Archives Of Oral Biology[JOURNAL]
Sun
200 papers
Polymicrobial periodontal infection selectively alters the fecal microbiome in mice: Implications for the oral-gut microbial axis.
Jeepipalli S, Gurusamy P, Martins ARL … +4 more , Reddy SSP, Sahay B, Chan EKL, Kesavalu L
Arch Oral Biol · 2026 May · PMID 42242180 · Publisher ↗
OBJECTIVE(S): This study aimed to evaluate the impact of polybacterial oral infection with Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia on the g...
OBJECTIVE(S): This study aimed to evaluate the impact of polybacterial oral infection with Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia on the gut microbiota in a murine model. DESIGN: We investigated alterations in fecal bacterial microbiome in infected mice. Fecal samples were collected after the 15th week of infection. Libraries of 16S rRNA amplicons generated from fecal DNA were sequenced using the Illumina sequencing platform. RESULTS: Feces from infected mice showed upregulation in the classes Verrucomicrobiae, Bacteroidia, Bacilli, and downregulation of Actinomycetia, Coriobacterota, and Clostridia. The genera Lactobacillus (p-value < 0.001) were significantly upregulated, and Acutalibacter (p-value < 0.05), Limosilactobacillus (p-value < 0.05) were downregulated in the infection compared to sham-infected mice. The infection process upregulated 15 strains of bacteria most prominently Akkermansia muciniphila and Dubosiella and downregulated 19 strains. Feces from sham infection had 21 strains of bacteria that completely disappeared in the infected mice, and the feces from infected mice detected 16 strains (Bacteroides, Bifidobacterium globosum) absent in sham-infected mice. Fecal microbiome data indicate that bacterial infection disrupts gut microbiome composition (selective dysbiosis) at class, genus, and strain levels. Periodontal infection appeared to eliminate certain bacterial strains and promoted the emergence of new strains. CONCLUSION: Using the Illumina sequencing platform, the present study found that polymicrobial periodontal infection selectively altered the gut microbiome at the class, genus, and strain levels of fecal bacteria. The genomic DNA for S. gordonii, F. nucleatum, and P. gingivalis was detected in the infected mice's feces.
Development of arecoline-induced mouse model for oral submucous fibrosis: An in vitro and in vivo study.
Pal S, Sharma D, Sahoo D … +7 more , Verma S, Mugale MN, Agrahari K, Singh VK, Kumar S, Banerjee M, Yadav NP
Arch Oral Biol · 2026 May · PMID 42235204 · Publisher ↗
OBJECTIVE: To establish an arecoline-induced preclinical model of oral submucous fibrosis (OSMF) and to investigate associated fibrotic and inflammatory mechanisms using in vitro and in vivo approaches. DESIGN: In vitro,...
OBJECTIVE: To establish an arecoline-induced preclinical model of oral submucous fibrosis (OSMF) and to investigate associated fibrotic and inflammatory mechanisms using in vitro and in vivo approaches. DESIGN: In vitro, hTERT and HaCaT cells were exposed to varying concentrations of arecoline to assess fibrotic markers, inflammatory cytokines, and reactive oxygen species (ROS), quantified by ELISA and qRT-PCR analysis. In vivo, Swiss albino mice were administered with arecoline (1 mg/kg for 25 days or 2 mg/kg for 15 days) via the sub-buccal route. OSMF induction was evaluated by body weight, mouth opening diameter estimation, cytokine expression, histopathological and immunohistochemical analysis, confirming fibrotic and inflammatory activation, characteristic of OSMF. RESULTS: In vitro, arecoline exposure induced dose-dependent increase in intracellular ROS generation, with elevated cytokines (IL-6, IL-13, TNF-α) and fibrosis-related genes (TGF-β1, Col1α2, Col3α1), and downregulated anti-fibrotic (IFN-γ) marker, indicating role of inflammatory activation and oxidative stress in inducing fibrosis. In vivo, arecoline-induced OSMF-like condition in mice showed reduction in body weight and mouth opening diameter. Histopathological findings also revealed epithelial atrophy, subepithelial hyalinization, and collagen accumulation in buccal and tongue tissues in arecoline-treated mice. Immunohistochemical analysis further confirmed overexpression of TGF-β1 and NF-κB in arecoline-treated mice, along with upregulation of TGF-β1, inflammatory cytokines (IL-6, IL-1β, TNF-α), and decline in IFN-γ, as determined by ELISA. CONCLUSION: The study demonstrates that arecoline induces OSMF-like condition in both cultured cells and mice, providing practical model for preliminary evaluation of potential anti-OSMF therapeutic agents by assessing fibrotic, inflammatory, oxidative stress markers, key molecular regulators of OSMF.
THE incidence of medication-related osteonecrosis of the jaws (MRONJ) in rodent animal models: A systematic review and meta-analysis.
Maciel GBM, Maciel RM, Custodio MZ … +3 more , Oliveira LM, Zanatta FB, Danesi CC
Arch Oral Biol · 2026 May · PMID 42235203 · Publisher ↗
OBJECTIVES: This systematic review with meta-analysis aimed to identify the main factors influencing the incidence of medication-related osteonecrosis of the jaws (MRONJ) in rodent models. DESIGN: A systematic search of...
OBJECTIVES: This systematic review with meta-analysis aimed to identify the main factors influencing the incidence of medication-related osteonecrosis of the jaws (MRONJ) in rodent models. DESIGN: A systematic search of experimental studies involving rat and mouse models of MRONJ was conducted across multiple databases up to April 2025. Risk of bias was assessed using Systematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Primary outcomes were the incidence of histological osteonecrosis and/or exposed bone or fistula in the oral cavity. RESULTS: A total of 119 studies were included, with 105 were eligible for meta-analysis. The pooled incidence of histological osteonecrosis was 28.60% (95% CI 20.24%-37.61%; I² = 90.3%) in rats and 23.81% (95% CI 8.24%-43.05%; I² = 88.6%) in mice. The overall incidence of bone exposure was 19.96% (95% CI 13.20%-27.50%; I² = 88.9%) in rats and 8.6% (95% CI 3.2%-15.5%; I² = 75.7%) in mice. Across both species, the MRONJ induction protocol and cumulative zoledronic acid (ZOL) dose were the main determinants of histological osteonecrosis, with higher incidences observed in ZOL plus tooth extraction protocols. In rats, the highest bone exposure rates occurred in ZOL-plus-extraction protocols associated with bone regularization, infection, or dexamethasone. In mice, greater bone exposure was associated with ZOL combined with cyclophosphamide or dexamethasone. Meta-regression models explained up to 78% of between-study heterogeneity. Statistically significant publication bias was detected only for bone exposure in rats. CONCLUSION: The induction protocol and ZOL dose are critical determinants of MRONJ incidence in rodent models.
Azoxystrobin induces mitochondrial apoptosis by inhibiting cytochrome b Qo site of mitochondrial complex Ⅲ in oral leukoplakia cells and a mouse model.
Li L, Lu Y, Shen Y … +6 more , Wang W, Yang J, Wang M, Miao C, Zhang M, Tang X
Arch Oral Biol · 2026 May · PMID 42229196 · Publisher ↗
OBJECTIVE: Oral leukoplakia (OLK) is an oral potentially malignant disorder with the potential to transform into oral squamous cell carcinoma. Our previous study demonstrated that azoxystrobin (AZOX), a natural product,...
OBJECTIVE: Oral leukoplakia (OLK) is an oral potentially malignant disorder with the potential to transform into oral squamous cell carcinoma. Our previous study demonstrated that azoxystrobin (AZOX), a natural product, reduced malignant transformation in a mouse model. Building on these findings, the present study aims to investigate the molecular mechanisms underlying AZOX-induced mitochondrial apoptosis in OLK. DESIGN: In vitro, mitochondrial complex III activity and adenosine triphosphate generation were assessed using a microplate reader. Mitochondrial reactive oxygen species levels were detected by flow cytometry and fluorescence microscopy, whereas mitochondrial membrane potential was evaluated using JC-1 staining. The apoptosis rate was quantified by flow cytometry. In tongue OLK tissues obtained from the animal model, the expression of mitochondrial apoptosis-related markers was examined by immunohistochemistry. In dysplastic oral keratinocyte cells, the expression of mitochondrial apoptosis-related markers was investigated by quantitative real-time polymerase chain reaction and western blot. In addition, the binding of AZOX to cytochrome b (Cyt b) was verified using cellular thermal shift assay. RESULTS: AZOX induced mitochondrial dysfunction and modulated the expression of mitochondrial apoptosis-related markers in both in vivo and in vitro models. Mechanistically, AZOX triggered mitochondrial apoptosis by inhibiting the Qo site of Cyt b in mitochondrial complex III. Direct binding of AZOX to Cyt b was further confirmed. CONCLUSION: AZOX induces mitochondrial dysfunction and apoptosis by targeting the Cyt b Qo site of mitochondrial complex III in OLK, thereby providing a mechanistic basis for its potential therapeutic application.
Impact of oral biotin supplementation on periodontal disease progression and therapy in male rats.
Barra RHD, Ervolino E, Matheus HR … +6 more , Furquim EMA, Vitória OAP, Simionato GC, Santos EO, Fiorin LG, de Almeida JM
Arch Oral Biol · 2026 May · PMID 42229195 · Publisher ↗
OBJECTIVE: This study investigated the effects of oral biotin supplementation on periodontal tissues using a standardized in vivo rat model under three conditions: periodontal health, untreated experimental periodontitis...
OBJECTIVE: This study investigated the effects of oral biotin supplementation on periodontal tissues using a standardized in vivo rat model under three conditions: periodontal health, untreated experimental periodontitis, and tissue response following mechanical periodontal instrumentation. DESIGN: One hundred and forty male Wistar rats received daily oral gavage with biotin (0.4 mL of a 5 mg/mL solution) or vehicle for 30 days. Experimental periodontitis was induced in 98 animals by ligature placement around the mandibular first molar. Of these, 70 animals remained untreated, while 28 underwent mechanical periodontal instrumentation 15 days after disease induction. The remaining 42 animals served as healthy controls. After euthanasia, hemimandibles were evaluated by microcomputed tomography, histological and histometric analyses, Picrosirius Red staining, and immunohistochemistry for tartrate-resistant acid phosphatase, osteocalcin, interleukin-1beta (IL-1β) and tumour necrosis factor-α (TNF-α). RESULTS: Biotin supplementation improved trabecular bone thickness, reduced bone porosity, and increased bone fill in the furcation region, particularly after mechanical periodontal instrumentation. Enhanced collagen fiber maturation was observed across all experimental conditions. Animals receiving biotin after instrumentation exhibited reduced osteoclastic activity, while increased osteocalcin expression was detected only in healthy periodontal tissues. In addition, biotin supplementation was associated with reduced immunolabeling of the pro-inflammatory cytokines IL-1β and TNF-α following mechanical periodontal instrumentation. In contrast, no significant differences in the inflammatory profile were observed under healthy conditions or during active experimental periodontitis. CONCLUSION: Biotin supplementation favorably modulated periodontal bone and connective tissue responses, with more pronounced effects following mechanical periodontal therapy.
Eradication of ampicillin-resistant Enterococcus faecalis in root canal infections using tannic acid: A tooth model investigation.
Elango R, Gunasekaran V, Sathishkumar P
Arch Oral Biol · 2026 Aug · PMID 42217419 · Publisher ↗
OBJECTIVE: Enterococcus faecalis is the most prevalent pathogen in the persistent root canal infections. Especially, drug-resistant E. faecalis plays a major role in the root canal treatment failure. The present study ai...
OBJECTIVE: Enterococcus faecalis is the most prevalent pathogen in the persistent root canal infections. Especially, drug-resistant E. faecalis plays a major role in the root canal treatment failure. The present study aimed to find an effective natural therapeutic drug to combat the ampicillin-resistant Enterococcus faecalis (AREF) infection in the root canal system. DESIGN: The antibacterial effect of various phenolic compounds (curcumin, fisetin, hesperetin, morin, naringin, quercetin, rutin, and tannic acid) was screened against AREF, which was isolated from the infected root canals. The antibiofilm potential of tannic acid was assessed with CV staining, MTT assay, CFU counting, and CLSM analysis. The HR-SEM analysis of the tannic acid-treated AREF-infected root canals (a tooth model) was performed. Targeted interaction of tannic acid with biofilm-forming proteins such as ACE, DisA, ESP, and SrtC was investigated using Dock6. The biocompatibility of tannic acid was analysed on human RBCs and HGF cells. RESULTS: Tannic acid demonstrates excellent antibacterial effect against AREF. The ZOI and MIC values of tannic acid against AREF were 19.3 ± 0.57 mm and 80 µM, respectively. The 100% deadness of AREF infection was observed in the root canals at 1xMIC (80 µM) treatment after 7 days. Tannic acid demonstrated strong binding to biofilm-forming proteins, including ACE, DisA, ESP, and SrtC. The hemocompatibility and cytocompatibility of tannic acid were observed up to 150 µM and 100 µM, respectively. CONCLUSION: The present study recommends that tannic acid may be an efficient and safe natural phytocompound for combating AREF, thereby preventing root canal treatment failure.
Stimulated whole salivary flow is correlated with xerostomia severity and unstimulated whole salivary flow in adults with xerostomia taking anticholinergic medications.
Pedroso A, Arany-Lao-Kan G, Pereira KDP … +3 more , Barmak AB, Eliav E, Arany S
Arch Oral Biol · 2026 Aug · PMID 42217418 · Full text
OBJECTIVES: This study primarily investigated whether stimulated whole salivary (SWS) flow is correlated with minor salivary flow (MSF) in adults with xerostomia taking anticholinergic medications, and, secondarily, exam...
OBJECTIVES: This study primarily investigated whether stimulated whole salivary (SWS) flow is correlated with minor salivary flow (MSF) in adults with xerostomia taking anticholinergic medications, and, secondarily, examined correlations between SWS and unstimulated whole salivary (UWS) flow and xerostomia severity. DESIGN: We conducted a cross-sectional study of 85 middle-aged adults (mean age: 57.1 ± 5.2 years, range: 45-64) taking anticholinergic medications. Salivary flow rates for SWS, UWS, and labial MSF were measured, and xerostomia severity was assessed using the Xerostomia Inventory (XI). Based on established cutoff values for SWS and UWS, participants were grouped into categories with or without UWS or SWS hyposalivation, and into a combined SWS and UWS hyposalivation category. Correlation and multivariable regression analyses were conducted to examine associations among SWS, MSF, UWS, XI, and anticholinergic burden, with adjustments made for age, sex, and comorbidities. RESULTS: SWS was moderately and significantly correlated with MSF. Lower SWS was also significantly correlated with lower UWS and greater xerostomia severity. Women exhibited significantly lower SWS and MSF flow rates and reported higher XI scores compared with men. Subjects with combined SWS and UWS hyposalivation had the lowest MSF rates, whereas participants without hyposalivation had the highest (p = 0.0002). CONCLUSIONS: Our findings indicate that SWS flow is associated with xerostomia severity and with UWS flow in adults with xerostomia taking anticholinergic medications. However, SWS and UWS hyposalivation did not always co-occur according to established thresholds, suggesting that measuring both may improve the characterization of salivary dysfunction.
Effects of Coriandrum sativum L. (coriander) essential oil on Candida spp. in oral infection: Scoping review.
Veras MNB, de Castro RD, Araújo IGA
Arch Oral Biol · 2026 Aug · PMID 42214910 · Publisher ↗
OBJECTIVE: This is an scoping review aimed at mapping the effects of Coriandrum sativum essential oil (CSEO) on oral fungal infection caused by Candida. DESIGN: Scoping review was conducted according to the methodology o...
OBJECTIVE: This is an scoping review aimed at mapping the effects of Coriandrum sativum essential oil (CSEO) on oral fungal infection caused by Candida. DESIGN: Scoping review was conducted according to the methodology of the Joanna Briggs Institute and guided by the research question: What are the effects of CSEO on Candida in oral infection? Searches were performed in the following databases: SciELO, MEDLINE/PubMed, Web of Science, Scopus, Cochrane Library, the CAPES Journal Portal and Google Scholar. Publications in Portuguese, English, and Spanish were included, with no restrictions on date or population. MeSH/DeCS descriptors were used. Study inclusion and review development followed the PRISMA-ScR checklist. RESULTS: Out of the 245 studies identified, 30 were included. The findings revealed that the plant part, extraction method, environmental conditions, and genetic factors influenced variations in the phytochemical profile. Linalool was the major component extracted from seeds, fruits and flowers, while 1-decanol, decanal, 2E-decenol were predominant in leaf extracts. Although no clinical trial and in vivo experimental studies were found, in vitro experimental studies were identified, which demonstrated significant antioxidant, anti-inflammatory and antifungal activities, both against resistant strains and biofilms, in addition to synergistic effects with conventional antifungals and low to moderate toxicity. CONCLUSION: This review identified significant effects of CSEO against Candida, suggesting it is a promising candidate or potential adjuvant. However, further clinical and in vivo validation, with methodological standardization, to assess the safety, tolerability, and efficacy of this oil.
DDX24 exacerbates inflammation-induced immunosuppression in oral squamous cell carcinoma progression through IL-17 signaling pathway.
Liu W, Cui H, Li B … +7 more , Tian Z, Lan Z, Yang Y, Zhu Z, Yu J, Zhao Y, Yu G
Arch Oral Biol · 2026 Aug · PMID 42208160 · Publisher ↗
OBJECTIVE: DEAD-box ATPase 24 (DDX24) plays crucial roles in the development and progression of cancers, including oral squamous cell carcinoma (OSCC). However, its regulatory mechanism and functional role remain unclear...
OBJECTIVE: DEAD-box ATPase 24 (DDX24) plays crucial roles in the development and progression of cancers, including oral squamous cell carcinoma (OSCC). However, its regulatory mechanism and functional role remain unclear. This study aims to investigate the regulatory mechanism of DDX24 in OSCC. DESIGN: DDX24 expression and its clinical significance in OSCC and normal tissues were analyzed through bioinformatics analysis. Small interfering RNA (siRNA) was utilized to knockdown (KD) DDX24 expression in CAL27 cells, and assessed biological functions using CCK8, wound healing assays and transwell assay. RNA sequencing was further employed to elucidate the molecular mechanisms underlying DDX24 promotes malignant phenotypes in OSCC. A stable DDX24 knockdown cell line was established, and inflammatory factors expression were quantified by quantitative PCR. An OSCC mouse xenograft model was developed to evaluate the effects of DDX24 knockdown on tumor growth and the immune microenvironment in vivo. Clinical validation pinpoints the importance of the DDX24/ Interleukin-17(IL-17) axis in OSCC using tissue microarray analysis. RESULTS: DDX24 expression correlates with poor prognosis and reduced survival in OSCC patients. DDX24 KD inhibits OSCC proliferation in vitro and in vivo. RNA sequencing analysis revealed that DDX24 KD markedly attenuated the activity of the IL-17 signaling pathway. Mechanistically, DDX24 facilitates the malignant progression of OSCC by regulating inflammatory factor secretion via the IL-17 signaling pathway, thereby exacerbating tumor-associated inflammation and promoting an immunosuppressive tumor microenvironment. CONCLUSION: This study identifies the DDX24/IL-17 axis as a key promoter of OSCC progression and provides a theoretical basis for developing targeted therapies.
Effects of low-magnitude high-frequency vibration on proliferation and cartilage phenotype of chondrocytes in the rat mandibular condyle.
Hou W, Yu M, Shen T … +1 more , Li W
Arch Oral Biol · 2026 Aug · PMID 42208159 · Publisher ↗
OBJECTIVE: This study explored low-magnitude high-frequency (LMHF) mechanical vibration as a strategy to expand mandibular condylar chondrocyte (MCC) populations with enhanced chondrogenic phenotypes, providing high-qual...
OBJECTIVE: This study explored low-magnitude high-frequency (LMHF) mechanical vibration as a strategy to expand mandibular condylar chondrocyte (MCC) populations with enhanced chondrogenic phenotypes, providing high-quality cellular resources for cartilage tissue engineering. DESIGN: Primary MCCs from 3-week-old Sprague-Dawley rat condylar cartilage were subjected to LMHF vibration stimulation (0.49 g, 40 Hz) using a GJX-5 vibration device. Cell proliferation was evaluated via lactate dehydrogenase (LDH) assay and flow cytometry-based cell cycle analysis. The maintenance and enhancement of the chondrogenic phenotype were determined by enzyme-linked immunosorbent assay (ELISA) for glycosaminoglycan (GAG) secretion and Western blotting for the expression of key markers, including Aggrecan (AGG), bone morphogenetic protein 7 (BMP7), Collagen X, β-catenin, and the autophagy-related protein Atg12. Additionally, alkaline phosphatase (ALP) activity was measured to assess chondrocyte maturation. RESULTS: LMHF vibration exerts no significant effect on the proliferation of MCCs, and its regulatory effect is mostly manifested as a time-dependent pattern. Compared with the control group, LMHF vibration reduced MCC proliferation on Days 1 and 3 but increased it on Day 5, with increased S-phase fraction (SPF)(P < 0.001). ALP activity rose continuously in the vibration group, peaking on day 14. The vibration group showed a 56.5% increase in GAG secretion on day 3 (P < 0.01), upregulated the expression of chondrogenic markers (AGG, BMP7, Collagen X), and downregulated the autophagy-related protein Atg12 (P < 0.05). CONCLUSIONS: Appropriate LMHF mechanical vibration (0.49 g, 40 Hz) effectively enhances the chondrogenic phenotype of MCCs. This non-invasive strategy holds significant promise for cartilage tissue engineering and chondrocyte-based therapy.
Oral squamous cell carcinoma arising in the background of oral submucous fibrosis: A systematic review of molecular and microenvironmental differences.
Gadbail AR, Yuwanati MB, Gondivkar SM … +4 more , Thakare E, Fande P, Choudhari SS, Sarode SC
Arch Oral Biol · 2026 Aug · PMID 42202685 · Publisher ↗
OBJECTIVE: This systematic review aimed to synthesize and critically appraise molecular differences between oral squamous cell carcinoma arising in the background of oral submucous fibrosis (OSCC-OSMF) and OSCC without O...
OBJECTIVE: This systematic review aimed to synthesize and critically appraise molecular differences between oral squamous cell carcinoma arising in the background of oral submucous fibrosis (OSCC-OSMF) and OSCC without OSMF (OSCC-non-OSMF) across genomic, transcriptomic, proteomic, and immunohistochemical domains. DESIGN: A comprehensive literature search of PubMed/MEDLINE, Scopus, and Web of Science was conducted from database inception to November 2025 following PRISMA 2020 guidelines (PROSPERO: CRD420251152208). Human observational studies directly comparing molecular biomarkers between OSCC-OSMF and OSCC-non-OSMF were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Narrative synthesis was performed due to heterogeneity in study design, biomarkers, and analytical methods. RESULTS: Nineteen studies met inclusion criteria. Core carcinogenic pathways including p53 dysregulation, telomerase activation, and fibrosis-related mediators were largely comparable between OSCC-OSMF and OSCC-non-OSMF. In contrast, OSCC-OSMF consistently demonstrated enhanced epithelial-mesenchymal transition (EMT) and stemness signatures, increased genomic instability, and a markedly immunosuppressive tumor microenvironment characterized by regulatory T-cell predominance, PD-1/PD-L1 upregulation, and dendritic cell depletion. Paradoxically, OSCC-OSMF showed lower proliferative and angiogenic activity compared with OSCC-non-OSMF. CONCLUSIONS: Available evidence supports OSCC-OSMF as a fibrosis-conditioned clinic-molecular phenotype within the broader spectrum of OSCC. These findings highlight limitations of conventional prognostic markers and underscore the potential utility of immune, EMT, and genomic-related biomarkers for refined risk stratification and targeted therapy.
3D human cell culture models in periodontal research: A scoping review.
Esther A, Gegout PY, Auger C … +2 more , Petit C, Huck O
Arch Oral Biol · 2026 Aug · PMID 42190486 · Publisher ↗
OBJECTIVE(S): Despite the increasing use of 3D in vitro models in periodontal research, there is currently no comprehensive synthesis explicitly mapping how effectively these models translate structural achievements into...
OBJECTIVE(S): Despite the increasing use of 3D in vitro models in periodontal research, there is currently no comprehensive synthesis explicitly mapping how effectively these models translate structural achievements into functional biological fidelity. Thus, this scoping review aims to map the existing literature while critically evaluating the biological complexity and translational value of current human 3D in vitro periodontal models. DESIGN: PubMed, Cochrane Library, and Web of Science databases were searched to identify relevant original studies detailing the development and application of human 3D in vitro models in periodontal research. RESULTS: A substantial increase in publications since 2018 was observed, reflecting a growing interest in physiologically relevant in vitro systems. However, our analysis highlights a critical gap between structural innovation and biological fidelity. Most studies (76.2%) employ single-cell-type culture systems, predominantly utilizing periodontal ligament stem cells. Methodologically, conventional fabrication techniques remain dominant (84.8%), particularly solid scaffolds and hydrogels, whereas scaffold-free approaches are less frequent. Only 23.8% of the models incorporate multiple cell types, and the integration of immune components is mostly absent. Furthermore, complex dysbiotic microbial communities, which play a central role in periodontal pathogenesis, are rarely included. CONCLUSIONS: While the structural biofabrication of periodontal models has significantly advanced, their functional biological relevance remains restricted. To better recapitulate disease mechanisms and enhance clinical predictivity, future models must shift toward integrating multicellular microenvironments, immune system components, and dynamic host-microbiome interactions.
Decitabine inhibits the malignant transformation of oral potentially malignant disorders by upregulating SOX1 expression via demethylation to modulate the wnt pathway in a male rat model.
Wang T, Wang P, Zhan X … +10 more , Zhang H, Sun P, Guo Y, Yuan M, Jiao M, Chi J, Wang K, Liu Z, Deng J, Yu X
Arch Oral Biol · 2026 Aug · PMID 42166845 · Publisher ↗
OBJECTIVE: To explore the treatment effects of Decitabine (DAC) on Oral potentially malignant disorders (OPMDs) and understand the mechanism involved. DESIGN: Whole-genome bisulfite sequencing (WGBS) was performed on cli...
OBJECTIVE: To explore the treatment effects of Decitabine (DAC) on Oral potentially malignant disorders (OPMDs) and understand the mechanism involved. DESIGN: Whole-genome bisulfite sequencing (WGBS) was performed on clinical OPMDs samples to identify differentially methylated genes, with SRY-box transcription factor 1 (SOX1) selected as a potential target. A rat model was established to evaluate therapeutic efficacy and biosafety of decitabine. In vitro experiments used dysplastic oral keratinocyte (DOK) cell line, with proliferation assessed by Cell Counting Kit-8 (CCK-8), apoptosis and cell cycle analyzed by flow cytometry, and pathway regulation verified by Western blotting (WB) and Quantitative real-time PCR (qRT-PCR). RESULTS: WGBS revealed aberrant DNA methylation in OPMDs, identifying SOX1 as a hypermethylated candidate gene. In vivo, decitabine inhibited malignant progression, with intermittent local injection showing optimal efficacy and biosafety. In vitro, decitabine suppressed DOK cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis. Targeted bisulfite sequencing, qRT-PCR, and Western blotting indicated that decitabine reduces SOX1 methylation, thereby regulating the Wnt signaling pathway. CONCLUSION: Decitabine effectively inhibits malignant progression of OPMDs without apparent toxicity, potentially through SOX1 demethylation and subsequent Wnt pathway regulation, suggesting promising clinical value in preventing malignant transformation of OPMDs.
Long non-coding RNA TMPO-AS1 promotes chronic periodontitis progression by negatively regulating miR-383-5p expression in human periodontal stromal cells.
Sun J, Shen J
Arch Oral Biol · 2026 Aug · PMID 42166844 · Publisher ↗
OBJECTIVES: This study aimed to investigate the molecular mechanisms by which TMPO-AS1 regulates inflammation and osteogenic differentiation in chronic periodontitis (CP). DESIGN: 125 CP patients and 125 healthy controls...
OBJECTIVES: This study aimed to investigate the molecular mechanisms by which TMPO-AS1 regulates inflammation and osteogenic differentiation in chronic periodontitis (CP). DESIGN: 125 CP patients and 125 healthy controls were enrolled. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect serum levels of TMPO-AS1 and microRNA-383-5p (miR-383-5p). Human periodontal ligament stromal cells (hPDLSCs) were induced to undergo in vitro osteogenic differentiation. An inflammatory model was established using lipopolysaccharide (LPS). Using cell counting kit-8 (CCK-8) assays, alkaline phosphatase (ALP) activity assays, enzyme-linked immunosorbent assay (ELISA), RNA immunoprecipitation (RIP), and dual luciferase reporter assays to investigate the targeted regulatory relationship and biological functions of TMPO-AS1 and miR-383-5p. RESULTS: Serum TMPO-AS1 expression was significantly elevated in CP patients and positively correlated with inflammatory cytokines and periodontal clinical indicators, demonstrating potential as a candidate auxiliary diagnostic indicator for CP. LPS exerted a concentration-dependent upregulation of TMPO-AS1 expression while suppressing miR-383-5p expression. Knockdown of TMPO-AS1 reduced LPS-induced inflammatory responses and promoted proliferation and osteogenic differentiation of hPDLSCs, whereas overexpression of TMPO-AS1 produced opposite effects. Moreover, TMPO-AS1 directly targeted and bound miR-383-5p, exerting a negative regulatory effect. Reversal experiments demonstrated that inhibiting miR-383-5p significantly reversed the regulatory effects of TMPO-AS1 knockdown on inflammation and osteogenic differentiation, manifested as enhanced inflammatory response, suppressed cell proliferation, and reduced osteogenic differentiation capacity. CONCLUSIONS: TMPO-AS1 promoted LPS-induced inflammatory responses and inhibited osteogenic differentiation of hPDLSCs by targeting and negatively regulating miR-383-5p, thereby contributing to the development and progression of CP.
The role of FAT family cadherins in craniofacial development: A scoping review.
Yuan Q, Liu Y, Degen M … +4 more , Tao Z, He H, Zhao T, Hua F
Arch Oral Biol · 2026 Aug · PMID 42161188 · Publisher ↗
OBJECTIVES: To map the existing evidence on the role of FAT family cadherins in craniofacial development, identify knowledge gaps, and inform future research directions in this field. DESIGN: Electronic searches were con...
OBJECTIVES: To map the existing evidence on the role of FAT family cadherins in craniofacial development, identify knowledge gaps, and inform future research directions in this field. DESIGN: Electronic searches were conducted in PubMed, Embase, Scopus, Web of Science Core Collection, and ProQuest Dissertations & Theses Global from their inception to January 2026, complemented by manual searches. Studies investigating FAT family cadherins in craniofacial development were included without restrictions on language or publication year. Search strategy and eligibility criteria were pre-determined based on the population, concept and context framework of the Joanna Briggs Institute. Eligible studies included case reports and original studies encompassing bioinformatics analyses, in vitro experiments, animal studies, and human genetic studies. RESULTS: Twenty-one studies were included, encompassing craniofacial bone formation, cranial suture development, upper lip and palate formation, and tooth development. Among the FAT family members, FAT4 was the most frequently studied (n = 12), followed by FAT1 (n = 7). None of the included studies investigated the role of FAT2 in craniofacial development. These cadherins exhibit prominent, stage-specific expression patterns during craniofacial morphogenesis, including the mesenchyme of the medial nasal processes, zygomatic-maxillary suture, and alveolar bone. Six case reports described four congenital syndromes that present with craniofacial abnormalities. CONCLUSIONS: The available evidence indicates that FAT family cadherins are substantially involved in craniofacial morphogenesis. However, important research gaps remain, particularly regarding their cooperative functions and precise spatiotemporal roles during craniofacial development, critical for understanding craniofacial anomalies. REGISTRATION: This review was registered at the Open Science Framework database (https://osf.io/wcxrj).
Silver diamine fluoride for dental caries: the good, the bad, and the ugly - insights from preclinical evidence.
Ezhilarasan D
Arch Oral Biol · 2026 Aug · PMID 42161187 · Publisher ↗
OBJECTIVE: Dental caries remains a major global public health problem, particularly in early childhood. Silver diamine fluoride (SDF) has gained attention as a cost-effective agent for arresting caries and enhancing remi...
OBJECTIVE: Dental caries remains a major global public health problem, particularly in early childhood. Silver diamine fluoride (SDF) has gained attention as a cost-effective agent for arresting caries and enhancing remineralization. This narrative review highlights the anticariogenic benefits (the good), cytotoxic concerns (the bad), and tooth discoloration (the ugly) associated with SDF. DESIGN: Relevant literature was identified through electronic searches of PubMed, Scopus, Embase, Google Scholar, Web of Science, and selected book chapters. Search terms included "silver diamine fluoride," "SDF," "SDF and anticaries," "SDF and cytotoxicity," and "SDF and tooth discoloration." Publications available up to November 30, 2025, were considered. RESULTS: Experimental evidence demonstrates that SDF exhibits potent antibacterial and antifungal activity against key cariogenic microorganisms, leading to reduced biofilm formation and inhibition of enamel demineralization. Despite these advantages, SDF has notable limitations. In vitro studies report cytotoxic effects on pulp cells, gingival fibroblasts, epithelial cells, and deciduous tooth stem cells, mediated by oxidative stress and apoptosis. In addition, permanent black discoloration of treated lesions remains a major aesthetic concern. CONCLUSION: From a "good" perspective, preclinical and clinical evidence shows that SDF demonstrates strong anticaries and antimicrobial efficacy by inhibiting cariogenic bacteria, reducing biofilm formation, and promoting dentin remineralization. From a "bad" perspective, it exhibits cytotoxic effects on oral cells at higher concentrations, necessitating cautious professional use. From an "ugly" perspective, clinically, tooth discoloration remains a key limitation. Hence, careful case selection, standardized protocols, and long-term in vivo studies are essential to optimize its safety, efficacy, and acceptance.
Salivary protein profile of PLHIV on long-term antiretroviral therapy suggests latent reservoir and immune exhaustion.
Macedo NF, Baggio GL, de Oliveira JC … +9 more , Buccio IP, Silva NDGD, Ventura TMO, Carvalho TS, Souza PHC, Rosa EAR, Lima AAS, Buzalaf MAR, Alanis LRA
Arch Oral Biol · 2026 Aug · PMID 42155959 · Publisher ↗
OBJECTIVE: To compare salivary protein profiles in people living with HIV (PLHIV) undergoing antiretroviral therapy (ART) for different durations. This cross-sectional study examined how long-term ART affects the salivar...
OBJECTIVE: To compare salivary protein profiles in people living with HIV (PLHIV) undergoing antiretroviral therapy (ART) for different durations. This cross-sectional study examined how long-term ART affects the salivary proteome in PLHIV. DESIGN: Unstimulated saliva was collected from 23 adult men: those on ART for more than 7 years (group HIV.UP7, n = 11) and for up to 7 years (group HIV.DOWN7, n = 12). Samples were analyzed by nano-LC-ESI-MS/MS, followed by label-free quantification and bioinformatic analysis using the UNIPROT database. Differential protein expression was assessed using Student's t-test (p < 0.05). RESULTS: Mean age was 48.36 (±14.94) years in HIV.UP7 and 32.08 (±5.75) in HIV.DOWN7. ART duration averaged 13 (±4.92) and 3 (±1.62) years, respectively. A total of 187 proteins were identified. Compared to HIV.DOWN7, HIV.UP7 showed 34 up-regulated and 22 down-regulated proteins. Up-regulated proteins included Hemoglobin subunit alpha, Histones H2B, Albumin, Actin aortic smooth muscle, Actin alpha cardiac muscle 1, and POTE ankyrin domain family member E. Down-regulated proteins included Leukocyte elastase inhibitor and Immunoglobulin heavy variable (IGHV3). CONCLUSIONS: Long-term ART in PLHIV is linked to proteomic alterations that may contribute to sustaining the latent HIV reservoir. Reduced expression of immune-related proteins suggests immune exhaustion, potentially weakening immune responsiveness over time.
Assessing convolutional neural networks architectures for orthopantomography image analysis: Judicial dental age threshold classification.
Palmela Pereira C, Figueiras A, Nushi V … +5 more , Elbawab M, Francisco A, Oliveira A, Vaz C, Santos R
Arch Oral Biol · 2026 Aug · PMID 42155958 · Publisher ↗
OBJECTIVE: Forensic dental age assessment is required when documentary evidence is absent or unreliable, and judicial decisions often depend on whether an individual falls below or above legally defined age thresholds. T...
OBJECTIVE: Forensic dental age assessment is required when documentary evidence is absent or unreliable, and judicial decisions often depend on whether an individual falls below or above legally defined age thresholds. This pilot study evaluates ImageNet pretrained convolutional neural network architectures for binary age threshold classification. DESIGN: Orthopantomograms from individuals aged 0-25 years (1887 males and 1664 females) was selected using predefined inclusion criteria and labelled by chronological age. For each legal threshold (10, 12, 14, 16, 18 and 21 years), images were stratified into training and validation sets using an 80 20 split while preserving class distributions. Preprocessing included contrast enhancement with contrast limited adaptive histogram equalization, automated cropping, resizing to model specific input dimensions and ImageNet normalisation. Data augmentation was applied only to training images. Seven convolutional neural network architectures (ResNet 50, ResNet 152, VGG19, DenseNet 121, DenseNet 169, EfficientNetV2 M and Xception) were fine tuned in PyTorch using binary cross entropy loss with early stopping. Hyperparameters were optimised through Bayesian search targeting macro F1 score. Model interpretability was assessed using Grad CAM heatmaps reviewed by dental experts. RESULTS: EfficientNetV2 M showed the best performance for the 10-year threshold (accuracy: 0.935), DenseNet 169 for the 12-year threshold (accuracy: 0.945) and Xception for the remaining thresholds (accuracy: 14-year: 0.924; 16-year: 0.947; 18-year: 0.906; 21-year: 0.890). Errors clustered near age cut offs and increased at higher thresholds. Grad CAM highlighted posterior dento alveolar regions associated with root development. CONCLUSION: These results support convolutional neural network based orthopantomogram analysis as a judicial decision support approach and guided model selection for large scale evaluation.
P75NTR promotes radiation-induced submandibular gland epithelial cell apoptosis via the ceramide signaling.
Li SS, Tian XD, Song JK … +3 more , Wu YD, Wang WL, Tang ZL
Arch Oral Biol · 2026 Aug · PMID 42134022 · Publisher ↗
OBJECTIVE: Radiotherapy for head and neck cancers often damages normal tissues, including radiation-induced sialadenitis. The role of the p75 neurotrophin receptor (p75NTR) in radiation injury is dual; however, its mecha...
OBJECTIVE: Radiotherapy for head and neck cancers often damages normal tissues, including radiation-induced sialadenitis. The role of the p75 neurotrophin receptor (p75NTR) in radiation injury is dual; however, its mechanisms in salivary glands are unclear. This study examines p75NTR's role in radiation-induced submandibular gland injury. DESIGN: Acinar-like human salivary gland epithelial cells (HSG-AZA3) were irradiated after p75NTR overexpression (oe-p75NTR) or knockdown (sh-p75NTR). We assessed apoptosis, ceramide levels, oxidative stress, inflammatory factors, and apoptosis-related gene/protein expression. Additionally, we explored the impact of sh-p75NTR combined with the ceramidase inhibitor (Ceranib2) on irradiated HSG-AZA3 cells. Animal experiments evaluated the effects of sh-p75NTR and Ceranib2 on radiation damage to mouse mandibular glands. RESULTS: Oe-p75NTR increased radiation-induced oxidative stress, inflammatory responses, and apoptosis, whereas sh-p75NTR offered protection by reducing these effects. Ceranib2 reversed sh-p75NTR's protective effects, increasing ceramide levels, oxidative stress, and apoptosis. In mice, sh-p75NTR protected against radiation-induced gland injury, while Ceranib2 diminished this protection and increased damage. CONCLUSIONS: Interfering with p75NTR provides protection against radiation-induced salivary gland cell injury, while Ceranib2 negates this by boosting ceramide levels and promoting apoptosis. These findings suggest new molecular pathways involved in radiation-induced salivary gland injury and potential targets for developing radiation protection strategies.
Evidence of a millennia-old association between a methanogenic archaeon and a bacterium in dental calculus: A re-analysis of ancient and modern metagenomic datasets.
Pilliol V, Beye M, Boualam MA … +7 more , Tellissi L, Slimani A, Drancourt M, Aboudharam G, Tassery H, Grine G, Terrer E
Arch Oral Biol · 2026 Aug · PMID 42119184 · Publisher ↗
OBJECTIVES: Granehäll et al. (2021) identified TS-2 as an unknown Methanobrevibacter lineage abundant in ancient dental calculus, less prevalent in modern samples, and not linked to any cultivated representative. We aime...
OBJECTIVES: Granehäll et al. (2021) identified TS-2 as an unknown Methanobrevibacter lineage abundant in ancient dental calculus, less prevalent in modern samples, and not linked to any cultivated representative. We aimed (i) to determine whether TS-2 corresponds to the cultivated oral archaeon Methanobrevibacter massiliense using genome-based species delineation, and (ii) to assess the antiquity of the association between M. massiliense and Pyramidobacter piscolens in ancient and modern dental calculus. DESIGN: This fully in silico study combined comparative genomics with re-analysis of 97 ancient and modern dental calculus metagenomic datasets. Species-level relationships were assessed using average nucleotide identity, digital DNA-DNA hybridization, and 16S rRNA phylogeny. Metagenomic associations were examined using Kraken2-based taxonomic profiling, with Methanobrevibacter sp. YE315 as a proxy because M. massiliense was absent from the classifier database, and direct competitive read mapping to M. massiliense. Associations with P. piscolens were evaluated using Spearman correlation and negative binomial regression. RESULTS: Comparative genomics supported TS-2 and M. massiliense as the same species-level taxon, with > 95% average nucleotide identity and > 90% digital DNA-DNA hybridization. In metagenomic analyses, the YE315 proxy was positively associated with P. piscolens in Kraken2 Spearman analysis (ρ = 0.3506, q = 0.0026), and mapped M. massiliense reproduced this pattern (ρ = 0.2939, q = 0.0153). Negative binomial models showed concordant but weaker support, whereas the signal for M. oralis was less consistent. CONCLUSION: These results identify M. massiliense as the cultivated representative of TS-2 and support an ancient, recurrent association between M. massiliense and P. piscolens in dental calculus.
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