A cleaved adhesin DNA vaccine targeting dendritic cell against Porphyromonas gingivalis-induced periodontal disease.

BACKGROUND: Arg-gingipain A (RgpA) is the primary virulence factor of Porphyromonas gingivalis and contains hemagglutinin adhesin (HA), which helps bacteria adhere to cells and proteins. Hemagglutinin's functional domains include cleaved adhesin (CA), which acts as a hemagglutination and hemoglobin-binding actor. Here, we confirmed that the HA and CA genes are immunogenic, and using adjuvant chemokine to target dendritic cells (DCs) enhanced protective autoimmunity against P. gingivalis-induced periodontal disease. METHODS: C57 mice were immunized prophylactically with pVAX1-CA, pVAX1-HA, pVAX1, and phosphate-buffered saline (PBS) through intramuscular injection every 2 weeks for a total of three administrations before P. gingivalis-induced periodontitis. The DCs were analyzed using flow cytometry and ribonucleic acid sequencing (RNA-seq) transcriptomic assays following transfection with CA lentivirus. The efficacy of the co-delivered molecular adjuvant CA DNA vaccine was evaluated in vivo using flow cytometry, immunofluorescence techniques, and micro-computed tomography. RESULTS: After the immunization, both the pVAX1-CA and pVAX1-HA groups exhibited significantly elevated P. gingivalis-specific IgG and IgG1, as well as a reduction in bone loss around periodontitis-affected teeth, compared to the pVAX1 and PBS groups (p < 0.05). The expression of CA promoted the secretion of HLA, CD86, CD83, and DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) in DCs. Furthermore, the RNA-seq analysis revealed a significant increase in the chemokine (C-C motif) ligand 19 (p < 0.05). A notable elevation in the quantities of DCs co-labeled with CD11c and major histocompatibility complex class II, along with an increase in interferon-gamma (IFN-γ) cells, was observed in the inguinal lymph nodes of mice subjected to CCL19-CA immunization. This outcome effectively illustrated the preservation of peri-implant bone mass in rats afflicted with P. gingivalis-induced peri-implantitis (p < 0.05). CONCLUSIONS: The co-administration of a CCL19-conjugated CA DNA vaccine holds promise as an innovative and targeted immunization strategy against P. gingivalis-induced periodontitis and peri-implantitis.

Prognostic signature related to the immune environment of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) prognosis remains poor. Here we aimed to identify an effective prognostic signature for predicting the survival of patients with OSCC. Gene-expression and clinical data were obtained from the Cancer Genome Atlas database. Immune microenvironment-associated genes were identified using bioinformatics. Subtype and risk-score analyses were performed for these genes. Kaplan-Meier analysis and immune cell infiltration level were explored in different subtypes and risk-score groups. The prognostic ability, independent prognosis, and clinical features of the risk score were assessed. Furthermore, immunotherapy response based on the risk score was explored. Finally, a conjoint analysis of the subtype and risk-score groups was performed to determine the best prognostic combination. We found 11 potential prognostic genes and constructed a risk-score model. The subtype cluster 2 and a high-risk group showed the worst overall survival; differences in survival status might be due to the different immune cell infiltration levels. The risk score showed good performance, independent prognostic value, and valuable clinical application. Higher risk scores showed higher Tumor Immune Dysfunction and Exclusion scores, indicating that patients with a high-risk score were less likely to benefit from immunotherapy. Finally, conjoint analysis for the subgroups and risk groups showed the best predictive ability.

Study on the utilization factors of oral health services of children aged 7-8 years in Weifang.

OBJECTIVES: This study aims to determine factors influencing the oral health service utilization behavior of children aged 7-8 years in Weifang based on Anderson health services utilization model. METHODS: Based on the National Comprehensive Oral Disease Intervention Project, 1 826 children aged 7-8 years were selected from 10 elementary schools in four districts of Weifang City by whole-group random sampling as the study population. The modified Anderson model was used as the theoretical framework to explore the effects of situational characteristics, population characteristics, and medical behavior on children ' s oral health service utilization. RESULTS: The oral visit rate of children within 1 year was 39.8% (726 cases), of which 47.2% (342 cases) were curative visits, 20.9% (152 cases) were consultative visits, and 10.7% (78 cases) were preventive visits. Multi-factor logistic regression analysis showed that frequent parental supervision during tooth brushing, frequent parental observation of dental health, parental education level of college and above, experience of dental pain or discomfort in the last year, and poor oral health evaluated by physician were the main factors that influenced the utilization of oral health services among children (P<0.05). CONCLUSIONS: The rate of preventive dental visits of children is low, and parents' awareness of children ' s oral health care affects the utilization rate of oral health services. Hence, parents should be taught more about children ' s oral health care to improve the utilization of children ' s health services.

Targeting lncRNA PSMA3-AS1, a Prognostic Marker, Suppresses Malignant Progression of Oral Squamous Cell Carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) represents the most common maxillofacial malignancy. This study elucidated the clinicopathological value and molecular mechanisms of PSMA3 antisense RNA 1 (PSMA3-AS1) in OSCC. METHODS: Totally, 135 OSCC patients were recruited. PSMA3-AS1 expression and its prognostic value were assessed in this cohort. si-PSMA3-AS1 was transfected into HN4 and CAL-27 OSCC cells. Then, cell proliferation was evaluated by CCK-8, colony formation, and EdU staining. Migration and invasion were investigated through wound healing, transwell, and western blot. The PSMA3-AS1/miR-136-5p and miR-136-5p/FN1 interactions were validated by dual luciferase report, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot. RESULTS: PSMA3-AS1 upregulation was determined in OSCC tissues. The upregulation indicated pessimistic patients' outcomes. Multivariate Cox regression analyses confirmed PSMA3-AS1 as an independent prognostic indicator. Its upregulation was also found in OSCC cells. Under transfection with si-PSMA3-AS1, proliferation, migration, and invasion were all restrained in HN4 and CAL-27 OSCC cells. Furthermore, its knockdown induced the increase in E-cadherin expression and the reduction in N-cadherin and Vimentin expression. PSMA3-AS1 was a sponge of miR-136-5p. Mutual inhibition was found between two and the interactions were confirmed by dual luciferase report. It was confirmed that FN1 was a target of miR-136-5p. FN1 expression was increased by miR-136-5p inhibitors, which was lessened by si-PSMA3-AS1 cotransfection. CONCLUSION: Collectively, PSMA3-AS1 as a risk factor facilitated malignant behaviors of OSCC cells, related to the miR-136-5p/FN1 axis. Hence, PSMA3-AS1 as a potential therapeutic target for OSCC deserved further exploration.

Circular RNA FNDC3B Protects Oral Squamous Cell Carcinoma Cells From Ferroptosis and Contributes to the Malignant Progression by Regulating miR-520d-5p/SLC7A11 Axis.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy with increasing mortality and high recurrence. Ferroptosis is an emerging programed cell death and plays an essential role in tumorigenesis. Circular RNAs (circRNAs) have been reported as a type of critical regulators in OSCC development. In this study, we identified the function of circular RNA FNDC3B (circFNDC3B) in regulating ferroptosis during the malignant progression of OSCC. Our data demonstrated that the silencing of circFNDC3B by shRNA inhibited GPX4 and SLC7A11 expression and enhanced ROS, iron, and Fe2+ levels in OSCC cells. CircFNDC3B knockdown reinforced erastin-induced inhibitory effect on OSCC cells. The depletion of circFNDC3B repressed cell proliferation and enhanced cell apoptosis of OSCC cells. Mechanically, circFNDC3B was able to increase SLC7A11 by targeting miR-520d-5p. The overexpression of SLC7A11 reversed circFNDC3B depletion or miR-520d-5p-induced ferroptosis phenotypes of OSCC cells. Moreover, tumorgenicity assays in nude mice showed that the depletion of circFNDC3B repressed OSCC cell growth in vivo. Taken together, we concluded that circFNDC3B attenuated ferroptosis of OSCC cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC.