A novel compound alleviates oxidative stress via PKA/CREB1-mediated DJ-1 upregulation.

Oxidative stress is one of the major culprits causing dopaminergic neuron loss in Parkinson's disease (PD). DJ-1 is a protein with multiple actions against oxidative stress, apoptosis, neuroinflammation, etc. DJ-1 expression is decreased in sporadic PD, therefore increasing DJ-1 expression might be beneficial in PD treatment. However, drugs known to upregulate DJ-1 are still lacking. In this study, we identified a novel DJ-1-elevating compound called ChemJ through luciferase assay-based high-throughput compound screening in SH-SY5Y cells and confirmed that ChemJ upregulated DJ-1 in SH-SY5Y cell line and primary cortical neurons. DJ-1 upregulation by ChemJ alleviated MPP+-induced oxidative stress. In exploring the underlying mechanisms, we found that the transcription factor CREB1 bound to DJ-1 promoter and positively regulated its expression under both unstressed and 1-methyl-4-phenylpyridinium-induced oxidative stress conditions and that ChemJ promoted DJ-1 expression via activating PKA/CREB1 pathway in SH-SY5Y cells. Our results demonstrated that ChemJ alleviated the MPP+-induced oxidative stress through a PKA/CREB1-mediated regulation of DJ-1 expression, thus offering a novel and promising avenue for PD treatment.

Expressions of melanoma-associated antigen A1 as a prognostic factor in Chinese patients with resectable oesophageal squamous cell carcinoma.

OBJECTIVES: Melanoma-associated antigen A1 (MAGEA1) is a potential target for immunotherapy and has been associated with poor survival rate in several cancers. However, little is known about the prognostic predictive value of MAGEA1 in oesophageal squamous cell carcinoma (OSCC). This study aims to determine whether the expression of MAGEA1 is an independent predictor of survival in patients with resectable OSCC. METHODS: A retrospective analysis was performed on a large cohort of 197 patients with OSCC who underwent radical surgical treatment in the Department of Thoracic Surgery between January 2006 and December 2012. The expression of MAGEA1 in OSCC and matched normal oesophageal mucosa specimens from these patients was detected by immunohistochemistry with tissue microarray technology. RESULTS: The MAGEA1 protein was expressed in the cytoplasm and nucleus of tumour cells. The positive expression rate of MAGEA1 was significantly higher in OSCC tissue than in normal oesophageal mucosa (73.6% vs 5.6%, P < 0.001). MAGEA1 expression had no correlations with sex, age, history of smoking, alcohol consumption, family history of upper gastrointestinal cancer, T stage, lymph node metastasis, grade/location of the tumour or TNM stage (all at P > 0.05). Compared with those with negative MAGEA1 expression, patients with positive MAGEA1 expression were associated with a reduced overall survival rate (5-year survival rate: 53.8% vs 37.2%; P = 0.018). The multivariable analysis revealed that MAGEA1 expression is an independent predictor of prognosis (P = 0.007, hazard ratio 1.85, 95% confidence interval 1.19-2.89). CONCLUSIONS: The expression of MAGEA1 is abundant in Chinese patients with OSCC and is related to a worse clinical outcome. MAGEA1 may be a useful prognostic factor in patients with resectable OSCC.