OBJECTIVE: To investigate the temporal evolution and predictive value of individual histopathological features of oral epithelial dysplasia (OED) during carcinogenesis, and to evaluate the diagnostic utility of optical f...OBJECTIVE: To investigate the temporal evolution and predictive value of individual histopathological features of oral epithelial dysplasia (OED) during carcinogenesis, and to evaluate the diagnostic utility of optical fluorescence imaging in a murine model. DESIGN: A 4-nitroquinoline 1-oxide (4NQO) mouse model was used to induce oral squamous cell carcinoma (OSCC). Histological evaluation of 20 architectural and cytological OED features was performed at seven time points over 24 weeks. Data were analyzed using descriptive statistics, Spearman's correlation, logistic regression, and principal component analysis (PCA). A random forest model was developed to classify malignant transformation and evaluated using F1-score, cross-validation, ROC, and precision-recall curves. Optical fluorescence imaging was assessed for early lesion detection. RESULTS: Cumulative feature burden, particularly involving loss of stratification, reverse polarity, nuclear atypia, and mitotic activity, was more predictive of transformation than any single feature. PCA revealed two major axes-structural disorganization and proliferative instability. The random forest model achieved high predictive performance (F1 = 0.88, ROC-AUC = 0.97, PR-AUC = 0.98). Autofluorescence failed to improve early detection. CONCLUSION: Feature accumulation is a robust predictor of OSCC risk in dysplastic lesions. Histological quantification combined with machine learning offers potential for improved prognostic modeling in oral precancer.
OBJECTIVES: Hyperlipidemia is associated with dental peri-implantitis. Long-term success of dental implant relies on good peri-implant soft tissue barrier. This study aims to investigate the effect of high-lipid environm...OBJECTIVES: Hyperlipidemia is associated with dental peri-implantitis. Long-term success of dental implant relies on good peri-implant soft tissue barrier. This study aims to investigate the effect of high-lipid environment on biological activities of gingival fibroblast on titanium surface so as to explore the effect of hyperlipidemia on peri-implant soft tissue. DESIGN: Human gingival fibroblast-1(HGF-1) was seeded on the titanium surfaces and cultured in normal and high-lipid culture medium for 4 days. Cell adhesion and proliferation were assessed by cell counting and morphological observation following fluorescent staining. RNA sequencing were performed afterwards, followed by differentially expressed genes analysis, several enrichment analyses and Protein-Protein Interaction (PPI) analysis. RESULTS: The number of HGF-1 cells significantly decreased and the morphology of HGF-1 changed in high-lipid culture environment. Moreover, the expression levels of several hub genes, including Interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), and Activating Transcription Factor 3 (ATF3), as well as the activity of pathways such as the IL-17 signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway, were elevated. Meanwhile, the down-regulation of cell proliferation activities, like DNA replication and cell division was also observed. CONCLUSIONS: High-lipid environment impaired the adhesion and proliferation of HGF-1 on titanium surface, which may be associated with the upregulation of specific genes and pathways, alongside the downregulation of cell proliferation-related activities.
OBJECTIVE: This study aimed to investigate the effect of M2-exos on osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs) and the underlying mechanism. DESIGN: Exosomes were isolated from M2-polar...OBJECTIVE: This study aimed to investigate the effect of M2-exos on osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs) and the underlying mechanism. DESIGN: Exosomes were isolated from M2-polarized RAW 264.7 macrophages and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. hPDLSCs were treated with M2-exos, and osteogenic differentiation was assessed using alkaline phosphatase and Alizarin Red S staining, along with reverse transcription-quantitative polymerase chain reaction analysis of osteogenic markers. Inflammation-related cytokines were measured by enzyme-linked immunosorbent assay. Bioinformatics analysis identified miR-494-3p as a key miRNA in M2-exos, and its interaction with calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was validated by RNA pull-down and dual luciferase reporter assays. Functional experiments were performed using a miR-494-3p inhibitor and CAMK2D knockdown in hPDLSCs. RESULTS: M2-exos exhibited typical exosomal characteristics and were internalized by hPDLSCs. Additionally, M2-exos suppressed inflammation and enhanced osteogenic differentiation. Mechanistically, miR-494-3p was highly enriched in M2-exos and directly targeted CAMK2D. Moreover, inhibition of miR-494-3p exacerbated inflammation and impaired osteogenesis, while CAMK2D knockdown reversed these effects, restoring osteogenic potential. CONCLUSIONS: RAW 264.7-derived exosomes inhibited inflammation and promoted osteogenic differentiation in hPDLSCs, a process that involves, at least in part, the delivery of miR-494-3p. These findings highlight a novel mechanism and the therapeutic potential of targeting the miR-494-3p/CAMK2D axis in periodontal bone regeneration.
OBJECTIVE: The study aims to systematically examine the accuracy of the application of different dental age estimation (DAE) methods on children with chromosomal syndromes and evaluate its performance based on various po...OBJECTIVE: The study aims to systematically examine the accuracy of the application of different dental age estimation (DAE) methods on children with chromosomal syndromes and evaluate its performance based on various populations and regions. DESIGN: A systematic search of the literature applying the PRISMA-NMA-compliant method was conducted using the databases PubMed, Web of Science, Science Direct, Google Scholar, and Scopus between 1981 and 2020; that estimate dental development of children with chromosomal syndrome based on populations, intervention, comparisons, and outcomes (PICO) search strategy identified. The literature quality was assessed using QUADAS-2. A network meta-analysis was performed to compare the effects of different chromosomal syndromes on the accuracy of estimated dental age (DA). Mean differences were calculated for difference of DA to chronological age (CA) by using the random effects model. RESULTS: From 60 titles retrieved utilising a standardized search strategy, 45 titles met the qualitative analysis criteria, and 28 titles qualified for the quantitative analysis requirements. Twenty-four comparative studies and twenty-one non-comparative studies suggested five DAE methods within this population used in combination or alone, namely Demirjian, Willems, Nolla, Haavikkoo, and London Atlas. Down's syndrome is the highest contributing literature relating to DAE and chromosomal syndrome. CONCLUSIONS: Underestimations were seen in Amelogenesis Imperfecta and Osteogenesis Imperfecta for Demirjian method. Other methods were lacking primary studies to make a reliable inference. This suggests that no single dental age estimation (DAE) method works consistently across diverse syndromes, emphasizing the importance of personalized approaches in clinical and forensic settings. Publication bias was minor, indicating solid findings.
OBJECTIVE: Oral candidiasis is a common opportunistic infection caused by Candida albicans, particularly in individuals with local or systemic risk factors. This study aimed to investigate how antifungal therapy affects...OBJECTIVE: Oral candidiasis is a common opportunistic infection caused by Candida albicans, particularly in individuals with local or systemic risk factors. This study aimed to investigate how antifungal therapy affects the composition of the oral bacterial microbiome. DESIGN: Unstimulated saliva samples were collected from ten patients diagnosed with acute pseudomembranous oral candidiasis before and after fluconazole treatment. Microbiome profiles were assessed using 16S rRNA gene sequencing. Quantitative PCR was performed to validate changes in specific bacterial species. RESULTS: Alpha diversity did not change significantly, whereas beta-diversity analyses indicated modest compositional shifts. Antifungal therapy was associated with an increase in Streptococcus salivarius, a commensal linked to mucosal health. The signal was confirmed by species-specific qPCR in paired samples. CONCLUSIONS: Fluconazole treatment for oral candidiasis induces modest shifts in the oral bacterial community, particularly increasing the abundance of S. salivarius. These changes may reflect partial recovery of microbial homeostasis, supporting the role of microbiome monitoring and probiotic approaches in post-treatment care.
OBJECTIVE: Using finite element analysis (FEA), this study aims to investigate the impact of different tooth root morphologies and implant designs, including a standard implant and a custom root-analogue implant on stres...OBJECTIVE: Using finite element analysis (FEA), this study aims to investigate the impact of different tooth root morphologies and implant designs, including a standard implant and a custom root-analogue implant on stress and strain distribution across the mandible. DESIGN: Six models were created by varying the root morphology of one tooth (the mandibular first molar) under identical loading scenarios: an original molar root, an incisor root, a canine root, a taurodont root, a standard implant, and a custom root-analogue implant replicating the original root morphology. RESULTS: Models with the original molar and custom implant exhibited similar stress and strain distributions over the mandible and had higher principal strains (tensile and compressive) compared to the single-rooted and standard implant models. Specifically, the maximum tensile and compressive strain values in the mandible of the custom implant model reach 94.89 % and 99.15 % of those in the original tooth root model. In contrast, the other models show less than 55.68 % similarity. CONCLUSIONS: Custom root-analogue implants, which mimic natural root morphology, demonstrated more favourable stress distribution patterns, similar to those of the natural molar, compared to single-root implants. Our findings suggest that multi-rooted teeth are biomechanically optimized for dissipating masticatory loads, and standard single-root implants may not adequately replicate these properties, leading to poor load distribution and increased failure risk in posterior locations. Further research is needed to refine custom root-analogue implant designs and optimize their clinical application to better match the natural biomechanical environment of the maxilla and mandible.
OBJECTIVE: This study aimed to ascertain the significance of microRNA-34b-3p (miR-34b-3p) in the prognosis and tumor angiogenesis associated with the development of oral squamous cell carcinoma (OSCC). DESIGN: The relati...OBJECTIVE: This study aimed to ascertain the significance of microRNA-34b-3p (miR-34b-3p) in the prognosis and tumor angiogenesis associated with the development of oral squamous cell carcinoma (OSCC). DESIGN: The relative abundances of miR-34b-3p and tumor angiogenesis-associated genes were quantified using quantitative real-time polymerase chain reaction. Cellular events were monitored using the Cell Counting Kit-8 and Transwell assays. Additionally, a luciferase reporter assay was carried out to verify the interaction between miR-34b-3p and Sex Determining Region Y-box Protein 5 (SOX5). RESULTS: MiR-34b-3p was significantly decreased in tissue samples from OSCC patients in comparison to healthy individuals (P < 0.001) and displayed a robust diagnostic accuracy in distinguishing OSCC patients from healthy controls. Moreover, OSCC patients expressing low miR-34b-3p levels displayed a short overall survival time (P = 0.002). Additionally, low miR-34b-3p expression was an independent predictor for the clinical outcome of OSCC patients (P = 0.011, HR=0.447, 95 %CI=0.239-0.834). Through biological experiments, downregulation of miR-34b-3p could promote cell proliferation, migration and invasion of OSCC cells. Notably, following transfection miR-34b-3p inhibitor, VEGFA and MMP9 mRNA expressions were dramatically enhanced (P < 0.001). SOX5 was identified as a potential target of miR-34b-3p. Recovery experiments verified that the knockdown of SOX5 counteracted the impacts of miR-34b-3p on cellular activities and angiogenesis. CONCLUSIONS: Downregulated miR-34b-3p expression promoted OSCC progression by enhancing cellular activities and upregulating the expression of pro-angiogenic factors via targeting SOX5.
AIM: The aim of this study was to assess the dose-dependent effects of radiotherapy on the progression of apical periodontitis (AP) in rats. METHODS: Forty-five animals were divided into five groups based on radiation do...AIM: The aim of this study was to assess the dose-dependent effects of radiotherapy on the progression of apical periodontitis (AP) in rats. METHODS: Forty-five animals were divided into five groups based on radiation dose and apical periodontitis induction (n = 9): AP-RT7 (irradiated with a dose of 7.5 Gy + AP); AP-RT10 (10 Gy dose + AP); AP-RT15 (15 Gy dose + AP); AP (AP without radiation), and Control (no intervention). Radiation therapy was administered on the first day of the experiment. After seven days, the apical periodontitis induction was carried out in all groups except Control. All animals were euthanized after 21 days of AP progression (day 28), and the area and volume of AP were analyzed using radiography, micro-CT, and histological analyses. Inflammation intensity and extent were assessed histologically. Statistical analysis was performed using ANOVA and Student's t test for quantitative data, and Kruskal-Wallis for ordinal data (P < 0.05). RESULTS: The AP-RT15 group exhibited significantly larger apical periodontitis lesions compared to the AP-RT7.5, AP-RT10, and AP groups, as demonstrated by radiographic (p < 0.05), micro-CT (p < 0.0001), and histological analyses (p < 0.0001). Histological examination further revealed a more extensive and intense inflammatory response in the AP-RT15 group (p < 0.01). Overall, radiotherapy contributed to increased apical bone resorption and exacerbated inflammation in a dose-dependent manner. CONCLUSIONS: The progression of apical periodontitis in irradiated animals follows a dose-dependent pattern, with higher radiation doses markedly amplifying the lesion's area, volume, and inflammatory severity.
OBJECTIVE: Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndromic tooth agenesis, yet their influence on non-syndromic tooth agenesis (NSTA) has not been thoroughly elucidated. This study aim...OBJECTIVE: Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndromic tooth agenesis, yet their influence on non-syndromic tooth agenesis (NSTA) has not been thoroughly elucidated. This study aimed to investigate the genetic basis of NSTA and to identify pathogenic EDA mutations in two Chinese families using whole-exome sequencing, and explore the underlying mechanisms involved. DESIGN: Two unrelated individuals with NSTA and their families were enrolled in this study, and genomic DNA was extracted from peripheral blood samples. Whole-exome sequencing was performed, followed by variants detection and filtering to identify pathogenic genes and mutations. The identified genetic mutations were further validated by Sanger sequencing and confirmed to be absent in 300 unrelated healthy individuals. Conservation analysis, three-dimensional (3D) modeling, and electrostatic potential calculations were conducted accordingly. RESULTS: We identified a novel mutation c.827 G>T (p.Arg276Leu) and a previously reported mutation c.1069 C>T (p.Arg357Trp) in the EDA gene, with the latter showing previously unreported phenotypic characteristics. Both mutations are located in the tumor necrosis factor (TNF) domain of EDA, which is crucial for binding with ectodysplasin A receptor (EDAR). Conservation analysis indicated that these mutations are evolutionarily conserved across various species. In silico predictions and 3D modeling analyses suggested that these mutations may be pathogenic, potentially due to alterations in the hydrogen bonding and electrostatic potential, thereby affecting EDA-EDAR interaction. CONCLUSIONS: Our findings broaden the mutation spectrum of EDA gene associated with NSTA by identifying a novel mutation and provide a basis for future genetic counseling.
OBJECTIVE: This study aimed to investigate the effect of the periodontal bacterium Filifactor alocis on proinflammatory cytokine production by osteoblasts. Specifically, we examined the mechanisms underlying interleukin...OBJECTIVE: This study aimed to investigate the effect of the periodontal bacterium Filifactor alocis on proinflammatory cytokine production by osteoblasts. Specifically, we examined the mechanisms underlying interleukin (IL)-6 production by osteoblasts stimulated with live and lyophilized F. alocis, and F. alocis-derived extracellular vesicles (EVs). DESIGN: MC3T3-E1 mouse osteoblasts were stimulated with live bacteria of F. alocis and, as a comparative control, P. gingivalis. Furthermore, cells were treated with F. alocis lyophilized whole cells or EVs, and IL-6 production was quantified by ELISA; cytokine expression profiled using membrane-based array; and mRNA expression analyzed by RT-qPCR. Signaling pathways were analyzed using specific inhibitors. Statistical analyses were performed using non-parametric tests with significance set at p < 0.05. RESULTS: F. alocis live bacteria, lyophilized whole cells, and F. alocis-derived EVs induced IL-6, leukemia inhibitory factor, and chemokines in MC3T3-E1 cells. Mechanistically, IL-6 production by F. alocis involved osteoblast activation via Toll-like receptor (TLR) 2 on the bacterial surface or released EVs. Lyophilized F. alocis induced IκB-ζ mRNA expression in osteoblasts. Moreover, F. alocis-derived EVs induced IL-6 production in osteoblasts via protein kinase C (PKC). CONCLUSIONS: Live and lyophilized F. alocis and F. alocis-derived EVs induce the production of proinflammatory cytokines by osteoblasts, including IL-6. Additionally, the induction of IL-6 by F. alocis-derived EVs involves the activation of TLR2 and PKC. Conclusively, these findings suggest that F. alocis-induced cytokine production by osteoblasts may induce osteoclast differentiation, highlighting its role in the pathogenesis of periodontitis.
OBJECTIVE: Oral squamous cell carcinoma (OSCC) has a poor prognosis and high mortality. This study aims to investigate the potential molecular mechanisms of NFIC/DEPTOR/mTOR signaling in glycolysis and tumor immune escap...OBJECTIVE: Oral squamous cell carcinoma (OSCC) has a poor prognosis and high mortality. This study aims to investigate the potential molecular mechanisms of NFIC/DEPTOR/mTOR signaling in glycolysis and tumor immune escape in OSCC. DESIGN: In vitro, the effects of the NFIC/DEPTOR/mTOR axis on the proliferative capacity and apoptosis of HN30 and SCC-25 cells were investigated using colony formation assays, EdU staining, and TUNEL after lentiviral gene interference. The glycolytic activity of OSCC cells was analyzed through glucose uptake, ECAR, and lactate production. CD8 T cells were co-cultured with OSCC cells to analyze the cytotoxic activity of CD8 T cells. SCC-25 cells with different genetic interventions were injected subcutaneously into NOG mice to investigate the effects of NFIC/DEPTOR/mTOR on subcutaneous tumor growth, tumor microenvironment (TME) acidity, and CD8 T cell infiltration and activity. ChIP-qPCR and dual-luciferase assays were used to investigate the regulatory relationship between NFIC and the DEPTOR promoter in OSCC cells. RESULTS: NFIC and DEPTOR were significantly downregulated in OSCC cells and tissues, accompanied by enhanced mTOR signaling. NFIC activated DEPTOR by binding to its promoter. Overexpression of either NFIC or DEPTOR significantly inhibited OSCC cell proliferation, glycolytic activity, and enhanced CD8 T cell killing capacity. Similarly, they inhibited tumor growth in vivo, blocked TME acidification, and weakened tumor immune escape. Combined DEPTOR knockdown rescued the malignant progression of OSCC inhibited by NFIC overexpression. CONCLUSION: NFIC mediates DEPTOR transcription to repress mTOR signaling, thereby hindering OSCC progression by suppressing cell proliferation, glycolytic activity, and CD8 T cell-related immune escape.
OBJECTIVE: This study examines the impact of Pudilan mouthwash in conjunction with the smc gene of Streptococcus mutans (S. mutans) on biofilm formation. DESIGN: We constructed the smc gene null mutant strains of S. muta...OBJECTIVE: This study examines the impact of Pudilan mouthwash in conjunction with the smc gene of Streptococcus mutans (S. mutans) on biofilm formation. DESIGN: We constructed the smc gene null mutant strains of S. mutans (Δsmc) via homologous recombination, and overexpression strains (smc^OE) and complementary strains (smc^Comp) through chemical transformation of smc recombinant plasmid. We then tested Pudilan's MIC and MBC on UA159 parent strains and smc mutants. Growth curves were used to analyze growth rates. Bacterial viability was assessed with Live/Dead Staining. Biofilm formation and structure were examined using crystal violet staining, confocal laser scanning microscopy, and scanning electron microscopy. Genes involved in exopolysaccharides (EPS) metabolism were quantified by qRT-PCR. Network pharmacology built a compound-target network, and molecular docking studied interactions between Pudilan's components and S. mutans proteins. RESULTS: The combination of Pudilan and knockout of smc gene exhibited a synergistic antibacterial effect on S. mutans. Results indicated that this pairing effectively inhibited the growth and viability of S. mutans, reduced biofilm biomass, and rearranged the structure of 8-hour and 24-hour biofilms. Additionally, Pudilan treatment downregulated gene expression related to water-soluble glucan in Δsmc. Compounds like (S)-cheilanthifoline in Pudilan may significantly influence dental plaque development by modulating GtfD activity. CONCLUSIONS: This finding demonstrates that Pudilan enhances the inhibitory effect caused by smc deletion on S. mutans growth and viability, reduces biofilm EPS, and downregulates the expression of genes involved in water-soluble glucan synthesis.
OBJECTIVES: To compare gingival crevicular fluid (GCF) levels of soluble Triggering Receptor Expressed on Myeloid cells 1 (sTREM-1) between patients with chronic periodontitis (CP) and those with healthy periodontal (HP)...OBJECTIVES: To compare gingival crevicular fluid (GCF) levels of soluble Triggering Receptor Expressed on Myeloid cells 1 (sTREM-1) between patients with chronic periodontitis (CP) and those with healthy periodontal (HP) status, and evaluate its predictive value for periodontal disease progression. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, MEDLINE, Cochrane, Web of Science, EMBASE, CNKI, and Wanfang were searched through December 2024. Manual searches were performed. ELIGIBILITY CRITERIA: Only studies reporting GCF sTREM-1 CP patients and HP controls were included. Clinical trials, cross-sectional, and observational studies were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the quality. Sensitivity analyses ensured result stability. Quality assessment was performed according to the Newcastle-Ottawa Scale. Random-effects model calculated standardized mean differences (SMD)with 95 % CI via Review Manager software. Publication bias was evaluated using funnel plots and Egger's tests. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: Among 128 screened studies, 9 articles met eligibility criteria of the systematic review, and 6 articles (147 CP patients, 116 HP controls) were included in the meta-analysis. GCF sTREM-1 levels were higher in the CP group than HP group (SMD = 0.70; Z = 3.25; P<0.001, 95 % CI). CONCLUSIONS: This study found higher GCF sTREM-1 levels in CP patients compared to HP controls, suggesting potential as a diagnostic marker. However, small sample sizes and methodological variability limit the findings. PROSPERO REGISTRATION NUMBER: CRD42022326022.
OBJECTIVE: To conduct exploratory bioinformatics analyses of the potential prognostic value of DNA methylation patterns in MIR375 regulatory regions and of expression levels of its encoded microRNA, hsa‑miR‑375 (miR-375)...OBJECTIVE: To conduct exploratory bioinformatics analyses of the potential prognostic value of DNA methylation patterns in MIR375 regulatory regions and of expression levels of its encoded microRNA, hsa‑miR‑375 (miR-375), in head and neck squamous cell carcinoma (HNSCC). DESIGN: Data from 490 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA), 50 of which were paired non-tumor surgical margins. Clinicopathological data, DNA methylation data from regions associated with MIR375, and miR-375 expression data were analyzed. Kaplan-Meier curves and Cox regression analyses were used to determine overall survival (OS) and disease-free survival (DFS) at 5 years in each group. RESULTS: Differentially methylated regions were associated with miR-375 expression in HNSCC. Specially, hypermethylation in N shore region was independently associated with poor OS and DFS. After adjusting for methylation patterns in other regions and miR-375 expression, these associations remained significant. DFS was also associated with methylation patterns in the enhancer region. After adjusting for confounding factors (the most robust model), hypermethylation in the N shore region was found to be an unfavorable predictor of OS and DFS. Clinicopathological and lifestyle factors also influenced the OS and DFS rates. CONCLUSIONS: Methylation in DNA regions that may influence MIR375 transcription can be considered as predictors of OS and DFS in HNSCC, particularly those in the N shore region. This region should be a target for future investigations into MIR375 methylation pattern and its role in modulating miR-375 expression in HNSCC.
OBJECTIVE: Progesterone (PG) is a sex steroid hormone that has the potential to control bone loss in periodontitis. This study aimed to reveal the underlying mechanisms of action of PG on osteogenesis in periodontitis an...OBJECTIVE: Progesterone (PG) is a sex steroid hormone that has the potential to control bone loss in periodontitis. This study aimed to reveal the underlying mechanisms of action of PG on osteogenesis in periodontitis and to identify key target genes in vitro. DESIGN: Primary human periodontal mesenchymal stem cells (hPDLSCs) were isolated and treated with lipopolysaccharide (LPS) in combination with or without PG. Subsequently, RNA sequencing was performed after osteogenic induction, and the differential expressed genes (DEGs), functional enrichment (GO and KEGG), and protein-protein interaction (PPI) were bioinformatically analysed. The expression of two key DEGs, BUB1 and UBE2C, were verified by qRT-PCR. Relevant regulatory mechanisms involving osteogenesis were verified by detecting the levels of osteogenesis-related proteins, Runx2 and ALP (Western blot) after silencing. RESULTS: A total of 212 DEGs (104 up-regulated and 108 down-regulated genes) were identified between the LPS and LPS + PG groups. These DEGs were mainly enriched in the GO terms of cell division, adhesion, sodium/potassium channel, etc., and in the KEGG terms of oocyte meiosis, estrogen signalling, cell apoptosis, and adhesion. In the PPI networks, most of the hub proteins are related to cell cycle and division. Of note, BUB1 and UBE2C, two node genes, were down-regulated in LPS-treated hPDLSCs. The intervention of PG significantly eliminated the effects of LPS on the down-regulation of BUB1 and UBE2C. Upon LPS treatment, silencing of BUB1 and UBE2C both reversed the PG-induced osteogenesis in hPDLSCs. CONCLUSIONS: BUB1 and UBE2C, two important mediators of osteogenesis, are potential molecular targets of PG. PG may promote the osteogenesis of hPDLSCs under inflammatory conditions through the up-regulation of BUB1 and UBE2C, suggesting a potential mechanism that may contribute to the remission of periodontitis.
OBJECTIVE: The study aimed to investigate the cytotoxic and anti-inflammatory potential of the methanolic stem bark extract of Elaeodendron buchananii (EB) through in vitro assays and LC-MS based phytochemical profiling....OBJECTIVE: The study aimed to investigate the cytotoxic and anti-inflammatory potential of the methanolic stem bark extract of Elaeodendron buchananii (EB) through in vitro assays and LC-MS based phytochemical profiling. DESIGN: The cytotoxicity of EB was evaluated using the MTT assay on cell lines: RAW 264.7 (murine macrophages), HGF-1 (human gingival fibroblasts), and SCC-25 (human tongue squamous carcinoma cells). Oxidative stress and membrane damage were evaluated using reactive oxygen species (ROS) and lactate dehydrogenase (LDH) assays, respectively, while susceptibility to oxidative stress was examined through H₂O₂ challenge. A Griess reagent assay was used to determine EB's anti-inflammatory properties in LPS-stimulated RAW 264.7 cells. RESULTS: EB exhibited no toxicity to HGF-1 across a concentration range of 50-800 µg/mL, while showing moderate cytotoxicity against RAW 264.7 cells, at 1000 µg/mL (cell viability 67.63 ± 2.81 %). Notably, EB demonstrated selective cytotoxicity against SCC-25 cells (IC₅₀ = 581.9 µg/mL). Additionally, a significant reduction in nitric oxide (NO) production by EB was observed against RAW 264.7 cells when stimulated with LPS, indicating anti-inflammatory (IC₅₀ = 401.40 µg/mL) properties. LC-MS analysis identified 16 phytochemicals, including various secondary metabolites (such as ursolic acid, elaeodendroside F, and oleandrin), each recognized for their pharmacological relevance. CONCLUSION: The findings demonstrate that EB possesses selective cytotoxicity toward tongue carcinoma cells and exhibits significant anti-inflammatory effects. These findings support its traditional medical application and point to its potential for additional phytopharmaceutical development. This report is the first to explore the in vitro cytotoxic effects of E. buchananii on tongue cancer cells.
OBJECTIVE: This study aimed to investigate the effects of resistance exercise on the progression of periodontal disease in rats, focusing on alveolar bone loss, attachment loss, and local inflammatory and bone metabolic...OBJECTIVE: This study aimed to investigate the effects of resistance exercise on the progression of periodontal disease in rats, focusing on alveolar bone loss, attachment loss, and local inflammatory and bone metabolic markers. MATERIALS AND METHODS: Forty male Wistar albino rats were allocated into four experimental groups in a 2 × 2 factorial design: G1 or G2 and G3 or G4. The exercise protocol consisted of progressive swimming sessions over eight weeks, with resistance provided by weights tied to the animals. In the final week, MBT was performed, and rats were sacrificed for histomorphometric and immunohistochemical analysis. RESULTS: The values for alveolar bone loss and attachment loss were significantly lower in the exercised groups compared to both the G1 and G2 groups (p < 0.001). Among the rats with periodontitis, TNF-α expression was significantly lower in the exercised group (p = 0.002), whereas IL-10 levels showed no significant differences (p > 0.005). RANKL expression was elevated in G2 (p = 0.039), with no significant variation in OPG among groups. In MBT, G2 showed significantly higher values compared to G1 and G3 (p = 0.004). G4 displayed intermediate values, higher than G3 but lower than G2, without statistical significance (p > 0.005). CONCLUSION: Physical exercise reduced TNF-α levels in the presence of periodontitis and increased IL-10, although the latter change was not statistically significant. Exercise also contributed to a decrease in RANKL/OPG expression, suggesting a protective effect on alveolar bone resorption. MBT findings further indicate that exercise may alleviate periodontitis-associated behavioral alterations, supporting its potential role as an adjunctive therapy in managing periodontitis.
OBJECTIVE: To investigate the relationship of nutrient canals with jaw cysts, trabecular bone density, and dental regions using cone-beam computed tomography (CBCT). DESIGN: This retrospective study analyzed 120 CBCT ima...OBJECTIVE: To investigate the relationship of nutrient canals with jaw cysts, trabecular bone density, and dental regions using cone-beam computed tomography (CBCT). DESIGN: This retrospective study analyzed 120 CBCT images from 60 patients with unilateral jaw cysts. Nutrient canals were identified and localized on both the cyst-affected side and contralateral, unaffected side of the jaw for each patient. Alveolar trabecular structure was assessed by comparing Hounsfield Unit (HU) values between affected and unaffected sides. Statistical analyses included paired t-tests, Fisher's exact test, and intra-observer reliability assessment. RESULTS: Nutrient canals were significantly more prevalent in cyst-affected jaw regions. Their presence was associated with areas exhibiting pericystic trabecular sclerosis, as reflected by elevated HU values. While nutrient canals were commonly observed in the anterior regions of both healthy and affected jaws, their presence in premolar and molar regions was restricted to cyst-affected areas. CONCLUSIONS: Nutrient canals, typically found in the anterior jaws, appear to develop in posterior regions in association with jaw cysts, particularly in the presence of trabecular sclerosis. Their identification on CBCT scans is important for treatment planning and for minimizing potential surgical complications.
OBJECTIVE: To investigate the molecular mechanisms underlying how Twinfilin actin-binding protein 1 (TWF1) drives the malignant progression of head and neck squamous cell carcinoma (HNSCC). DESIGN: A pan-cancer analysis...OBJECTIVE: To investigate the molecular mechanisms underlying how Twinfilin actin-binding protein 1 (TWF1) drives the malignant progression of head and neck squamous cell carcinoma (HNSCC). DESIGN: A pan-cancer analysis of TCGA datasets was performed to evaluate TWF1 expression and prognostic significance, followed by validation using quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) in clinical HNSCC specimens. Functional assays (CCK-8, colony formation, wound healing, and Transwell invasion) were conducted following siRNA-mediated TWF1 knockdown in SCC9 cells. Additionally, the same functional assays were conducted in an HSC3 cell model overexpressing TWF1 to further evaluate its oncogenic function. The involvement of the AKT signaling pathway was examined by Western blot and validated through rescue experiments with the AKT activator SC79. RESULTS: TWF1 was found to be upregulated in 13 cancer types, including HNSCC. Elevated TWF1 expression, advanced T stage, and lymph node metastasis were identified as independent prognostic indicators in HNSCC. qPCR confirmed increased TWF1 expression, and IHC showed higher TWF1 protein levels in HNSCC tissues. TWF1 knockdown suppressed SCC9 cell proliferation, migration, and invasion, and reduced phosphorylated AKT levels. Conversely, TWF1 overexpression in HSC3 cells promoted proliferation, migration, and invasion while enhancing AKT phosphorylation. SC79 treatment partially reversed the malignant phenotypes suppressed by TWF1 knockdown, supporting TWF1's regulatory role through AKT phosphorylation. CONCLUSION: TWF1 acts as an oncogenic driver in HNSCC, promoting tumor progression through the AKT signaling pathway. It may serve as a potential therapeutic target in precision medicine for HNSCC.
OBJECTIVE: This study investigates how dolichol phosphate mannose synthase (DPMS) subunits DPM1/2/3 affect oral squamous cell carcinoma (OSCC) prognosis and their associations with OSCC. DESIGN: To evaluate the connectio...OBJECTIVE: This study investigates how dolichol phosphate mannose synthase (DPMS) subunits DPM1/2/3 affect oral squamous cell carcinoma (OSCC) prognosis and their associations with OSCC. DESIGN: To evaluate the connections between DPMS subunits DPM1/2/3 and OSCC, we utilized a wide array of databases and analytical resources, including The Cancer Genome Atlas (TCGA), Metascape, and MethSurv. For initial verification, we applied real-time quantitative polymerase chain reaction (RT-qPCR) to OSCC cell lines and tissues. RESULTS: DPM1 and DPM2 expression was higher in OSCC tissues than normal ones. Univariate and multivariate COX analyses showed high DPM1 expression independently correlated with poorer OSCC overall survival. Gene ontology (GO) analysis via Metascape revealed DPM1/2/3 and co-expressed genes enriched in cell cycle, nucleic acid metabolism, and translation. Gene set enrichment analysis (GSEA) linked them to pathways like complement activation, BCR signaling, and immune systems. Besides, high DPMS expression was tied to a more unfavorable prognosis in OSCC patients, and DPM1/2/3 was associated with the infiltration of tumor immune cells in OSCC patients. We found that methylation levels might be related to the prognosis of OSCC patients. By means of RT-qPCR, we ascertained the differential expression levels of DPM1 in human normal oral keratinocytes (HOK) and human tongue squamous cell carcinoma cells (Cal27, SCC9), cancer and paracancerous tissues of OSCC. CONCLUSION: Our findings imply that DPM1, a subunit of DPMS, can serve as a potential molecular indicator for poor prognosis in OSCC and may act as a novel target in OSCC treatment strategies.