Mori Cortex Radicis (MCR), the root bark of Morus alba L., consists of various phytochemicals and exhibits a strong inhibitory effect on tyrosinase. To enhance the tyrosinase inhibitory activity of MCR extract without further purification of bioactive compounds, whole MCR extract was biotransformed with crude enzyme extract from a selected lactic acid bacterium, Leuconostoc paramesenteroides PR (LP). Mulberroside A (MA), a major stilbene glucoside of MCR, contains two β-glucosyl residues at the C3 and C4' positions of oxyresveratrol (OXY). The crude enzyme of LP hydrolyzed the two glycosidic bonds of MA effectively, and 97.1% of MA was biotransformed into OXY within 2 h. Commercial almond β-glucosidase hydrolyzed only one site of the two glycosidic bonds of MA, and 68.7% of MA was biotransformed to OXY-glucoside. The tyrosinase inhibitory activity of the crude extract of MCR was increased approximately 6.5-fold by biotransformation using LP, and the IC(50) value of the transformed MCR was 3.7 µg/mL.

ABSTRACT. Mouse embryonic stem (mES) cells can be maintained in undifferentiated state in the presence of a cytokine, leukemia inhibitory factor (LIF). Many investigators found that STAT3 activation is important for the maintenance of pluripotency by LIF. However, the downstream pathways of STAT3 activation are still unknown. To look for STAT3-downstream target genes, we performed DD-RT PCR in the presence or absence of LIF. Through further confirmation, we finally selected 8 genes whose expressions were significantly dependent upon the presence of LIF. Among them, Jmjd1a was down-regulated after LIF withdrawal, and it was selected for further investigation. Its expression started to decrease 1 day after the removal of LIF, and disappeared on day 3. It was also shown that STAT3 could bind to the promoter region of Jmjd1a gene. These data demonstrate that Jmjd1a might be a critical signaling molecule underlying the maintenance of pluripotency in mES cells.

Reactivation of the p53 pathway by a potential therapeutic antagonist, which inhibits HDM2 and HDMX, is an attractive strategy for drug development in oncology. Developing blockers towards conserved hydrophobic pockets of both HDMs has mainly focused on small synthetic compounds; however, this approach has proved challenging. Here we describe an approach to generate a potent HDM dual inhibitor, p53LZ2, by rational protein grafting of the p53 transactivation domain onto a homodimeric leucine zipper. p53LZ2 shows tight binding affinity to both HDMs compared with wild-type p53 in vitro. X-ray crystallographic, comparative modelling and small-angle X-ray scattering studies of p53LZ2-HDM complexes show butterfly-shaped structures. A cell-permeable TAT-p53LZ2 effectively inhibits the cancer cell growth in wild-type but not mutant p53 by arresting cell cycle and inducing apoptosis in vitro. Thus, p53LZ2, designed by rational grafting, shows a potential therapeutic approach against cancer.