OBJECTIVES:Epidermal growth factor-like domain-containing protein 6 (EGFL6) is a member of the epidermal growth factor superfamily. It has been reported that it can enhance the osteogenic differentiation potential of stem cells and stimulate angiogenesis. However, its effects on the regulation of odontogenic differentiation of dental pulp stem cells (DPSCs) have not been studied. Therefore, we aimed to investigate the role of EGFL6 in pulp regeneration and its underlying mechanism. METHODS:The cytotoxicity and migration-inductive ability of EGFL6 were evaluated using cell counting kit-8 assay and transwell assay, respectively. A tube formation assay was performed to assess the angiogenic effect of EGFL6. The alkaline phosphatase (ALP) and alizarin red S staining were conducted for mineralization evaluation. The odontoblastic-related and angiogenesis-related markers were measured by quantitative real-time polymerase chain reaction and Western blot analysis. Western blot was also conducted to further examine the levels of key factors involved in MAPK signaling pathways. RESULTS:EGFL6 displayed no cytotoxicity and was capable of promoting cell migration and angiogenesis. Besides, EGFL6 enhanced the mineralization process and up-regulated the expression levels of odontoblastic-related markers (DSPP, DMP1, and BSP) after 5, 7, and 10 days. The expression levels of odontoblastic-related and angiogenesis-related proteins (DSPP, DMP1, VEGF, and ALP) could all be up-regulated by EGFL6. There was also an increase in the phosphorylation levels of ERK1/2 and P38. CONCLUSION:EGFL6 can promote the migration, angiogenesis, and odontogenesis differentiation of DPSCs via the activation of MAPK signaling pathways.

To elucidate the oncogenic role of DLGAP5 in salivary adenoid cystic carcinoma (SACC), we characterized its expression patterns and functional impact on malignant phenotypes including proliferation, migration, and invasion; we assessed DLGAP5 expression using the GEO database, examined its effects on SACC cells through DLGAP5 knockdown and overexpression experiments, verified these findings with a nude mouse subcutaneous tumor model, and employed virtual screening to identify the lead compound ZINC3809191 targeting DLGAP5, whose inhibitory effects on SACC were confirmed in vitro. Our results showed that DLGAP5 was highly expressed in SACC and correlated with clinical stage and pathological grade, and it promoted the proliferation, migration, and invasion of SACC cells via the PI3K/AKT signaling pathway; additionally, the lead compound ZINC3809191 demonstrated significant ability to inhibit the proliferation, migration, and invasion of SACC cells. Collectively, our findings indicate that DLGAP5 is upregulated in SACC, associated with clinical stage and pathological grade, and plays a regulatory role in key malignant phenotypes of SACC cells, while the identification of ZINC3809191 with potent anti-tumor activity against DLGAP5 provides a crucial theoretical foundation for the development of potential therapeutic strategies for SACC.

[This corrects the article DOI: 10.1016/j.ijpx.2025.100438.].

Diabetic periodontitis remains a formidable clinical challenge characterized by persistent infection, oxidative stress, and impaired alveolar bone regeneration. Here, we have developed an engineered core-shell microneedle (MN) patch that enables the staged release of doxycycline and simvastatin to achieve coordinated antibacterial and osteogenic effects within periodontal lesions. The outer polyvinyl alcohol (PVA) shell rapidly dissolves upon insertion into gingival tissue, enabling burst release of doxycycline for immediate bacterial eradication. Subsequently, the polyvinylpyrrolidone (PVP) core, loaded with simvastatin-encapsulated polydopamine nanoparticles (Sim@PDA NPs), provides sustained release, leveraging the intrinsic reactive oxygen species (ROS)-scavenging capacity of PDA to mitigate local oxidative stress and promote osteogenic differentiation. A silk fibroin backing layer ensures long-term doxycycline release, preventing bacterial recolonization and maintaining a regenerative microenvironment. In vitro, Doxy/SIM-MNs exhibited potent antibacterial and antibiofilm activity against Porphyromonas gingivalis and Staphylococcus aureus, excellent cytocompatibility, and robust induction of alkaline phosphatase activity, mineralized nodule formation, and osteogenic gene expression in mesenchymal stem cells. In a rat model of diabetic periodontitis, Doxy/SIM-MNs markedly reduced inflammatory destruction, enhanced alveolar bone regeneration, and reestablished periodontal homeostasis by relieving negative regulation of Wnt signaling while suppressing NF-κB signaling and apoptosis. This hierarchically staged microneedle platform offers a clinically translatable strategy for the integrated management of infection, inflammation, and bone regeneration in diabetes-associated periodontitis and other chronic inflammatory bone diseases.

To address the issue of unsatisfactory repair outcomes in large bone defects due to insufficient vascularization in bone tissue engineering. In this study, a porous interpenetrating polymer network (IPN) scaffold featuring large pore sizes and excellent biological activity was constructed through salt leaching and collagen incorporation. Collagen incorporation not only increased the strength of the scaffold and regulated its physical properties, such as the swelling rate, degradation rate, and porosity but also improved its biological properties, such as early cell adhesion. By screening the particle size of the salt porogen, IPN scaffolds with various pore sizes were obtained by leaching after gelation. The scaffold with a pore size 150-255 mu m demonstrated optimal performance, promoting rBMSC proliferation and osteogenic differentiation in vitro, with in vivo experiments confirming its superior angiogenic and bone regenerative capabilities. RNA sequencing indicated that the scaffolds promoted osteogenic differentiation of cells by activating the PI3K/AKT pathway, thereby facilitating bone regeneration. In summary, the porous IPN scaffolds developed in this study can significantly enhance angiogenesis and bone regeneration, suggesting promising prospects for advancing bone tissue engineering from laboratory research to clinical application.

This study aimed to explore the relationship between periodontitis and gestational diabetes mellitus (GDM) and to ascertain the role of systemic inflammation in mediating this association. Data from 5,283 women of reproductive age ranging from 20 to 44 years were retrieved from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2009–2014 cycles. The female participants were categorized into three groups: non-diabetes, DM, and GDM. Multivariate logistic and linear regression models were employed to assess the correlations between periodontal variables and diabetes status. Additionally, a mediation analysis was performed to explore the role of systemic inflammatory biomarkers. Compared to non-periodontitis, women with periodontitis have a 1.68 times higher risk of having GDM (OR = 1.68, 95

Salivary gland (SG) dysfunction is a hallmark manifestation of Sjögren's disease (SjD). While SHP2 has been implicated in several autoimmune diseases, its specific function in SjD remains to be elucidated. Here, we investigated the involvement of SHP2 in SjD-induced SG damage and elucidate the underlying molecular mechanisms. Our findings revealed that SHP2 is elevated in SG tissues of SjD patients and SjD-like animals, with predominant localization to salivary gland epithelial cells (SGECs) of acini and ducts. Notably, pharmacological inhibition of SHP2 with the allosteric inhibitor SHP099 significantly alleviates SG histopathological damage and reduces inflammatory cell infiltration in SjD-like animals. In vitro studies in the human SGEC line A253 revealed that SHP2 inhibition attenuated poly(I:C)-induced SGEC apoptosis and proinflammatory cytokine production. Mechanistically, SHP099 treatment disrupted the IL-17RA/ACT1/TRAF6 signaling axis, phenocopying the effects of SHP2 knockdown and direct IL-17R antagonism, which leads to downregulation of JAK/STAT3 and NF-κB pathways. Collectively, our findings highlight the significant involvement of SHP2 in the pathogenesis of SjD and suggest that targeting SHP2 or its downstream signaling pathways may represent a promising therapeutic approach for SjD treatment.

Establishing a prognostic risk model based on immunological and disulfidptosis signatures enables precise prognosis prediction of oral squamous cell carcinoma (OSCC). Differentially expressed immune and disulfidptosis genes were identified in OSCC and normal tissues. We examined the model’s clinical applicability and its relationship to immune cell infiltration. Additionally, the risk score, ssGSEA, ESTIMATE, and CIBERSORT were used to evaluate the intrinsic molecular subtypes, immunological checkpoints, abundances of tumor-infiltrating immune cell types and proportions between the two risk groups. GO-KEGG and GSVA analyses were performed to identify enriched pathways. We analyzed the correlation immune genes based on the 14 disulfidptosis-related genes, and found 379 disulfidptosis-related immune genes (DRIGs). After univariate Cox regression we obtained 30 DRIGs and least absolute shrinkage and selection operator (LASSO) regression to reduce the number of genes to 16. Finally we created a nine-DRIGs risk model, of which four were upregulated and five were downregulated. The analysis results showed that disulfidptosis was tightly related to immune cells, immunological-related pathways, the tumor microenvironment (TME), immune checkpoints, human leukocyte antigen (HLA), and tumor mutational burden (TMB). The nomogram, integrating the risk score and clinical factors, accurately predicted overall survival. This novel risk model highlights the role of disulfidptosis-related immune genes in OSCC prognosis. With this model, we can more accurately predict the prognosis of patients with OSCC, as well as assess the potential effects of their TME and immunotherapy.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by xerostomia and autoimmune sialadenitis. Interferon-γ (IFN-γ) induces ferroptosis in salivary gland epithelial cells (SGECs), leading to salivary gland (SG) hypofunction. We previously demonstrated the beneficial effects of melatonin (MLT) in alleviating SG dysfunction and inflammation in a pSS animal model. However, the precise underlying mechanism remains unclear. Female NOD/ltj and ICR mice were used as the pSS mouse model and control group, respectively. MLT was administered via intraperitoneal injection to NOD/ltj mice to detect its effect on ferroptosis in SGs. Primary human SGECs and A253 cells were treated with IFN-γand ferroptosis inducers, with or without MLT. Exogenous MLT alleviated pathological SG alterations and promoted saliva production through inhibiting SGEC ferroptosis. MLT inhibited SGEC ferroptosis induced by IFN-γ and ferroptosis inducers via nuclear factor erythroid 2-related factor 2/heme oxygenase-1/glutathione peroxidase 4 (NRF2/HO-1/GPX4) pathway activation. Moreover, MLT suppressed the nuclear factor-kappa B (NF-κB) pathway, which is triggered by ferroptosis in SGECs. Nevertheless, ML385-mediated NRF2 inhibition abrogated the antiferroptotic protective effects of MLT on SGECs. MLT inhibits SGEC ferroptosis through NRF2/HO-1/GPX4 pathway activation and thus attenuates ferroptosis-triggered NF-κB activity. Melatonin represents a potential therapeutic approach for pSS owing to its capacity to regulate ferroptosis.

This report describes a 60-year-old female presenting with recurrent oral bleeding for 1.5 months after a fall-induced right buccal trauma, during which a branch pierced her check. After undergoing external debridement and suturing at a local hospital without intraoral repair, she developed a right buccal mass and severe anemia. Clinical examination revealed facial asymmetry, a right buccal depression with hyperpigmented skin, and an irregular cord-like scar-accompanied by a tender, nonpulsatile mass anterior to the right pterygomandibular ligament. Laboratory tests confirmed severe anemia (hemoglobin 55.8 g/L). Contrast-enhanced CT of the maxillofacial region identified a 40×27 mm pseudoaneurysm in the C1 segment of the right internal carotid artery, with adjacent soft tissue hematoma. Subsequent neurosurgical consultation confirmed the diagnosis of stab wound-induced internal carotid pseudoaneurysm. The patient underwent urgent transcatheter stent-assisted embolization under general anesthesia, and follow-up CT angiography demonstrating resolution of the pseudoaneurysm and patent carotid artery.

Purpose This study investigated TMED2 expression in oral squamous cell carcinoma (OSCC) and its effects on SCC9 cell behaviors, including proliferation, migration, invasion, and autophagy, to support OSCC diagnosis and treatment. Methods TMED2 expression was analyzed in TCGA and GEO databases, and protein levels in OSCC tissues were examined via HE staining and tissue microarrays. SCC9 cells, with high TMED2 expression, were used to assess TMED2's effects on cell proliferation, invasion, and cell cycle. TMED2 knockdown was performed with lentiviral vectors, and RT-PCR and Western blotting explored the autophagy and AKT/mTOR pathways. Tumor growth was tested in TMED2 knockdown and control cells in nude mice. Results TMED2 was highly expressed in OSCC, correlating with poor prognosis. Knockdown of TMED2 significantly reduced SCC9 cell proliferation, migration, and invasion, induced G0/G1 cell cycle arrest, reduced AKT/mTOR pathway activity, and increased autophagy, prolonging survival in tumor-bearing mice. Conclusion TMED2 is upregulated in OSCC, correlates with poor prognosis, and regulates cell proliferation, invasion, and autophagy, indicating it as a potential therapeutic target.

The development of artificial biomaterials that simulate the extracellular matrix of bone tissue is a promising strategy for bone regeneration. Hydrogel has become a feasible alternative, yet its lack of biological activity still needs to be improved. Herein, a piezoelectric composite hydrogel (TBP) based on tripolyglycerol monostearate (TM) and loaded with barium titanate (BTO) nanoparticles through hydrogen bonding provided by polydopamine has been developed to promote osteogenesis. In vitro, TBP exhibits excellent injectability, shape adaptability and biodegradability, ensuring the feasibility of its biological applications. Moreover, by virtue of the piezoelectric conversion capability of BTO, TBP has the response ability to low-intensity pulsed ultrasound (LIPUS) and can generate local electrical signals. Meanwhile, TBP performs outstandingly in promoting the proliferation, migration, adhesion and osteogenic differentiation of MC-3 T3-E1 cells. More importantly, TBP combined with LIPUS stimulation can regulate mitochondrial oxidative phosphorylation (OXPHOS) through the AKT/GSK3(3/(3-catenin signaling cascade, thereby accelerating osteogenesis. In vivo, the application of TBP hydrogel to the bone defect site of rats, combined with LIPUS stimulation, shows satisfactory effects in promoting bone regeneration. To sum up, this piezoelectric composite hydrogel is expected to become a promising candidate for bone tissue engineering.

Porphyromonas gingivalis (P. gingivalis) infection in oral squamous cell carcinoma (OSCC) undermines patient responses to standard therapies by driving chemoresistance, tumor progression, and immune suppression. Mounting research evidence—including our staining of clinical OSCC biopsies—confirms intratumoral P. gingivalis colonization and CXCL2 overexpression as risk factors for poor prognosis. Therefore, precisely eliminating tumor-promoting microorganisms and alleviating immune suppression are crucial for improving the treatment efficacy. Inspired by validated observations, we have developed a unique clinically oriented nanoparticle platform (MC-MM@MPDA) that integrated precise intracellular antibiotic delivery, photothermal tumor ablation, photothermal bactericidal and immune activation. Despite growing interest in OSCC photothermal ablation, this platform is the first to utilize the dual anti-tumor and antibacterial functions of photothermal therapy aiming to achieve targeted therapy tailored to P. gingivalis-infected OSCC. Minocycline (MC) was loaded into mesoporous polydopamine (MPDA) nanoparticles and encapsulated with macrophage membranes, enabling selective homing to infected tumor sites and efficient uptake by cancer cells. Subsequently, the nanoplatform utilized photothermal effects to ablate tumor tissue, eliminate intracellular bacteria and induce immunogenic cell death (ICD). pH-triggered antibiotic release eradicated residual bacteria and unleashed bacterial tumor associated antigens. Alongside damage-associated molecular patterns (DAMPs) generated by ICD, these signals reprogrammed the immunosuppressive microenvironment and established a synergistic antitumor network. In P. gingivalis infected OSCC xenograft models, this platform dramatically suppressed tumor growth, cleared pathogen burden, and overcame bacteria-mediated therapy resistance. By leveraging membrane-mimetic targeting, and synergistic photothermal-immunotherapy, MC-MM@MPDA offered a scalable, biocompatible, and readily translatable strategy to address pathogen-driven barriers in OSCC therapy.

Soft tissue wounds result in the loss of essential functions, including sensation and barrier protection. Mild photothermal therapy (PTT) has emerged as a promising therapeutic strategy for promoting wound healing and tissue regeneration, primarily through its ability to precisely regulate tissue temperature and thereby influence cellular proliferation and differentiation. In this study, gold nanorods (AuNRs) were employed as photosensitizers and co-cultured with fibroblasts to evaluate the effects of mild PTT on collagen organization and wound healing under the irradiation of 808 nm near-infrared (NIR) laser. AuNRs-mediated photothermal stimulation raised the temperature of the culture medium from 18.0 °C to 37.8 °C within 7 min. This controlled thermal stimulation significantly enhanced fibroblast proliferation and led to a more random distribution of collagen fibers. Moreover, AuNR-mediated mild PTT promoted the differentiation of fibroblast into myofibroblasts and reduced scar tissue formation. These findings highlight the therapeutic potential of mild PTT in soft tissue regeneration by modulating fibroblast behavior and remodeling collagen architecture.

BACKGROUND:Idiopathic condylar resorption (ICR) is a rare temporomandibular joint disease characterized by progressive condylar degeneration with an unknown etiology. A comprehensive quantitative analysis of the morphological differences in the condyle between ICR patients and normal individuals is crucial, yet limited by small sample sizes in existing literature. METHODS:This systematic review and meta-analysis were conducted following PRISMA guidelines. A random-effects model was employed to synthesize the mean differences in key condylar measurements between ICR patients and normal controls. RESULTS:The analysis revealed that ICR patients had significantly smaller condylar dimensions compared to normal individuals. The meta-analysis quantified the following reductions: Condylar height: -3.71 mm. Condylar width: -3.38 mm. Condylar length: -1.19 mm. Axial angle: -13.70°    . CONCLUSION:This study provides synthesized quantitative data on condylar morphology in ICR, however, the conclusions should be interpreted with caution due to the presence of heterogeneity and potential biases in the included studies.

Complete edentulism affects the quality of life and overall health. Identifying environmental factors linked to teeth lost may help address the global public health burden of oral health. This study aimed to estimate the association between neighborhood-level cumulative environmental burden and the prevalence of complete edentulism among the elderly across the US. This cross-sectional study of 72 333 US neighborhoods using US Census tract-level data on environmental burden index (EBI) from the US CDC. Mixed-effects linear regression was applied to assess the relationship between neighborhood EBI and the prevalence of edentulism among the elderly, overall and by levels of neighborhood characteristics. The associations between 5 environmental burden domains and complete edentulism prevalence were further investigated. In addition, age proportion score-based matching and geospatially-based matching analyses were conducted to verify the robustness of the findings. Across the US, compared to neighborhoods with the low-EBI, neighborhoods with the high-EBI were more likely to be located in the urban, to be more social vulnerable, have a lower percentage of males and the elderly (P < 0.001). After fully adjustment, the beta[95

How to accurately diagnose and treat bacterial infections in vivo remains a huge challenge. Therefore, we have developed a targeted delivery nanosystem by coextruding the pretreated macrophage membrane of S. aureus with carbon dots (M@CD). The M@CD nanosystem demonstrates potent antibacterial effects both in vivo and in vitro through the generation of reactive oxygen species (ROS). Furthermore, M@CD exhibits enhanced targeting ability and stable fluorescence properties, addressing issues such as poor targeting efficiency and high immunogenicity in vivo. This innovative approach enables infection site specific aggregation and elimination of bacterial infections, thereby providing a promising strategy for the integrated diagnosis, treatment, and monitoring of bacterial infections.

Introduction The relationship between vertical facial patterns and the morphology of the alveolar bone and teeth is crucial for successful orthodontic treatment planning. This study aimed to evaluate the relationship between vertical facial patterns, bone thickness, and root-crown dimensions in the maxillary anterior teeth. Methods This retrospective study screened 300 cone-beam computed tomography (CBCT) scans of orthodontic patients between December 2022 and November 2023, with 115 meeting the inclusion criteria. Buccal and lingual alveolar bone thickness, along with crown and root lengths of maxillary anterior teeth, were measured and compared across short, normal, and long facial types, classified according to the Frankfort-Mandibular Plane Angle. One-way ANOVA, independent-samples Kruskal-Wallis, and post-hoc tests were used for statistical analysis. Results Significant differences in alveolar bone thickness were observed across facial types, with short facial types showing consistently greater thickness in the apical and mid-palatal regions compared to normal and long facial types (p < 0.05). No significant differences in crown or root lengths were found among the facial types. Conclusion Facial type significantly influences alveolar bone thickness, particularly in short facial types, which demonstrate greater bone support. These findings underscore the importance of considering facial type in orthodontic treatment planning to minimize complications.

BACKGROUND:Ubiquitination, small ubiquitin-related modifiers, and NEDDylation are now found to function in cancer biology; however, its role in the oral cancer patients remains unclear.METHODS:A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ubiquitin and ubiquitin-like (UB/UBL) genes. A UB/UBL-related risk score was developed via correlation analyses, univariate Cox regression, and multivariate Cox regression. Nomogram analysis evaluates the model's prediction performance. The drug sensitivity analysis, immune profiles of UB/UBL-classified oral squamous cell carcinoma (OSCC) patients, and their related function pathway were investigated, and the role of UB/UBL-related genes in drug therapy was analyzed.RESULTS:A total of six prognostic UB/UBL-related genes were obtained. PSMD3, PCGF2, and H2BC10 were significantly downregulated in OSCC tissue and associated with longer survival time. OSCC patients in the high-risk group showed a significantly lower overall survival and enriched in cancer-related pathways. The prognostic potential of genes associated with UB/UBL was discovered, and patients with high-risk scores showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve of the annual survival rate was 0.616, 0.671, and 0.673, respectively. Besides, patients in the high-risk group are more sensitive to docetaxel, doxorubicin, and methotrexate therapy.CONCLUSIONS:We construct a prognosis model for OSCC patients with UB/UBL-related genes and try to find a new approach to treating oral cancer patients. The UB/UBL-related signature is helpful in developing new tumor markers, prognostic prediction, and in guiding treatment for OSCC patients.

Targeting tumor angiogenesis is an important approach in advanced tumor therapy. Here we investigated the effect of the suppressor of variegation 3-9 homolog 1 (SUV39H1) on tumor angiogenesis in oral squamous cell carcinoma (OSCC). The GEPIA database was used to analyze the expression of SUV39H1 in various cancer tissues. The expression of SUV39H1 in OSCC was detected by immunohistochemistry, and the correlation between SUV39H1 and Notch1 and microvascular density (MVD) was analyzed. The effect of SUV39H1 inhibition on OSCC was investigated in vivo by chaetocin treatment. The migration and tube formation of vascular endothelial cells by conditioned culture-medium of different treatments of oral squamous cell cells were measured. The transcriptional level of SUV39H1 is elevated in various cancer tissues. The transcription level of SUV39H1 in head and neck squamous cell carcinoma was significantly higher than that in control. Immunohistochemistry result showed increased SUV39H1 expression in OSCC, which was significantly correlated with T staging. The expression of SUV39H1 was significantly correlated with Notch1 and CD31. In vivo experiment chaetocin treatment significantly inhibit the growth of tumor, and reduce SUV39H1, Notch1, CD31 expression. The decreased expression of SUV39H1 in OSCC cells lead to the decreased expression of Notch1 and VEGF proteins, as well as the decreased migration and tube formation ability of vascular endothelial cells. Inhibition of Notch1 further enhance this effect. Our results suggest inhibition of SUV39H1 may affect angiogenesis by regulating Notch1 expression. This study provides a foundation for SUV39H1 as a potential therapeutic target for OSCC.