etm.2020.9204","article-title":"Mechanisms of the lipopolysaccharide-induced inflammatory response in alveolar epithelial cell\/macrophage co-culture","volume":"20","author":"Li","year":"2020","journal-title":"Exp Ther Med"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2020.1725570","article-title":"IL-2 regulates oral mucosa inflammation through inducing endoplasmic reticulum stress and activating the NF-\u03baB pathway","volume":"40","author":"Li","year":"2020","journal-title":"J Recept Signal Transd Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.4161\/derm.15026","article-title":"Regulation of keratin expression by retinoids","volume":"3","author":"Torma","year":"2011","journal-title":"Dermatoendocrinol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3390\/biom14030334","article-title":"Limonene exerts anti-inflammatory effect on LPS-induced jejunal injury in mice by inhibiting NF-\u03baB\/AP-1 pathway","volume":"14","author":"Kathem","year":"2024","journal-title":"Biomolecules"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/life11040317","article-title":"Bromelain: A potential bioactive compound\u2014A comprehensive overview from a pharmacological perspective","volume":"11","author":"Chakraborty","year":"2021","journal-title":"Life (Basel)"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.27041","article-title":"Diagnostic utility of cytokeratin 17 expression in oral squamous cell carcinoma: A review","volume":"14","author":"Gyanchandani","year":"2022","journal-title":"Cureus"},{"key":"B67","doi-asserted-by":"publisher","first-page":"4089549","DOI":"10.1155\/2021\/4089549","article-title":"Diagnostic value of cytokeratin 17 during oral carcinogenesis: An immunohistochemical study","volume":"2021","author":"Sanguansin","year":"2021","journal-title":"Int J Dent"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4103\/IJPM.IJPM_324_19","article-title":"Collagen fibers in oral submucous fibrosis-A polarizing microscopy study using two special stains","volume":"62","author":"Nishat","year":"2019","journal-title":"Indian J Pathol Microbiol"},{"key":"B69","article-title":"Histochemical analysis of polarizing colors of collagen using Picrosirius Red staining in oral submucous fibrosis","volume":"6","author":"Velidandla","year":"2014","journal-title":"J Int Oral Health"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4103\/0975-8844.124258","article-title":"Image analyses of collagen types and thickness in oral sub mucous fibrosis stained with picrosirius red under polarizing microscope","volume":"5","author":"Kamath","year":"2013","journal-title":"J Orofac Sci"},{"key":"B71","first-page":"111","article-title":"Comparative study of clinical staging of oral submucous fibrosis with qualitative analysis of collagen fibers under polarized microscopy","volume":"10","author":"Modak","year":"2015","journal-title":"Iran J Pathol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.4103\/0973-029X.84481","article-title":"Clinical and histopathological evaluation of collagen fiber orientation in patients with oral submucous fibrosis","volume":"15","author":"Smitha","year":"2011","journal-title":"J Oral Maxillofac Pathol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.4103\/0970-9290.57356","article-title":"Comparative study of clinicofunctional staging of oral submucous fibrosis with qualitative analysis of collagen fibers under polarizing microscopy","volume":"20","author":"Ceena","year":"2009","journal-title":"Indian J Dent Res"},{"key":"B74","doi-asserted-by":"publisher","first-page":"99","DOI":"10.4103\/2277-8632.98350","article-title":"Quantitative and qualitative analysis of collagen in oral submucous fibrosis","volume":"1","author":"Ashalata","year":"2012","journal-title":"J Dr YSR Univ Health Sci"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14852","article-title":"Molecular analysis of the extracellular microenvironment: From form to function","volume":"598","author":"Macdonald","year":"2024","journal-title":"FEBS Lett"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1369\/0022155416659249","article-title":"Comparison of Picrosirius red staining with second harmonic generation imaging for the quantification of clinically relevant collagen fiber features in histopathology samples","volume":"64","author":"Drifka","year":"2016","journal-title":"J Histochem Cytochem"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118768","article-title":"Evaluation of in-vitro antioxidant activity, acute oral toxicity, and pancreatic and hepatic protective effects of Aloe rubroviolacea flowers extract against CCl4 toxicity in a rat model","volume":"337","author":"Elkomy","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.jvir.2022.11.026","article-title":"Experimental VX2 rabbit liver tumor model in carbon tetrachloride-induced cirrhosis of the liver","volume":"34","author":"Santana","year":"2023","journal-title":"J Vasc Interv Radiol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S1348-8643(17)30021-6","article-title":"Effect of areca nut on rabbit oral mucosa: evidence of oral precancerous condition by protein expression and genotoxic analysis","volume":"15","author":"Das","year":"2018","journal-title":"Oral Sci Int"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081575","article-title":"Three-dimensional printing of an apigenin-loaded mucoadhesive film for tailored therapy to oral leukoplakia and the chemopreventive effect on a rat model of oral carcinogenesis","volume":"14","author":"Takashima","year":"2022","journal-title":"Pharmaceutics"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.18006\/2023.11(5).822.833","article-title":"Comparative evaluation of Masson\u2019s trichrome and picrosirius red staining for digital collagen quantification using ImageJ in rabbit wound healing research","volume":"11","author":"Sharun","year":"2023","journal-title":"J Exp Biol Agric Sci"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.916145","article-title":"Main pathological changes of benign ureteral strictures","volume":"9","author":"Tan","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14295\/bds.2021.v24i3.2366","article-title":"Evaluation of muscle involvement and degeneration in advanced oral submucous fibrosis using three different stains: A retrospective cross-sectional study","volume":"24","author":"Umashankar","year":"2021","journal-title":"Braz Dent Sci"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.30699\/IJP.14.2.127","article-title":"Histochemical and immunohistochemical analysis of collagen fibers and microvascular density in various grades of oral submucous fibrosis","volume":"14","author":"Thakkannavar","year":"2019","journal-title":"Iran J Pathol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123168","article-title":"Chitosan-based buccal mucoadhesive patches to enhance the systemic bioavailability of tizanidine","volume":"642","author":"Arpa","year":"2023","journal-title":"Int J Pharm"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3390\/ph14060493","article-title":"Chlorhexidine mucoadhesive buccal tablets: The impact of formulation design on drug delivery and release kinetics using conventional and novel dissolution methods","volume":"14","author":"Al-Ani","year":"2021","journal-title":"Pharmaceuticals"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1847576\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:10:21Z","timestamp":1779912621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1847576\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":86,"alternative-id":["10.3389\/fimmu.2026.1847576"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1847576","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]},"article-number":"1847576"}}