DNp63, the N-terminal truncated isoform of p63, has been found to be overexpressed in several human epithelial cancers, including nasopharyngeal carcinomas (NPCs), suggesting a function in carcinogenesis. Trans-resveratrol (RSV) has been shown to exert proapoptotic activities through a p53-dependent or p53-independent pathway in various cancer cells. However, the effects of RSV on NPC are still unexplored. In this study, we investigated the apoptotic effects of RSV on DNp63-overexpressing NPC cell lines. We showed that RSV (12-100 mM) induced dose-dependent growth suppression, cell-cycle arrest in the S phase and caspasedependent apoptosis in NPC-TW076 and NPC-TW039 cells. The RSV effect was accompanied by the downregulation of DNp63 and the upregulation of p53 protein in a dose-dependent manner. By using small-interfering RNA (siRNA) technology, we found that the targeted silencing of DNp63 induced apoptosis and sensitized the NPC cells to RSV-induced apoptosis through caspase-3 activation, whereas suppression of p53 by siRNA did not inhibit RSV-induced apoptosis. Furthermore, transfection with p53 siRNA or pretreatment with caspase inhibitors (Z-VAD-fmk or Z-DEVD-fmk) had no influence on the RSV downregulation of DNp63. Interestingly, ecoptic expression of DNp63 did not significantly block RSV-induced cell death and was also downregulated after RSV treatment. Downregulation of DNp63 by RSV was shown to occur at the mRNA transcript and post-translational levels. Importantly, RSV enhanced chemotheraptic drug-induced apoptosis in NPC and two human carcinoma cell lines, HT1376 and Hep3B cells. These results suggested that DNp63, but not p53, is a molecular target of RSV-induced apoptosis and the regulation of DNp63 expression by RSV may provide a therapeutic effect of RSV in human NPC.

Rheumatoid arthritis (RA)

No abstract

Nonketotic hyperglycemia (NKH) is a clinical syndrome consisting of hyperglycemia, hyperosmolality and intracellular dehydration but not ketoacidosis. This prospective study evaluated the clinical and magnetic resonance imaging abnormalities in six patients with NKH complicated with simple or complex partial seizures. Subcortical T2 hypointensity rather than hyperintensity together with contrast enhancement was a characteristic feature of seizures associated with NKH. Restricted diffusion on DWI and decreased NAA and/or Choline on MRS studies were also noted.

No abstract