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Archives Of Oral Biology[JOURNAL]

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Construction of a DNA damage response-related signature for prognostication and therapeutic response prediction in head and neck squamous cell carcinoma.

Li R, Bu X, Qi N … +3 more , Diao P, Wu Y, Cheng J

Arch Oral Biol · 2026 May · PMID 41747404 · Publisher ↗

OBJECTIVE: This study aimed to construct a novel signature utilizing DNA damage response-related genes (DRGs) for head and neck squamous cell carcinoma (HNSCC) prognostication and therapeutic prediction. DESIGN: A progno... OBJECTIVE: This study aimed to construct a novel signature utilizing DNA damage response-related genes (DRGs) for head and neck squamous cell carcinoma (HNSCC) prognostication and therapeutic prediction. DESIGN: A prognostic signature specific to HNSCC was developed using univariate Cox regression, Kaplan-Meier survival analysis, and least absolute shrinkage and selection operator (LASSO)-penalized multivariate Cox regression analyses. A nomogram incorporating this signature along with selected clinicopathological factors was obtained through multivariate Cox regression. The effectiveness of this DRG signature in predicting immune status and chemotherapeutic or immunotherapeutic responses was evaluated. Gene function was assessed via a pharmacological approach in vitro. RESULTS: The 10-gene DRG signature/nomogram demonstrated well prognostic performance across various independent cohorts. Pharmacological inhibition of PLK1 from the DRG signature led to cell death and apoptosis which were probably resulted from impaired DNA damage response. Higher DRG signature scores were negatively correlated with the abundance of tumor-infiltrating immune cells and linked to several chemotherapeutic drugs, radiotherapy, and immunotherapy sensitivities. CONCLUSIONS: Our findings indicated that this novel DRG-derived signature/nomogram serves as a robust prognostic biomarker and viable therapeutic response predictor in HNSCC.

Viral landscape in saliva: Polyomavirus and Herpesvirus detection in HIV-positive and HIV-negative.

Khijmatgar S, Cenzato N, Dolci M … +7 more , Tartaglia FC, Ismail A, Tellez M, Casati S, Favi E, Delbue S, Signorini L

Arch Oral Biol · 2026 May · PMID 41747403 · Publisher ↗

BACKGROUND: Saliva is a non-invasive way to study oral viruses, but we lack specific data on Human Polyomaviruses (HPyVs) and Herpesviruses (HHVs) in HIV-positive patients. Currently, the co-infection patterns and viral... BACKGROUND: Saliva is a non-invasive way to study oral viruses, but we lack specific data on Human Polyomaviruses (HPyVs) and Herpesviruses (HHVs) in HIV-positive patients. Currently, the co-infection patterns and viral loads in this population are not well understood compared to healthy individuals. Our study fills this gap by analyzing these viral profiles and microRNAs in saliva. This work helps establish saliva as a dependable diagnostic method for these infections. METHODS: A cross-sectional study assessed the prevalence of six Human Polyomaviruses (HPyVs) and five Human Herpesviruses (HHVs) in saliva samples collected from two cohorts: 20 HIV-positive individuals undergoing antiretroviral therapy (ART) and 37 HIV-negative subjects. Molecular analyses were performed using quantitative PCR (Q-PCR), with absolute quantification of viral loads and detection of JCPyV and MCPyV microRNAs (miRNAs). RESULTS: The results showed higher overall prevalence of HPyVs (60 % vs. 32.4 %) and HHVs (75 % vs. 51.3 %) in the HIV-positive group compared to the HIV-negative group. MCPyV and EBV were the most frequently detected viruses in both cohorts, but their mean loads were significantly higher in the HIV-positive group. Viral co-infections were more common among HIV-positive individuals (40.0 % vs. 32.4 %), with a predominance of HPyV/HHV co-infections. Notably, HPyV miRNAs were detected also in samples negative for the corresponding viral genomes. CONCLUSION: Our findings confirm saliva's utility for detecting viral co-infections and highlight the need to determine if oral HPyVs and HHVs act as bystanders or pathogens in HIV-positive patients.

Age- and sex-related variations in jaw-opening and tongue functions in healthy adults.

Kaboosaya B

Arch Oral Biol · 2026 May · PMID 41740348 · Publisher ↗

OBJECTIVES: To characterize age- and sex-related variations in jaw-opening performance and tongue function, and to establish physiological reference ranges in healthy adults. DESIGN: A cross-sectional study was conducted... OBJECTIVES: To characterize age- and sex-related variations in jaw-opening performance and tongue function, and to establish physiological reference ranges in healthy adults. DESIGN: A cross-sectional study was conducted in 298 healthy participants (129 males, 169 females), aged 17-85 years. Maximum interincisal opening (MIO), tongue range of motion ratio (TRMR), maximum tongue strength, and tongue endurance were assessed using standardized protocols. Participants were stratified by age, and reference ranges were calculated as mean ± 2 SD. Associations across age groups, sex, and body mass index (BMI) were examined using correlation and regression analyses. RESULTS: Maximum tongue strength declined progressively across age groups in both sexes, decreasing by approximately 4.9 kPa per decade in females and 4.7 kPa in males, with substantially lower values in adults aged ≥ 65 years. Tongue endurance remained largely stable across age groups, showing only a mild upward trend in older females. MIO demonstrated an age-related reduction in males, whereas TRMR exhibited minimal age-dependent variation. Regression analysis identified age as a significant predictor of maximum tongue strength, while endurance and mobility were not significantly associated across age groups or BMI. CONCLUSIONS: Age-related reductions in tongue strength represent the most prominent physiological change in orofacial motor performance, whereas tongue mobility and endurance remain relatively preserved. The reference values established in this study provide clinically relevant benchmarks for future research on oral motor aging and craniofacial functional assessment.

Age-related changes in salivary gland-associated oral immune markers and effects of epigallocatechin gallate in male C57BL/6J mice.

Uemura I, Takahashi-Suzuki N, Sano A … +3 more , Yamada S, Nakata A, Satoh T

Arch Oral Biol · 2026 May · PMID 41740347 · Publisher ↗

OBJECTIVE: To evaluate age-related changes in oral frailty-related salivary function and salivary gland-associated oral defense markers in mice using β-defensin (Defb1/2) and immunoglobulin A (IgA) as markers, and examin... OBJECTIVE: To evaluate age-related changes in oral frailty-related salivary function and salivary gland-associated oral defense markers in mice using β-defensin (Defb1/2) and immunoglobulin A (IgA) as markers, and examine the effects of epigallocatechin gallate (EGCG). DESIGN: Thirty male C57BL/6 J mice were assigned to three groups. Young and aged control groups received 0.5 % methylcellulose-400 orally, and an aged EGCG group received EGCG (3.5 mg/kg) suspended in the same vehicle. Pilocarpine-stimulated salivary flow and secretion outputs (total protein and DEFB1), salivary IgA output, and immune-related markers in saliva and whole submandibular gland tissue were assessed. RESULTS: Aging reduced stimulated salivary flow and decreased total protein and DEFB1 secretion outputs, accompanied by lower Defb1/2 mRNA expression in the submandibular gland. EGCG enhanced salivary flow and secretion outputs and upregulated Defb1/2 transcripts in aged mice. Salivary IgA output increased with aging and was further elevated by EGCG; IgA signal in submandibular gland lysates showed a similar trend. Checkpoint-related transcripts (programmed cell death 1, cytotoxic T-lymphocyte-associated protein 4, lymphocyte-activation gene 3) were reduced in aged glands and shifted upward with EGCG when measured at the whole-tissue level. CONCLUSIONS: Aging was associated with oral frailty-relevant salivary hypofunction and altered salivary gland-associated host-defense and IgA-related markers, and oral EGCG modulated these measures in aged mice. These saliva/salivary-gland markers may provide accessible, host-side indicators of age-associated changes in oral defense.

Synthesis of Tridax procumbens mediated TiO nanoparticles, investigation of antibacterial and anti-cancer activity against selected oral pathogens.

Hu J, Zeng X, Zhang Q

Arch Oral Biol · 2026 May · PMID 41740346 · Publisher ↗

OBJECTIVE: Oral pathogens, including Enterococcus faecalis and Streptococcus mutans, cause infections and have been associated with oral cancer. The rise of drug-resistant bacterial pathogens needs novel treatment strate... OBJECTIVE: Oral pathogens, including Enterococcus faecalis and Streptococcus mutans, cause infections and have been associated with oral cancer. The rise of drug-resistant bacterial pathogens needs novel treatment strategies. This study aimed to develop and evaluate Tridax procumbens-mediated titanium dioxide (TiO₂) nanoparticles as a dual-functional, eco-friendly nanotherapeutic agent with antibacterial and anticancer potential. DESIGN: A green synthesis strategy was used with T. procumbens extract as a bioreductant. TiO₂ NPs were analyzed by UV-Visible, FTIR, XRD, and SEM. Antibacterial activity was evaluated against Streptococcus mutans, Enterococcus faecalis, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) using the well diffusion and microdilution methods. The anticancer activity against KB oral cancer cells was assessed using the MTT assay, morphological evaluation, DAPI staining, and analysis of apoptotic gene expression. RESULTS: UV-Vis examination revealed an absorption peak at 294.45 nm, indicating TiO₂ NP production with an average crystalline size of 24.36 nm. The nanoparticles demonstrated excellent antibacterial activity, with inhibition zones reaching 22 mm and MIC values as low as 3.9 μg/mL. Cytotoxic experiments demonstrated dose- and time-dependent suppression of KB cell growth, with IC₅₀ values of 61 μg/mL (24 h) and 29 μg/mL (48 h). Apoptosis induction was validated by increased BAX, Caspase-3, and Caspase-9 expression, as well as decreased BCL2. CONCLUSIONS: Tridax procumbens-mediated TiO₂ nanoparticles show strong antibacterial and anticancer properties, indicating their promise as eco-friendly, dual-function nanotherapeutic agents for treating oral diseases.

Differentiation of neural stem cells derived from human stem cells from apical papilla into neuronal-like cells undergoing maturation via 3D-neurospheres formation and neurogenic induction.

Phugdiprapai N, Leelapattaraphan A, Vichitvigrom A … +7 more , Balit T, Thongsuk A, Chodchavanchai T, Ruangsawasdi N, White KL, Thonabulsombat C, Songsaad AT

Arch Oral Biol · 2026 May · PMID 41707579 · Publisher ↗

OBJECTIVE: Human stem cells from apical papilla (hSCAPs) are a promising ectomesenchyme‑ derived cell source with neuronal differentiation potential. Under 3D-neurospheres induction, hSCAPs can be induced into neural ste... OBJECTIVE: Human stem cells from apical papilla (hSCAPs) are a promising ectomesenchyme‑ derived cell source with neuronal differentiation potential. Under 3D-neurospheres induction, hSCAPs can be induced into neural stem cells (NSCs) and further committed toward neuronal lineages. This study aimed to demonstrate the differentiation of NSCs‑hSCAPs into neuronal‑like cells undergoing maturation through 3D-neurospheres formation and subsequent neurogenic induction. DESIGN: The characterized hSCAPs were induced into NSCs via 3D-neurospheres formation. The intraspheroidal cells were verified for early neural stemness properties and subsequently dissociated and cultured under neurogenic induction conditions for 7 days. Neuronal differentiation was evaluated by identification of Nissl substance, immunofluorescent analysis of neuronal‑associated proteins, quantitative mRNA expression, and depolarization‑evoked intracellular Ca imaging. RESULTS: Following 3D neurosphere induction, hSCAPs formed clusters of intraspheroidal cells exhibiting typical NSCs characteristics, including high expression of Nestin and SOX2 and self‑reaggregation ability. After 7 days of neurogenic induction, the differentiated cells displayed distinct neuronal‑like morphologies, reduced expression of early neuronal markers (Nestin/NES and SOX2/SOX2), and increased expression of early neuronal differentiation-associated markers (Beta‑III tubulin/TUBB3) at both protein and mRNA levels. The synaptic vesicle‑associated gene (SV2A) was highly detected at the mRNA level. Furthermore, depolarization‑evoked Ca responses after KCl stimulation were observed, indicating membrane excitability and voltage‑gated calcium channel in the differentiated cells. CONCLUSIONS: NSCs‑hSCAPs possess the capacity to generate neuronal‑like cells undergoing maturation via 3D-neurospheres formation and neurogenic induction.

Lubricating properties of the dental pellicle: A scoping review.

Schestakow A, Meyer-Probst CT, Hannig C … +1 more , Hannig M

Arch Oral Biol · 2026 May · PMID 41707578 · Publisher ↗

OBJECTIVES: This scoping review aimed to evaluate the pellicles' protective potential against mechanical tooth wear and to explore the underlying mechanisms. METHODS: A systematic search was conducted in Medline, Scopus,... OBJECTIVES: This scoping review aimed to evaluate the pellicles' protective potential against mechanical tooth wear and to explore the underlying mechanisms. METHODS: A systematic search was conducted in Medline, Scopus, and Web of Science up to May 2025. Studies examining pellicles formed on enamel, dentin, or hydroxyapatite, using human saliva or salivary proteins, and subjected to mechanical challenges were included. Studies combining erosion or involving diseased subjects or non-dental substrates were excluded. Only original research articles published in English or German were considered. No supplementary approaches to identify studies were performed. RESULTS: Out of 893 records, 26 studies met the inclusion criteria. The majority focused on pellicles formed on enamel or hydroxyapatite. Outcome measures included wear, abrasion resistance, friction coefficient, and viscoelastic properties. While most studies found that the pellicle reduced friction and wear, its abrasion resistance to high mechanical stress was weak. Since the majority of studies were conducted in vitro, the extent to which these findings apply to the dynamic oral environment is uncertain. CONCLUSIONS: The pellicle may offer limited protection against mechanical wear, primarily through a boundary lubrication regime, while evidence regarding its structural integrity and resistance under mechanical stress remains inconclusive, highlighting the need for further research to validate relevant parameters and clarify underlying mechanisms.

Corrigendum to "Evaluation of the effects induced by radiotherapy on dentin during endodontic instrumentation using a novel methodology for assessing wear resistance" [Archives of Oral Biology 183 (2026) Article Number 106493].

Teodosio LM, Barbosa AFS, de Queiroz AM … +8 more , de Oliveira HF, Zamperini CA, Mazzi-Chaves JF, Sousa-Neto MD, Silva-Sousa YTC, Rached-Junior FJA, Alfredo E, Lopes-Olhê FC

Arch Oral Biol · 2026 May · PMID 41689897 · Publisher ↗

Abstract loading — click title to view on PubMed.

Nature, nurture, or noise? Fluctuating asymmetry in permanent dentitions depends on trait plasticity and developmental timing.

Moes E, Edgar HJ

Arch Oral Biol · 2026 May · PMID 41679116 · Publisher ↗

OBJECTIVES: Dental fluctuating asymmetry (FA) is thought to reflect developmental instability. It has varied relationships with other early life measures of stress. We examine whether this variation is due to FA reflecti... OBJECTIVES: Dental fluctuating asymmetry (FA) is thought to reflect developmental instability. It has varied relationships with other early life measures of stress. We examine whether this variation is due to FA reflecting sensitive windows of development or susceptibility to disruption, based on the traits considered. DESIGN: Buccolingual and mesiodistal dimensions of all permanent teeth and molar intercuspal distances were measured from dental casts of 303 child participants of the Burlington Growth Study. Metric traits were aggregated into six discrete FA indices based on estimated age of trait development, trait susceptibility to environmental disturbances, or both. Early life biocultural factors were sourced from associated health history records and grouped into latent dimensions using factor analysis of mixed data. Using logistic regression, factors were then compared to all FA indices, separated by sex. RESULTS: Model outcomes varied by FA index and sex. FA indices that consisted of molar intercuspal measurements were significantly associated with biocultural latent factors, but only among females. No predictive relationships were found among male-specific models. DISCUSSION: Sensitive windows of development and differences in trait susceptibility to disruption are responsible for variation in dental FA of permanent teeth. Selecting traits with a high plastic component (such as molar intercuspal distances) rather than genetic component (crown dimensions) is critical to consider FA a metric of early life stress. Additional variability in dental FA, regardless of how it is measured, may be due to inherent "noise" in the developmental system.

Hesperetin modulates osteoprogenitor cells and macrophages under zoledronic acid and inflammatory stress.

Mendes Soares IP, Liepman O, Anselmi C … +4 more , Chang S, Hebling J, Dal-Fabbro R, Bottino MC

Arch Oral Biol · 2026 May · PMID 41671744 · Full text

OBJECTIVES: To investigate the osteogenic and immunomodulatory effects of hesperetin (HT) on alveolar bone-derived mesenchymal stem cells (aBMSCs) and macrophages under zoledronic acid (ZA) and inflammatory stress. DESIG... OBJECTIVES: To investigate the osteogenic and immunomodulatory effects of hesperetin (HT) on alveolar bone-derived mesenchymal stem cells (aBMSCs) and macrophages under zoledronic acid (ZA) and inflammatory stress. DESIGN: aBMSCs were exposed to ZA (0-10 µM) for 3 days, followed by HT (0-1000 µM) for 3 days. Cell viability was assessed for 3 days of treatments, and osteogenic activity was evaluated by alizarin red quantification at 14 and 21 days. THP-1-derived macrophages were polarized to M1 using lipopolysaccharides (LPS, 1 µg/mL) and treated with HT (1-50 µM) to evaluate cell viability and synthesis of cytokines (ELISA). A co-culture system of aBMSCs and macrophages (1:1 ratio) was established under inflammatory stimulation (LPS ± 20 µM HT) to assess cell viability, cytokine release and mineralized matrix formation. Data were analyzed by ANOVA/post-hoc tests (α = 5 %). RESULTS: ZA significantly reduced aBMSCs viability and mineralization in a dose-dependent manner. HT (5-50 µM) enhanced mineralization in healthy aBMSCs and partially restored it after ZA exposure. In M1 macrophages, HT (5-20 µM) decreased TNF-α, IL-1α, and IL-6 synthesis without affecting viability. In inflammatory co-cultures, HT (20 µM) preserved cell viability, increased mineralized matrix deposition, and reduced cytokine release compared to LPS-only controls. CONCLUSIONS: This study evidenced that HT can concurrently stimulate osteogenic differentiation and suppress inflammatory responses under ZA- and LPS-induced stress. HT emerges as a promising osteoimmunomodulatory adjuvant to enhance bone regeneration and mitigate bisphosphonate-related osteonecrosis.

Substance P involvement in the interaction between Streptococcus mutans and human aortic endothelial cells.

Oho T, Nagata E, Tamaki N

Arch Oral Biol · 2026 Apr · PMID 41650655 · Publisher ↗

OBJECTIVES: Streptococcus mutans, a causative organism of dental caries, has also been implicated in the pathogenesis of cardiovascular disease (CVD). Substance P (SP) involvement in physiological and pathological proces... OBJECTIVES: Streptococcus mutans, a causative organism of dental caries, has also been implicated in the pathogenesis of cardiovascular disease (CVD). Substance P (SP) involvement in physiological and pathological processes within the cardiovascular system is currently the foci of research. The role of SP in modulating the human aortic endothelial cells (HAECs) response to S. mutans within the context of CVD pathogenesis has not been examined. This study aimed to investigate SP expression in S. mutans-stimulated HAECs and to clarify the role of SP in the interaction between S. mutans and HAECs, considering its cooperative action with an innate immune factor DMBT1. DESIGN: HAECs were stimulated with S. mutans strains. SP expression was analyzed by dot blot assay and RT-PCR. S. mutans binding to SP was determined using ELISA. S. mutans aggregation was evaluated by monitoring decrease in optical density and phase-contrast microscopy. Effects of SP and/or DMBT1 on the interaction between S. mutans and HAECs were examined by invasion assay, cytokine assay, and cytotoxicity assay. RESULTS: All tested S. mutans strains induced SP production in HAECs. S. mutans bound directly to SP. SP agglutinated S. mutans and pronounced aggregation was induced by SP when used with DMBT1. SP reduced S. mutans invasion of HAECs, suppressed S. mutans-induced cytokine production in HAECs, and decreased S. mutans-mediated cytotoxicity to HAECs. These inhibitory effects of SP were further enhanced by DMBT1. CONCLUSION: These findings suggest that SP, acting in concert with DMBT1, exerts a protective role against S. mutans-induced CVD processes in HAECs.

Retraction notice to "p38 Mitogen-activated protein kinase modulates cisplatin resistance in head and neck squamous cell carcinoma cells" [Archives of Oral Biology 122 (2021)104981].

Roy S, Roy S, Anuja K … +4 more , Thakur S, Akhter Y, Padhi S, Banerjee B

Arch Oral Biol · 2026 Apr · PMID 41643485 · Publisher ↗

Abstract loading — click title to view on PubMed.

Exosome-related lactylation gene signature defines diagnostic biomarkers of periodontitis through integrative bulk and single-cell transcriptomics.

Liang X, Fu R, Chen X

Arch Oral Biol · 2026 Apr · PMID 41638162 · Publisher ↗

BACKGROUND: Exosomes and lactylation modification have been increasingly recognized as key regulators of diseases, yet their integrative role in periodontitis remains unclear. No diagnostic model based on exosome-related... BACKGROUND: Exosomes and lactylation modification have been increasingly recognized as key regulators of diseases, yet their integrative role in periodontitis remains unclear. No diagnostic model based on exosome-related lactylation genes (ERLGs) has been previously established for periodontitis. This study aimed to explore ERLGs as potential diagnostic biomarkers for periodontitis. METHODS: Integration of bulk and single-cell RNA sequencing (scRNA-seq) datasets, machine learning modeling, and experimental validation were employed to identify ERLG signatures and dissect their cellular context in periodontitis. RESULT: We identified 53 ERLGs that were significantly dysregulated in periodontitis and closely linked to metabolic reprogramming and immune regulation. ERLG-based clustering robustly distinguished periodontitis from healthy tissues and revealed distinct immune infiltration patterns. A machine learning-based diagnostic model using eight core ERLGs (AK3, CHST1, CHST2, MERTK, EGLN3, CXCR4, DSC2, KCNN4) achieved excellent predictive performance (AUC=0.938 in training cohort; validated in two independent cohorts). scRNA-seq uncovered heterogeneous lactylation modification patterns across major cell populations. Fibroblast subclustering revealed three disease-sensitive subsets (Fib_NTRK3, Fib_TNXB, Fib_MFAP5) that were reduced in periodontitis and exhibited reduced lactylation scores. Endothelial cell subclustering identified a disease-enriched Endo_TGM2 population characterized by high lactylation scores, activation of TGF-β, PI3K-AKT-mTOR, and TNFα/NF-κB signaling, and dynamic differentiation trajectories, and strong interactions with fibroblasts. Inflammatory stimulation enhanced exosomal lactylation and derived ERLG dysregulation in human gingival fibroblasts. CONCLUSION: This study establishes the first ERLG-based diagnostic model for periodontitis, demonstrates its robust predictive capability and delineates cell type-specific lactylation remodeling, which providing mechanistic insights and potential signature for diagnosis.

Salivary monoacetylated polyamines as noninvasive biomarkers for early detection and stratification of oral squamous cell carcinoma: A targeted metabolomics study.

Panneerselvam K, Krishnan R, Mahadevan S … +2 more , Ayyadurai MM, Sugimoto M

Arch Oral Biol · 2026 Apr · PMID 41633305 · Publisher ↗

OBJECTIVES: This study aimed to evaluate salivary monoacetylated polyamines as noninvasive biomarkers for the detection and staging of oral squamous cell carcinoma (OSCC). DESIGN: Unstimulated saliva samples were collect... OBJECTIVES: This study aimed to evaluate salivary monoacetylated polyamines as noninvasive biomarkers for the detection and staging of oral squamous cell carcinoma (OSCC). DESIGN: Unstimulated saliva samples were collected from healthy controls (n = 15), oral leukoplakia (OLK) patients (n = 15), and OSCC patients stratified into early (n = 28) and advanced stages (n = 46). Seven polyamines were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Diagnostic performance was assessed via receiver operating characteristic (ROC) analysis, logistic regression modeling, and multivariate clustering. RESULTS: N-acetylspermidine and N-acetylspermine showed progressive elevation from OLK to advanced OSCC, with AUCs of 0.87 and 0.81, respectively. A two-marker logistic model achieved a cross-validated AUC of 0.85, demonstrating good discriminatory performance between malignant and non-malignant states. Multivariate analysis confirmed their contribution to disease stratification, while calibration plots supported model reliability. CONCLUSIONS: Salivary N-acetylspermidine and N-acetylspermine are promising biomarkers for noninvasive OSCC detection and staging.

Smoking and systemic Th17/Treg immune alterations in periodontitis: A cross-sectional study.

Sidharthan S, Gopalakrishnan D, Kheur S … +2 more , Suryavanshi P, Sanap A

Arch Oral Biol · 2026 Apr · PMID 41619349 · Publisher ↗

OBJECTIVE: To investigate the impact of smoking on systemic and local immune responses in periodontitis, focusing on Th17 and regulatory T (Treg) cell frequencies and their associated cytokine expression. DESIGN: Forty-f... OBJECTIVE: To investigate the impact of smoking on systemic and local immune responses in periodontitis, focusing on Th17 and regulatory T (Treg) cell frequencies and their associated cytokine expression. DESIGN: Forty-five participants were categorized into healthy controls (n = 15), non-smokers with periodontitis (n = 15), and smokers with periodontitis (n = 15). Clinical periodontal parameters were recorded. Peripheral blood mononuclear cells were analyzed by flow cytometry to quantify CD4⁺ T cells, Th17 (CD4⁺IL-17A⁺), and Treg (CD4⁺CD25⁺FOXP3⁺) populations. Gingival biopsies from a subset of participants (n = 24) were assessed by qRT-PCR for IL-17A, FOXP3, IL-12(p35), and hEBI3 expression. Group comparisons and correlation analyses were performed using appropriate parametric or non-parametric tests. RESULTS: Smokers with periodontitis exhibited greater probing depth and clinical attachment loss than non-smokers and healthy controls (p < 0.001). Both periodontitis groups showed elevated circulating CD4⁺ T cells and Tregs, with Th17 frequencies highest in smokers. These systemic differences remained significant after false discovery rate (FDR) correction, with moderate effect sizes (η² = 0.25-0.44). Gingival expression of IL-17A, FOXP3, IL-12(p35), and hEBI3 did not differ significantly between groups after FDR adjustment, with small effect sizes (η² ≤ 0.09). No significant correlations were observed between smoking exposure and systemic or local immune markers. CONCLUSION: Periodontitis is associated with marked systemic immune alterations, whereas local transcriptional changes are subtle. Smoking modestly enhances systemic Th17 responses without robust changes in gingival cytokine expression, highlighting the need for adequately powered and longitudinal studies to clarify immune mechanisms in periodontitis.

Upregulated expressions of caspase-4 and -5 upon challenging with periodontal microorganisms in human gingival epithelial cells.

Makeudom A, Dechtham E, Kantrong N … +3 more , Meekhantong P, Laongnualpanich K, Krisanaprakornkit S

Arch Oral Biol · 2026 Apr · PMID 41616557 · Publisher ↗

OBJECTIVES: Gram-negative periodontal microorganisms may be recognized by caspase-4/-5, lipopolysaccharide sensors, in human gingival epithelial cells (HGECs). This study aimed to determine expressions of inflammasomal b... OBJECTIVES: Gram-negative periodontal microorganisms may be recognized by caspase-4/-5, lipopolysaccharide sensors, in human gingival epithelial cells (HGECs). This study aimed to determine expressions of inflammasomal biomolecules and to elucidate their signaling in epithelial cells upon challenging with cell wall extract of Porphyromonas gingivalis, Prevotella intermedia, or Fusobacterium nucleatum. DESIGN: HGECs were stimulated with 1 or 5 μg/ml of each extract for 24 h. Expressions of caspase-1, caspase-4/-5, and gasdermin D were assayed by RT-qPCR and immunoblotting. Interleukin (IL)-1β and IL-18 levels in conditioned medium were measured by ELISA. Apoptosis was analyzed by immunoblotting for caspase-3, BCL-2, and BAX expressions and by flow cytometry for annexin V and propidium iodide staining. Upon stimulation, phosphorylation of receptor-interacting serine/threonine-protein 2 (RIP2) kinase and localization of the p50 and p65 subunits of NF-kappaB were determined. RESULTS: Significantly upregulated expressions of caspase-4/-5 proteins, but not their gene, upon challenging with each extract were found (p < 0.05). However, gene and protein expressions of caspase-1 or gasdermin D were not significantly altered in the extract-stimulated HGECs, consistent with unchanged levels of IL-1β or IL-18, unaltered expressions of caspase-3, BCL-2, BAX, and non-differences in the percentages of apoptosis. Enhancement of phosphorylated RIP2 kinase and nuclear expression of the p50 and p65 subunits were instead observed in HGECs stimulated with each extract. CONCLUSION: The cell wall extract of Porphyromonas gingivalis, Prevotella intermedia, or Fusobacterium nucleatum upregulated expressions of caspase-4/-5 proteins in HGECs and activated RIP2 kinase that led to induced expression of NF-kappaB, without any sign of pyroptotic cell death.

Genetic polymorphisms in headache attributed to temporomandibular disorder: A case-control study.

Campello CP, Lemos CAA, Lima ELS … +2 more , Fernandes RSM, Muniz MTC

Arch Oral Biol · 2026 Apr · PMID 41610735 · Publisher ↗

OBJECTIVE: The aim of this study was to examine the relationship between three single nucleotide polymorphisms (SNPs): -308 G/A TNF-α, -174 G/C IL-6, and C677T MTHFR and the presence of headache attributed to temporomand... OBJECTIVE: The aim of this study was to examine the relationship between three single nucleotide polymorphisms (SNPs): -308 G/A TNF-α, -174 G/C IL-6, and C677T MTHFR and the presence of headache attributed to temporomandibular disorder (HATMD). DESIGN: This case-control study included a total of 68 patients with HATMD and 200 controls, aged 18 years and older. Both sets of participants included both genders. The diagnosis followed the diagnostic criteria for temporomandibular disorders (DC/TMD). The temporomandibular disorder pain screen was also applied. The -308 G/A TNF-α and 677 C/T MTHFR SNPs were genotyped using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP), and -174 G/C IL-6 SNP was performed by PCR. Allele frequencies and logistic regression analysis were used to assess the association between HATMD and genotypes. RESULTS: The results revealed that the AA genotype of -308 G/A TNF-α SNP (OR= 0.20, 95 % CI: 0.0568-0.7724,p = 0.0290) and the CT genotype of C677T MTHFR SNP (OR = 0.40, 95 % CI: 0.2224-0.7350, p = 0.0042) were protective factors for HATMD risk. No significant association was found between -174G/C IL-6 SNP and the risk of HATMD (OR = 0.58, 95 % CI: 0.2122-1.6367, p = 0.45). CONCLUSION: The -308 G/A TNF-α and C677T MTHFR SNPs were identified as protective factors against the development of HATMD.

Mouthrinses differentially rewire salivary virus-microbiome interaction dynamics in COVID-19 patients: A randomized controlled trial.

Widyarman AS, Bur R, Udawatte NS … +6 more , Agaristi PM, Razari I, Bahri S, Richi M, Astoeti TE, Seneviratne CJ

Arch Oral Biol · 2026 Apr · PMID 41610734 · Publisher ↗

OBJECTIVE: In this randomized clinical trial (RCT) we evaluated the efficacy of mouthrinses containing sodium chlorite (NaClO), povidone iodine (PVP-I), cetylpyridinium chloride (CPC) compared to sterile water control in... OBJECTIVE: In this randomized clinical trial (RCT) we evaluated the efficacy of mouthrinses containing sodium chlorite (NaClO), povidone iodine (PVP-I), cetylpyridinium chloride (CPC) compared to sterile water control in modulating salivary SARS-CoV-2 viral load and the oral microbiome in COVID-19 patients. METHODS: Forty PCR-confirmed COVID-19 patients were randomly allocated to four groups (n = 10 each) and rinsed with 10 ml of their assigned solution for 30 s. Saliva was collected pre-rinse and at 5-min, 3-hour, and 6-hour post-rinse. Viral load was quantified via RT-qPCR targeting N and ORF1ab genes, and oral microbiome was analyzed using 16S rRNA sequencing. RESULTS: CPC reduced viral load by 1.5-fold (P = 0.12), PVP-I by 1.2-fold (P = 0.18), and NaClO by 1.1-fold (P = 0.34) at 6-hour, though not statistically significant. Overall oral microbiome diversity and composition remained stable (P = 0.67), although CPC and PVP-I significantly altered specific taxa such as Leptotrichia sp. and Lautropia mirabilis. Moreover, CPC and PVP-I disrupted the salivary microbiome network with SARS-CoV-2 genes, namely N and ORF1ab genes. CONCLUSION: This study to provide new insight into the modulation dynamics of mouthrinses on salivary SARS CoV-2 and oral microbiome, suggesting that CPC and PVP-I may provide potential health benefits by reducing viral load and modulating microbiome-virus networks.

Is salivary melatonin an indicator of periodontal disease severity? A systematic review and meta-analysis.

Santos RMD, Gonçalves FD, Carneiro LM … +7 more , Mattera MSLC, Nobumoto ACTY, Belardi BE, Tsosura TVS, Dias GZT, Tessarin GWL, Chiba FY

Arch Oral Biol · 2026 Apr · PMID 41604838 · Publisher ↗

OBJECTIVES: To evaluate, through a systematic review and meta-analysis, the differences in salivary melatonin (S-MEL) levels between individuals with periodontal disease and healthy individuals. DESIGN: A systematic sear... OBJECTIVES: To evaluate, through a systematic review and meta-analysis, the differences in salivary melatonin (S-MEL) levels between individuals with periodontal disease and healthy individuals. DESIGN: A systematic search was conducted in PubMed, EMBASE, SciELO, LILACS, and BIREME following PRISMA 2020 guidelines and PROSPERO registration. Human studies comparing patients with periodontal disease with healthy controls and reporting S-MEL were included. Screening occurred in two phases. Meta-analysis was performed in Jamovi using the MAJOR module, applying the standardized mean difference (SMD) (Hedges g), a random-effects model, heterogeneity statistics, and publication bias tests. Seventeen comparisons were included. RESULTS: The random-effects model showed significantly lower S-MEL levels in patients with periodontal disease (SMD = -2.04; 95 % confidence interval [CI] -3.44 to -0.63; p = 0.005), with high heterogeneity (I² = 97.8 %). Notably, most studies reported reduced melatonin levels, despite a few positive effects. Funnel plot asymmetry and Begg/Egger tests suggested publication bias, although trim-and-fill revealed no missing studies. The high fail-safe N supported the robustness of the findings. CONCLUSIONS: S-MEL levels were consistently lower in patients with periodontal disease, suggesting a potential biomarker relationship. Despite the substantial heterogeneity, the overall evidence supports this association. However, further standardized studies are needed.

Cellular passages modulate pre-osteoblast responses to bisphosphonate in high-passage cell models.

Lilakhunakon C, Patntirapong S

Arch Oral Biol · 2026 Apr · PMID 41579496 · Publisher ↗

OBJECTIVE: This study examined the effects of cell passages, drug treatment, or interaction between cell passage and drug treatment on pre-osteoblast growth and activities. DESIGN: Pre-osteoblasts, MC3T3-E1, were subcult... OBJECTIVE: This study examined the effects of cell passages, drug treatment, or interaction between cell passage and drug treatment on pre-osteoblast growth and activities. DESIGN: Pre-osteoblasts, MC3T3-E1, were subcultured until reaching high passages (passage 42; P42) and late passages (passage 62; P62). Cells were treated with oral bisphosphonate (BP), alendronate (ALN), at concentrations 1 and 5 μM. Cells were evaluated and compared for cell survival, migration, adhesion, actin cytoskeleton, cell spreading, and gene expressions. RESULTS: Two-way ANOVA showed that cell migration, cytoskeleton, nuclear condensation, and Intβ1 gene expression were impacted by the interaction between cell passage and ALN, while cell growth, death, adhesion, and spreading were affected by either cell passage or ALN. Cell growth was inhibited by cell passage and ALN. ALN at 5 μM (A5) increased cell death in P42. Cell adhesion was reduced in P62 compared to P42 in A1 condition. Higher cell passage and ALN promoted detachment under mechanical stress. Cell spreading was also disrupted by ALN. Adhesion-related gene expressions such as Intβ1 and FAK were downregulated by cell passage in A5 treatment. CONCLUSION: These findings demonstrated differential cellular responses to BPs based on cell passage and interaction between cell passage and ALN. High and late passage cells exhibited distinct sensitivities and behaviors. This underscores the importance of using higher-passage cell models to better mimic aged osteoblasts in vitro when evaluating preclinical studies.
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