Oral lichen planus (OLP), known as a common and chronic mucosal inflammatory disease. Due to its potential for cancerous transformation, this disease has long been a subject of significant concern. Its pathogenesis is that an unknown antigen activates oral keratinocytes and antigen-presenting cells (APCs) in the epithelium, leading to a T cell-mediated immune response. This study investigates the regulatory role of HIF-1α transcription factor and the potential role of autophagy in a simulated OLP inflammatory cell model. In this study, by comparing the control group with the model group, we observed a notable up-regulation of HIF1A mRNA expression. Additionally, both the autophagy marker protein LC3-II and its substrate p62 exhibited abnormal accumulation, suggesting that autophagy is impaired at the lysosomal degradation stage. Furthermore, mechanistic studies have shown that HIF-1α leads to dysfunction of the autophagy-lysosomal pathway by inhibiting the expression of lysosomal-related genes, while knockdown of HIF-1α alleviates the disruption of autophagic and promotes the improvement of cell activity. In experiments with C. elegans, stimulation with Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) shortens worms’ lifespan, but knocking down the hif-1 gene reverses this effect. Similarly, deletion of the key autophagy genes bec-1 and lgg-1 reduces worm survival rates. Results indicate that HIF-1α plays a vital role in regulating autophagy-lysosomal function and cellular homeostasis. In summary, the excessively high expression of HIF-1α aggravates cellular and systemic damage by impairing autophagy-lysosomal function in OLP. Conversely, the targeted inhibition of HIF-1α restores autophagy function, suggesting a potential therapeutic strategy.

Chelerythrine is a natural benzophenanthridine alkaloid with various pharmacological activities. However, whether Chelerythrine can influence innate immunity and its underlying molecular mechanisms remain unclear. In this study, we found that 10 μM Chelerythrine significantly extended the lifespan of Caenorhabditis elegans infected with Candida albicans (C. albicans) and inhibited the proliferation of C. albicans. This enhanced host resistance to infection was not achieved by reducing the intestinal fungal burden. Transcriptomic sequencing analysis revealed that Chelerythrine activates the FoxO and Fatty acid metabolism pathways in C. elegans. Interestingly, the lifespan-extending effect of Chelerythrine was completely abolished in daf-16 and nhr-49 mutants. Similarly, mutations in the fatty acid desaturase genes fat-5, fat-6, and fat-7 also blocked this protective effect. RT-qPCR results confirmed that Chelerythrine treatment significantly upregulated the expression of FoxO pathway downstream genes (sod-3, thn-2, lys-7) and fatty acid metabolism-related genes (nhr-49, mdt-15, fat-5, fat-6, fat-7). Fluorescent reporter gene assays further demonstrated that Chelerythrine promotes the nuclear localization of DAF-16::GFP and enhances the fluorescence expression of SOD-3::GFP, FAT-5::GFP, FAT-6::GFP, and FAT-7::GFP. Additionally, broad-spectrum antibacterial assays showed that 10 μM Chelerythrine had no direct inhibitory activity against various pathogens, including Listeria monocytogenes, Enterococcus faecalis, Pseudomonas aeruginosa, and Salmonella enterica, indicating that it does not enhance host immunity by directly suppressing pathogen growth. In summary, this study demonstrates that Chelerythrine enhances the innate immune response of C. elegans against C. albicans by activating the DAF-16/FoxO pathway and the NHR-49-mediated fatty acid metabolism pathway. Our work reveal that Chelerythrine is a potential therapeutic candidate for the treatment of C. albicans infections.

ObjectiveThis review summarizes current evidence on modifiable risk factors for periodontitis in adolescents and young adults, with a focus on their underlying inflammatory pathways and mechanisms in early disease progression.MethodsA structured literature search was performed in PubMed/MEDLINE and Web of Science for human studies published from 2000 to 2025, examining gingival and periodontal outcomes in relation to four major modifiable exposure clusters: tobacco use, obesity and metabolic health, diet and related behaviors, and plaque-retentive or iatrogenic factors.ResultsAvailable evidence indicates that early inflammatory indicators of periodontal risk, particularly bleeding on probing and calculus, are highly prevalent in young populations and closely associated with these modifiable exposures. These factors drive periodontal pathogenesis by increasing inflammatory burden, promoting microbial dysbiosis, impairing host immune and metabolic responses, and accelerating the transition from gingivitis to periodontitis. Importantly, modifiable risks and early periodontal burden are not uniformly distributed across the population, but cluster within distinct high-risk subgroups.ConclusionsThese findings indicates that early periodontitis in youth arises from concentrated risk exposure rather than a population-wide downward shift in age at onset. Targeted, multi-level preventive strategies for high-risk subgroups that address underlying modifiable inflammatory pathways may effectively delay the onset and progression of periodontitis and exert beneficial effects on long-term periodontitis-related systemic health outcomes.

Cisplatin remains a first-line chemotherapeutic agent in the treatment of oral squamous cell carcinoma (OSCC). However, the efficacy of cisplatin is frequently compromised by the development of drug resistance. This review systematically examines the multidimensional mechanisms underlying cisplatin resistance in OSCC and the corresponding strategies to overcome this resistance. Mechanisms of chemoresistance involve complex, multi-layered molecular networks, encompassing dysregulation of key gene expression and signaling pathways, epigenetic remodeling, metabolic reprogramming, evasion of regulated cell death, acquisition of epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties, as well as the formation of an immunosuppressive tumor microenvironment (TME). In response to these challenges, multimodal combinatorial approaches are being developed, including small-molecule inhibitors targeting specific resistance nodes, nanotechnology-based targeted drug delivery systems, combination therapies with immune checkpoint inhibitors, and interventions targeting metabolic vulnerabilities. Furthermore, emerging technologies are enabling more precise strategies: patient-derived organoids provide a platform for individualized drug sensitivity testing; single-cell sequencing allows for dissection of cellular heterogeneity within resistant populations and the interactions of these populations with the microenvironment; and artificial intelligence (AI) aids in predictive model building and drug discovery by integrating multi-omics data. In summary, a comprehensive understanding of the systems biology of cisplatin resistance, integrated with novel research paradigms such as nanotechnology, immunotherapy, metabolic targeting, organoid models, single-cell technologies, and AI, will be pivotal for developing personalized combination therapies to ultimately overcome cisplatin resistance in OSCC.

Background: To evaluate the long-term cost-effectiveness of integrating periodontal intervention with diabetes management for Chinese adults with comorbid type 2 diabetes mellitus (T2DM) and periodontitis. Methods: A 9-state Markov cohort model (1-year cycle; 40-year horizon) was constructed for a hypothetical cohort of 50-year-old Chinese adults with comorbid T2DM and periodontitis. Three strategies were compared: usual care (UC), scaling and root planing plus intensified diabetes management (SRP+DM), and comprehensive integrated management (CIM). Transition probabilities, costs (2024 CNY; 5% discount rate), and utilities were derived from Chinese national data and systematic reviews. One-way and probabilistic sensitivity analyses (PSA; 10,000 Monte Carlo simulations) were performed. Willingness-to-pay (WTP) thresholds were CNY 90,000/QALY (1 × GDP per capita) and CNY 270,000/QALY. Results: Usual care generated CNY 104,028 and 11.749 QALYs. SRP+DM yielded an incremental cost-utility ratio (ICUR) of CNY 5,308/QALY versus UC; CIM yielded CNY 6,608/QALY. Both strategies were cost-effective at CNY 90,000/QALY. In patients with uncontrolled diabetes (HbA1c ≥7%), both were cost-saving. CIM reduced cumulative 40-year DM complication incidence by 11.9 percentage points, tooth loss by 12.7 percentage points, and all-cause mortality by 4.8 percentage points versus UC. CIM was cost-optimal in 99.4% of simulations. Conclusions: Subject to the model's assumptions—notably extrapolation of short-term randomized-trial effects over a lifetime, pooled estimates of periodontal recurrence and HbA1c-benefit durability, and indirectly derived utilities—integrated periodontal–diabetes management appears cost-effective in China across all WTP thresholds tested in deterministic and probabilistic sensitivity analyses. In durability scenario analyses, this conclusion remained robust when the treatment effect was lost after 1, 3, or 5 years, except when the benefit disappeared within 1–3 years while maintenance costs continued. These findings support including periodontal intervention in China's national diabetes care pathway but require confirmation by long-term empirical studies.

BACKGROUND:Conventional cytomegalovirus (CMV) promoter-type periodontitis vaccines can offer protection against periodontitis; however, their antigen genes can be widely expressed in the body, resulting in significant toxic effects. This study aimed to modify the CMV promoter for targeted expression of antigen genes, investigate appropriate methods for regulating its expression, and explore its regulatory mechanism. METHODS:We searched for the MUC2 promoter sequence in the UCSC database, replaced the original broad-spectrum CMV promoter type pVAX1-CMVpro-HA2-fimA periodontitis DNA vaccine candidate with the MUC2 promoter sequence, and constructed the pVAX1-MUC2pro-HA2-fimA-EGFP periodontitis DNA vaccine. We assessed the intestinal-specific expression ability of the MUC2 promoter-type periodontitis DNA vaccine candidate by transfecting different tissue cells. Subsequently, various concentrations of Lactobacillus rhamnosus supernatant were used to stimulate intestinal tissue cells transfected with the MUC2pro periodontitis DNA vaccine. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) assays were used to confirm the regulatory effect of Lactobacillus rhamnosus supernatant. After transfection, TGF-β pathway inhibitors were used to target intestinal tissue cells cultured with Lactobacillus rhamnosus supernatant. RT-qPCR and WB assays were used to assess the impact of TGF-β inhibitors on the regulatory effect of Lactobacillus rhamnosus supernatant. All statistical analyses were performed using SPSS 29.0, with one-way ANOVA for multiple group comparisons and LSD/Tamhane's T2 for post-hoc tests; P < 0.05 was considered statistically significant. RESULTS:After transfection with the MUC2 promoter-type periodontitis vaccine plasmid, green fluorescence was exclusively detected in LS-174T cells, while it was absent in LX-2, BEAS-2B, and U251 cells. Compared with the control group of LS 174T cells transfected without SN, the 2% SN group exhibited no enhancement of vaccine antigen expression (P > 0.05). The 4% SN group enhanced vaccine antigen expression (P < 0.05), while the 8% SN group significantly promoted vaccine antigen expression (P < 0.01). Compared with the control group without SN, the PFD group exhibited no inhibitory effect on vaccine antigen expression in transfected LS-174T cells (P > 0.05). Compared with the 8% SN group, the expression of vaccine antigens in LS-174T cells transfected with the 8% SN + PFD group was significantly inhibited (P < 0.05). CONCLUSIONS:Periodontitis DNA vaccine candidate plasmid pVAX1-MUC2pro-HA2-fimA-EGFP was engineered for intestinal tissue-specific expression. Additionally, an appropriate concentration of Lactobacillus rhamnosus supernatant enhances MUC2 promoter-type periodontitis DNA vaccine candidate expression, which may be associated with TGF-β pathway regulation. EGFP was used as a surrogate marker for HA2/fimA expression in this study, and P2A cleavage efficiency was assumed but not validated, representing an indirect readout of antigen expression.

Periodontitis is a prevalent chronic inflammatory disease characterized by progressive destruction of periodontal supporting tissues. Although DNA vaccines targeting periodontal pathogens have shown potential, insufficient immunogenicity remains a major limitation. A MyD88-adjuvanted DNA vaccine targeting Porphyromonas gingivalis antigens was developed and administered intranasally in a rat model of periodontitis. Rats were randomly assigned to five groups (n = 3–7 per group). Vaccine‑induced immune responses, alveolar bone loss, and safety were systematically evaluated. Intranasal immunization with the MyD88-adjuvanted vaccine elicited significantly enhanced mucosal and systemic antibody responses, including elevated salivary secretory IgA and serum antigen‑specific IgG and IgA. The vaccine promoted coordinated activation of B cells and follicular helper T cells in mucosal and systemic lymphoid tissues. Importantly, vaccinated rats exhibited markedly reduced alveolar bone loss compared with disease controls and the non‑adjuvanted vaccine group. Quantitatively, intranasal MyD88-adjuvanted vaccination significantly decreased alveolar bone loss (one-way ANOVA, F(4,10) = 137.1, P < 0.05). The mean bone loss was reduced from approximately 0.78 mm in the periodontitis group to approximately 0.56 mm in the MyD88-adjuvanted group. No significant adverse effects or pathological changes were observed. These findings indicate that MyD88 effectively enhances the immunogenicity and protective efficacy of a periodontal DNA vaccine. This intranasal MyD88-adjuvanted DNA vaccine may be useful as a preventive and adjunctive immunotherapeutic strategy and warrants further translational studies in oral health.

Exosome-based vaccines hold significant promise in cancer immunotherapy, yet their native forms face inherent challenges, including imprecise targeting, suboptimal immunogenicity, and poor controllability of antigen loading. This review posits that engineering is pivotal to transforming exosomes from passive carriers into active, programmable therapeutic platforms. We systematically dissect the multifaceted antitumor mechanisms of exosomes and critically evaluate how various engineering strategies (e.g., physical loading, genetic modification, membrane functionalization) are designed to address these specific biological bottlenecks, thereby establishing a coherent “biological limitation–engineering solution” framework. Building on this foundation, we assess their application potential and ongoing challenges in areas such as personalized neoantigen vaccines.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with poor patient outcomes. The long non-coding RNA NEAT1 (lncRNA NEAT1) has emerged as a critical driver of HNSCC pathogenesis. This review synthesizes current knowledge on lncRNA NEAT1's aberrant expression, molecular mechanisms, and functional roles in HNSCC. LncRNA NEAT1 is significantly upregulated in tumors and promotes progression by acting as a competing endogenous RNA (ceRNA) for multiple miRNAs, such as miR-125b-5p, miR-204, and miR-34a-5p, thereby regulating downstream targets including SLC1A5, ZEB1, and components of the Wnt/β-catenin pathway. These interactions drive key oncogenic processes, including proliferation, metastasis, epithelial-mesenchymal transition, therapy resistance, and cell death inhibition. Clinically, high lncRNA NEAT1 expression correlates with advanced T stage, lymph node metastasis, and reduced survival, underscoring its potential as a diagnostic and prognostic biomarker. Therapeutically, emerging approaches such as nanoparticle-mediated delivery of siRNA/shRNA offer a promising strategy to target lncRNA NEAT1, potentially synergizing with existing immunotherapies. Although clinical translation remains challenging, lncRNA NEAT1 represents a highly promising biological target for future precision oncology in HNSCC.

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy associated with high morbidity and mortality. RAD51 recombinase (RAD51), a central DNA repair protein, plays a crucial role in homologous recombination and has been implicated in cancer progression through mechanisms such as genomic instability, chemoresistance and immune modulation. However, its specific function and regulatory mechanisms in OSCC remain incompletely elucidated. We conducted an integrated multiomics analysis including differential expression, single-cell transcriptomics, prognostic evaluation, functional enrichment and immune infiltration profiling. Experimental validation was performed using siRNA-mediated RAD51 knockdown in OSCC cell line HSC-3, followed by functional assays to assess proliferation, migration, invasion, reactive oxygen species (ROS) accumulation and chemosensitivity. RAD51 was significantly overexpressed across multiple cancers, including OSCC, and exhibited high diagnostic accuracy for OSCC (AUC = 0.956). Single-cell RNA sequencing revealed elevated RAD51 expression in malignant and proliferating T cells, associating it with aggressive phenotypic traits. High RAD51 expression predicted poor prognosis in OSCC and other cancers. Functional analyses indicated its involvement in the Fanconi anaemia pathway, DNA damage repair and cell cycle regulation. Immune infiltration analysis revealed significant negative correlations with multiple immune cell subtypes and tumour microenvironment scores. Experimentally, RAD51 knockdown suppressed malignant behaviours and enhanced ROS production and chemosensitivity in HSC-3 cells. RAD51 drives OSCC progression by enhancing malignant phenotypes, suppressing immune infiltration, promoting aberrant DNA repair, elevating oxidative stress and promoting therapy resistance. These findings support RAD51's potential as both a prognostic biomarker and a therapeutic target in OSCC.

The causal relationship between serum 25-hydroxyvitamin D levels and oral diseases remains uncertain due to confounding and reverse causation in observational studies. This bidirectional 2-sample Mendelian randomization (MR) study aims to elucidate the causal relationship between serum 25-hydroxyvitamin D levels and multiple oral pathologies while addressing confounding factors and reverse causation observed in conventional observational studies. Utilizing summary-level genome-wide association study data from the IEU OpenGWAS project, we analyzed serum 25-hydroxyvitamin D levels (“ebi-a-GCST90000618,” n = 4,96,946 Europeans) and oral disease phenotypes from Finnish biobank registries. Instrumental variables for serum 25-hydroxyvitamin D levels were selected under genome-wide significance ( P < 5 × 10 −8 ) with strict clumping thresholds ( r 2 < 0.001, kb = 10,000) and F -statistics > 30. For oral disease exposures, relaxed criteria ( P < 1 × 10 −5 , r 2 < 0.001, F -statistic > 10) were applied to ensure sufficient instrumental variables. Primary analyses employed inverse-variance weighted and MR-Egger methods, supplemented by sensitivity analyses including Cochran’s Q test, leave-one-out validation, funnel plots, and MR-PRESSO for horizontal pleiotropy assessment. Forward MR analysis demonstrated significant inverse causal relationships between genetically elevated serum 25-hydroxyvitamin D levels and risks of perioral dermatitis and lip, oral cavity, pharyngeal malignancies. No statistically significant associations were observed with other oral diseases. Reverse MR analysis revealed a nominal positive association between lichen planus and serum 25-hydroxyvitamin D levels that did not persist after multiple testing correction, with no other reverse causal effects detected. Our findings provide genetic evidence supporting a protective role of serum 25-hydroxyvitamin D levels against specific oral disorders, particularly perioral dermatitis and oropharyngeal malignancies. The bidirectional design effectively mitigated reverse causation concerns, underscoring the robustness of these causal inferences. These results warrant further investigation into vitamin D supplementation as a potential preventive strategy for targeted oral pathologies.

Prevalence of fluoride and sulfur dioxide (SO2) cocontamination in the environment poses a serious threat to various human organs, especially the teeth. However, direct evidence linking coexposure to fluoride and SO2 with enamel mineralization disorders is lacking. Here, we investigated the mechanisms through which fluoride and SO2 exposure, either alone or in combination, affects enamel mineralization in mouse and LS8 cell models. Coexposure to fluoride and SO2 resulted in more severe enamel mineralization disorders compared with those in the control or individual exposure groups. The coexposure caused significant pathological changes and retention of enamel matrix. Furthermore, the coexposure upregulated the expression of membrane calcium channels (Cav1.2), calmodulin-dependent protein kinase II (CaMKII), endoplasmic reticulum calcium ion(Ca2+)-release channel (IP3R), and endoplasmic reticulum stress (ERS) marker protein (GRP78), and significantly downregulated the expression of endoplasmic reticulum (ER) Ca2+-uptake pump protein (SERCA2) and calreticulin (CRT). Investigations using Amlodipine (Am), Tunicamycin (Tm) and CDN1163 revealed that the coexposure exacerbated enamel mineralization disorders by disrupting calcium homeostasis and subsequently triggering ERS. Overall, this study highlights that coexposure to fluoride and SO2 affects ER Ca2+ content through cytoplasmic calcium overload, triggers ERS, and increases the risk of enamel mineralization disorders. Activation of ERS, induced by disruption of calcium homeostasis, may play a key role in fluoride and SO2-induced enamel mineralization disorders. The insights obtained from this study should be valuable for devising strategies to mitigate the effects of fluoride and SO2 coexposure on enamel mineralization disorders.

Limited research has explored the link between the Literature-Based Dietary Index for Gut Microbiota (LBDI-GM) and Obstructive Sleep Apnea (OSA). This study aims to examine the relationship between these two conditions. This cross-sectional analysis utilized data from the 2015–2018 National Health and Nutritional Examination Survey (NHANES). Obstructive sleep apnea (OSA) served as the independent variable, evaluated through self-reported questionnaires. The dependent variable was the novel literature-Based Dietary Index for Gut Microbiota, which quantified dietary patterns linked to intestinal microbiome characteristics. Weighted multivariable logistic regression modeling explored associations between LBDI-GM and OSA. Supplementary subgroup and interaction evaluations were performed. A total of 8,707 participants were included in the final analysis, with a mean age of 47.66 years (SD = 0.43). The study population was nearly equally distributed by sex, with 4,460 males (51.2

ABSTRACT Background Epigallocatechin gallate (EGCG) has anti‐inflammatory and antioxidative stress effects in periodontitis. However, the specific mechanisms involved remain unclear. Our study explored whether the mechanism by which EGCG on alleviates inflammation and oxidative stress in human periodontal ligament fibroblasts (hPDLCs) involves HDAC6. Methods We treated hPDLCs with lipopolysaccharide (LPS) and EGCG, and detected the resultant effects on cell proliferation by the CCK‐8 method. Cells were divided into three groups: control, LPS, and EGCG + LPS. The expression of tumor necrosis factor α (TNF‐α) and interleukin‐1β (IL‐1β) was detected by enzyme‐linked immunosorbent assay (ELISA), and the expression of reactive oxygen species (ROS) was detected using 2′,7′‐dichlorofluorescein diacetate. The expression of histone deacetylase 6 (HDAC6), p62, heat shock protein 70 (Hsp70), Kelch‐like ECH‐associating protein (Keap1), nuclear factor E2‐related factor 2 (Nrf2), and heme oxygenase‐1(HO‐1) mRNA was detected by real‐time quantitative polymerase chain reaction (RT‐qPCR). The protein expression of HDAC6, Nrf2, and nod‐like receptor protein 3 (NLRP3) was detected by western blotting. Results At concentrations of less than 100 μmol/L, EGCG can promote cell proliferation and significantly inhibit the levels of TNF‐α and IL‐1β. Moreover, EGCG can activate the Nrf2 pathway and inhibit ROS production. Furthermore, EGCG inhibited the expression of HDAC6 and promoted the expression of p62 and Hsp70, indicating that the anti‐inflammatory and antioxidant effects of EGCG are closely related to HDAC6. Conclusions EGCG can regulate LPS‐induced oxidative stress levels of hPDLCs through the Keap1/Nrf2/HO‐1 pathway and reduce the expression of HDAC6‐related factors. Therefore, HDAC6 may be a potential target for EGCG in the treatment of periodontal inflammation and oxidative stress.

Periodontitis, a prevalent inflammatory oral disease, is intricately linked to disruptions in the oral microbiome, a state known as microbial dysbiosis. This review explores the pivotal roles of key pathogens, including Porphyromonas gingivalis and Tannerella forsythia, in driving periodontitis and examines the underlying molecular mechanisms that disrupt microbial homeostasis. We discuss how interactions among bacterial species affect the oral ecosystem’s balance and how microbial metabolites influence the host immune responses, contributing to disease progression. Leveraging these insights, we propose cutting-edge therapeutic approaches aimed at restoring microbial equilibrium. These include personalized pharmacological interventions tailored to individual microbiome profiles and innovative microbiome-targeted strategies such as probiotic formulations and bacteriophage therapy. By precisely modulating microbial communities, these strategies hold promise for enhancing treatment efficacy, preventing disease recurrence, and mitigating issues like antimicrobial resistance. Overall, this review paves the way for novel prevention and management techniques in periodontitis, offering significant improvements in oral health outcomes for patients.

OBJECTIVE:The removal of impacted third molars by surgery may occur with a series of complications, whereas limited information about the postoperative pathogenesis is available. The objective of this study is to identify changes in gene expression after flap surgical removal of impacted third molars and provide potential information to reduce postoperative complications. METHODS:The gingival tissues of twenty patients with flap surgical removal of impacted third molars and twenty healthy volunteers were collected for gene expression testing. The collected gingival tissues were used RNA sequencing technology and quantitative real-time PCR validation was performed. DEG was mapped to protein databases such as GO and KEGG for functional annotation and, based on annotation information, for mining of differential expression genes in patients with mpacted third molars. RESULTS:A total of 555 genes were differentially expressed. Among the top up-regulated genes, HLA-DRB4, CCL20, and CXCL8 were strongly associated with immune response and signal transduction. Among the top down-regulated genes, SPRR2B, CLDN17, LCE3D and LCE3E were related to keratinocyte differentiation, IFITM5, and BGLAP were related to bone mineralization, UGT2B17 is associated with susceptibility to osteoporosis. KEGG results showed that the DEGs were related to multiple disease-related pathways. CONCLUSION:This first transcriptome analysis of gingival tissues from patients with surgical removal of impacted third molars provides new insights into postoperative genetic changes. The results may establish a basis for future research on minimizing the incidence of complications after flap-treated third molars.

Background Excessive intake of fluoride during enamel growth and development can impair the normal physiological function of ameloblasts, resulting in the formation of dental fluorosis. However, little is known about the function of miRNAs in the formation of dental fluorosis. Aim This study aimed to explore the effects of key miRNAs on the PI3K/AKT signaling pathway and ameloblasts under high fluoride conditions. Materials and Methods LS8 cells were treated with NaF at concentrations of 0.4, 0.8, 1.6, 3.2, and 6.4 mmol/L for 24 h, and cell viability and apoptosis were measured using the CCK-8 assay and flow cytometry. The expression of apoptosis-related proteins was detected by Western blotting. Transcriptome sequencing was performed on FS8 cells after treatment with 1.6 and 3.2 mmol/L NaF for 24 h to identify key miRNAs and validate them. After cell transfection, the effect of miR-214-3p on ameloblasts and the PI3K/AKT signaling pathway was assessed. Results and Discussion NaF treatment significantly reduced the viability and accelerated the apoptosis of LS8 cells. The down-regulated miRNAs predicted target genes that were most enriched in the PI3K/AKT signaling pathway, and the most critical miRNA was miR-214-3p. The expression levels of p-PI3K, p-AKT, and Bcl-2 were significantly up-regulated after overexpression of miR-214-3p in LS8 cells, while the expression of PI3K, AKT, and Bax was significantly down-regulated, which was partially reversed by LY294002. Conclusion Excess fluoride could affect the morphology of ameloblast-like cell lines and induce apoptosis. Overexpression of miR-214-3p inhibited NaF-induced apoptosis in LS8 cells by regulating the PI3K/AKT signaling pathway, inhibiting its phosphorylation, down-regulating the Bax protein, and up-regulating the Bcl-2 protein.

Fluoride (F) and sulfur dioxide (SO2) contamination is recognized as a public health concern worldwide. Our previous research has shown that Co-exposure to F and SO2 can cause abnormal enamel mineralization. Ameloblastin (AMBN) plays a crucial role in the process of enamel mineralization. However, the process by which simultaneous exposure to F and SO2 influences enamel formation by regulating AMBN expression still needs to be understood. This study aimed to establish in vivo and in vitro models of F-SO2 Co-exposure and investigate the relationship between AMBN and abnormal enamel mineralization. By overexpressing/knocking out the Fibroblast Growth Factor 9 (FGF9) gene, we investigated the impact of FGF9-mediated Mitogen-Activated Protein Kinase (MAPK) signaling on AMBN synthesis to elucidate the mechanism underlying the induction of abnormal enamel mineralization by F-SO2 Co-exposure in rats. The results showed that F-SO2 exposure damaged the structure of rat enamel and ameloblasts. When exposed to F or SO2, gradual increases in the protein expression of FGF9 and phosphorylated p38 mitogen-activated protein kinase (p-P38) were observed. Conversely, the protein levels of AMBN, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK) were decreased. AMBN expression was significantly correlated with FGF9, p-ERK, and p-JNK expression in ameloblasts. Interestingly, FGF9 overexpression reduced the levels of p-ERK and p-JNK, worsening the inhibitory effect of F-SO2 on AMBN. Conversely, FGF9 knockout increased the phosphorylation of ERK and JNK, partially reversing the F-SO2-induced downregulation of AMBN. Taken together, these findings strongly demonstrate that FGF9 plays a critical role in F-SO2-induced abnormal enamel mineralization by regulating AMBN synthesis through the JNK and ERK pathways.

Objective To investigate the clinical effect of lithium disilicate glass ceramic cantilever resin-bonded fixed partial dentures (CRBFPDs) on single anterior tooth loss to provide a reference for the selection of restoration methods for single anterior tooth loss. Methods This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Forty-two patients with less than two anterior teeth with monomaxillary loss were included in this study. After 6 months, 1 year, 2 years, and 3 years, the aesthetic and functional effects of the restorations and the periodontal health status were evaluated, and the visual analog scale (VAS) was used to assess patient satisfaction. Results During the observation period, the connector fractured in one case within 3 months. One case had debonded within 2 years. The aesthetic restoration effect of all lithium disilicate glass ceramic CRBFPDs was categorized as Class A. The periodontal health was good, there was no clinical absorption in the soft and hard tissues of the abutment or subbridge, periodontal status according to the evaluation indices was classified as class A, and the total satisfaction rate of the patient was 100%. Conclusion For single anterior tooth loss patients, lithium disilicate glass ceramic cantilever resin-bonded fixed partial denture can achieve the restoration effect of less invasion, better adhesion, aesthetics, comfort and good biocompatibility. With high patient satisfaction, it can be considered an ideal restoration method for replacing a single anterior tooth.

Purpose: To study the therapeutic effect of hemagglutinin-2 and fimbrial (HA2-FimA) vaccine on experimental periodontitis in rats. Materials and Methods: The first batch of rats was divided into two groups and i mmu nised with pure water or pVAX1-HA2FimA at the age of 6, 7, and 9weeks. After sacrificing the animals, total RNA was extracted from the spleens for RNA highthroughput sequencing (RNA-Seq) analysis. The second batch of rats was divided into four groups (A, B, C, D), and an experimental periodontitis rat model was established by suturing silk thread around the maxillary second molars of rats in groups B, C, and D for 4weeks. The rats were immunised with pure water, pVAX1-HA2-FimAvaccine, empty pVAX1 vector, and pure water at 10, 11, and 13 weeks of age, respectively. Secretory immunoglobulin A (SIgA) antibodies and cathelicidin antimicrobial peptide (CAMP) levels in saliva were measured by enzyme-linked immunosorbent assay (ELISA). All rats were euthanised at 17weeks of age, and alveolar bone loss was examined using micro-computed tomography (Micro-CT). Results: Through sequencing analysis, six key genes, including Camp, were identified. Compared with the other three groups, the rats in the periodontitis+pVAX1-HA2-FimA vaccine group showed higher levels of SIgA and CAMP (p<0.05). MicroCT results showed significantly less alveolar bone loss in the periodontitis+pVAX1-HA2-FimA vaccine group compared to the periodontitis+pVAX1group and periodontitis+pure water group (p<0.05). Conclusion: HA2-FimA DNA vaccine can increase the levels of SIgA and CAMP in the saliva of experimental periodontitis model rats and reduce alveolar bone loss.