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To investigate hypoxia's effect in lymph node metastasis by prion protein (PRNP) expression changes and its main partners. The study was performed through 2 consecutive steps: In the first step, bioinformatics and cell culture were performed and then a case-control study comparing patients with head and neck squamous cell carcinoma (HNSC) with and without lymph node metastasis. The Cancer Genome Atlas (TCGA) data validated the hypothesis. Bioinformatics analysis suggests that hypoxia-inducible factor-1α (HIF1A) is associated with HSPA4, HSP90AA1, and PRNP expression. TCGA data validate the hypothesis that higher HSP90AA1, HSPA4, and PRNP are related to metastases and low survival. The cell study demonstrated that muted PRNP did not respond to hypoxia. These findings showed the importance of PRNP and its upregulation molecules in metastases. It was possible to conclude that PRNP promotes HNSC lymph node metastasis progression through the upregulation of HSPA4, HSP90AA1, and HIF1A. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Chronic dental periapical lesions result from chronic inflammation of periapical tissues caused by continuous antigenic stimulation from infected root canals. Recent findings have suggested that T helper (Th) 1 and Th2-like cytokines are important in the pathogenesis of chronic periapical inflammatory diseases. However, the mechanisms regulating these immunoinflammatory pathways have not been fully elucidated. Thus, the aim of this study was to evaluate interleukin (IL)-4, IL-12, and interferon γ (IFN-γ) protein levels in human radicular cysts and periapical granulomas. Methods: Archived samples of cysts (n = 52) and granulomas (n = 27) were sectioned and submitted to immunohistochemistry to evaluate the tissue expression of IL-4, IL-12, and IFN-γ. The data were analyzed using the Mann-Whitney U test (P < .05). Results: An increased expression of IFN-γ was observed in radicular cysts. IL-4 expression was stronger in periapical granulomas than in radicular cysts. IL-12 was not detected in any of the samples. Conclusions: Our study showed that IFN-γ protein levels are increased in radicular cysts, whereas IL-4 expression is stronger in samples of periapical granulomas. Further studies are necessary to elucidate the signaling pathways mediated by these cytokines and to facilitate the development of more effective periapical disease management strategies. [Copyright &y& Elsevier]