The number of women with sensitive skin has increased recently. Sensitive skin is associated with a decline in barrier function of the stratum corneum induced by a weak inflammation. However, other causes of sensitive skin, including skin color, have not been investigated in detail. We investigated skin-related complications in women between the ages of 25 and 40 years using a web search in Japan and selected representative panels. Among those with sensitive skin, we focused on women who have repeated skin problems. Women who repeatedly develop skin-related complications have concerns about dryness and redness. Sensitive skin has higher transepidermal water loss values and lower skin water content compared with normal skin; in addition, the stratum corneum in those with sensitive skin can be peeled off easily. Moreover, the indexes of both red and black skin coloration were increased in women with sensitive skin. These increases probably occurred because of repeated inflammation in the surface skin on the face. Next, we performed detailed investigations for determining reasons for skin redness, and our results indicated that redness occurred owing to increased flow in the blood vessels of the cheek. On observing the cheek of panels using a video microscope, the entire skin surface was red, specifically the area with blood vessels and the epidermis around the skin pores. These results suggest that sensitive skin may develop red and black coloration because of repeated skin problems compared to normal skin.

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The Japanese Cosmetic Science Society (JCSS) proposed an absolute scoring method of photos to evaluate anti-wrinkle products as guidelines. However, the relative evaluation of wrinkles using photos is also considered to be possible. In this study, 1-carbamimidoyl-l-proline (CLP) was used as an anti-wrinkle ingredient to compare those two methods. Subjects (n=126, 32–50 yrs) who had wrinkles on the right corner of their eyes were topically treated with a CLP (4%)-containing lotion or a placebo twice per day for 8 weeks. Photos and replicas of wrinkles on those areas were obtained at the start and the end of the test period. The absolute scoring method using photos proposed by the JCSS guidelines and the relative evaluation of wrinkles at the start and the end of the test were conducted to evaluate anti-wrinkle efficacy by trained expert for wrinkle evaluation. The relative evaluation of wrinkles was carried out by comparing the photos of the start with the end of the test by grading from 1 (apparent decrease) to 5 (apparent increase). Two- and three-dimensional roughness analyses of replicas were also carried out. The wrinkle score was significantly decreased in the CLP group compared with the placebo group (p<0.001). The relative evaluation method also showed a significant decrease of wrinkles in the CLP group (p<0.001) compared to the placebo group. A strong significant correlation (r=0.760, p<0.001) was observed between the absolute scoring method and the relative evaluation method. Significant correlations were also observed between the roughness analysis of replicas and the relative evaluation method. Consequently, our study suggests that the relative evaluation of wrinkles is equally useful for trained expert to evaluate anti-wrinkle products to the absolute scoring method.

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One of the most striking aspects of mammalian genomes is the extraordinary abundance of transposable elements (TEs). A recent reannotation of genome sequences indicated that 75% or more of the human genome may be a product of past TE activities. Mobilization of TEs can lead to natural insertion mutations that generally have negative effects on the host genome. Thus, host species have evolved control mechanisms that restrict TE activity. Recent studies have shown that TEs are largely repressed by epigenetic mechanisms which are frequently interrelated and mutually reinforced. One such mechanism is RNAi/RNA silencing, in which small RNAs 20–30 nucleotides in length trigger multiple forms of sequence-specific gene silencing by guiding Argonaute/Piwi complexes or RNA-induced silencing complexes (RISCs) to target RNAs by means of base-pairing. RNAi/RNA silencing is thought to have evolved as a form of nucleic acid-based immunity to inactivate viruses and transposable elements.

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In this short review, we first described future direction of animal-free mechanism-based human hazard evaluation systems and pointed out the importance of physiologically-relevant in vitro cultured tissue models. Good examples of such tissue models can be seen in the latest studies by Wyss Institute, Harvard University, that is, breathing lung on-a-chip realized by in vivo-like mechanical movements based on advanced microfluidic technologies. This suggests that we will eventually be able to overcome in vivo–in vitro discrepancies that exist in using very convenient but unphysiological plastic culture wares and synthesized culture medium, when we continue the effort to understand the differences and successfully reconstitute in vivo-like microenvironments. In addition to reconstituting typical 3D hierarchical microstructure comprising of epithelium, stromal layers and endothelium, we pointed out one blind side issue, oxygen supply in the static culture; oxygen is transported by a simple diffusion process from the air-liquid interface at the surface of the culture medium to the cells cultured at the bottom of the plates, but this oxygen diffusion flux does not always meet the oxygen demand of the cell layers, resulting in forcing cell to take low efficient anaerobic respiration. To solve this issue completely, we used oxygen-permeable silicone rubber, poly(dimethylsiloxane) (PDMS), as a culture surface at the bottom, so that oxygen can be supplied directly from the outer atmosphere to the cells. As the results, hepatic cells exhibited remarkable and spontaneous self-organizations; mul­tilayer formation, spherical aggregate formation at very high cell densities, better development of bile canaliculi and good survival beneath Caco-2 cell layers formed on cell culture inserts. Through integration of such technologies enabling better mimicry of in vivo situation in vitro, physiologically-relevant tissue models can be realized and can be used in combination with advanced/comprehensive bioanalyses and numerical simulations for animal-free mechanism-based human hazard evaluation in the near future.

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Membrane traffic represents a variety of transport processes connecting intracellular membrane-bounded compartments in eukaryotic cells. Small vesicles and tubules are the carriers of these processes. In addition to conventional molecular approaches such as genetics and biochemistry, live cell imaging has become a very powerful methodology to understand mechanisms of membrane traffic. We have developed a new microscopic method employing the spinning-disk confocal scanner and the ultra-high sensitivity detection system, in combination with mathematical data processing. This method enables us live imaging at very high resolution in both space and time, and we have named it SCLIM, standing for super-resolution confocal live imaging microscopy. Many questions and disputes about the molecular mechanisms underlying protein sorting during membrane traffic can be solved by SCLIM. As such examples, I describe the maturation of the Golgi cisternae and the hug-and-kiss action of the cis-Golgi towards the endoplasmic reticulum exit sites.

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All of our tissues contain the same 30,000 genes; however, in a given tissue and at a given stage, owing to an “epigenetic code,” only a few of these genes are expressed, giving rise to the “phenotype.” Disruption of the balance of epigenetic networks may cause several major diseases, including cancer, syndromes involving chromosomal instabilities, and mental retardation. However, the relevance of epigenetics to other physiopathological mechanisms in common diseases, such as metabolic syndrome, was less clear. Through genome wide identification of PPARγ targets by chromatin immunoprecipitation on Chip (ChIP-Chip) analysis, we identified several histone modification enzymes (HKMTs) and candidates' genes as new PPARγ targets. We show that these HKMTs function either anti-, or pro-adipogenic factor and coordinately regulated their gene expressions by PPARγ to promote adipogenesis. We therefore propose the novel action of PPARγ: controlling epigenomic status in fat cell differentiation. In addition, we demonstrate that JHDM2a, a demehtylase of H3K9me2, regulates metabolic genes related to energy homeostasis. Mice deficient in JHDM2a (JHDM2a-/-) develop adult onset obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia, and hyperleptinemia, which are hallmarks of metabolic syndrome. Thus, H3K9 demethylase JHDM2a is a crucial regulator of genes involved in energy expenditure and fat storage, which suggests it is a previously unrecognized key regulator of obesity and metabolic syndrome.

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