Archives Of Oral Biology[JOURNAL]
Sun
200 papers
Temporal histological and immunohistochemical characterization of experimental dental pulp inflammation in rats.
Alvarado JDA, Ricci R, de Oliveira Sales-Junior R … +9 more , de Moura Pereira B, da Silva Machado NE, Pereira-Neta MAL, Timpurim Silva MG, Dos Santos JM, Ervolino E, Ângelo Cintra LT, Kishen A, Gomes-Filho JE
Arch Oral Biol · 2026 Aug · PMID 42119183 · Publisher ↗
OBJECTIVE: To establish a temporal histological and immunohistochemical profile in a rat model of pulpitis by assessing cytokine immunoreactivity at the root canal orifice over time. DESIGN: This experimental animal stud...
OBJECTIVE: To establish a temporal histological and immunohistochemical profile in a rat model of pulpitis by assessing cytokine immunoreactivity at the root canal orifice over time. DESIGN: This experimental animal study included 28 male Wistar rats allocated to seven groups based on the time elapsed after pulp exposure: D0, D1, D2, D3, D4, D5, D6 (0-6 days). Pulp inflammation was induced in maxillary first molars, and hemimaxillae were processed for histological and immunohistochemical analyses. Cytokines (IL-17, TGF-β, IL-6, IL-1β, IL-10 and TNF-α) were evaluated using the immunoperoxidase technique, and immunoreactivity was semi-quantitatively scored. Inflammatory infiltrate was assessed histologically. Data were analyzed using Kruskal-Wallis and post hoc tests (α = 0.05). RESULTS: Histological analysis demonstrated a progressive increase in inflammation and tissue damage over time, ranging from absence or mild inflammatory changes in D0-D1 to complete necrosis at D6 (p < 0.05). Immunohistochemical analysis revealed detectable immunoreactivity for TGF-β and IL-17 at the earliest time points (D0-D1), while no significant temporal differences were observed among cytokines from D0 to D2 (p > 0.05). From D3 onwards, all cytokines exhibited a significant increase in immunoreactivity compared to D0 (p < 0.05), with sustained elevated expression through D6. CONCLUSION: Pulp inflammation was associated with time-dependent histological alterations and cytokine immunoreactivity at the root canal orifice. Early TGF-β and IL-17 expression was observed at initial time points, while a progressive increase in cytokine immunoreactivity from D3 onwards marked the development of an established inflammatory response and subsequent tissue damage.
mRNA and lncRNA expression profiles as potential targets for diagnosis and treatment of oral lichen planus.
Kim J, Kim JW, Yun SJ … +5 more , You H, Choi YD, Lee B, Kim OJ, Kim Y
Arch Oral Biol · 2026 Aug · PMID 42119182 · Publisher ↗
OBJECTIVE: This study aimed to identify differentially expressed (DE) mRNAs and long noncoding RNAs (lncRNAs) between oral lichen planus (OLP) and skin lichen planus (SLP) to elucidate the molecular mechanisms driving th...
OBJECTIVE: This study aimed to identify differentially expressed (DE) mRNAs and long noncoding RNAs (lncRNAs) between oral lichen planus (OLP) and skin lichen planus (SLP) to elucidate the molecular mechanisms driving the higher malignant transformation risk associated with OLP. DESIGN: Tissue samples were collected from SLP and OLP patients who were diagnosed at between 2008 and 2012. RNA sequencing was conducted to analyze the differentially expressed (DE) mRNAs and lncRNAs in OLP compared to SLP. We performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Protein-Protein Interaction (PPI) Network analyses using the identified DE mRNAs in OLP. RESULTS: Analysis revealed 1106 OLP-specific DE mRNAs (555 upregulated) and 348 DE lncRNAs (201 upregulated). KEGG and GSEA highlighted significant enrichment in IL-17 and TNF-α/NF-κB signaling pathways. PPI network analysis identified key hub genes (CXCL1, CXCL2, CXCL8, JUN, IL1B, IL6) linked to IL-17 signaling. Notable dysregulation included upregulated oncogenic lncRNAs (H19, MIR31HG, SNHG15) and downregulated tumor suppressors (CA3-AS1, HAND2-AS1). Furthermore, 1228 co-expressed lncRNA-mRNA pairs were identified through trans-target prediction. CONCLUSION: The identified DE mRNAs enriched in IL-17 and TNF-α/NF-κB signaling pathways, along with the dysregulation of oncogenic and tumor suppressor lncRNAs, provide molecular evidence for the higher risk of malignant transformation associated with OLP compared to SLP. These DE mRNAs and lncRNAs, along with their target genes, represent potential novel biomarkers or therapeutic targets for the diagnosis and management of OLP.
DPSCs-generated contraction force regulates vessel network morphogenesis via YAP1/TGF-β1/Smad2 signaling.
Chen Y, Wang W, Hu M … +5 more , Lin S, Li X, Wu Z, Xu J, Zhang C
Arch Oral Biol · 2026 Aug · PMID 42107923 · Publisher ↗
OBJECTIVES: This study aimed to explore the contribution of dental pulp stem cell (DPSC)-generated contraction force to vessel formation and reveal the role of yes-associated protein 1 (YAP1) in DPSCs during this process...
OBJECTIVES: This study aimed to explore the contribution of dental pulp stem cell (DPSC)-generated contraction force to vessel formation and reveal the role of yes-associated protein 1 (YAP1) in DPSCs during this process. DESIGN: The contraction force generated by DPSCs during vessel formation was evaluated in fluorescently labeled gels. DPSCs were treated with transforming growth factor beta 1 (TGF-β1), Cytochalasin D (CytoD), and Y27632 to investigate the correlation between F-actin-dependent contractility and YAP1. Furthermore, the involvement of YAP1 in DPSC differentiation into smooth muscle cells (SMCs) and the effect of YAP1-deficient DPSCs on impairing vascular morphology were assessed. RESULTS: Enhanced matrix remodeling was observed during vessel formation, suggesting that DPSCs control vascular network formation via enhanced contraction force. DPSCs treated with Y27632 and CytoD showed reduced contractility, leading to decreased YAP1 nuclear translocation and changes in F-actin morphology. Western blot analysis showed that knocking down YAP1 in DPSCs significantly reduced phosphorylated Smad2, resulting in low expression of SMC markers. Furthermore, the loss of YAP1 in DPSCs weakened active cellular force, leading to deficient vessel network formation, including increased vessel diameter on day 4, reduction of vessel average length and loss of DPSC recruitment on day 7. In vivo results showed increased vessel diameter at day 7 and reduced human umbilical vein endothelial cell survival in the siYAP1-DPSC group. CONCLUSION: YAP1 in DPSCs targets the TGF-β1/Smad2 pathway to mediate DPSC differentiation toward SMCs and to enhance contractile force, thereby controlling vessel network formation and maintenance.
Candida-bacteria interactions in peri-implantitis: A narrative review of evidence, mechanisms, and clinical implications.
De Avila-Arias M, Fang L, Hoyos-Hoyos V … +4 more , Harris Ricardo J, Cadena-Cruz C, Villarreal-Camacho JL, Fortich Mesa N
Arch Oral Biol · 2026 Aug · PMID 42096854 · Publisher ↗
OBJECTIVE: To critically synthesize clinical, molecular, and mechanistic evidence on the contribution of the oral mycobiome, particularly Candida albicans, to peri-implantitis, and to evaluate how fungal-bacterial intera...
OBJECTIVE: To critically synthesize clinical, molecular, and mechanistic evidence on the contribution of the oral mycobiome, particularly Candida albicans, to peri-implantitis, and to evaluate how fungal-bacterial interactions influence biofilm pathogenicity, host responses, and potential therapeutic implications. DESIGN: Narrative review of peer-reviewed studies including clinical and epidemiological investigations, molecular analyses (quantitative polymerase chain reaction [qPCR] and next-generation sequencing [NGS] targeting the internal transcribed spacer [ITS] region for fungal profiling and the 16S ribosomal RNA [16S rRNA] gene for bacterial profiling), in vitro and in vivo interkingdom biofilm models, and immunological mechanistic studies. Evidence was evaluated qualitatively, with emphasis on detection methods, study design, and translational relevance. RESULTS: Molecular studies detect Candida spp. in a notable fraction of peri-implantitis sites, with higher detection by qPCR/NGS than by culture. Co-occurrence of C. albicans with periodontopathogens (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum) is frequently reported. Mechanistic studies show that C. albicans forms hyphal scaffolds, consumes oxygen to create microanaerobic niches, mediates bacterial adhesion via Als adhesins, and participates in metabolic exchange and cooperative proteolysis. These processes enhance biofilm resilience, promote inflammatory signalling pathways (nuclear factor kappa B [NF-κB] and mitogen-activated protein kinase [MAPK]), activate the NLRP3 inflammasome, and increase antimicrobial tolerance. No randomized controlled trials of antifungal or interkingdom-directed therapies are currently available. CONCLUSIONS: Evidence supports an interkingdom, polymicrobial model of peri-implantitis in which fungi contribute to biofilm stability and inflammation. However, heterogeneity in definitions, sampling, and detection methods limits causal inference. Longitudinal and interventional studies are required before mycobiome-directed therapies can be recommended.
Kir2.1 regulates peri-implant bone resorption by inhibiting Wnt/β-catenin signaling and increasing the RANKL/OPG ratio in osteoblasts.
Zu C, Shi J, Hanati D … +5 more , Su W, Wang Y, Meng Y, Lei L, Li H
Arch Oral Biol · 2026 Aug · PMID 42085897 · Publisher ↗
OBJECTIVE: Kir2.1, an inwardly rectifying potassium channel, is implicated in bone metabolism and inflammatory responses. This work holds the objective of investigating its role in bone remodeling in osteoblasts under th...
OBJECTIVE: Kir2.1, an inwardly rectifying potassium channel, is implicated in bone metabolism and inflammatory responses. This work holds the objective of investigating its role in bone remodeling in osteoblasts under the inflammatory conditions of peri-implantitis (PI). DESIGN: Kir2.1 expression was evaluated in human gingival and mice peri-implant tissues by immunohistochemistry. Mouse osteoblasts (MC3T3-E1) were stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g-LPS). The expression of Kir2.1, IL-6, RANKL, OPG, and Wnt/β-catenin pathway markers was evaluated using qRT-PCR and Western blot. After Kir2.1 inhibition or knockdown, ALP and ARS staining were measured to evaluate bone formation. Conditioned medium from osteoblasts following Kir2.1 knockdown was used to treat BMDMs, and subsequent osteoclast differentiation was evaluated by TRAP staining. β-catenin localization was detected by immunofluorescence. RESULTS: Significant upregulation was observed for both Kir2.1 and IL-6 in PI tissues from both human patients and mice models compared to the healthy controls. In vitro, P.g-LPS upregulated Kir2.1 expression and increased the RANKL/OPG ratio in osteoblasts. Inhibiting or knock-down of Kir2.1 effectively lowered the RANKL/OPG ratio, enhanced matrix mineralization and reduced osteoclast differentiation. Furthermore, Kir2.1 knock-down triggered nuclear translocation of β-catenin, stimulating the activation of the Wnt/β-catenin signaling pathway which could partially regulate the RANKL/OPG balance. CONCLUSION: Kir2.1 plays a vital role in PI by regulating bone remodeling via the Wnt/β-catenin/RANKL-OPG axis. Targeted inhibition of Kir2.1 could offer a novel strategy to mitigate bone loss in PI.
New studies on the mechanism of action and clinical application of long non-coding RNAs in oral squamous cell carcinoma.
Li Y, Zhang X, Hu K … +3 more , Wang Z, Li Y, Reng Y
Arch Oral Biol · 2026 Aug · PMID 42068670 · Publisher ↗
OBJECTIVES: The regulatory mechanisms and clinical significance of long non-coding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC) have become a research hotspot in recent years. DESIGN: We conducted a narrative re...
OBJECTIVES: The regulatory mechanisms and clinical significance of long non-coding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC) have become a research hotspot in recent years. DESIGN: We conducted a narrative review of PubMed, CNKI, and Wanfang databases (2014-2024). Using Boolean combinations of "lncRNA," "OSCC," and "pathogenesis," we screened original studies. Selection focused on human OSCC functional mechanisms and clinical biomarkers, while excluding papers with insufficient data or irrelevant cancer types. RESULTS: lncRNAs regulate gene expression and signaling pathways by interacting with their targets (including nucleic acids and proteins), playing a key role in the occurrence, development, metastasis, and drug resistance of OSCC.Advances in non-invasive testing technologies such as liquid biopsy, as well as breakthroughs in lncRNA-targeting techniques based on CRISPR and antisense oligonucleotides (ASO), have provided new tools for related research and applications. CONCLUSION: This article systematically summarizes the molecular mechanisms of lncRNA in OSCC and explores its clinical application prospects, aiming to provide direction for future theoretical research and clinical translation.
Tooth macrowear analysis of Indigenous Australian people from Yuendumu.
Fiorenza L, Hernaiz-García M, Towle I … +2 more , Oxilia G, Westaway M
Arch Oral Biol · 2026 Aug · PMID 42066708 · Publisher ↗
OBJECTIVE: The transition from foraging to farming occurred throughout the Neolithic was characterized by an increase in oral pathologies, such as caries and antemortem tooth loss, due to the consumption of softened food...
OBJECTIVE: The transition from foraging to farming occurred throughout the Neolithic was characterized by an increase in oral pathologies, such as caries and antemortem tooth loss, due to the consumption of softened foods rich in starch and sugars. The introduction of agricultural foods led to a disequilibrium in the masticatory apparatus, which is ultimately reflected in their dental wear. DESIGN: Here we analyze the molar macrowear patterns of the Warlpiri people (N = 33) from Yuendumu (Central Australia), a contemporary population that was at an early stage of transition from a nomadic and hunter-gatherer existence to a more westernized lifestyle. We employ the occlusal fingerprint analysis with the aim of tracking dental functional aspects associated with diet and cultural changes. RESULTS: The results show that the Warlpiri macrowear pattern was more similar to hunter-gatherers with a mixed diet, reflecting thus the consumption of hard (forager) and soft (westernized) foods. Moreover, we found a more oblique wear in the Warlpiri people if compared to those of recent hunter-gatherers. We also observed a high prevalence of tooth chipping, which is likely related to mastication of gritty and hard foods, and to a wide variety of non-masticatory uses. CONCLUSIONS: The analysis of the molar macrowear patterns indicate little changes in the masticatory system of the Warlpiri people, typical of a forager population. However, we do observe variations in tooth wear, which are probably caused by the introduction of softer foods in their daily diet, which is especially evident in younger individuals.
Molecular architecture and targeted killing mechanisms of T cell immune synapses in oral lichen planus.
Wang X, Jiang Z, Ji Y
Arch Oral Biol · 2026 Aug · PMID 42061287 · Publisher ↗
OBJECTIVE(S): This review focuses on the formation, molecular composition, and functional dynamics of T cell immune synapses within oral lichen planus (OLP) lesions. It aims to systematically elucidate how these speciali...
OBJECTIVE(S): This review focuses on the formation, molecular composition, and functional dynamics of T cell immune synapses within oral lichen planus (OLP) lesions. It aims to systematically elucidate how these specialized junctions direct cytotoxic T cells to recognize and eliminate basal keratinocytes, which is central to OLP pathogenesis. DESIGN: We synthesized recent advances in the field to dissect the key cellular events at the T cell-keratinocyte interface. The review provides an in-depth analysis of the dynamic regulation of immune synapses, evaluating their role in targeted cytotoxicity. RESULTS: The aberrant activation of T lymphocytes and their attack on epithelial keratinocytes in OLP are coordinated by immune synapses. We detail the critical signaling events, cytoskeletal reorganization, and polarized delivery of effector molecules (notably perforin and granzymes) that underpin this specific cytotoxicity. Furthermore, potential therapeutic strategies aimed at disrupting critical nodes within immune synapse assembly and function are evaluated. CONCLUSIONS: By integrating current knowledge, this review provides novel insights into the immunopathology of OLP. It lays a conceptual foundation for developing future precision immunotherapies that specifically target the dysregulated T cell-keratinocyte interface.
Immunohistochemical expression of SPARC and MMP-9 in odontogenic keratocysts and orthokeratinized odontogenic cysts.
Qu J, Yuan S, Zhang X … +7 more , Shang J, Wang L, Gao J, Li L, Liang F, Zhao C, Shen J
Arch Oral Biol · 2026 Aug · PMID 42054731 · Publisher ↗
OBJECTIVE: Odontogenic keratocysts (OKCs) are locally aggressive odontogenic cysts with high recurrence propensity, whereas orthokeratinized odontogenic cysts (OOCs) are indolent. Secreted protein acidic and rich in cyst...
OBJECTIVE: Odontogenic keratocysts (OKCs) are locally aggressive odontogenic cysts with high recurrence propensity, whereas orthokeratinized odontogenic cysts (OOCs) are indolent. Secreted protein acidic and rich in cysteine (SPARC) and matrix metalloproteinase 9 (MMP-9) have been implicated in tumor invasion. This study aimed to evaluate and compare the immunohistochemical expression of SPARC and MMP-9 in sporadic OKCs and OOCs, and to further explore the potential association between these two proteins in both types of cysts. DESIGN: SPARC and MMP-9 expression were evaluated in 24 sporadic OKCs and 22 OOCs using immunohistochemistry. RESULTS: In the epithelium of OKCs and OOCs, SPARC was absent. In the connective tissue, SPARC was predominantly detected in fibroblast cytoplasm, with significantly higher expression in OKCs than in OOCs (p = 0.006). MMP-9 was localized in both epithelium and connective tissue. Compared with OOCs, OKCs showed upregulated MMP-9 expression in the epithelium (p = 0.035), whereas no significant difference in MMP-9 expression was observed in the connective tissue between the two types of cysts (p = 0.678). A positive correlation was observed between SPARC and MMP-9 in the connective tissue of OKC. Furthermore, both SPARC and MMP-9 demonstrated a significant positive association with inflammatory infiltration in OKCs. CONCLUSION: Increased SPARC expression in sporadic OKCs compared to OOCs suggests that SPARC may play a role in OKC aggressiveness. Differential expression of SPARC may aid in distinguishing between OKC and OOC. Moreover, the putative association between SPARC and MMP-9 in OKCs may contribute to their local invasiveness.
Assessment of oxidative and inflammatory biomarkers in denture-related traumatic ulcers treated with different topical agents.
Okicic N, Milojevic Samanovic A, Jovanovic M … +10 more , Jakovljevic V, Zivkovic V, Kocovic A, Nikolic M, Andjic M, Lazarevic N, Petrovic A, Stanisic D, Mladenovic R, Milosavljevic M
Arch Oral Biol · 2026 Jul · PMID 42025121 · Publisher ↗
OBJECTIVE: To investigate the potential role of oxidative and inflammatory status in saliva during the healing of denture-related traumatic ulcers, applying various topical agents. DESIGN: The prospective cohort study in...
OBJECTIVE: To investigate the potential role of oxidative and inflammatory status in saliva during the healing of denture-related traumatic ulcers, applying various topical agents. DESIGN: The prospective cohort study included 100 participants with denture-related traumatic ulcers, divided into five groups: traumatic ulcers that were not treated and treated with topical agents (0.2% hyaluronic acid gel, 0.3% hyaluronic acid-taurine gel, a gel based on an herbal preparation, and panthenol mouthwash) for seven days. Unstimulated saliva samples were collected. Oxidative stress parameters were determined spectrophotometrically. Inflammatory markers and vascular endothelial growth factor (VEGF) were analyzed using an enzyme-linked immunosorbent assay. Data were analysed by Kruskal-Wallis and Mann-Whitney U test (P < 0.05). RESULTS: The values of superoxide anion radical, index of lipid peroxidation, and hydrogen peroxide were significantly decreased in groups that used gels based on hyaluronic acid or hyaluronic acid-taurine compared to other groups (P < 0.05); conversely, superoxide dismutase, catalase, and reduced glutathione were significantly increased (P < 0.05). The levels of interleukin-6, interleukin-17, and tumor necrosis factor alpha were significantly decreased (P < 0.05), while the levels of interleukin-10 and VEGF were significantly increased in the hyaluronic acid or hyaluronic acid-taurine groups in comparison to other treatments (P < 0.05). CONCLUSION: Hyaluronic acid or hyaluronic acid-taurine gels were associated with pronounced changes in salivary biomarkers, reflecting improvements in redox status, inflammation balance, and angiogenesis. The current research may help clarify the potential molecular mechanisms influencing the healing of traumatic ulcers after the placement of new removable dentures using various topical agents, with due consideration of study limitations.
Raman spectroscopy enables highly sensitive profiling of osteogenic mineralization in periodontal organoids.
Aidukaitė G, Talaikis M, Tunaitis V … +5 more , Romenskaja-Avgul D, Mažylytė K, Niaura G, Brukienė V, Pivoriūnas A
Arch Oral Biol · 2026 Jul · PMID 42019144 · Publisher ↗
OBJECTIVES: This study aimed to assess the capability of Raman spectroscopy to detect osteogenic differentiation in structurally intact organoids derived from human periodontal ligament stem cells (PDLSC) and to compare...
OBJECTIVES: This study aimed to assess the capability of Raman spectroscopy to detect osteogenic differentiation in structurally intact organoids derived from human periodontal ligament stem cells (PDLSC) and to compare the mineral deposition capacity between PDLSC monolayers and organoids. DESIGN: PDLSC organoids were generated using a scaffold-free cell sheet culture technique. Organoids and monolayers were subjected to osteogenic induction and/or inflammatory stimulation for 14 days. Samples were analysed by morphological assessment, weighing, histology, reverse transcription quantitative polymerase chain reaction (RT-qPCR), Alizarin Red staining and Raman spectroscopy. RESULTS: Osteogenic induction resulted in more than a threefold increase in organoid mass, partly due to enhanced cellularization confirmed by 4',6-diamidino-2-phenylindole (DAPI) staining. Histological analysis showed uniform cell distribution in both undifferentiated and differentiated organoids. Undifferentiated organoids exhibited higher baseline expression of osteogenesis-related genes (BMP2, MSX2, OP) compared with monolayers, suggesting inherent osteogenic priming. Calcium deposition increased by 2.2-fold in differentiated organoids and 1.3-fold in monolayers. Raman spectroscopy demonstrated superior sensitivity, revealing a 47.2-fold increase in the mineral-to-matrix (M:M) ratio in differentiated organoids versus a 3.7-fold increase in monolayers. Inflammatory stimulation did not significantly alter organoid mass, calcium deposition or M:M ratio during osteogenic induction. CONCLUSIONS: Raman spectroscopy provides a precise, quantitative and non-destructive approach for assessing osteogenic differentiation in structurally intact periodontal organoids. These findings support its potential as a valuable tool for periodontal disease modelling and therapeutic screening.
Effect of temperature and ultrasonic activation on the antibacterial efficacy of sodium hypochlorite alone and combined with etidronic acid in an internal root resorption model.
Gündüz M, Kurnaz S, Gülbandılar A
Arch Oral Biol · 2026 Jul · PMID 42019143 · Publisher ↗
OBJECTIVES: This study compared the antibacterial efficacy of sodium hypochlorite (NaOCl) and a NaOCl-1-hydroxyethane-1,1-diphosphonic acid (NaOCl/HEDP) mixture at 25°C and 37°C, with or without passive ultrasonic irriga...
OBJECTIVES: This study compared the antibacterial efficacy of sodium hypochlorite (NaOCl) and a NaOCl-1-hydroxyethane-1,1-diphosphonic acid (NaOCl/HEDP) mixture at 25°C and 37°C, with or without passive ultrasonic irrigation (PUI), in an internal root resorption (IRR) model infected with Enterococcus faecalis biofilm. DESIGN: Standardized IRR cavities were prepared in extracted maxillary incisors. After 21-day biofilm maturation, specimens were allocated to eight subgroups (NaOCl or NaOCl/HEDP; 25°C or 37°C; conventional needle irrigation [CNI] or PUI; n = 8 each) and a saline control (n = 8). Antibacterial activity was assessed by colony-forming unit (CFU) reduction, and biofilm morphology was evaluated via scanning electron microscopy (SEM). Data were analyzed using factorial ANOVA (irrigant type×temperature×activation), with partial η² and Cohen's f reported (α=0.05). RESULTS: All experimental groups showed significant bacterial reduction compared with the control (P < 0.001). Significant main effects were observed for temperature (F=89.7, P < 0.001, η²=0.62), activation (F=50.6, P < 0.001, η²=0.48), and irrigant type (F=19.8, P < 0.001, η²=0.26). Temperature had a stronger enhancing effect in the NaOCl/HEDP groups. The greatest reduction occurred with NaOCl/HEDP at 37°C combined with PUI. SEM images confirmed cleaner dentine surfaces and reduced debris in the 37°C and PUI groups, particularly with NaOCl/HEDP. CONCLUSIONS: Both temperature elevation and PUI improved antibacterial efficacy, and NaOCl/HEDP demonstrated the strongest temperature-dependent response. Their combined use resulted in the highest bacterial reduction, although complete bacterial removal was not achieved.
Macrophage repolarization by epigallocatechin-3-gallate via NF-κB and CREB1/HO-1.
Ida T, Edanami N, Kasimoto S … +4 more , Sotozono M, Takenaka S, Ohkura N, Noiri Y
Arch Oral Biol · 2026 Jul · PMID 42013538 · Publisher ↗
OBJECTIVE: Epigallocatechin-3-gallate (EGCG) is known for having the highest physiological activity in catechins. However, the molecular mechanism of EGCG regarding macrophage polarization/repolarization remains unclear....
OBJECTIVE: Epigallocatechin-3-gallate (EGCG) is known for having the highest physiological activity in catechins. However, the molecular mechanism of EGCG regarding macrophage polarization/repolarization remains unclear. This study aimed to reveal whether EGCG can directly induce M2 and lead M1 to M2 repolarization mediated by nuclear factor-κB p65 and cAMP response element binding protein 1 (CREB1)/heme oxygenase-1 (HO-1). DESIGN: To confirm the function of EGCG on macrophage polarization, RAW264.7 cells were treated with EGCG for 12 h, M1 and M2 markers were evaluated (mRNA and protein level, n = 3). Additionally, to clarify whether EGCG can shift the macrophage polarization from M1 to M2, RAW264.7 cells pretreated with lipopolysaccharide from Porphyromonas gingivalis for 12 h were then exposed to EGCG for 12 h, M1 and M2 markers were analyzed (n = 3). Furthermore, to elucidate the molecular mechanism of these results, the mRNA and protein levels of inflammation regulators such as p65, CREB1, and HO-1 and their phosphorylation were analyzed (n = 3). Significance was assessed using the one-way analysis of variance for comparisons and GraphPad Prism software. RESULTS: EGCG enhanced the expression of the M2 markers CD206 and CD163 while inhibiting that of the M1 markers iNOS and MMP9. Moreover, EGCG changed the macrophage phenotype from M1 to M2. EGCG was found to suppress p65 phosphorylation; however, it promoted HO-1, resulting in the upregulation of CREB1 phosphorylation. CONCLUSION: Our results indicated that EGCG had a great potential in macrophage-mediated immune regulation, leading to the control of excessive tissue damage and promoting tissue repair during inflammation.
Salivary biomarkers and their diagnostic importance in oral diseases.
Thangasamy B, Sivagnanam A
Arch Oral Biol · 2026 Jul · PMID 41996891 · Publisher ↗
OBJECTIVE: This review critically evaluates the diagnostic potential of salivary biomarkers in oral diseases, highlighting their role as non-invasive tools for early detection, disease monitoring, and precision oral heal...
OBJECTIVE: This review critically evaluates the diagnostic potential of salivary biomarkers in oral diseases, highlighting their role as non-invasive tools for early detection, disease monitoring, and precision oral healthcare. DESIGN: A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2005 and 2026. Keywords included salivary biomarkers, salivaomics, oral diseases and diagnosis. Only English peer-reviewed articles focusing on salivary biomarkers and analytical methods in oral diseases were included, while studies lacking clinical relevance were excluded. RESULTS: Saliva harbors a variety of molecular biomarkers, such as proteins or nucleic acids, that mirror local and systemic pathological phenomena8. In oral squamous cell carcinoma, salivary biomarkers like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) have a sensitivity of 70-90% and a specificity of 75-95%; however, salivary microRNAs display strong discriminatory power with AUC values ≥ 0.85. For periodontal diseases, MMP-8, among others, found in the biomarkers, shows high accuracy (AUC > 0.80). Recent progress in salivaomics, including proteomics, genomics, metabolomics, and microbiomics, has notably increased detection sensitivity, specificity, and clinical applicability. However, heterogeneity of biomarker expression, lack of a clinically validated standardized protocol for the collection and processing of saliva, and insufficient large-scale clinical validation are still significant limitations to everyday clinical utilization. CONCLUSIONS: Salivary biomarkers are non-invasive and offer an opportunity to complement traditional diagnostic sources in oral health. Further standardization, clinical validation and adaptation of multi-omics and artificial intelligence-based technologies are necessary to facilitate their positive translation into precision oral medicine.
Targeted treatment of oral candidiasis caused by Candida albicans and Candida parapsilosis using diosmetin: A phytotherapeutic approach in dentistry.
Gunasekaran V, Shirin F, Pujakrishna GS … +3 more , Ali S, Somasundaram J, Sathishkumar P
Arch Oral Biol · 2026 Jul · PMID 41966614 · Publisher ↗
OBJECTIVE: Oral candidiasis is a fungal infectious disease in the oral cavity caused by several Candida species, especially in immunocompromised individuals. To address this issue, an effective treatment approach must be...
OBJECTIVE: Oral candidiasis is a fungal infectious disease in the oral cavity caused by several Candida species, especially in immunocompromised individuals. To address this issue, an effective treatment approach must be developed. This study aimed to find an effective and alternative anticandidal therapeutics from natural sources to combat Candida species that are predominantly involved in oral candidiasis. DESIGN: Candida strains were screened from oral candidiasis cases. The anticandidal effect of different phytocompounds were screened against C. albicans and C. parapsilosis via ZOI, MIC, and MFC assessment. Further, the antibiofilm effect of diosmetin was evaluated using CV staining, MTT assay, CFU count, and CLSM analysis. Molecular docking of diosmetin with virulence protein secreted aspartyl protease of Candida species was investigated using Auto Dock Tools and PyMOL. The biocompatibility nature of diosmetin was checked on human RBCs and human gingival epithelial cells (HGECs). RESULTS: Diosmetin exhibits excellent anticandidal effect against different Candida species. The MIC and MFC of diosmetin against C. albicans and C. parapsilosis were found as 102-143 µM and 200 µM, respectively. Diosmetin demonstrates effective eradication of mature biofilm at 1.25xMIC (128-179 µM) within 48 h treatment. Diosmetin forms a strong binding affinity with secreted aspartyl proteases. It has great biocompatibility on human RBCs and cytocompatibility on HGECs up to 10 mM and 200 µM, respectively. CONCLUSIONS: The present study suggests that diosmetin might be an effective, safe and alternative anticandidal therapeutic agent to treat oral candidiasis caused by Candida species in humans.
Dual biomarkers ALOX5AP and INPP4A are associated with lipid metabolism and neutrophil extracellular traps in periodontitis: A bioinformatics and clinical validation study.
Zhao Y, Zhan J, He L … +9 more , Xu C, Li B, Li Z, Shao L, Li Z, Zhang J, Li X, Su J, Zhang W
Arch Oral Biol · 2026 Jul · PMID 41962331 · Publisher ↗
OBJECTIVE(S): Periodontitis is a chronic inflammatory disease characterized by progressive alveolar bone destruction. While lipid metabolism and neutrophil extracellular traps (NETs) are implicated in periodontitis patho...
OBJECTIVE(S): Periodontitis is a chronic inflammatory disease characterized by progressive alveolar bone destruction. While lipid metabolism and neutrophil extracellular traps (NETs) are implicated in periodontitis pathogenesis, their precise molecular mechanisms remain unclear and require further investigation. DESIGN: RNA sequencing datasets were acquired from public databases. Differential expression analysis identified differentially expressed genes in periodontitis tissues and those associated with NETs and lipid metabolism. Machine learning algorithms screened for key genes, and a nomogram assessed their diagnostic value. Comprehensive analyses included enrichment analysis, immune infiltration profiling, chemical-gene interaction prediction, and transcription factor regulatory network construction. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation was performed using clinical periodontitis and healthy gingival samples. RESULTS: ALOX5AP (arachidonate 5-lipoxygenase-activating protein) and INPP4A (inositol polyphosphate-4-phosphatase type I A) were identified as key biomarkers showing significant correlation. These genes demonstrated co-enrichment in 129 pathways including endoplasmic reticulum protein processing. Immune infiltration analysis revealed ALOX5AP exhibited strongest positive correlation with plasma cells, while INPP4A showed strongest negative correlation. Three target transcription factors were predicted and a miRNA-mRNA-lncRNA network was constructed. Twenty compounds predicted to interact with these biomarkers were identified for periodontitis treatment. RT-qPCR validation confirmed significant upregulation of both ALOX5AP and INPP4A in periodontitis tissues, consistent with bioinformatics findings. CONCLUSIONS: This study identifies ALOX5AP and INPP4A as potential periodontitis biomarkers and reveals their predicted association with lipid metabolism and NETs-related pathways, providing insights into the molecular mechanisms that may underlie periodontitis.
Lipoteichoic acid induces IL-6 production in human pulp stromal cells through TLR2-mediated NF-κB nuclear translocation.
Akamp T, Linnebank M, Schreiber L … +5 more , Rosendahl A, Fetscher E, Pohl S, Buchalla W, Widbiller M
Arch Oral Biol · 2026 Jul · PMID 41950554 · Publisher ↗
OBJECTIVE: This study aimed to investigate the inhibition of Toll-like receptor 2 (TLR2) signaling in lipoteichoic acid-induced NF-κB activation and interleukin-6 (IL-6) production in primary human dental pulp stromal ce...
OBJECTIVE: This study aimed to investigate the inhibition of Toll-like receptor 2 (TLR2) signaling in lipoteichoic acid-induced NF-κB activation and interleukin-6 (IL-6) production in primary human dental pulp stromal cells (DPSCs). DESIGN: Primary human DPSCs were cultured with lipoteichoic acid from Staphylococcus aureus (LTA-SA; 10, 25, 50 µg/ml) for up to 72 h to assess time- and concentration-dependent IL-6 production. IL-6 secretion was quantified by ELISA, while cell counts were determined via cell counter. To evaluate TLR2-dependent signaling, cells were pre-incubated with the TLR2 inhibitor C29 (100 µM) prior to LTA-SA stimulation. IL6 gene expression was analyzed by RT-qPCR, and NF-κB nuclear translocation was assessed by Western blot analysis. Non-parametric statistical analyses were applied to compare all groups and time points (Mann-Whitney U test or Kruskal-Wallis test; α = 0.05). RESULTS: LTA-SA stimulation induced a significant, time- and concentration-dependent increase in IL6 gene expression and IL-6 secretion, accompanied by enhanced NF-κB nuclear translocation. Inhibition of TLR2 with C29 reduced nuclear translocation of NF-κB, along with a decrease in IL6 gene expression and IL-6 secretion, exhibiting both time- and concentration-dependent effects. CONCLUSIONS: LTA induces IL-6 production in DPSCs via TLR2-mediated activation of the canonical NF-κB pathway. Targeted modulation of TLR2 signaling may represent a potential strategy for controlling pulpal inflammation.
α-Smooth muscle actin (Myofibroblast) as a marker of disease progression and malignant transformation in oral submucous fibrosis: A systematic review and meta-analysis.
Gadbail AR, Yuwanati MB, Gondivkar SM … +3 more , Bagri-Manjrekar K, Chaudhary MS, Sarode SC
Arch Oral Biol · 2026 Jul · PMID 41950553 · Publisher ↗
OBJECTIVE: This systematic review and meta-analysis sought to evaluate whether stromal myofibroblast assessed by alpha-smooth muscle actin (α-SMA) expression serves as a reliable biomarker of disease progression and mali...
OBJECTIVE: This systematic review and meta-analysis sought to evaluate whether stromal myofibroblast assessed by alpha-smooth muscle actin (α-SMA) expression serves as a reliable biomarker of disease progression and malignant transformation (MT) potential in oral submucous fibrosis (OSMF). DESIGN: A systematic review and meta-analysis was carried out using the PRISMA protocol, which was registered in the PROSPERO database. The databases searched included PubMed, Scopus, and Web of Science, and the search period was up to January 2026. The included studies had data regarding the assessment of α-SMA expression in normal oral mucosa (NOM), OSMF, and oral squamous cell carcinoma (OSCC). The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. Random effects models using standardized mean difference (SMD) and odds ratio (OR) were used. RESULTS: Seventeen studies included meeting the inclusion criteria. Narrative synthesis revealed a stepwise increase in stromal α-SMA expression from NOM to early OSMF, advanced OSMF, and OSCC with transition in architecture from focal to diffuse and networked pattern of stroma. Quantitative meta-analysis results demonstrated significantly higher α-SMA expression in OSMF compared to NOM (SMD = 1.82), in advanced compared with early OSMF (SMD = 1.17), and in OSCC compared with OSMF (SMD = 1.51). Dichotomous analysis revealed an overall significantly increased odds of high α-SMA expression in OSMF (OR = 7.28) and OSCC (OR = 11.19). Fifteen studies had a low risk of bias. CONCLUSION: The increase in the expression of α-SMA demonstrates a strong graded association with OSMF severity and MT, supporting its value as a reproducible histopathologic biomarker for disease stratification and prognostic assessment.
Recent advances in drug repurposing for dentin repair.
Jaimon E, Alenizy M, Weir MD … +3 more , Ma T, Xu HHK, Schneider A
Arch Oral Biol · 2026 Jul · PMID 41950552 · Publisher ↗
OBJECTIVE: Exposure of a vital dental pulp following deep caries removal, accidental restorative procedures or trauma can severely affect the dentin-pulp complex in adult permanent teeth. To preserve a biologically funct...
OBJECTIVE: Exposure of a vital dental pulp following deep caries removal, accidental restorative procedures or trauma can severely affect the dentin-pulp complex in adult permanent teeth. To preserve a biologically functional healthy pulp, promote dentin repair, and minimize invasive and costly procedures, direct pulp capping is commonly used in vital pulp therapies. Despite its well-accepted therapeutic value, current pulp capping inorganic hydraulic calcium-silicate cements like mineral trioxide aggregate show limited targeted bioactive effects. Therefore, repurposing clinically approved drugs or investigational small bioactive agents targeting intracellular signaling pathways relevant to reparative dentinogenesis may translate into novel therapeutic approaches for dentin repair. Here, we review studies published over the past decade that explore two agents for potential repurposing in dentin repair: tideglusib, a glycogen synthase kinase‑3 inhibitor, and metformin, a widely used anti‑diabetic biguanide DESIGN: PubMed was used as the single, web-based search engine and database. Only studies using dental pulp stem cells in which the drugs were investigated as single agents were included. RESULTS: While incorporated into different biomaterial formulations, both tideglusib and metformin, trigger significant upregulation of odontoblastic differentiation markers and mineral synthesis in dental pulp stem cells in vitro. Tideglusib has also been shown to significantly enhance reparative dentinogenesis in experimental animal models. CONCLUSIONS: Leveraging drug repurposing for dentin repair underscores the significance of translating into dentistry knowledge gained from basic, pre-clinical and clinical research in other medical conditions, laying the groundwork for cost-effective therapeutic strategies and improved outcomes in regenerative dental medicine.
Standardized Centella asiatica extract (ECa 233) mitigates chlorhexidine-induced cytotoxicity and promotes oral wound repair via immunomodulation and angiogenesis.
Rotpenpian N, Puengsurin D, Arayapisit T … +3 more , Surarit R, Tantisira MH, Wanasuntronwong A
Arch Oral Biol · 2026 Jul · PMID 41950551 · Publisher ↗
OBJECTIVE: Although 0.12% Chlorhexidine (CHX) is the gold standard oral antiseptic, its significant cytotoxicity often delays tissue repair. This study investigated the potential of ECa 233, a standardized Centella asiat...
OBJECTIVE: Although 0.12% Chlorhexidine (CHX) is the gold standard oral antiseptic, its significant cytotoxicity often delays tissue repair. This study investigated the potential of ECa 233, a standardized Centella asiatica extract, to mitigate CHX-induced damage and promote oral wound regeneration. DESIGNS: Antimicrobial efficacy was assessed via minimum inhibitory concentration (MIC) against key oral pathogens. Human Gingival Fibroblasts (HGFs) were treated with CHX and ECa 233 to evaluate viability (MTT) and migration (scratch assay). Anti-inflammatory effects were measured by quantifying CD80 expression and cytokine secretion (TNF-alpha, IL-6) in LPS-stimulated U937 cells, while angiogenesis was evaluated using the chick embryo chorioallantoic membrane (CAM) assay. RESULTS: Results demonstrated that ECa 233 preserved the antimicrobial activity of CHX. While 0.12% CHX alone significantly inhibited HGF viability and migration (p < 0.001), the addition of 0.05% ECa 233 significantly rescued these cellular parameters (p < 0.05). ECa 233 effectively downregulated the M1 macrophage marker CD80 and suppressed the secretion of TNF-alpha and IL-6, indicating potent immunomodulatory activity. Furthermore, ECa 233 significantly enhanced vascular density and branching complexity in the CAM assay (p < 0.005). CONCLUSION: The ECa 233-CHX formulation maintains essential antimicrobial efficacy while reducing cytotoxicity and actively promoting fibroblast migration, immunomodulation, and angiogenesis. This dual-action approach addresses the clinical limitation of antiseptic-induced tissue toxicity, offering a superior biological strategy for enhancing oral wound healing and post-surgical recovery.
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