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Metformin is the most commonly prescribed drug for type 2 diabetes mellitus. In recent years, in addition to glucose lowering, several studies have presented evidence suggesting some potential role for metformin, such as antitumor effect, antiaging effect, cardiovascular protective effect, neuroprotective effect or an optional treatment for polycystic ovary syndrome. This paper will critically review the role of metformin to provide reference for doctors and researchers.

GW112 is a novel gene that has little homology to other known genes. It is overexpressed in a number of human tumor types, especially in those of the digestive system. We show here that GW112 is associated with GRIM-19, a protein known to be involved in regulating cellular apoptosis. Functionally, GW112 could significantly attenuate the ability of GRIM19 to mediate retinoic acid-IFN-␤-mediated cellular apoptosis and apoptosis-related gene expression. In addition, GW112 demonstrated strong antiapoptotic effects in tumor cells treated with other stress exposures such as hydrogen peroxide. Finally, forced overexpression of GW112 in murine prostate tumor cells led to more rapid tumor formation in a syngeneic host. Taken together, our data suggest that GW112 is an important regulator of cell death that plays important roles in tumor cell survival and tumor growth.

Transplantation of exogenous dopaminergic neuron (DA neurons) is a promising approach for treating Parkinson's disease (PD). However, a major stumbling block has been the lack of a reliable source of donor DA neurons. Here we show that a combination of five transcriptional factors Mash1, Ngn2, Sox2, Nurr1, and Pitx3 can directly and effectively reprogram human fibroblasts into DA neuron-like cells. The reprogrammed cells stained positive for various markers for DA neurons. They also showed characteristic DA uptake and production properties. Moreover, they exhibited DA neuron-specific electrophysiological profiles. Finally, they provided symptomatic relief in a rat PD model. Therefore, our directly reprogrammed DA neuron-like cells are a promising source of cell-replacement therapy for PD.

QBlC* lets users find pictorial information in large image and video databases based on color, shape, texture, and sketches. QBIC technology is part of several I B M products. 'To run an interacnve query, vult the QBIC Web sewer at http //imwqbic almaden ibm COW Semantic versus nonsemantic information icture yourself as a fashion designer needing images of fabrics with a particular mixture of colors, a museum cataloger looking P for artifacts of a particular shape and textured pattern, or a movie producer needing a video clip of a red car-like object moving from right to left with the camera zooming. How do you find these images? Even though today's technology enables us to acquire, manipulate, transmit, and store vast on-line image and video collections, the search methodologies used to find pictorial information are still limited due to difficult research problems (see "Semantic versus nonsemantic" sidebar). Typically, these methodologies depend on file IDS, keywords, or text associated with the images. And, although powerful, they don't allow queries based directly on the visual properties of the images, are dependent on the particular vocabulary used, and don't provide queries for images similar to a given image. Research on ways to extend and improve query methods for image databases is widespread, and results have been presented in workshops, conferences,'.* and surveys. We have developed the QBIC (Query by Image Content) system to explore content-based retrieval methods. QBIC allows queries on large image and video databases based on example images, user-constructed sketches and drawings, selected color and texture patterns,

a b s t r a c tHepatocellular carcinoma (HCC) is the most common type of liver cancer. HDAC6 is a transcriptional regulator of the histone deacetylase family, subfamily 2. Previous studies have shown that HDAC6 plays critical roles in transcription regulation, cell cycle progression and developmental events. However, its biological roles in the development of HCC remain largely unexplored. In the present study, we found that mRNA and protein levels of HDAC6 were up-regulated in HCC tissues and cell lines. The proinflammatory cytokines, which were up-regulated in the human HCC microenvironment, increased HDAC6 expression through a proximal NF-kappaB binding site on the HDAC6 gene promoter. Furthermore, overexpression of HDAC6 could promote cell proliferation in HCC cell lines. In contrast, HDAC6 knockdown using small interfering RNA inhibited cell proliferation. At the molecular level, we demonstrated that HDAC6 could interact with p53 and attenuate its transcriptional activity through promotion of its degradation. Therefore, our results suggest a previously unknown HDAC6-p53 molecular network controlling HCC development.

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