This study explored the role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in hippocampal neuron autophagy in rats with chronic intermittent hypoxia (CIH). Sixty-four male Sprague-Dawley rats were randomly divided to normoxic control (CON), CIH (subdivided into groups A, B, and C undergoing intermittent hypoxia for 2, 4, and 6 weeks, respectively), solvent (CIH+Veh), or p38MAPK inhibitor (CIH+SB203580) groups. DMSO and SB203580 were injected intraperitoneally 30 min before hypoxia in CIH+Veh and CIH+SB203580 group rats, respectively. Rat learning and memory were evaluated via the Morris water maze test. Ultrastructural changes in the hippocampal CA1 region autophagic vesicles and neurons were observed under transmission electron and light microscopy. Hippocampal microtubule-associated proteins were detected by western blot. Morris water maze test showed that CIH+SB203580 group rats spent significantly more time on the platform quadrant and crossed the platform more times than CIH+Veh group rats (P < 0.01). HE staining showed greater rat cell damage in the CIH+SB group than in the CIH and CIH+Veh groups. Western blot analysis showed that CIH+SB group rats had significantly lower p-p38MAPK/p38MAPK, LC3I, and p62 expression and higher beclin-1 expression than CIH+Veh group rats (P < 0.01). Electron microscopy showed that CIH+SB203580 group rats had several small hippocampal neuron autophagic vesicles. On immunofluorescence analyses, it showed a higher LC3II expression in CIH+SB203580 group rats than in CIH+Veh group rats (P < 0.01). These results indicate that inhibition of the CIH p38MAPK signaling pathway can activate autophagy and protect hippocampal neurons in rats.

Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide. E2Fs are a group of transcription factors involved in the carcinogenesis and progression of various cancers. However, the exact roles of each member of E2F family in the development and progression of HNSCC are still unknown. Methods RNASeq and clinical follow-up information were extracted from The Cancer Genome Atlas (TCGA). The expressions of E2Fs and their roles in HNSCC progression were explored using the R software and the cBioPortal database. Results Our results showed that the mRNA levels of E2Fs were significantly higher in HNSCC tumors than in normal tissues. E2F1, E2F3, E2F4, E2F6, and E2F7 were identified as reliable diagnostic markers. E2Fs (except for E2F3) expressions were closely related to the clinical features (excluding metastasis) of HNSCC. High E2F6 mRNA expression was an independent risk factor for the OS of female HNSCC patients. In addition, high E2F4 expression could lead to poor prognosis in HNSCC in both males and females, high expressions of E2F5, E2F6, and E2F7 were associated with poor OS of female HNSCC patients, while high E2F2 and E2F8 expressions were positively correlated with the OS of male HNSCC patients. Interestingly, E2Fs expressions had stronger associations with immune cell infiltrations in male HNSCC patients than in female HNSCC patients. Conclusion The expressions of E2Fs were found to be correlated with the progression of HNSCC. E2F1, E2F3, E2F4, E2F6, and E2F7 could be good diagnostic molecules for HNSCC. In addition, E2F6 was an independent risk factor for the prognosis of female HNSCC patients.

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