Up-regulation of TNF-alpha/NFkB/SIRT1 axis drives aggressiveness and cancer stem cells accumulation in chemoresistant oral squamous cell carcinoma.

Tumor resistance remains an obstacle to successfully treating oral squamous cell carcinoma (OSCC). Cisplatin is widely used as a cytotoxic drug to treat solid tumors, including advanced OSCC, but with low efficacy due to chemoresistance. Therefore, identifying the pathways that contribute to chemoresistance may show new possibilities for improving the treatment. This work explored the role of the tumor necrosis factor-alpha (TNF-alpha)/NFkB signaling in driving the cisplatin resistance of OSCC and its potential as a pharmacological target to overcome chemoresistance. Differential accessibility analysis demonstrated the enrichment of opened chromatin regions in members of the TNF-alpha/NFkB signaling pathway, and RNA-Seq confirmed the upregulation of TNF-alpha/NFkB signaling in cisplatin-resistant cell lines. NFkB was accumulated in cisplatin-resistant cell lines and in cancer stem cells (CSC), and the administration of TNF-alpha increased the CSC, suggesting that TNF-alpha/NFkB signaling is involved in the accumulation of CSC. TNF-alpha stimulation also increased the histone deacetylases HDAC1 and SIRT1. Cisplatin-resistant cell lines were sensitive to the pharmacological inhibition of NFkB, and low doses of the NFkB inhibitors, CBL0137, and emetine, efficiently reduced the CSC and the levels of SIRT1, increasing histone acetylation. The NFkB inhibitors decreased stemness potential, clonogenicity, migration, and invasion of cisplatin-resistant cell lines. The administration of the emetine significantly reduced the tumor growth of cisplatin-resistant xenograft models, decreasing NFkB and SIRT1, increasing histone acetylation, and decreasing CSC. TNF-alpha/NFkB/SIRT1 signaling regulates the epigenetic machinery by modulating histone acetylation, CSC, and aggressiveness of cisplatin-resistant OSCC and the NFkB inhibition is a potential strategy to treat chemoresistant OSCC.

HIV-Infected Individuals Do Not Present Significant Differences regarding Periodontal Status: A Systematic Review and Meta-Analysis.

Objective: To evaluate, through a systematic literature review, whether periodontal status in HIV-infected individuals is different from those non-HIV-infected. Materials and Methods: A systematic search for published observational studies within six electronic databases and grey literature was conducted, PROSPERO database number CRD42020160062. Results from studies reporting clinical periodontal parameters: probing pocket depth, bleeding on probing, clinical attachment level, plaque index, and gingival index, in HIV- and non-HIV-infected individuals were reviewed. The quality of the assessment was evaluated according to the Joanna Briggs Institute Appraise Checklist. Results: Twenty-three observational studies met the eligibility criteria and were included for analysis. The qualitative analysis indicated similarities in periodontal parameters within both groups, with no significant mean difference (MD) within both groups regarding clinical periodontal parameters; severe heterogeneity was also detected. Conclusions: No significant differences were found in the periodontal profile of HIV-infected and non-HIV-infected individuals. However, the high heterogeneity among the studies calls for caution in interpreting these findings. Further investigations using standardized methods for periodontal evaluation are needed to clarify the association between HIV infection and periodontal conditions.