OdontologyPub Date : 2026-10-20DOI: 10.1007/s10266-026-01575-1
Zeynep Ünal, Funda Fundaoğlu Küçükekenci
{"title":"Influence of final irrigation with EDTA and chitosan on apical microleakage of different apical repair materials in simulated immature teeth: a confocal laser scanning microscopy study.","authors":"Zeynep Ünal, Funda Fundaoğlu Küçükekenci","doi":"10.1007/s10266-026-01575-1","DOIUrl":"https://doi.org/10.1007/s10266-026-01575-1","url":null,"abstract":"<p><p>This study assessed the effects of different final irrigation solutions and apical repair materials on apical microleakage in simulated immature teeth using confocal laser scanning microscopy (CLSM). Ninety-six extracted human permanent maxillary incisors were used to create a model of immature teeth with open apices. The teeth were randomly allocated into three groups according to the final irrigation solution: distilled water, 17% EDTA, and 0.2% chitosan. Each group was divided into four subgroups according to apical repair material: Biodentine, MTA Repair HP, TotalFill BC RRM Fast Set Putty (TotalFill FSP), and Endocem MTA Premixed Regular (EMPR). After material placement, the specimens were immersed in 0.2% rhodamine B dye, then sectioned longitudinally and analyzed using CLSM. Microleakage was quantified with ImageJ. Data were analyzed using aligned rank transform (ART) ANOVA followed by ART-based pairwise contrasts using the art.con() function with Tukey-adjusted p-values (p < .05). Final irrigation solutions, apical repair materials, and their interaction significantly affected apical microleakage (p < .05). Chitosan showed the lowest microleakage, followed by EDTA and distilled water (p < .05). Microleakage differed significantly among apical repair materials (p < .05), with increased values in the TotalFill FSP, Biodentine, MTA Repair HP, and EMPR groups. The chitosan-TotalFill FSP combination demonstrated the lowest microleakage values (1.24 ± 0.02 mm; p < .05), whereas the distilled water-EMPR combination showed the highest microleakage values (3.35 ± 0.03 mm; p < .05). Within the limitations of this in vitro study, final irrigation with chitosan and the use of TotalFill FSP improved the apical sealing in immature teeth with open apices.</p>","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-20DOI: 10.1007/s10266-026-01572-4
Izadora Ramos de Almeida, Lana Cardoso-Silva, Alexandra Mussolino de Queiroz, Rafaela Manente, Karen Martineli Mendes, Soraya Coelho Leal, David John Manton, Francisco Wanderley Garcia de Paula-Silva, Fabrício Kitazono de Carvalho
{"title":"Correction: Uncovering the hidden costs of Molar Incisor Hypomineralization (MIH): the impact of later diagnosis on clinical outcomes and financial cost.","authors":"Izadora Ramos de Almeida, Lana Cardoso-Silva, Alexandra Mussolino de Queiroz, Rafaela Manente, Karen Martineli Mendes, Soraya Coelho Leal, David John Manton, Francisco Wanderley Garcia de Paula-Silva, Fabrício Kitazono de Carvalho","doi":"10.1007/s10266-026-01572-4","DOIUrl":"https://doi.org/10.1007/s10266-026-01572-4","url":null,"abstract":"","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Influence of chronic high-salt diet intake on experimental periodontitis: a preclinical study in rodents.","authors":"Hatem Abuohashish, Omar Omar, Nabras Alrayes, Norah AlQahtani, Muhaseena Muhamood, Hussain Alhawaj, Taleb Alkhamis, Khalid Almas","doi":"10.1007/s10266-026-01585-z","DOIUrl":"https://doi.org/10.1007/s10266-026-01585-z","url":null,"abstract":"<p><p>This study explored how chronic consumption of a high-salt diet (HSD) would affect periodontal tissues and periodontitis (PD) progression and remission using a PD ligation model. Male Wistar rats received a control diet (CD) or HSD for 16 weeks. Animals with each diet were allocated into healthy, PD (by ligation), and PD-remission (PD-R) groups. After 10 days, animals were sacrificed, except the PD-R groups, which had ligature removal and were sacrificed after another 10 days. PD severity and alveolar bone loss were evaluated clinically, morphometrically, and histologically in the right maxilla. The gene expression analysis assessed the molecular pathways behind the diet and PD effects in the left maxilla. Clinical assessment of the gingival bleeding index (GBI), probing pocket depth (PPD), and tooth mobility (TM) revealed that HSD exacerbated PD and reduced its recovery. Bone metabolic markers were elevated in HSD groups, particularly CTX and TRAP. Micro-CT assessment showed increased alveolar crest heights (ACH) and impaired alveolar bone microstructure in PD groups, while HSD worsened these impairments. Likewise, the gingival histological alterations by PD were aggravated in HSD animals. In the alveolar bone, expressions of bglap, ctsk, and hif1a were downregulated by HSD. Meanwhile, in the gingival tissues, expressions of eln, il6, mmp9, and tnf genes were increased by HSD without PD, while expressions of eln, il6, mmp9, tnf, and vegf genes were decreased in the PD-R groups. Chronic HSD intake was associated with altered periodontal structure, aggravated ligature-induced PD, and impaired early periodontal remission after ligature removal.</p>","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-20DOI: 10.1007/s10266-026-01587-x
Halil Ata Bıçakçıoğlu
{"title":"Does clinical improvement indicate biological resolution after periodontal therapy? An evidence-informed narrative review.","authors":"Halil Ata Bıçakçıoğlu","doi":"10.1007/s10266-026-01587-x","DOIUrl":"https://doi.org/10.1007/s10266-026-01587-x","url":null,"abstract":"<p><p>Periodontal therapy reduces the subgingival microbial burden and improves clinical parameters, yet residual pockets and recurrent inflammation persist in some patients and sites. This evidence-informed narrative review examines whether clinical improvement reflects restoration of periodontal tissue homeostasis. PubMed/MEDLINE, Embase, Scopus, and Web of Science Core Collection were searched from inception to 1 August 2026, supplemented by the Cochrane Library and citation screening. Forty publications were included in the core synthesis, while 23 additional publications provided biological or mechanistic context. Evidence was classified by proximity to the treated periodontal setting, and design-specific methodological appraisal was undertaken. Human post-treatment studies indicate that residual disease sites may retain dysbiotic microbial features, altered inflammatory mediator profiles, or activated stromal-cell populations. Evidence from active periodontitis, periodontal experimental systems, and inflammatory models supports the plausibility of impaired resolution pathways, trained immunity-like and epigenetic reprogramming, fibroblast activation, cytokine feedback, macrophage-fibroblast crosstalk, inflammatory cell death and DAMP amplification, and extracellular matrix regulation. However, these mechanisms have not been shown to persist simultaneously in clinically stable treated sites or predict recurrence independently of clinical and microbial factors. Plaque control, anatomical conditions, and supportive periodontal care remain central to stability. Residual immune activity may reflect physiological surveillance, persistent or recurrent dysbiosis, or altered host responsiveness and should not be interpreted in isolation. The proposed self-reinforcing lesion-susceptibility framework is hypothesis-generating and does not imply microbial independence. Longitudinal human studies integrating clinical, microbial, cellular, and molecular measurements are needed to determine whether resolution-associated pathways provide information beyond established periodontal indicators.</p>","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-20DOI: 10.1007/s10266-026-01589-9
Miaofeng Fan, Mengting Fan
{"title":"Association between functional tooth units and frailty in older adults: a cross-sectional study using NHANES 2005-2018.","authors":"Miaofeng Fan, Mengting Fan","doi":"10.1007/s10266-026-01589-9","DOIUrl":"https://doi.org/10.1007/s10266-026-01589-9","url":null,"abstract":"<p><p>Dental status, dietary intake, and frailty are closely interrelated among older adults. Nevertheless, the association between posterior occlusal support and frailty, and whether diet-related indicators can statistically account for part of this association, remain insufficiently elucidated. To primarily investigate the association between functional tooth units (FTUs) and frailty. This study used data from the NHANES 2005-2018. Weighted multivariate logistic regression models were applied to examine the associations of FTUs, overall dietary index for gut microbiota (DI-GM), and its specific components with frailty. Restricted cubic spline (RCS) analysis was performed to test the nonlinear relationship between FTUs and frailty, and further subgroup analyses were conducted. Exploratory mediation analyses were used to assess whether DI-GM and its components statistically partially explained the association between FTUs and frailty. 6,758 individuals were included, with a frailty prevalence of 18.34%. Following comprehensive covariate adjustment, higher FTUs were associated with lower odds of frailty (OR = 0.94, 95% CI: 0.91-0.96, P < 0.001). RCS analysis revealed no significant nonlinear association between FTUs and frailty (P-for-non-linearity > 0.05). Subgroup analyses showed no significant interactions between FTUs and frailty (P-interaction > 0.05). Among older adults in the United States, higher FTUs are associated with lower odds of frailty. Nevertheless, these findings only suggest interrelationships among oral status and frailty in older adults and cannot establish causal relationships.</p>","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-20DOI: 10.1007/s10266-026-01586-y
Yanhui Wu, Bo Li, Zhongxin Yang
{"title":"Cellular senescence and the SASP in the oral-metabolic axis: a putative link between periodontitis and type 2 diabetes mellitus.","authors":"Yanhui Wu, Bo Li, Zhongxin Yang","doi":"10.1007/s10266-026-01586-y","DOIUrl":"https://doi.org/10.1007/s10266-026-01586-y","url":null,"abstract":"<p><p>Periodontitis and type 2 diabetes mellitus (T2DM) are chronic inflammatory disorders with a bidirectional clinical association. Although microbial, immune, and metabolic mechanisms contribute to this relationship, they do not fully explain the persistence of inflammation and defective tissue repair. Cellular senescence and the senescence-associated secretory phenotype (SASP) may provide an additional framework for understanding this interaction. Within periodontal tissues, sustained microbial and metabolic stress may promote senescence-associated changes that disturb local immune regulation, tissue regeneration and bone homeostasis. These processes could interact with microbial dysbiosis and systemic inflammation as part of the oral-metabolic axis. However, the available evidence remains uneven. Diabetes-related stress can promote senescence-like changes in periodontal tissues, whereas direct evidence that periodontal senescence impairs distant metabolic organs is limited. This review examines the evidence linking cellular senescence to periodontal inflammation and T2DM, and discusses the emerging preclinical evidence for targeting senescent cells and the SASP.</p>","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-20DOI: 10.1007/s10266-026-01588-w
Ziqiang Liu, Xin Li
{"title":"The miR-196a2 rs11614913 polymorphism may be associated with susceptibility to early childhood caries in Han Chinese children.","authors":"Ziqiang Liu, Xin Li","doi":"10.1007/s10266-026-01588-w","DOIUrl":"https://doi.org/10.1007/s10266-026-01588-w","url":null,"abstract":"<p><p>The genetic basis of susceptibility to early childhood caries (ECC) requires further research. To examine the possible association between the miR-196a2 rs11614913 polymorphism and susceptibility to ECC. This case-control study recruited 200 children with ECC and 200 non-ECC children. Genotyping of the rs11614913 polymorphism was performed by the TaqMan method, and the levels of miR-196a2 in saliva were quantified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Logistic regression models were employed to analyse risk factors associated with ECC. Spearman's correlation analysis was conducted to assess the relationship between miR-196a2 and the caries severity index. T allele and TT genotype were associated with a substantially increased risk of ECC (odds ratio (OR) = 1.697, 95% confidence interval (95% CI) = 1.277-2.255; OR = 1.588, 95% CI = 1.050-2.402). miR-196a2 expression was elevated in children with ECC and demonstrated excellent diagnostic value (AUC = 0.8783). Furthermore, miR-196a2 was positively correlated with the severity of ECC. Within the ECC group, carriers of the TT genotype exhibited the highest levels of miR-196a2 expression and more severe caries. Logistic regression analysis confirmed that miR-196a2 expression was an independent risk factor (OR = 5.700, 95% CI = 3.645-8.911, P < 0.001). The miR-196a2 rs11614913 polymorphism may be associated with susceptibility to ECC in Han Chinese children.</p>","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-13DOI: 10.1007/s10266-026-01581-3
Basel Kharbot, Allam Al-Abdi, Falk Schwendicke, Sebastian Paris, Haitham Askar
{"title":"Effect of moisture control on root caries progression adjacent to different restorative materials in an in-vitro biofilm model.","authors":"Basel Kharbot, Allam Al-Abdi, Falk Schwendicke, Sebastian Paris, Haitham Askar","doi":"10.1007/s10266-026-01581-3","DOIUrl":"https://doi.org/10.1007/s10266-026-01581-3","url":null,"abstract":"<p><p>This study aimed to assess the impact of moisture control on the risk of caries progression to root restorations (CAR) made of resin composite (RC) or glass ionomer cements (GIC) under conditions of absolute or inadequate moisture control in an in vitro model. In each of the sixty caries-free human maxillary premolars, standardized mesial and distal cavities were prepared 5 mm apical to the cemento-enamel junction. The specimens were randomly allocated to the experimental groups RC-Z250 (Scotchbond Universal SE & Z250, 3M, Seefeld, Germany), GIC-DF (DeltaFil, DMG, Hamburg, Germany), GIC-EF (Equia Forte, GC, Tokyo, Japan), and GIC-KF (Ketac Fil, 3M, Seefeld, Germany) (n = 15). In each group, restorations were placed either simulating conditions of absolute (Control) or inadequate (Test) moisture control. After water storage for 100d (37°C, 100% humidity), specimens were subjected to thermocycling (10.000 thermal cycles; 5-55°C), and a continuous-culture Lactobacillus rhamnosus biofilm model for 10d. The integrated mineral loss ΔZ was measured along the tooth-restoration interface (dentin wall lesion; DWL) and the outer surface of the root dentin (dentin surface lesion; DSL) using transverse microradiography. Only group RC-Z250 exhibited significant differences in mineral losses ΔZ between Control and Test lesions in DSLs (ΔZ<sub>ctrl</sub>: 704; 517/1329 vol%×µm; ΔZ<sub>test</sub>: 1629; 1460/1996 vol%×µm; p < 0.05, Wilcoxon) whereas no significant Control-Test difference was observed for DWLs in RC-Z250 or for DSLs and DWLs in the tested GIC groups. In DSLs, the RC-Z250 Controls demonstrated significantly less mineral loss compared to all GIC groups, while the mineral loss adjacent to the Test-restorations did not differ significantly from that of the other groups (p < 0.05, Kruskal-Wallis/Dunn-Bonferroni). The differences in mineral loss (ΔΔZ = ΔZ<sub>test</sub> - ΔZ<sub>ctrl</sub>) across all groups were not significant (Kruskal-Wallis; p > 0.05). Direct comparison of moisture-associated differences in mineral loss did not reveal significant differences among restorative materials. Under ideal moisture-control conditions, RC-Z250 showed lower mineral loss in DSLs than the investigated GICs, but this finding should be interpreted cautiously due to the simplified model.</p>","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-13DOI: 10.1007/s10266-026-01569-z
Lamiaa Said Elfadaly, Mohamed Shafik
{"title":"Multimodal artificial intelligence in dental diagnosis: influence of reasoning depth and domain-specific medical model on diagnostic performance.","authors":"Lamiaa Said Elfadaly, Mohamed Shafik","doi":"10.1007/s10266-026-01569-z","DOIUrl":"https://doi.org/10.1007/s10266-026-01569-z","url":null,"abstract":"<p><p>Large language models are increasingly explored as clinical decision-support tools, but the relationship between configurable reasoning effort and multimodal diagnostic performance remains unclear. This study evaluated the association between API-configured reasoning effort and multimodal oral and dental diagnostic performance in GPT-5 and compared its outputs with those of the compact open-weight medical-domain model MedGemma-1.5-4b-it. Eight anonymized multimodal case reports representing dental trauma, odontogenic cysts, odontogenic tumors, implant-associated infection, oral mucosal disorders, hereditary mucosal disease, and restorative management were reformatted into structured evaluation scenarios. Final diagnostic labels, definitive treatment plans, author interpretations, answer-revealing captions, and postoperative outcomes were excluded to reduce answer leakage. Five configurations were evaluated: GPT-5 under four API-configured reasoning-effort settings (high, medium, low, and minimal) and MedGemma-1.5-4b-it as a compact medical-domain comparator. Outputs were assessed using a six-domain 0-5 rubric covering diagnostic accuracy, diagnostic completeness, reasoning quality, treatment planning, safety and risk awareness, and scope adherence. Diagnostic scores were checked against the exact archived outputs and source reference diagnoses before final analysis, and a domain-level Safety Override was applied to clinically dangerous recommendations. Repeated-measures differences were analyzed at the case level, with complementary exploratory analyses of primary-diagnosis agreement, reference-diagnosis inclusion, clinical-pathway appropriateness, and safety. Inter-rater reliability of the original independent blinded ratings was excellent (intraclass correlation coefficient = 0.92; 95% confidence interval, 0.87-0.95). Total scores differed across configurations (Friedman χ²(4) = 27.24, p = 0.000018; Kendall's W = 0.85). Mean scores were 28.0 ± 2.5 for GPT-5 high, 27.8 ± 1.6 for medium, 22.8 ± 4.0 for low, 18.9 ± 2.8 for minimal, and 17.1 ± 3.3 for MedGemma-1.5-4b-it. Primary-diagnosis agreement with the published reference diagnosis occurred in 6/8 cases for GPT-5 high, 6/8 for medium, 5/8 for low, 4/8 for minimal, and 1/8 for MedGemma; reference-diagnosis inclusion either as the primary diagnosis or within the differential occurred in 8/8, 8/8, 8/8, 7/8, and 3/8 cases, respectively. One safety-critical error occurred in GPT-5 low; none occurred in the other configurations. GPT-5 high and medium had the highest observed mean scores, but no pairwise Wilcoxon comparison remained significant after Holm correction. Primary-diagnosis agreement, reference-diagnosis inclusion, clinical-pathway appropriateness, and safety provided complementary views of open-ended clinical performance. MedGemma showed lower primary-diagnosis agreement and reference-diagnosis inclusion, while no MedGemma response met the final source-verified safety-critical crite","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OdontologyPub Date : 2026-10-13DOI: 10.1007/s10266-026-01583-1
Nitya Krishnasamy
{"title":"Untargeted salivary metabolomics for early prediction of chemotherapy-induced oral toxicities in patients with oral squamous cell carcinoma.","authors":"Nitya Krishnasamy","doi":"10.1007/s10266-026-01583-1","DOIUrl":"https://doi.org/10.1007/s10266-026-01583-1","url":null,"abstract":"<p><p>Chemotherapy-induced oral toxicities, including oral mucositis, xerostomia, and dysgeusia, are common complications in patients with oral squamous cell carcinoma (OSCC), often leading to impaired quality of life, treatment interruptions, and poor therapeutic outcomes. Reliable non-invasive biomarkers capable of predicting these toxicities before severe clinical manifestations remain limited. This study investigated salivary metabolomic alterations associated with chemotherapy-induced oral toxicities using untargeted liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). A prospective observational study was conducted among 60 patients with histopathologically confirmed OSCC receiving platinum-based chemotherapy. Unstimulated saliva samples were collected before and after chemotherapy and analyzed using untargeted LC-QTOF-MS. Metabolomic data were processed using Agilent MassHunter software and annotated against HMDB, METLIN, LipidMaps, and KEGG databases. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), variable importance in projection (VIP) analysis, hierarchical clustering, volcano plot analysis, KEGG pathway enrichment, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis were performed to identify biomarkers associated with chemotherapy-induced oral toxicities. Oral mucositis occurred in 63.3% of patients, xerostomia in 55.0%, dysgeusia in 48.3%, and severe mucositis in 18.3%. Untargeted metabolomic profiling identified significant perturbations in lipid metabolism, oxidative stress, and amino acid metabolism. Ceramide, lysophosphatidylcholine (LPC), glutathione disulfide, arachidonic acid, taurine, and citrulline were among the most significantly dysregulated metabolites. PCA and PLS-DA demonstrated distinct metabolic separation between patients with and without oral toxicity (R² = 0.86; Q² = 0.74; permutation p < 0.001). KEGG pathway analysis revealed significant enrichment of glycerophospholipid, sphingolipid, glutathione, arachidonic acid, arginine, and taurine metabolic pathways. Ceramide (adjusted OR = 4.82, 95% CI: 2.11-10.96), LPC (adjusted OR = 3.64, 95% CI: 1.78-7.52), and glutathione (adjusted OR = 2.92, 95% CI: 1.39-6.12) were independent predictors of severe oral toxicity. ROC analysis demonstrated strong discriminatory performance for ceramide (AUC = 0.91), LPC (AUC = 0.88), and glutathione (AUC = 0.85), while the combined metabolomic model achieved an AUC of 0.95, with 90.9% sensitivity and 91.2% specificity. Untargeted salivary LC-QTOF-MS metabolomics identified distinct metabolic signatures associated with chemotherapy-induced oral toxicities in patients with OSCC. Dysregulation of lipid metabolism, oxidative stress pathways, and amino acid metabolism appears to play a central role in the development of oral mucositis, xerostomia, and dysgeusia. Ceramide, lysophosphatidylcholine, and glutathione emerged as promisi","PeriodicalId":19390,"journal":{"name":"Odontology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}