Oxidative stress is one of the main pathogenic factors of neurodegenerative diseases. As the ligand of cannabinoid type 1 (cB1) and 2 (cB2) receptors, anandamide (AEA) exerts benign antioxidant activities. However, the instability of AEA results in low levels in vivo, which limit its further application. Based on the structure of AEA, N-linoleyltyrosine (NITyr) was synthesized in our laboratory and was hypothesized to possess a similar function to that of AEA. To the best of our knowledge, the present study demonstrates for the first time, the activities and mechanisms of NITyr. NITyr treatment attenuated hydrogen peroxide (H 2 O 2)-induced cytotoxicity, with the most promiment effect observed at 1 µmol/l. Treatment with NITyr also suppressed the H 2 O 2-induced elevation of reactive oxygen species (ROS) and enhanced the expression of the autophagy-related proteins, Lc3-II, beclin-1, ATG 5 and ATG13. The autophagic inhibitor, 3-methyladenine, reversed the effects of NITyr on ROS levels and cellular viability. Furthermore, AM251, a cB1 receptor antagonist, but not AM630 (a cB2 receptor antagonist), diminished the effects of NITyr on cell viability, ROS generation and autophagy-related protein expression. However, NITyr increased the protein expression of both the cB1 and cB2 receptors. Therefore, NITyr was concluded to protect Pc12 cells against H 2 O 2-induced oxidative injury by inducing autophagy, a process which may involve the cB1 receptor.

Background Hepatocellular carcinoma (HCC) is considered to be a malignant tumor with a high incidence and a high mortality. Accurate prognostic models are urgently needed. The present study was aimed at screening the critical genes for prognosis of HCC. Methods The GSE25097, GSE14520, GSE36376 and GSE76427 datasets were obtained from Gene Expression Omnibus (GEO). We used GEO2R to screen differentially expressed genes (DEGs). A protein-protein interaction network of the DEGs was constructed by Cytoscape in order to find hub genes by module analysis. The Metascape was performed to discover biological functions and pathway enrichment of DEGs. MCODE components were calculated to construct a module complex of DEGs. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. ONCOMINE was employed to assess the mRNA expression levels of key genes in HCC, and the survival analysis was conducted using the array from The Cancer Genome Atlas (TCGA) of HCC. Then, the LASSO Cox regression model was performed to establish and identify the prognostic gene signature. We validated the prognostic value of the gene signature in the TCGA cohort. Results We screened out 10 hub genes which were all up-regulated in HCC tissue. They mainly enrich in mitotic cell cycle process. The GSEA results showed that these data sets had good enrichment score and significance in the cell cycle pathway. Each candidate gene may be an indicator of prognostic factors in the development of HCC. However, hub genes expression was weekly associated with overall survival in HCC patients. LASSO Cox regression analysis validated a five-gene signature (including CDC20, CCNB2, NCAPG, ASPM and NUSAP1). These results suggest that five-gene signature model may provide clues for clinical prognostic biomarker of HCC.