Causal Relationship between Mitochondrial Biological Function and Periodontitis: Evidence from a Mendelian Randomization Study.

A growing number of studies indicate that mitochondrial dysfunction serves as a pathological mechanism for periodontitis. Therefore, this two-sample Mendelian randomization (MR) study was carried out to explore the causal associations between mitochondrial biological function and periodontitis, because the specific nature of this causal relationship remains inconclusive in existing MR studies. Inverse variance weighting, Mendelian randomization-Egger, weighted mode, simple mode, and weighted median analyses were performed to assess the causal relationships between the exposure factors and periodontitis. The results of the present study revealed a causal association between periodontitis and medium-chain specific acyl-CoA dehydrogenase (MCAD), malonyl-CoA decarboxylase (MLYCD), glutaredoxin 2 (Grx2), oligoribonuclease (ORN), and pyruvate carboxylase (PC). Notably, MCAD and MLYCD are causally linked to periodontitis, and serve as protective factors. However, Grx2, ORN, and PC function as risk factors for periodontitis. Our study established a causal relationship between mitochondrial biological function and periodontitis, and such insights may provide a promising approach for treating periodontitis via mitochondrial regulation.

Survival Rates of Splinted and Nonsplinted Prostheses Supported by Short Dental Implants (≤8.5 mm): A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate and compare the implant survival rates, marginal bone loss, and mechanical complications of prostheses supported by splinted and nonsplinted short implants (≤8.5 mm). MATERIAL AND METHODS: Electronic database (MEDLINE, CENTRAL, Web of Science, and EMBASE) and manual searches up to May 2021 were conducted to identify studies comparing splinted and nonsplinted short implants (≤8.5 mm). The primary outcome was implant survival rate. Secondary outcomes were marginal bone loss and mechanical complications. The quality of included studies and risk-of-bias were assessed according to the Newcastle-Ottawa Scale. A random-effects model was used to analyze the data. RESULTS: Twelve studies fulfilled the inclusion criteria and featured 1506 short implants (596 nonsplinted and 910 splinted) with a follow-up time ranging from 1 to 16 years. Quantitative analysis found no statistically significant differences between splinted and nonsplinted short implants (≤8.5 mm) for survival rate (RR = 0.98; 95% CI 0.96, 1.01; p = 0.26)) and marginal bone loss (SMD = -0.08; 95% CI - 0.23, 0.07; p = 0.28). Veneer chipping, abutment screw breakage, screw loosening, and loss of retention were reported in the selected studies as common complications. However, no statistically significant difference was found between splinted and nonsplinted short implants (RR = 0.56; 95% CI 0.20, 1.54; p = 0.26). CONCLUSIONS: Within the limitations of the present meta-analysis, it might be concluded that splinted short implants (≤8.5 mm) do not present superior performance in survival rate, marginal bone maintenance and prevention of mechanical complications compared with single-unit prostheses.

Comprehensive Characterization of Immune Landscape Based on Epithelial-Mesenchymal Transition Signature in OSCC: Implication for Prognosis and Immunotherapy.

Current anatomic TNM stage classification fails to capture the immune heterogeneity of oral squamous cell carcinoma (OSCC). Increasing evidence indicates the strong association between epithelial-mesenchymal transition (EMT) and tumor immune response. In this study, we employed an EMT signature to classify OSCC patients into epithelial- (E-) and mesenchymal- (M-) phenotypes using TCGA and GSE41613 transcriptome data. The ESTIMATE and CIRBERSORT analyses implied that the EMT signature genes originated from the stroma of the bulk tissue. The M-subtype tumors were characterized as "immune-hot" with more immune cell infiltration than the E-subtype ones. The low infiltration of active immune cells, the high infiltration of inactive immune cells, and the high expressions of immune checkpoints demonstrated an immunosuppressive characteristic of the M-subtype tumors. Moreover, we developed and validated a novel prognostic classifier based on the EMT score, the expressions of seven immune checkpoints, and the TNM stages, which could improve the prediction efficiency of the current clinical parameter. Together, our findings provide a better understanding of the tumor immune heterogeneity and may aid guiding immunotherapy in OSCC.

Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma.

Immunotherapy has been demonstrated as a promising strategy in controlling head and neck squamous cell carcinoma (HNSC). The AID/APOBEC family is well characterized as DNA mutator and considered to play critical roles in immune responses in HNSC. However, the expression pattern and deamination-dependent demethylation roles of AID/APOBECs in HNSC are unclear. In this study, the RNA-seq and DNA methylation profiles of HNSC from TCGA database and cell-based experiments were applied to analyze the relationships between AID/APOBEC expression levels, patients' clinical outcomes, methylation alterations, and immune responses. Here, we found that APOBEC3H was abnormally upregulated in HNSC patients. HPV+ patients tended to have higher APOBEC3H levels than HPV- patients. Remarkably, patients with high APOBEC3H levels showed a favorable overall survival. Furthermore, tumors with high APOBEC3H levels exhibited a genome-wide DNA hypomethylation pattern. APOBEC3H was identified to demethylate and upregulate CXCL10 and improve CD8+ T cell tumor infiltration in the tumor microenvironment. Collectively, APOBEC3H plays critical roles in CD8+ T cell immune infiltration and activation in HNSC, which may be a potential biomarker for oncoimmunotherapy in HNSC.