Synthesis of two new lipid mediators from docosahexaenoic acid by combinatorial catalysis involving enzymatic and chemical reaction.

Omega-3 polyunsaturated fatty acids (PUFAs) have been known to have beneficial effects in the prevention of various diseases. Recently, it was identified that the bioactivities of omega-3 are related to lipid mediators, called pro-resolving lipid mediators (SPMs), converted from PUFAs, so they have attracted much attention as potential pharmaceutical targets. Here, we aimed to build an efficient production system composed of enzymatic and chemical catalysis that converts docosahexaenoic acid (DHA) into lipid mediators. The cyanobacterial lipoxygenase, named Osc-LOX, was identified and characterized, and the binding poses of enzyme and substrates were predicted by ligand docking simulation. DHA was converted into three lipid mediators, a 17S-hydroxy-DHA, a 7S,17S-dihydroxy-DHA (RvD5), and a 7S,15R-dihydroxy-16S,17S-epoxy-DPA (new type), by an enzymatic reaction and deoxygenation. Also, two lipid mediators, 7S,15R,16S,17S-tetrahydroxy-DPA (new type) and 7S,16R,17S-trihydroxy-DHA (RvD2), were generated from 7S,15R-dihydroxy-16S,17S-epoxy-DPA by a chemical reaction. Our study suggests that discovering new enzymes that have not been functionally characterized would be a powerful strategy for producing various lipid mediators. Also, this combination catalysis approach including biological and chemical reactions could be an effective production system for the manufacturing lipid mediators.

Low-level laser irradiation facilitates fibronectin and collagen type I turnover during tooth movement in rats.

The aim of this study was to investigate the effects of low-level laser (LLL) irradiation on the turnover of fibronectin and collagen type I in periodontal tissue during tooth movement in rats by immunohistochemistry. Thirty male Sprague-Dawley rats aged 15 weeks were assigned to either an experimental group (n = 15) that underwent LLL irradiation during tooth movement, or a control group (n = 15). In the experimental group, the gallium-aluminum-arsenide (Ga-Al-As) diode LLL (wavelength 808 nm; output 96 mW) was used to irradiate three areas on both the palatal side and the labial side of the maxillary incisor. The radiation was administered by the contact method for 10 s at 0.83 J/cm(2) energy dose, once a day for 7 days. Total energy dose over the complete schedule was 34.86 J/cm(2). The animals were killed on days 1, 3, 7, 14 and 21. There was no difference between the two groups in the amount of tooth movement. The immunohistochemistry results showed that the expression of fibronectin and collagen type I in the experimental group had significantly increased from day 1, with a more even distribution than in the control group, and that this difference was maintained until the end of the experiment. These results suggest that LLL irradiation facilitates the reorganization of the connective tissues during tooth movement in rats.

Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells.

AIM OF THIS STUDY: Korean red ginseng (KRG, Panax ginseng C.A. Meyer Radix rubra) has been used to treat various diseases including cancer. However, the molecular mechanisms responsible for KRG extract induced apoptosis and telomerase inhibition remain unclear. MATERIALS AND METHODS: The hot water extract from KRG was used to evaluate the mechanism of induction of apoptosis in U937 human leukemia cells and its effects on cyclooxgenase-2 (COX-2) and telomerase activity. RESULTS: KRG extract treatment to U937 cells resulted in growth inhibition and induction of apoptosis in a concentration-dependent manner as measured by hemacytometer counts, MTT assay, fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. The increase in apoptosis was associated with the down-regulation of antiapoptotic Bcl-2, Bcl-X(L), and IAPs family members, and the activation of caspase-3. KRG extract treatment also decreased the expression levels of COX-2 and inducible nitric oxide synthase. Furthermore, KRG extract treatment progressively down-regulated the expression of human telomerase reverse transcriptase, a main determinant of the telomerase enzymatic activity, with inhibiting the expression of c-Myc in a concentration-dependent manner. CONCLUSIONS: These results provide important new insights into the possible molecular mechanisms of the anticancer activity of KRG extract.