Destruction of collagen is a hallmark of photoaging. The major enzyme responsible for collagen 1 digestion, matrix metalloproteinase-1 (MMP-1), is induced by exposure to sunlight. To study the molecular trigger for this induction, human skin was ultraviolet-B (UVB)-irradiated and treated with liposome-encapsulated DNA repair enzymes. The photolyase-mediated DNA repair of epidermal UV damage was associated with a reduction of MMP-1 mRNA and protein expression in both the epidermal and dermal compartments of the skin. The role of the epidermal cells in MMP-1 induction in the fibroblasts was examined when human epidermal keratinocytes were irradiated with UVB and their media were transferred to unirradiated human dermal fibroblasts. Transfer of media from irradiated keratinocytes to unirradiated fibroblasts enhanced MMP-1 mRNA and protein. Thus, UV damage to keratinocytes of the epidermis may participate in the destruction of collagen in the dermis by release of soluble mediators that signal fibroblasts to release MMP-1. The MMP-1 induction was reduced when the keratinocytes were treated with DNA repair enzymes T4 endonuclease V or UV endonuclease prior to transfer of the media to fibroblasts. This implies that UVB, which deposits most of its energy on the chromatin of the epidermal keratinocytes and to a lesser extent in the upper dermis, has a significant role in photoaging. DNA damage in the keratinocytes initiates one of the signals for MMP-1 release, and enhancing DNA repair can reduce MMP-1 expression in human skin cells and tissue.

Erlotinib failed to show an improvement in PFS or OS compared with docetaxel in an EGFR-unselected patient population.

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Ergothioneine (EGT) is a sulfur‐containing amino acid, and is presumed to function as a natural antioxidant. The purpose of this study was to identify the nature of the antioxidant activity and investigate the effects of EGT on UV‐induced cellular response. In chemical studies, EGT scavenged the superoxide anion radical (•O2–) and singlet oxygen (1O2). In cultured fibroblasts, EGT suppressed TNF‐α upregulation by UVB irradiation. In addition, in fibroblasts exposed to UV‐A, EGT suppressed the expression of matrix metalloproteinase 1 (MMP‐1) protein by nearly 50% and reduced MMP‐1 mRNA expression. From these results, we conclude that EGT scavenges reactive oxygen species generated by both type I and type II photosensitization and suppresses both TNF‐α expression and MMP‐1 at their transcriptional level. EGT may reduce skin anti‐aging effects after UV irradiation by the scavenging of •O2– and 1O2, and reducing signals for protease and inflammatory activity.

It is recognized that reactive oxygen species (ROS) are responsible for skin damage due to UVB-radiation (UVB-R). However, the triggering substance(s) for ROS generation after UVB-R is uncertain with respect to the activation of NADPH oxidase (Nox), xanthine oxidase (XOD), and respiratory chain-chain reactions in mitochondria. As a first step in identifying the trigger(s) for UVB-induced ROS generation, we examined the relationship between Ca(2+) levels and ROS generation in HaCaT keratinocytes. UVB-R exposure of HaCaT keratinocytes resulted in an immediate elevation of ROS that recurred 7 hours later. This was accompanied by immediately elevated intracellular Ca(2+) . A Ca(2+) chelating agent, BAPTA, abolished the elevation of ROS after UVB-R completely. In addition, exogenous H(2)O(2) did not increase intracellular Ca(2+) levels. This suggests that intracellular Ca(2+) is the first trigger for UVB-induced ROS generation.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 50-52; doi:10.1038/jidsymp.2009.12.

The dependence on laser intensity and pulse duration in energetic proton acceleration by irradiation of ultrashort laser pulses on a 5μm thick copper tape target was measured. The laser intensity was varied from 8.5×1017W∕cm2 to 1.1×1019W∕cm2, and the pulse duration from 55 fs to 400 fs. The maximum proton energy increased as the pulse duration was increased while the laser intensity was kept constant. The dependence of the maximum proton energy on laser intensity and pulse duration was in good agreement with an analytical plasma-expanding model.

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