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Archives Of Oral Biology[JOURNAL]

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Prevalence and eradication of mixed biofilms of Streptococcus mutans and Candida albicans using naringin: In vitro and in silico investigations.

Reddy CSS, Venkatesan LS, Ganapathy D … +1 more , Sathishkumar P

Arch Oral Biol · 2026 Mar · PMID 41420929 · Publisher ↗

OBJECTIVE: To identify a potential natural therapeutic agent to treat the mixed biofilms of Streptococcus mutans and Candida albicans, thereby preventing dental caries. DESIGN: The coexisting S. mutans and C. albicans wa... OBJECTIVE: To identify a potential natural therapeutic agent to treat the mixed biofilms of Streptococcus mutans and Candida albicans, thereby preventing dental caries. DESIGN: The coexisting S. mutans and C. albicans was isolated from dental caries. Antimicrobial activity of various natural components was assessed against S. mutans and C. albicans. Antibiofilm efficacy of naringin was assessed against the biofilm of mixed S. mutans and C. albicans. The cell viability in mixed biofilm was determined using MTT assay and CLSM investigations. The molecular docking analysis of naringin with secreted aspartic proteinase (SAP2) of C. albicans and glucosyltransferase-I (GtfB) of S. mutans was performed using AutoDock and PyMOL tools. The biocompatibility of naringin was determined on human RBCs and HGF cells. RESULTS: The natural components such as curcumin, naringin, quercetin, morin, rutin, and hesperetin shows the antimicrobial effects against the clinical isolates S. mutans and C. albicans. Among these, naringin exhibits the significant antimicrobial effect against S. mutans (MIC:183 ± 5.70 µM), C. albicans (MIC:196 ± 0.00 µM), and their mixed culture (MIC:200 ± 10.00 µM). The MTT and CLSM results indicates that 2xMIC (400 µM) of naringin demonstrates the potential eradication of mature biofilm of mixed S. mutans and C. albicans. Naringin establishes the strong binding interaction with enzymes GtfB of S. mutans and SAP2 of C. albicans. The IC value of naringin towards HGF cells was noted as 711.5 µM. CONCLUSIONS: The flavonoid naringin demonstrates the effective and safe therapeutic potential to treat coexisting S. mutans and C. albicans biofilm virulence to prevent the dental caries.

Rutin (Vitamin P) attenuates oxidative stress, modulates cytokine profile, and preserves alveolar bone microarchitecture and density in a rat periodontitis model.

Keskin SB, Üremiş MM, Türköz Y … +1 more , Aral CA

Arch Oral Biol · 2026 Mar · PMID 41418396 · Publisher ↗

OBJECTIVES: To evaluate the anti-inflammatory and antioxidant effects of rutin in experimental periodontitis. DESIGN: Wistar Albino rats were divided into four groups (n = 8 per group): 1) Healthy Control (HC), 2) Period... OBJECTIVES: To evaluate the anti-inflammatory and antioxidant effects of rutin in experimental periodontitis. DESIGN: Wistar Albino rats were divided into four groups (n = 8 per group): 1) Healthy Control (HC), 2) Periodontitis (P), 3) P + Rutin 50 mg/kg (PR-50), and 4) P + Rutin 100 mg/kg (PR-100). Rutin was administered orally throughout the 14-day experimental period. Gingival levels of interleukin-1 beta (IL-1β), interleukin-10 (IL-10), glutathione peroxidase (GPX), malondialdehyde (MDA), and superoxide dismutase (SOD) and were measured using enzyme-linked immunosorbent assay, while oxidative stress index (OSI), total oxidant (TOS), and antioxidant status (TAS) were analysed spectrophotometrically. Alveolar bone was assessed by micro-computed tomography, including linear (ABL), volumetric (BV/TV), microarchitectural (BS/BV, Tb.Th, Tb.N, Tb.Sp), and densitometric (GV, HU, BMD) parameters. RESULTS: IL-1β/IL-10 ratio was lower, and IL-10 and GPX levels were higher in PR-100 group than in P group (p < 0.05). SOD levels were higher in HC and PR-100 groups than in P group (p < 0.001). OSI was highest in P (p < 0.001). TOS was higher in P versus HC, whereas TAS was lower in PR-50 versus HC (p < 0.05). ABL and BV/TV analyses showed significant bone preservation in both rutin groups compared to P (p < 0.01). Microstructural and densitometric indices further confirmed less alveolar bone deterioration in rutin-treated rats. CONCLUSION: Rutin exerts dose-dependent anti-inflammatory, antioxidant, and bone-protective effects in experimental periodontitis, suggesting its potential as an adjunctive therapeutic agent.

Effect of phenotype switched Candida auris mono-culture and co-culture biofilms on the morphology, viability, and adhesion of hTERT TIGKs and ORL-48 cell lines.

Zainal M, Sarmin N'M, Ibrahim MJ … +3 more , Cirillo N, Dashper SG, Arzmi MH

Arch Oral Biol · 2026 Feb · PMID 41412107 · Publisher ↗

OBJECTIVES: This study aims to determine the paracrine effects of Candida auris phenotypic switching in mono- and co-culture with Staphylococcus aureus on oral epithelial homeostasis and oncogenic progression in phenotyp... OBJECTIVES: This study aims to determine the paracrine effects of Candida auris phenotypic switching in mono- and co-culture with Staphylococcus aureus on oral epithelial homeostasis and oncogenic progression in phenotypically normal (hTERT TIGKs) and malignant (ORL-48) oral keratinocytes. DESIGN: C. auris switched phenotype was scored using Phloxine B, and mono- and co-culture biofilms with S. aureus were developed. hTERT TIGKs and ORL-48 cell lines were independently seeded into 6-well and 96-well plates for dispase and viability test, respectively. The oral cell lines were exposed to phenotypically switched C. auris mono- and co-culture biofilm test cell growth medium (TCGM) for 24 h. Outcomes included cell morphology, metabolic activity/viability (CCK-8), and cell-cell adhesion (dispase assay). RESULTS: Microscopic observation revealed that the biofilm induced damage and disrupted epithelial cell integrity in a paracrine manner. The mono- and co-culture TCGM suppressed the growth of normal cells while promoting the metabolic activity of cancer cells. The adhesion analysis of hTERT TIGKs indicated a strong intercellular cohesion, while ORL-48 cells downregulated intercellular adhesion and compromised cell-cell cohesion. CONCLUSION: C. auris biofilms promote the development of a malignant phenotype by regulating cell viability, promoting epithelial-mesenchymal transition, and adhesion in a switched generation-dependent manner.

Escitalopram exposure compromises osteogenic potential of human osteoblastic cells.

Pasotti ADP, Girondo RMF, Haddad B … +4 more , Franchin M, Benso B, Motta RHL, Abdalla HB

Arch Oral Biol · 2026 Feb · PMID 41412106 · Publisher ↗

OBJECTIVE: This study aimed to assess the impact of escitalopram on bone metabolism by evaluating its effects on cell viability and proliferation, wound-healing capacity, osteogenic activity, bone formation markers, and... OBJECTIVE: This study aimed to assess the impact of escitalopram on bone metabolism by evaluating its effects on cell viability and proliferation, wound-healing capacity, osteogenic activity, bone formation markers, and collagen deposition. DESIGN: The effects of escitalopram were studied on human osteoblastic SAOS-2 cells. Escitalopram (1-1000 µM) was tested in a dose-response curve. Cell viability was measured by MTT assay, and proliferation by hemocytometer counting. Cell migration was examined with the Scratch assay over 72 h. Osteogenic differentiation was assessed by gene expression of RUNX2, Osterix (Osx), bone sialoprotein (BSP), type I collagen (COL1), and osteocalcin (OCN) using RT-qPCR. Alkaline phosphatase (ALP) activity was analyzed at 4 and 8 days. Mineralization was determined by Alizarin Red staining (days 10, 14, 21). For last, Immunofluorescence was carried out for collagen 1 staining (days 3, 7 and 10). RESULTS: Escitalopram induced cytotoxicity in doses greater than 100 µM, reducing cell viability within 24 h. At non-toxic concentrations (≤30 µM), proliferation was enhanced in 30 µM after 7 days. Conversely, escilalopram reduced the migration capacity in a concentration-dependent manner. Moreover, the gene expression of RUNX2, OSX, BSP, COL1, and OCN were diminished when exposed to escitalopram. In the functional tests, escitalopram significantly decreases ALP activity at day 4, but not at day 8. Mineralization was dose-dependently impaired at 14 and 21 days. Collagen type I immunofluorescence exhibit weaker staining when escitalopram exposure. CONCLUSION: Escitalopram compromises osteoblast differentiation, extracellular matrix formation, and migratory potential. These results provide mechanistic insight into the adverse skeletal effects of SSRIs and suggest the need for monitoring bone health in long-term users.

Submandibular saliva from male rats modulates osteogenic differentiation of bone marrow progenitor cells In Vitro.

Troncoso GR, Gangoiti MV, Fernández-Solari J … +2 more , Mohn CE, Molinuevo MS

Arch Oral Biol · 2026 Feb · PMID 41406859 · Publisher ↗

OBJECTIVE: To investigate the effect of submandibular saliva from male rats on the proliferation and osteoblastic differentiation of bone marrow progenitor cells. DESIGN: Saliva was collected and pooled from adult male r... OBJECTIVE: To investigate the effect of submandibular saliva from male rats on the proliferation and osteoblastic differentiation of bone marrow progenitor cells. DESIGN: Saliva was collected and pooled from adult male rats, and the total protein content was measured. Bone marrow progenitor cells (BMPC) from adult male rats were incubated with varying concentrations of salivary protein (ranging from 0 to 30 µg/mL) to assess cell proliferation. Osteoblastic differentiation was evaluated by measuring alkaline phosphatase activity, collagen type 1 production, mineral nodule formation, and molecular markers of differentiation after 7, 15, or 21 days of saliva exposure in a differentiating culture medium. The pro-inflammatory effects of saliva on BMPC were assessed by measuring tumor necrosis factor-alpha, interleukin 1 beta, prostaglandin E2, and matrix metalloproteinases 2 and 9. RESULTS: Low saliva concentration stimulated BMPC, promoting a pro-secretory and proliferative state. In contrast, higher concentration inhibited both processes under basal conditions. Furthermore, in osteogenic medium, saliva decreased alkaline phosphatase activity, collagen-1 production, and matrix mineralization in BMPC, demonstrating a dose- and time-dependent effect. Saliva also increased the secretion of interleukin 1β, tumor necrosis factor α, prostaglandin E2, and metalloproteinase activity in these cells, which inhibited osteoblastic differentiation. CONCLUSION: Submandibular saliva has a biphasic effect on the osteogenic commitment of bone marrow progenitor cells, depending on the concentration and duration of exposure. This finding underscores the active role of saliva in the repair and regeneration of tooth sockets.

Exploring the relationship between gut microbiota-metabolite axis and Jiawei Danxuan Koukang's therapeutic effects in male rats with oral submucous fibrosis: A multi-omics analysis.

Wang C, Dai Y, Ye Y … +2 more , Zeng Q, Tan J

Arch Oral Biol · 2026 Feb · PMID 41401479 · Publisher ↗

OBJECTIVE: This work aims to explore how Jiawei Danxuan Koukang (JDK) ameliorates Oral Submucous Fibrosis (OSF) via regulating the gut microbiota and its metabolites. DESIGN: We established an OSF rat model via oral muco... OBJECTIVE: This work aims to explore how Jiawei Danxuan Koukang (JDK) ameliorates Oral Submucous Fibrosis (OSF) via regulating the gut microbiota and its metabolites. DESIGN: We established an OSF rat model via oral mucosal arecoline injection. Rats were randomly divided into five groups: control, model, lycopene-treated, quercetin-treated, and JDK-treated. After intervention, we analyzed: serum metabolites by Liquid Chromatography-Mass Spectrometry -based untargeted metabolomics; gut microbiota profiling via 16S rDNA sequencing; oral mucosal histopathology and fibrosis using hematoxylin-eosin and Masson trichrome staining; expressions of fibrosis-related proteins (Transforming Growth Factor-β1 (TGF-β1), Collagen Type I Alpha 1 Chain (COL1A1)) by western blot; and cytokines (Interleukin-1β, Interleukin-6, Interleukin-10) in serum, oral and colon tissues via enzyme-linked immunosorbent assay. RESULTS: In the OSF model group, 120 serum metabolites were upregulated and 39 were down-regulated. When comparing the JDK group with the model group, 83 metabolites were upregulated and 132 were downregulated in the JDK group. Specifically, JDK targeted key metabolites: prostaglandins, leukotrienes, lysophosphatidylcholine, and 4-hydroxyproline. JDK also regulated two critical metabolic pathways: gly-cine-serine-threonine metabolism and tryptophan metabolism. JDK reduces the pro-inflammatory Ruminococcus and restores the butyrate-producing Lachnospiraceae_NK4A136_group. JDK downregulated Interleukin-1β and Interleukin-6 levels systemically and locally, concurrently increasing Interleukin-10, and reduced the expression of fibrosis-related proteins (TGF-β1, COL1A1) in the oral mucosa. CONCLUSIONS: JDK alleviates OSF by normalizing inflammation and fibrosis-related metabolic pathways, linking gut microbiota remodeling to metabolic homeostasis.

Oral green and red propolis attenuate bone resorption and inflammation in experimental apical periodontitis.

da Silva JA, Capalbo LC, Dal-Fabbro R … +5 more , de Oliveira Sales-Junior R, de Moura Pereira B, Ervolino E, Gomes-Filho JE, Cosme-Silva L

Arch Oral Biol · 2026 Feb · PMID 41389736 · Publisher ↗

OBJECTIVE: To test whether systemic green or red propolis modulates inflammation and bone resorption in rat apical periodontitis (AP). DESIGN: Twenty-four male Wistar rats received AP induction in the first mandibular mo... OBJECTIVE: To test whether systemic green or red propolis modulates inflammation and bone resorption in rat apical periodontitis (AP). DESIGN: Twenty-four male Wistar rats received AP induction in the first mandibular molars and were randomized to Control, Green propolis, or Red propolis (n = 8/group). Propolis (100 mg/kg in water) or vehicle was administered daily by gavage for 30 days. On day 30, periapical tissues were evaluated by micro-CT, histology (inflammatory score), and immunohistochemistry for RANKL, OPG, and TRAP-positive osteoclasts. Data were analyzed with Shapiro-Wilk, Kruskal-Wallis/Dunn, or one-way ANOVA/Tukey (α=0.05). RESULTS: Both propolis groups showed significantly less periapical bone resorption than the control group on micro-CT analysis (p < 0.05). Histological evaluation revealed predominantly chronic inflammatory infiltrates, with significantly lower inflammation scores in the propolis-treated groups (p < 0.05). Immunohistochemical analysis demonstrated a significant reduction in RANKL expression, an increase in OPG levels, and fewer TRAP-positive multinucleated cells in both propolis groups compared to the control (p < 0.05). No significant differences were observed between green and red propolis. CONCLUSION: Thirty days of systemic green or red propolis similarly attenuated periapical inflammation and osteoclast-mediated bone resorption in experimental AP, reflected by lower resorption volumes, reduced RANKL/TRAP, and higher OPG, indicating that propolis may serve as a host-modulatory adjunct to preserve periapical bone.

Inhibition of protein kinase C activity enables mineralization of senescent dental follicle cells with almost no osteogenic differentiation potential.

Morsczeck C, Reck A, De Pellegrin M … +1 more , Reichert TE

Arch Oral Biol · 2026 Feb · PMID 41353917 · Publisher ↗

OBJECTIVE: Dental follicle cell lines with a senescence phenotype have a poor differentiation potential into biomineralizing cells. Previous studies have shown that protein kinase C (PKC) and protein kinase B (AKT) regul... OBJECTIVE: Dental follicle cell lines with a senescence phenotype have a poor differentiation potential into biomineralizing cells. Previous studies have shown that protein kinase C (PKC) and protein kinase B (AKT) regulate the differentiation of DFCs. This study investigates the extent to which regulation of PKC and AKT can improve the differentiation of dental follicle cells with poor osteogenic potential. DESIGN: Human senescence dental follicle cells with poor osteogenic differentiation potential were osteogenic differentiated with cell culture media containing dexamethasone or bone morphogenetic protein (BMP) 2 as an inducer. GÖ6976 was used as a PKC inhibitor, and MK-2206 as an AKT inhibitor. The AKT activator SC-79 was also used. Western blot analyses were performed with specific antibodies for the active form of AKT, phosphorylated substrate of PKC and collagen 1. Osteogenic differentiation was quantitatively determined by measuring alkaline phosphatase (ALP) activity and biomineralization using alizarin staining. The gene expression of sclerostin (SOST) and PTHLH was quantitatively determined using real-time RT-PCRs. RESULTS: The results showed that both the inhibitor MK-2206 inhibits AKT and the activator SC-79 can activate AKT in DFCs. Only inhibition of AKT slightly but significantly enhanced osteogenic differentiation. While inhibition of PKC activity apparently only occurred from day 14 of differentiation using the inhibitor GÖ6976, PKC inhibition promoted osteogenic differentiation and inhibits the expression of SOST and Parathyroid hormone-related protein (PTHLH). CONCLUSION: Our results suggest that the addition of GÖ6976 is an efficient method to induce biomineralization in senescent DFCs.

Third-molar agenesis shifts mandibular second-molar mineralisation timeline: An orthopantomographic study in South Indian children.

Chinni SS, Chaitanya NC, Shahnaz W … +3 more , Gangavarapu U, Mungala SR, Balla SB

Arch Oral Biol · 2026 Feb · PMID 41352330 · Publisher ↗

BACKGROUND AND OBJECTIVE: In many jurisdictions, the 14-year threshold is a legally significant factor in determining criminal responsibility and related decisions. We investigated whether third-molar agenesis is associa... BACKGROUND AND OBJECTIVE: In many jurisdictions, the 14-year threshold is a legally significant factor in determining criminal responsibility and related decisions. We investigated whether third-molar agenesis is associated with differences in the mineralisation stage of the mandibular second molar in South Indian children. DESIGN: Orthopantomograms from 570 children (240 males, 330 females; 10-14.99 years) were staged using Demirjian A to H criteria. Descriptive comparisons were supplemented with a proportional-odds ordinal logistic regression, modelling second-molar stage as the ordered outcome, with agenesis extent, age, and sex as predictors. Results are reported as adjusted odds ratios (aORs). RESULTS: Each additional year of age was associated with substantially higher odds of being in a more advanced second-molar stage (aOR 5.41, 95 % CI 4.47-6.56). Males had lower odds than females of being in a higher stage (aOR 0.58, 95 % CI 0.41-0.81). Relative to children with no third-molar agenesis, the odds of being in a higher second-molar stage were progressively lower with greater agenesis: one missing (aOR 0.53, 95 % CI 0.31-0.91), two missing (aOR 0.39, 95 % CI 0.24-0.62), three missing (aOR 0.26, 95 % CI 0.11-0.62), and all four missing (aOR 0.04, 95 % CI 0.02-0.09). CONCLUSION: Third-molar agenesis was associated with less advanced mandibular second-molar stages after accounting for age and sex. Agenesis status and extent may be relevant for the 14-year threshold. Future work should develop and externally validate prediction models that integrate third molar agenesis to improve accuracy and minimise misclassification.

BBI608 induces apoptosis in mucoepidermoid carcinoma cells by targeting a post-transcriptional regulatory mechanisms of myeloid cell leukemia-1.

Choi DI, Kim HJ, Park DG … +3 more , Lee JH, Porntaveetus T, Cho SD

Arch Oral Biol · 2026 Feb · PMID 41352329 · Publisher ↗

OBJECTIVES: BBI608 has demonstrated antitumor activity in several human cancers. However, its efficacy against mucoepidermoid carcinoma (MEC) remains unexplored. This study investigated the antitumor potential of BBI608... OBJECTIVES: BBI608 has demonstrated antitumor activity in several human cancers. However, its efficacy against mucoepidermoid carcinoma (MEC) remains unexplored. This study investigated the antitumor potential of BBI608 in MEC cell lines. DESIGN: The antitumor activity of BBI608 in MC3 and YD-15 mucoepidermoid carcinoma (MEC) cell lines was assessed using trypan blue exclusion, Live/Dead, and sphere formation assays. Apoptotic effects were investigated via western blotting, 4',6-diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) double staining, and reverse transcription-quantitative PCR. RESULTS: BBI608 exhibited growth-inhibitory effects in MEC cell lines, decreasing cell viability and sphere formation capacity while increasing cell death. BBI608-induced apoptosis was confirmed by increased cleaved caspase-3 and PARP expression, nuclear morphological changes characteristic of apoptosis, and increased Annexin V positivity. Furthermore, BBI608 significantly downregulated Mcl-1 expression, which contributed to apoptosis induction in MEC cells. This Mcl-1 downregulation appeared to be mediated by both proteasome-dependent protein degradation and translational regulatory mechanisms in MC3 and YD-15 cells, respectively. CONCLUSION: These findings demonstrate that BBI608 effectively inhibits MEC cell proliferation in vitro by inducing Mcl-1-dependent apoptosis. This suggests BBI608 warrants further investigation as a potential therapeutic agent for MEC.

Retraction notice to "Berberine reduces inflammation of human dental pulp fibroblast via miR-21/KBTBD7 axis" [Archives of Oral Biology 110 (2020) 104630].

Jia S, Qishan W, Jin J … +4 more , Degang S, Fang W, Bingchang X, Qi C

Arch Oral Biol · 2026 Feb · PMID 41344156 · Publisher ↗

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Evaluation of the correlativity of SOX4 and epithelial-mesenchymal transition markers expression in the prognosis of oral squamous cell carcinoma.

Zhao P, Lin X, Cao Y … +8 more , Zhao Z, Zhang X, Zhao Y, Liu S, Hu B, Cao W, Li W, Zhang X

Arch Oral Biol · 2026 Feb · PMID 41330082 · Publisher ↗

OBJECTIVES: To investigate the prognostic significance of Sex-determining region Y-box 4 (SOX4) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, TWIST1) in oral squamous cell carcinoma (OSCC)... OBJECTIVES: To investigate the prognostic significance of Sex-determining region Y-box 4 (SOX4) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, TWIST1) in oral squamous cell carcinoma (OSCC) and to evaluate their functional role. DESIGN: A total of 250 OSCC tissues and 80 normal oral mucosa specimens were analyzed by immunohistochemistry for SOX4, E-cadherin, N-cadherin, and TWIST1 expression. Kaplan-Meier survival curves with log-rank tests, Cox proportional hazards regression (univariate and multivariate), and Spearman correlation were performed to assess prognostic value and clinicopathological associations. Functional validation was conducted by SOX4 knockdown and overexpression in OSCC cell lines, followed by migration, invasion, and EMT marker analyses. RESULTS: High SOX4, N-cadherin, and TWIST1 expression correlated with larger tumor size, lymph node metastasis, advanced clinical stage, and poor differentiation (p < 0.05). SOX4 expression showed positive correlation with N-cadherin and TWIST1, and negative correlation with E-cadherin. Kaplan-Meier analysis demonstrated that high SOX4, N-cadherin, and TWIST1 expression were associated with significantly poorer overall survival. Functional assays confirmed that SOX4 overexpression promoted EMT and cell motility, whereas knockdown reversed these effects. CONCLUSIONS: In summary, our study identified SOX4, N-cadherin, TWIST1, E-cadherin, lymph node metastasis, and clinical staging as independent factors influencing the prognosis of OSCC. SOX4 promotes EMT, thereby influencing the progression and prognosis of OSCC.

Impact of stress on pain sensitization and emotional responses in a rat model of persistent TMJ inflammation.

Mazzi-Chaves JF, Novaes APR, Nascimento GC … +1 more , Leite-Panissi CRA

Arch Oral Biol · 2026 Feb · PMID 41308473 · Publisher ↗

OBJECTIVE: Temporomandibular disorders (TMDs) are frequently associated with psychological distress, including anxiety and depression, which can modulate pain perception and sensitivity. This study investigated the impac... OBJECTIVE: Temporomandibular disorders (TMDs) are frequently associated with psychological distress, including anxiety and depression, which can modulate pain perception and sensitivity. This study investigated the impact of acute and chronic stress on the progression of temporomandibular joint (TMJ) pain, secondary hyperalgesia, and stress-induced affective disturbances. DESIGN: Using a well-established preclinical model, Wistar-Hannover rats underwent persistent TMJ inflammation via intra-articular administration of Freund's complete adjuvant (CFA). Orofacial mechanical allodynia and secondary hyperalgesia were assessed using von Frey test in the orofacial region and hot plate test in the hind paw. To evaluate the influence of stress on affective behaviors, Acute stress (AS), chronic restraint stress (CRS) and Unpredictable chronic stress (UCS) paradigms were implemented, followed by behavioral assessments using the elevated plus maze (EPM), open field (OF), and sucrose preference tests. RESULTS: Results demonstrated that chronic stress exacerbated CFA-induced orofacial allodynia. TMJ inflammation induced secondary hyperalgesia, with AS partially restoring baseline nociception, while UCS amplified central sensitization. Notably, CRS did not influence hind paw nociception in CFA-injected rats. Behavioral analyses revealed that CFA injection heightened anxiety-like behavior by decreased open-arm exploration. Acute stress further intensified anxiety and impaired exploratory activity, whereas chronic stresses significantly worsened both anxiety- and depression-like behaviors. CONCLUSION: These findings underscore the complex interplay between stress and pain processing in TMDs, highlighting the detrimental role of chronic stress in exacerbating pain sensitivity and emotional dysregulation. Understanding these mechanisms could lead to more effective, targeted treatments, improving patient outcomes.

Effects of Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri on oral microbial balance and host cell functions: Implications for the prevention and management of oral diseases.

Zhu Z, Li X, Liu J … +7 more , Chen L, Zhan Y, Wang L, Zhou L, Jiang D, Peng X, Jiang X

Arch Oral Biol · 2026 Feb · PMID 41274116 · Publisher ↗

OBJECTIVES: This study aimed to evaluate the effects of three probiotic samples-Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri-on oral pathogens, commensal bacteria, and host oral cells, there... OBJECTIVES: This study aimed to evaluate the effects of three probiotic samples-Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus reuteri-on oral pathogens, commensal bacteria, and host oral cells, thereby exploring their potential roles in maintaining microbial balance and promoting host defense. DESIGN: Probiotic culture supernatants (postbiotic fractions) were tested against oral pathogens (S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans) and commensal species (S. sanguinis, V. parvula) using optical density assays. Primary human gingival fibroblasts and oral keratinocytes were co-cultured with probiotic preparations to assess cell viability, inflammatory cytokine secretion, and barrier gene expression (FLG, LOR). RESULTS: B. longum, L. rhamnosus, and L. reuteri samples showed strain- and concentration-dependent inhibition of oral pathogens, while exhibiting minimal effects on beneficial commensals. Appropriate concentrations of probiotic samples preserved fibroblast viability and enhanced keratinocyte survival. Notably, B. longum, L. rhamnosus, and L. reuteri upregulated barrier-associated genes (FLG, LOR) and suppressed IL-6 secretion in inflamed keratinocytes, suggesting immunomodulatory and protective roles. CONCLUSIONS: Probiotic-derived metabolites exert selective antimicrobial and cytoprotective effects in the oral microenvironment. These findings support the dual functions of probiotics in reshaping oral microbial balance and modulating host cell functions and highlight the potential for personalized probiotic strategies in oral disease prevention and management.Further exploration of combined probiotic formulations is warranted to optimize clinical translation.

Optimization and evaluation of antibacterial extracts from Acacia nilotica, Psidium guajava, Syzygium aromaticum, and Salvadora persica to inhibit dental caries.

Kandasamy C, Baladhandapani A, Ponnuswamy RD … +3 more , Eswaran H, Karthikeyan V, Rajendran S

Arch Oral Biol · 2026 Jan · PMID 41270298 · Publisher ↗

OBJECTIVE: Dental caries is a significant global issue, which affects approximately 44 % of the global population. The objective of this research is to extract crude phytochemicals from Psidium guajava, Acacia nilotica,... OBJECTIVE: Dental caries is a significant global issue, which affects approximately 44 % of the global population. The objective of this research is to extract crude phytochemicals from Psidium guajava, Acacia nilotica, Syzygium aromaticum, and Salvadora persica and also optimizing using RSM. Therefore, this aims to maximize the antibacterial potential of the extracts at effective inhibition of dental caries METHOD: The crude extracts from the plants samples, with varying extraction parameters, such as ethanol concentrations, temperatures, and solid-solvent ratios was done using Soxhlet method and antibacterial activity was determined through well and disc diffusion methods along with optimization was performed by Response Surface Methodology (RSM). RESULTS: The results depict that Psidium guajava exhibited the strongest antibacterial activity against S. mutans and Lactobacillus, with inhibition zones of 36 mm & 20 mm and 32 mm & 24 mm for both well and disc diffusion. Similarly, Syzygium aromaticum also shows slight stronger inhibition zones, Acacia nilotica exhibited moderate activity and in contrast, Salvadora persica showed limited activity. RSM optimization was validated and with well fitted quadratic models R² values ranging from 0.69 to 0.79. Predicted and experimental values are in close agreement between with differences below 0.5 %. CONCLUSION: These findings suggest that P. guajava, S. aromaticum and A. nilotica have strong potential as natural antibacterial agents in oral care formulations.

Is there geometric morphometric evidence for the selection against impaction? A comparative cross-sectional study of specific tooth-agenesis patterns.

Boussali S, Cavaré A

Arch Oral Biol · 2026 Feb · PMID 41265154 · Publisher ↗

OBJECTIVES: Reductions in tooth number and facial prognathism may reflect shared genetic and evolutionary mechanisms but have been inconsistently reported by traditional cephalometric analyses. This study aimed to assess... OBJECTIVES: Reductions in tooth number and facial prognathism may reflect shared genetic and evolutionary mechanisms but have been inconsistently reported by traditional cephalometric analyses. This study aimed to assess whether common patterns of dental agenesis are associated with craniofacial morphology using geometric morphometric methods. DESIGN: This retrospective comparative cross-sectional study included 538 patients aged 10-19 years from a French orthodontic population. Individuals with hypodontia (n = 269), restricted to third molars, maxillary lateral incisors, or second premolars, were matched by age and sex with controls without agenesis (n = 269). Craniofacial morphology was assessed on lateral cephalograms using 18 landmarks and 87 semilandmarks. Multiple linear regression and Procrustes MANOVA were applied to evaluate differences in size and shape, adjusting for sex and age. RESULTS: No significant association was found between agenesis status and craniofacial size in the overall configuration as well as in the cranial base, maxilla, and mandible. A significant sex effect was detected in the mandible, with smaller centroid size in males (p = 0.012). Multivariate regression on shape confirmed allometric effects across all configurations. Procrustes MANOVA detected a significant effect of sex on overall shape (p = 0.003), but neither age nor hypodontia reached significance. CONCLUSION: In this large geometric morphometric study, no generalized or localized alterations in craniofacial morphology were detected, even in third molar agenesis, suggesting that the anthropological significance of hypodontia should be regarded with caution.

Immunohistochemical analysis of immune checkpoint proteins (PD-1, PD-L1 and PD-L2) in giant cell granulomas of the jaws and giant cell tumor of bone.

Barros EF, de Medeiros VA, da Silveira ÉJD … +3 more , Goulart Filho JAV, Alves PM, Nonaka CFW

Arch Oral Biol · 2026 Feb · PMID 41265153 · Publisher ↗

OBJECTIVE: To evaluate the immunoexpression of programmed cell death protein 1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) in giant cell granulomas of the jaws (central giant cell granuloma [CGCG], p... OBJECTIVE: To evaluate the immunoexpression of programmed cell death protein 1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) in giant cell granulomas of the jaws (central giant cell granuloma [CGCG], peripheral giant cell granuloma [PGCG]) and giant cell tumor of bone (GCTB). DESIGN: Thirty CGCG (15 non-aggressive and 15 aggressive), 15 PGCG, and 15 GCTB were selected. The percentages of cytoplasmic (PD-1, PD-L1, and PD-L2) and nuclear (PD-L1) staining in mononuclear cells (MC) and in non-cannibalistic (ncMGC) and cannibalistic MGC (cMGC) were determined. RESULTS: Cytoplasmic expression of PD-1 and PD-L1 was observed in all groups, with high median percentages of positivity in ncMGC and cMGC. Compared to CGCG and PGCG, GCTB exhibited higher expression of PD-L1 in MC (p < 0.05). In ncMGC, expression of PD-1 was higher in GCTB compared to non-aggressive CGCG (p < 0.05). Similarly, higher PD-L1 immunopositivity was found in ncMGC of GCTB compared to aggressive CGCG and PGCG (p < 0.05). For all cell types, lower median percentages of PD-L2 positivity were observed in GCTB compared to CGCG and PGCG (p > 0.05). In GCTB, there was a strong positive correlation between the cytoplasmic expression of PD-L1 in MC and PD-1 in ncMGC (r = 0.535; p < 0.05). All groups exhibited low nuclear immunoexpression of PD-L1. CONCLUSION: The results suggest the potential participation of PD-1, PD-L1, and PD-L2 in the pathogenesis of CGCG, PGCG, and GCTB. The locally aggressive behavior of GCTB could be associated with a higher osteoclastogenic and immunosuppressive microenvironment in these neoplasms.

Tetramethoxyluteolin, an active constituent in mulberry leaves, promotes osteogenesis of jaw bone marrow mesenchymal stem cells in periodontitis microenvironment via NF-κB inhibition.

Xia Y, Shan C, Wu Z … +1 more , Zhao J

Arch Oral Biol · 2026 Feb · PMID 41265152 · Publisher ↗

OBJECTIVE: This study aims to investigate the effects and mechanisms of tetramethoxyluteolin (TML), a bioactive compound in mulberry leaves, on jaw bone marrow mesenchymal stem cells (JBMMSCs) in a periodontitis microenv... OBJECTIVE: This study aims to investigate the effects and mechanisms of tetramethoxyluteolin (TML), a bioactive compound in mulberry leaves, on jaw bone marrow mesenchymal stem cells (JBMMSCs) in a periodontitis microenvironment. DESIGN: Network pharmacology and molecular docking were used to identify mulberry leaves' active constituents and their targets in periodontitis treatment. An inflammatory model was established in JBMMSCs using Porphyromonas gingivalis-lipopolysaccharide (5 μg/mL). TML's optimal concentration was determined via CCK-8 and ELISA. Osteogenic differentiation, inflammatory markers, and NF-κB pathway activity were assessed using ALP/ARS staining, RT-PCR, and Western blot (WB). A rat model of ligature-induced periodontitis was established, and TML's effects were evaluated through histopathological staining, micro-CT, RT-PCR, and WB. JBMMSCs from each animal experimental group were isolated for in vitro osteogenic validation. Mechanisms were clarified by comparing TML with the NF-κB inhibitor BAY11-7082. RESULTS: TML was identified as the key constituent targeting NF-κB and inflammatory mediators (IL-6, IL-1β, TNF-α). 5 μM TML significantly suppressed inflammatory cytokines, promoted osteogenic differentiation, and inhibited NF-κB activation in JBMMSCs. In rats, 30 mg/kg TML markedly reduced inflammation and alveolar bone loss, showing efficacy comparable to indomethacin, and JBMMSCs from TML-treated groups exhibited enhanced osteogenesis. TML's inhibition of NF-κB was similar to BAY11-7082. CONCLUSION: TML reduces periodontal inflammation and enhances the osteogenic potential of JBMMSCs by inhibiting the NF-κB pathway, providing a novel strategy for periodontitis-related bone regeneration.

Growing new teeth: A systematic review of functional whole-tooth regeneration in orthotopic animal models.

Wu PJ, Jovani-Sancho M

Arch Oral Biol · 2026 Feb · PMID 41265151 · Publisher ↗

OBJECTIVE: To identify and evaluate current strategies for functional whole-tooth regeneration in orthotopic animal models with high translational potential. DESIGN: A systematic review of in vivo studies involving ortho... OBJECTIVE: To identify and evaluate current strategies for functional whole-tooth regeneration in orthotopic animal models with high translational potential. DESIGN: A systematic review of in vivo studies involving orthotopic implantation of generated tooth constructs, analyzing experimental design, cell sources, scaffolding materials, implantation techniques, and outcome measures including histological, radiological, and functional evaluations. RESULTS: Considerable heterogeneity was observed in animal models, developmental stages at implantation, and cellular components. Polycaprolactone (PCL) membranes were often associated with improved eruption and reduced ankylosis, suggesting enhanced periodontal integration. CONCLUSIONS: PCL-based scaffolding systems may facilitate functional tooth regeneration, but further standardized in vivo research is needed to validate translational potential.

In vivo immunological evaluation of indomethacin and omega-3 nanocapsules for the treatment of rheumatoid arthritis in the temporomandibular joints of rats.

Dos Santos VAB, Groppo FC, Barbin T … +4 more , Sartoratto A, Ferreira LEN, Monteiro MHA, Figueroba SR

Arch Oral Biol · 2026 Feb · PMID 41240686 · Publisher ↗

OBJECTIVE: This study aimed to develop and characterize indomethacin nanocapsules with an omega-3 oily core and evaluate their potential for treating rheumatoid arthritis in rats, comparing their effects to free-form adm... OBJECTIVE: This study aimed to develop and characterize indomethacin nanocapsules with an omega-3 oily core and evaluate their potential for treating rheumatoid arthritis in rats, comparing their effects to free-form administration on cytokines IL-1β, IL-10, IL-6, and TNF-α in temporomandibular joint. DESIGN: Nanocapsules were synthesized with omega-3 as the oil phase containing indomethacin. They were characterized for mean hydrodynamic diameter, polydispersity index, zeta potential, morphology (TEM), encapsulation efficiency (HPLC), and cytotoxicity in RAW 264.7 macrophages (MTT assay). For in vivo evaluation, forty-eight adult male Wistar rats (n = 6) underwent rheumatoid arthritis induction via intradermal injection of Complete Freund's Adjuvant (CFA) and bovine type II collagen (CII) at the base of the tail. Rats were treated for 7 days by oral gavage with either nanocapsules (NC5, NC2.5), free indomethacin (IND5, IND2.5), or indomethacin combined with omega-3 (IND5 +ω3, IND2.5 +ω3). Cytokine levels in the temporomandibular joint were subsequently assessed. RESULTS: Nanocapsules displayed a spherical, well-defined morphology with diameters < 250 nm and exhibited lower cytotoxicity in RAW 264.7 cells compared to free-form treatments. In vivo, all treated groups showed significant reductions in IL-1β, IL-6, and TNF-α compared to the CFA group, along with a significant increase in IL-10. CONCLUSIONS: Indomethacin nanocapsules with omega-3 effectively reduced pro-inflammatory cytokines and increased anti-inflammatory IL-10, demonstrating a superior immunomodulatory profile compared to free-form treatments.
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