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Aims and Methods: Retrospectively, this paper compared the differences of the Epstein–Barr virus (EBV)-encoded small RNAs (EBERs), protein expression and gene mutations of tumor suppressor gene p53 (TP53) in keratinized nasopharyngeal squamous cell carcinoma (KNSCC) and nonKNSCC, and the relationships between pathological features and the prognosis of patients were analyzed. Results: The positive rate of EBERs hybridization and TP53 expressions was 76.3% and 52.2%, respectively, while the mutation rate of TP53 gene was 39.6%. Logistic regression analysis showed direct relationships between the subtypes of nasopharyngeal squamous cell carcinoma (NPSCC) and EBERs-positive, or frequent consumption of pickled food. Overall survival rates of patients with positive TP53 expression, the TP53 gene mutations, vascular invasions, organ metastases, lymph node metastasis, and clinical recurrence were significantly lower than those of patients without those symptoms. The poorer prognosis was related to regularly drinking and the advanced age. According to the Cox regression analysis, we found that the main prognostic factors of NPSCC patients were the aging, recurrence, TP53 gene mutations, especially exon 7 or 8 mutations. Conclusions: We concluded that there were the correlations between NPSCC subtypes with EBV infection and frequent intaking of pickled food, while aging, clinical recurrence, and TP53 gene mutations were independent predictors for the poor prognosis of nasopharyngeal carcinoma
ABSTRACT
OBJECTIVES: The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment. METHODS: Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-κB (NF-κB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague-Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1β (IL-1β) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting. RESULTS: In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1β, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1β levels were observed after stroke, and hypothermia treatment was associated with lower IL-1β levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome. CONCLUSIONS: Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.