B.D. Murchie, M.J. German, P.J. Waterhouse, F. Mullan
{"title":"The early wear susceptibility of dentine following exposure to citric acid: In vitro study","authors":"B.D. Murchie, M.J. German, P.J. Waterhouse, F. Mullan","doi":"10.1016/j.archoralbio.2025.106363","DOIUrl":"10.1016/j.archoralbio.2025.106363","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the effect of early erosion on the mechanical and structural properties of dentine, while comparing the influence of different citric acid pH and concentration levels.</div></div><div><h3>Design</h3><div>Twenty dentine specimens were randomly allocated into five groups, according to the citric acid (CA) solution: non-eroded; 1 % buffered CA (pH=3.8); 1 % unbuffered CA (pH=2.55); 6 % buffered CA (pH=3.8); and 6 % unbuffered CA (pH=2.06). Specimen numbers were determined from a sample size power calculation. Erosion groups were subjected to 6x cycles, each lasting 20 s, giving a total exposure of 2 min. Surface alterations were determined by atomic force microscopy (at nanoscale) after each cycle. Erosive changes were also assessed qualitatively/quantitatively with scanning electron microscopy and energy dispersive x-ray spectroscopy. Data were analysed by repeated measures ANOVA with Bonferroni correction.</div></div><div><h3>Results</h3><div>All erosion groups showed significant structural and mechanical changes after a 20 s exposure interval. Specimens exposed to 6 % unbuffered CA, revealed a significant reduction of modulus of elasticity (p < 0.01), and greater changes to topography and morphology, compared with other groups. The 1 % buffered group had the least erosive changes (p < 0.05). Dentine exposed to 1 % unbuffered CA had a comparably greater rate of erosion, compared with the 6 % buffered solution, as exposure times progressed.</div></div><div><h3>Conclusions</h3><div>Dentine was highly susceptible to early CA erosion, with significant changes occurring after 20 s, regardless of pH or concentration. Alterations to the pH and/or concentration significantly altered the rate and severity of erosion. Although, CA with a lower pH was the most critical factor for early dentine erosion.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106363"},"PeriodicalIF":2.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liping Xie , Yekun Zhuang , Yehua Lai , Jing Guo , Ziqiang Zhu , Hua Tian , Shanqiang Zhang , Fu Liu
{"title":"Puerarin enhances the efficacy of carboplatin in oral squamous cell carcinoma via dual targeting","authors":"Liping Xie , Yekun Zhuang , Yehua Lai , Jing Guo , Ziqiang Zhu , Hua Tian , Shanqiang Zhang , Fu Liu","doi":"10.1016/j.archoralbio.2025.106360","DOIUrl":"10.1016/j.archoralbio.2025.106360","url":null,"abstract":"<div><h3>Objective</h3><div>The purpose of this study was to explore the effects and molecular mechanisms by which puerarin, in combination with carboplatin, combats oral squamous cell carcinoma (OSCC).</div></div><div><h3>Design</h3><div>The effects of puerarin in combination with carboplatin on OSCC cell viability, proliferation, apoptosis, autophagy, DNA damage, and the Phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway were evaluated through molecular biology experiments and bioinformatics analyses. In addition, an OSCC animal model was established to further evaluate the <em>in vivo</em> anti-tumor effects of combination therapy.</div></div><div><h3>Results</h3><div>Puerarin synergized with carboplatin to inhibit OSCC cell viability and proliferation, induce DNA damage and apoptosis, and trigger autophagosome formation while blocking autophagic flux, thereby further promoting apoptosis. Combination therapy modulated both autophagy and apoptosis through suppression of the PI3K-AKT-mTOR signaling pathway. In addition, combination therapy improved <em>in vivo</em> efficacy and reduced the toxicity of low-dose carboplatin. The <em>in vivo</em> toxicity of puerarin monotherapy was not significant.</div></div><div><h3>Conclusion</h3><div>Puerarin enhanced the therapeutic effect of carboplatin on OSCC through a dual mechanism: activating the \"DNA damage-autophagic flux blockade-damage accumulation-apoptosis activation\" positive feedback loop and inhibiting the PI3K-AKT-mTOR pathway to promote autophagosome formation and apoptosis. The synergistic effect significantly improved the efficacy of carboplatin while reducing its toxicity, and puerarin showed no significant toxic side effects, providing a novel strategy for optimizing clinical combination therapy.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106360"},"PeriodicalIF":2.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Disha Sharma , Sarita Pal , Uma Shanker Pal , Narayan Prasad Yadav
{"title":"Elucidating the pathogenesis of oral submucous fibrosis: A comprehensive review","authors":"Disha Sharma , Sarita Pal , Uma Shanker Pal , Narayan Prasad Yadav","doi":"10.1016/j.archoralbio.2025.106362","DOIUrl":"10.1016/j.archoralbio.2025.106362","url":null,"abstract":"<div><h3>Objective</h3><div>Oral submucosal fibrosis (OSMF) is a progressive and potentially malignant disorder of the oral cavity. This review aims to explore the key mechanisms underlying OSMF pathogenesis and its malignant transformation to oral cancer, focusing on the role of associated cells, growth factors, and signaling pathways, by detailing the sequential events within each pathway and their interconnections.</div></div><div><h3>Design</h3><div>A comprehensive literature search was conducted using databases such as PubMed, Scopus, Google Scholar, and SciFinder to identify affected cells, pathways, and cellular mechanisms associated with OSMF and oral cancer.</div></div><div><h3>Results</h3><div>This review elaborates the signaling pathways responsible for the progression of OSMF through myofibroblast activation. It highlights the altered functionality of key cellular players, including epithelial, endothelial, immune cells, and fibroblasts. It also enhances the understanding of OSMF pathophysiology by revealing the specific growth factors (TGF-βs, PDGF, FGF, VEGF, CTGF) and signaling pathways such as PI3K/AKT, JAK/STAT, WNT/β-catenin, and NF-кB, that are involved in the initiation and progression of OSMF and its malignant transformation to oral cancer.</div></div><div><h3>Conclusion</h3><div>This review identifies potential therapeutic targets and biomarkers within signaling pathways, mainly TGF-β and PI3K/AKT, that regulate fibroblast activation, inflammation, reactive oxygen species generation, collagen synthesis, and degradation in OSMF, which further leads to oral cancer development. In order to develop new treatments that target particular biomarkers, a deeper understanding of these signaling cascades is necessary.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106362"},"PeriodicalIF":2.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guilherme Fantini Ferreira , Talita Malini Carletti , Ingrid Meira Andrade , Mayara Abreu Pinheiro , Ana Carolina Pero , Renata Cunha Matheus Rodrigues Garcia
{"title":"Mandibular movements and swallowing threshold in older adults with obesity using removable prostheses","authors":"Guilherme Fantini Ferreira , Talita Malini Carletti , Ingrid Meira Andrade , Mayara Abreu Pinheiro , Ana Carolina Pero , Renata Cunha Matheus Rodrigues Garcia","doi":"10.1016/j.archoralbio.2025.106361","DOIUrl":"10.1016/j.archoralbio.2025.106361","url":null,"abstract":"<div><h3>Objective</h3><div>In adults, obesity has been associated with reduced chewing ability. However, evidence for the association of obesity with chewing movements in partially edentate older adults is scarce. This study was conducted to evaluate the influence of obesity on the mandibular movements and swallowing thresholds of obese older adults using removable prostheses.</div></div><div><h3>Design</h3><div>Thirty-eight partially edentulous older adults were assigned to obese (<em>n</em> = 18, 71.11 ± 5.18 years) and control (<em>n</em> = 20, 70.00 ± 5.36 years) groups. All participants received new prostheses. Six months later, their mandibular range of motion, jaw movements during chewing, and swallowing thresholds were assessed using jaw-tracking methods. The data were compared using the independent <em>t</em> test (<em>α</em> = 5 %).</div></div><div><h3>Results</h3><div>Relative to controls, older adults with obesity had lesser vertical apertures (34.65 mm ± 2.26), and masticatory cycle times (600.53 ms ± 68.05), and longer mandibular closing times (242.15 ms ± 40.05; all <em>p</em> < 0.05). Additionally, the obese group exhibited larger median particle sizes (4.89 ± 0.70) and fewer chewing cycles before swallowing (20.44 ± 4.51; both <em>p</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Older adults with obesity wearers of removable dentures had reduced jaw range of motion and mandibular movements during chewing, and impaired masticatory function related to swallowing threshold relative to controls. These findings may contribute to the understanding of the complex relationship between obesity and masticatory function.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106361"},"PeriodicalIF":2.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patricio González-Hormazábal , Noemí Leiva , Rosa Pardo , José Suazo
{"title":"Association between CpG-SNPs and nonsyndromic cleft lip palate in a Chilean population","authors":"Patricio González-Hormazábal , Noemí Leiva , Rosa Pardo , José Suazo","doi":"10.1016/j.archoralbio.2025.106358","DOIUrl":"10.1016/j.archoralbio.2025.106358","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the association between common variants in CpG islands (CpG-SNPs) related to the expression of selected genes, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a Chilean sample.</div></div><div><h3>Design</h3><div>A total of 239 Chilean NSCL/P unrelated cases and 524 controls were genotyped using GSA array. Genotypes were imputed from the array, selecting those located within CpG islands coordinates and associated with the expression of genes differentially expressed in human cleft tissues. These selected SNPs were used for association analysis with NSCL/P based on logistic regression.</div></div><div><h3>Results</h3><div>A total of 96 CpG-SNP met the above-mentioned criteria. After multiple comparisons correction (p-value<0.000862), only rs12940418 remains significantly associated with NSCL/P (OR 0.644, 95 % CI 0.496–0.833, p-value=0.000859). Although this variant is located 540 Kb away from the transcription start site of <em>SHMT1,</em> it has evidence of modulating its expression.</div></div><div><h3>Conclusions</h3><div>The most plausible biological explanation for our results is cis/distal regulatory effect of rs12940418 on the expression of <em>SHMT1.</em> This gene encodes an enzyme implicated in folate/one-carbon metabolism, and its variants have been previously associated with NSCL/P in our population. Our results reveal the role of epigenetic mechanisms in birth defects expression such as DNA methylation and small RNAs.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106358"},"PeriodicalIF":2.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Azhar Dawasaz , Rafi A. Togoo , Zuliani Mahmood , Ahmad Azlina , Kannan Thirumulu Ponnuraj
{"title":"Dentinal remineralisation using self-assembling peptide P11-4 and chloro calcium phosphosilicate in obese children: An ex vivo study","authors":"Ali Azhar Dawasaz , Rafi A. Togoo , Zuliani Mahmood , Ahmad Azlina , Kannan Thirumulu Ponnuraj","doi":"10.1016/j.archoralbio.2025.106359","DOIUrl":"10.1016/j.archoralbio.2025.106359","url":null,"abstract":"<div><h3>Objective</h3><div>Saliva acts as primary oral defence agent. Obese children’s saliva differs in composition from healthy children. The objective of the study was to evaluate the remineralization effects in saliva from obese versus healthy children by using P11–4 and CCPS.</div></div><div><h3>Design</h3><div>After gel induced demineralisation, 20 P11–4 and 20 CCPS treated dentinal discs were submerged in natural whole saliva collected from healthy and obese children (n = 10). Micro-CT and Scanning Electron Microscopy (SEM) analyses were performed at baseline, 7-days (T1 stage), and 28-days (T2 stage).</div></div><div><h3>Results</h3><div>CCPS had enhanced mineral content percentage and significantly greater efficacy in lowering lesion depth. Group 2 displayed the most efficacy at 68.8 %, while Group 3 showed the lowest efficacy. P11–4 and CCPS demonstrated diminished efficacy when exposed to saliva from obese children compared to healthy ones. P11–4 exhibited a more significant reduction in lesion depth at the T1 stage; however, its effectiveness decreased with extended saliva exposure at T2 stage. The percentage of remineralisation efficacy was calculated after normalising the data against sound dentine values. Two-way ANOVA indicated significant differences across the groups exclusively at stage T2 (p < 0.005). SEM micrographs demonstrated significant mineral deposition and tubule obstruction. There were substantial disparities across groups, with CCPS controls demonstrating the most efficient tubule sealing. The P11–4 group exhibited the minimal tubular occlusion.</div></div><div><h3>Conclusion</h3><div>CCPS in healthy children saliva after 28-days had enhanced remineralisation efficacy compared to P11–4.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106359"},"PeriodicalIF":2.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ikuo Yonemitsu , Aikaterini Lagou , Balazs J. Denes , Takashi Ono , Stavros Kiliaridis
{"title":"Longitudinal changes in maxillary alveolar bone after molar extraction in young and adult male rats","authors":"Ikuo Yonemitsu , Aikaterini Lagou , Balazs J. Denes , Takashi Ono , Stavros Kiliaridis","doi":"10.1016/j.archoralbio.2025.106357","DOIUrl":"10.1016/j.archoralbio.2025.106357","url":null,"abstract":"<div><h3>Objective</h3><div>To study the changes in maxillary alveolar bone dimensions after unilateral molar extraction, considering the ipsilateral versus contralateral alveolar process cross-sectional area (CSA) and the height of the alveolar bone crest in relation to age.</div></div><div><h3>Design</h3><div>A total of 28 4-week-old (young) and 28 26-week-old (adult) male rats were randomly assigned to control (n = 12) and experimental (n = 16) groups at each age. The experimental groups underwent unilateral upper right molar extraction, and all rats were euthanized after 12 weeks. The skulls were longitudinally scanned immediately after extraction and at 4, 8, and 12 weeks after extraction using in vivo micro-CT. The CSA and alveolar bone height were measured using five standardised transverse sections of the maxillary first molars.</div></div><div><h3>Results</h3><div>The CSA and alveolar bone height in the young and adult control rats constantly increased, although to a lesser extent in the adults. Molar extraction caused a substantial decrease in the CSA and alveolar ridge heights in the edentulous region in young and adult rats, whereas those contralateral to the extraction side increased in the young and adult rats similar to that in the controls. The reduction in the CSA 12 weeks after extraction was more extensive in young than in adult rats.</div></div><div><h3>Conclusion</h3><div>The unilateral loss of maxillary molars reduced alveolar bone mass, as measured using the changes in the alveolar process CSA and alveolar process heights on the edentulous sides. These measures increased contralateral to the extraction and control sides, with some differences related to age and function.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106357"},"PeriodicalIF":2.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yutong Zhou , Congsheng Wen , Qixia Zhang , Ziteng Gu , Luya Lian , Kexin Xue , Tianyi Xu , Zhehao Lin , Weiguo Wang , Haihua Zhu
{"title":"Characteristics of oral microbiomics with soldiers in the army before and after high-intensity physical training","authors":"Yutong Zhou , Congsheng Wen , Qixia Zhang , Ziteng Gu , Luya Lian , Kexin Xue , Tianyi Xu , Zhehao Lin , Weiguo Wang , Haihua Zhu","doi":"10.1016/j.archoralbio.2025.106347","DOIUrl":"10.1016/j.archoralbio.2025.106347","url":null,"abstract":"<div><h3>Objectives</h3><div>This paper aims to investigate the changes in soldiers' oral microbiome and metabolic levels after a month of high-intensity training.</div></div><div><h3>Design</h3><div>We collected saliva samples from 10 soldiers with good oral health and hygiene habits before and after training. Subsequently, DNA extraction, metagenomic sequencing, and phylogenetic analysis of the oral microbiome were conducted.</div></div><div><h3>Results</h3><div>7733 bacterial species from 113 known bacterial phyla and 2017 genera detected in 20 samples. The diversity and richness of saliva microorganisms before and after training were similar <em>(p > 0.05)</em>, while beta diversity analysis showed structural differences in microbiota at the phylum and genus levels <em>(p < 0.05)</em>. The relative abundance of 27 genera such as <em>Proteobacteria</em>, <em>Neisseria</em>, <em>Morococcus cerebrosus</em> and <em>Eikenella</em> in soldiers' saliva significantly increased after high-intensity training <em>(p < 0.05)</em>. Conversely, the relative abundance of 20 genera such as <em>Bacteroidota</em>, <em>Veillonella</em>, <em>Parvimonas micra</em>, <em>Prevotella oris</em>, <em>Peptostreptococcus</em>, and <em>Treponema</em> decreased <em>(p < 0.05)</em>. At the metabolic level, training resulted in a relative increase <em>(p < 0.05)</em> in various pathways, including amino acid metabolism, sulfur metabolism, glutathione metabolism, and Tyrosine metabolism. By comparison, after training, carbohydrate metabolism, glycan biosynthesis, metabolism, the HIF-1 signaling pathway, and necroptosis revealed a relative decrease <em>(p < 0.05).</em></div></div><div><h3>Conclusions</h3><div>This paper reveals the changes in the saliva microbiome of soldiers after one month of high-intensity training, in which the relative abundance of biomarkers of periodontal disease, caries, and other oral diseases represented by <em>peptostreptococcus</em>, <em>prevotella oris</em>, <em>treponema</em>, etc., are significantly reduced, suggesting that long-term high-intensity training may have a positive effect on oral health.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106347"},"PeriodicalIF":2.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vi Pham , Antonio Hernandes Chaves Neto , Julia Zheng , Mary Elmeniawi , Krishna Kumar Kookal , Muhammad F. Walji , Mary C. Farach-Carson , Walid D. Fakhouri
{"title":"IRF6 regulates adherens junction proteins and inflammatory cytokines in salivary acinar cells and its expression is elevated in Sjӧgren’s syndrome","authors":"Vi Pham , Antonio Hernandes Chaves Neto , Julia Zheng , Mary Elmeniawi , Krishna Kumar Kookal , Muhammad F. Walji , Mary C. Farach-Carson , Walid D. Fakhouri","doi":"10.1016/j.archoralbio.2025.106348","DOIUrl":"10.1016/j.archoralbio.2025.106348","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the mechanism of Interferon Regulatory Factor 6 (IRF6) function in regulating adherens junction proteins and inflammatory cytokines in human salivary acinar cells and Sjögren’s syndrome biopsies.</div></div><div><h3>Design</h3><div>We used mouse model, salivary cell lines, and human salivary gland (SG) biopsies to investigate IRF6 function in SG cellular integrity and immunomodulation.</div></div><div><h3>Results</h3><div>In <em>Irf6</em>-null mice, we observed myoepithelial cell detachment from acinar cells of major SGs, and the acini were remarkably disorganized compared to wild-type littermates. At the molecular level, the acinar differentiation markers E-cadherin and MIST1 were markedly reduced in <em>Irf6</em>-null embryonic SG, while the proinflammatory cytokines, IL6, IL17A, and IL22, expression was elevated in major SG. In human salivary NS-SV-acinar and adenocarcinoma cells, IRF6 knockdown resulted in a reduction of β-catenin, RAB11b, and the inflammatory cytokines TGFβ3, IL6, IL17A, and IL22, while IRF6 overexpression led to an increase in adherens junction proteins and pro-inflammatory cytokines. Consequently, cell-cell contact and junction of acinar cells were disrupted. Additionally, treatment of acinar cells with TGFβ3 enhanced IRF6 and its target genes expression and rescued the branching morphogenesis during development of <em>Irf6</em>-null SG explants. In Sjögren’s syndrome (SS) biopsies, IRF6 level was remarkably elevated in salivary SS affected acini, along with increased levels of E-cadherin and inflammatory cytokines than control biopsies.</div></div><div><h3>Conclusion</h3><div>IRF6 plays a crucial role in regulating adherens junction proteins and inflammatory cytokines in acinar cells, and increased IRF6 levels in SS biopsies might explain the compromised intercellular space of acinar cells and elevated cytokines in affected SS biopsies.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106348"},"PeriodicalIF":2.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Swathi Jayan , Jeena John , Madhav Manoj K, Midhun T U, Rahul R S, Deepak D R, Vinod Krishnan
{"title":"KEAP1-NRF2-IKKβ crosstalk protects periodontal ligament fibroblasts subjected to mechanical vibratory forces","authors":"Swathi Jayan , Jeena John , Madhav Manoj K, Midhun T U, Rahul R S, Deepak D R, Vinod Krishnan","doi":"10.1016/j.archoralbio.2025.106345","DOIUrl":"10.1016/j.archoralbio.2025.106345","url":null,"abstract":"<div><h3>Objectives</h3><div>When cells experience acute trauma from forces, cytoprotective molecules such as NRF2 and activation of inflammatory pathways led by NFkB are synthesized and released. An action-binding protein, KEAP1, plays a central role in these activities. The present study aimed to determine the effect of differential magnitudes of vibratory mechanical force application on the KEAP1 molecule and its downstream regulators, such as NRF2 and IKKβ.</div></div><div><h3>Design</h3><div>A fibroblast cell culture was performed on periodontal ligament cells scraped from atraumatically extracted premolar teeth. These cells were subjected to low (50 Hz), medium, (100 Hz) high (150 Hz), and very high (200 Hz) vibratory settings for 20 min at 0, 24, and 48 h. mRNA and protein analysis of KEAP1, NRF2, and IKKβ was performed using real-time PCR, indirect ELISA test, and Western blot, respectively.</div></div><div><h3>Results</h3><div>The results indicated that vibratory mechanical force application interfered with cultured periodontal ligament fibroblasts' normal growth and homeostasis. While KEAP1's mRNA expression and protein activity were downregulated, NRF2's and IKKβ's were upregulated. As force magnitude increases, KEAP1's downregulation increases, while NRF2 and IKKβ's upregulation continues.</div></div><div><h3>Conclusions</h3><div>The study revealed an inverse relationship between KEAP1, NRF2, and IKKβ in periodontal ligament fibroblasts subjected to mechanical forces. A decrease in KEAP1 and an increase in NRF2 and IKKβ mRNA and protein levels to different vibrational frequencies can evoke cytoprotective responses in the cells.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"178 ","pages":"Article 106345"},"PeriodicalIF":2.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}