Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study

Objective  

DNA repair pathways are crucial to prevent accumulation of DNA damage and maintain genomic stability. Alterations of this pathway have been reported in many cancers. An increase in oxidative DNA damage or decrease in DNA repair capacity with aging or due to germline genetic variation may affect prostate cancer risk.     

Identification of novel 17\-estradiol (E2) target genes using cross-experiment gene expression datasets

17β-estradiol (E2) is an environmental estrogen-like chemicals that is known to affect mainly reproductive functions of exposed targets. Although microarray based toxicogenomics approach allows the investigation of the potential risks of E2 in DNA level, the underling mechanisms related to their toxic effect is not fully understood. In this work, we identified genes responding toE2 by analyzing cross-experiment public gene expression datasets that studied on E2 using RankProd algorithm. We have identified 348 DEGs which play important roles in fatty acid metabolism, infection, and DNA repair. This result was also compared with conventional PubMed data mining analysis.     

Postprandial hypoglycemic effect of mulberry leaf in Goto-Kakizaki rats and counterpart control Wistar rats

Postprandial hypoglycemic effect of mulberry leaf (Morus alba L.) was compared in two animal models: Goto-Kakizaki (GK) rats, a spontaneous non-obese animal model for type II diabetes, and their counterpart control Wistar rats. First, the effect of a single oral administration of mulberry leaf aqueous extract (MLE) on postprandial glucose responses was determined using maltose or glucose as substrate. With maltose-loading, MLE reduced peak responses of blood glucose significantly in both GK and Wistar rats (P < 0.05), supporting the inhibition of α-glucosidase by MLE in the small intestine. With glucose-loading, MLE also significantly reduced blood glucose concentrations, measured at 30 min, in both animal models (P < 0.01), proposing the inhibition of glucose transport by MLE. Next, dried mulberry leaf powder (MLP) was administered for 8 weeks by inclusion in the diet. By MLP administration, fasting blood glucose was significantly reduced at weeks 4 and 5 (P < 0.05), but then returned to values that were similar to those of the control at the end of experimental period in GK rats. Insulin, HOMA-IR, C-reactive protein, and triglycerides tended to be decreased by MLP treatment in GK rats. All other biochemical parameters were not changed by MLP administration in GK rats. Collectively, these findings support that MLE has significant postprandial hypoglycemic effect in both non-obese diabetic and healthy animals, which may be beneficial as food supplement to manage postprandial blood glucose. Inhibitions of glucose transport as well as α-glucosidase in the small intestine were suggested as possible mechanisms related with the postprandial hypoglycemic effect of MLE.     

PRODUCTION AND CHARACTERIZATION OF AN ANTI-IDIOTYPIC SINGLE CHAIN FV THAT RECOGNIZES AN ANTI-DNA ANTIBODY

A well-characterized recombinant anti-idiotype to an anti-DNA antibody can be useful for studies of the regulation of anti-DNA-producing B cells. Using a hybridoma technique, a monoclonal anti-idiotypic antibody, designated O2F3, was obtained, and its scFv gene was constructed. O2F3 single chain Fv (scFv) was produced against an idiotope of a monoclonal anti-DNA antibody, 3D8, that was obtained from an autoimmune-prone mouse, MRL-lpr/lpr. Here we describe the production and in vitro characterization of the O2F3 scFv, and compare it with its parent monoclonal antibody, O2F3 IgM. To characterize O2F3 scFv and O2F3 IgM, we generated recombinant 3D8 fragments, including 3D8 scFv, 3D8 V_H, and 3D8 V_L, that were used as antigens in several assays. ELISA and Western blot analysis showed that both O2F3 scFv and O2F3 IgM recognized a conformational determinant formed by the association of the variable region heavy and light chains of the 3D8 antibody, suggesting that O2F3 scFv retained a similar binding pattern to its parent O2F3 antibody. The idiotope recognized by O2F3 was shown by competitive ELISA to be outside of the DNA binding site of the 3D8 antibody. This characterized O2F3 scFv could be applied for the regulation of anti-DNA antibody production and the manipulation of recombinant antibody-based proteins to which toxins, enzymes, and chemical agents can be connected.     

Melatonin Induces Akt Phosphorylation through Melatonin Receptor- and PI3K-Dependent Pathways in Primary Astrocytes

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.