Parkinson’s disease (PD) is a quite common neurodegenerative disorder with a prevalence of approximately 1:800–1,000 in subjects over 60 years old. The aim of our study was to determine the candidate target genes in PD through meta-analysis of multiple gene expression arrays datasets and to further combine mRNA and miRNA expression analyses to identify more convincing biological targets and their regulatory factors. Six included datasets were obtained from the Gene Expression Omnibus database by systematical search, including five mRNA datasets (150 substantia nigra samples in total) and one miRNA dataset containing 32 peripheral blood samples. A chip meta-analysis of five microarray data was conducted by using the metaDE package and 94 differentially expressed (DE) mRNAs were comprehensively obtained. And 19 deregulated DE miRNAs were obtained through the analysis of one miRNAs dataset by Qlucore Omics Explorer software. An interaction network formed by DE mRNAs, DE miRNAs, and important pathways was discovered after we analyzed the functional enrichment, protein–protein interactions, and miRNA targetome prediction analysis. In conclusion, this study suggested that five significantly downregulated mRNAs (MAPK8, CDC42, NDUFS1, COX4I1, and SDHC) and three significantly downregulated miRNAs (miR-126-5p, miR-19-3p, and miR-29a-3p) were potentially useful diagnostic markers in clinic, and lipid metabolism (especially non-alcoholic fatty liver disease pathway) and mitochondrial dysregulation may be the keys to biochemically detectable molecular defects. However, the role of these new biomarkers and molecular mechanisms in PD requires further experiments in vivo and in vitro and further clinical evidence.

Nowadays, it is still quite challenging to achieve early diagnosis of Alzheimer's disease (AD) in clinic. The burgeoning near-infrared fluorescence (NIRF) imaging fulfills the requirements for precise diagnosis with good...

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Androgen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.

Job Stress and Carotid Intima-media Thickness in Chinese Workers: Weixian XU, et al. Department of Cardiology, Peking University ThirdHospital and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China-Objectives: Carotid intima-media thickness (CIMT) can be used as a surrogate marker for cardiovascular health, and job stress is a risk factor for cardiovascular disease. However, there have been a limited number of studies focusing on the association between job stress and CIMT. The goal of this study was to explore the association between job stress and CIMT in a Chinese working population. Methods: The study included 734 participants (508 males and 226 females) without coronary heart disease. Job stress was evaluated using the effort-reward imbalance (ERI) questionnaire at work. ERI is the ratio between efforts and rewards (weighted by number of items). High resolution carotid ultrasonographic studies were performed using a Sequoia 512 ultrasound system with an 8-13 MHz linear array transducer to assess CIMT. Results: This study detected gender-specific associations between the indictors of the ERI model and increased CIMT among the study participants in China. This study demonstrated a robust association in women between the key indicators of ERI, effort, overcommitment and ERI, and increased CIMT (adjusted r 2 =0.258, p=0.001; adjusted r 2 =0.261; p<0.001; adjusted r 2 =0.274; p<0.001, respectively). Reward was inversely correlated with CIMT (adjusted r 2 =0.282, p<0.001), controlling for age, hypertension, diabetes mellitus, hyperlipidaemia and body mass index. For men, a similar pattern of associations was observed, but the associations were lost after adjustment for confounders. Conclusions: Our resultsshow that effort, overcommitment and ERI may be associated with early atherosclerosis predicted by CIMT in women, and reward is inversely related to CIMT. (J Occup Health 2010; 52: 257-262)