Blood vessels sense dermal stiffness via a novel mechanotransducer, APJ.

Microvascular dysfunction accompanied by a dramatic alteration of stable capillary structure is a major hallmark of numerous age-related diseases. In skin, although the role of angiogenesis during dermal reconstitution is well documented, the functional relevance of the extracellular matrix (ECM) stiffness to vascular remodeling and its molecular mechanisms was poorly understood. Here, we developed an ex vivo 3-dimensional angiogenic model using human fat, revealing that "appropriate" stiffness induces vascular maturation associated with upregulated APJ expression, whereas the overexpression of APJ promotes the formation of large vessels even in the absence of the "appropriate" stiffness. Taken together, APJ could be a novel mechanotransducer that accelerates the maturation of cutaneous blood vessels, leading to the prevention of human skin aging.

Perception of human skin conditions and image statistics.

The color and texture of human skin provide useful information in evaluating a person's health, emotion, attractiveness, and so on. Whereas the appearance of skin is a product of optical properties originating from its own biophysical substrates, recent psychophysical studies of surface material perception indicate a possibility that humans can perceive skin conditions from relatively simple image features such as texture statistics. The present study investigated the structure of multidimensional perceptual rating data for 289 female skin images and analyzed diagnostic low-level image statistics. We found that various skin appearances can be summarized into two dimensions, pleasantness and glossiness, and either dimension is well correlated with a small set of subband luminance and color statistics. We confirmed that manipulations of these critical image statistics significantly alter the appearance of skin in the expected direction. The results support a notion that humans perceive skin properties essentially based on two cardinal dimensions as predicted by simple image statistics.

Generation of 'Unnatural Natural Product' library and identification of a small molecule inhibitor of XIAP.

Natural products have been utilized for drug discovery. To increase the source diversity, we generated a new chemical library consisting of chemically modified microbial metabolites termed 'Unnatural Natural Products' by chemical conversion of microbial metabolites in crude broth extracts followed by purification of reaction products with the LC-photo diode array-MS system. Using this library, we discovered an XIAP inhibitor, C38OX6, which restored XIAP-suppressed enzymatic activity of caspase-3 in vitro. Furthermore, C38OX6 sensitized cancer cells to anticancer drugs, whereas the unconverted natural product did not. These findings suggest that our library could be a useful source for drug seeds.