Quantitative changes in the secretion of exosomes from keratinocytes homeostatically regulate skin pigmentation in a paracrine manner.

The content and distribution of melanin in the epidermis determines the wide variety of skin colors associated with ethnic/racial diversity. Although it was previously reported that qualitative changes in keratinocyte-derived exosomes regulate melanocyte pigmentation in vitro, their practical involvement, especially in skin color development in vivo, has remained unclear. To address this unexplained scientific concern, the correlation of epidermal exosomes isolated from human skin tissues with melanosomal protein expression levels was demonstrated in this study for the first time.

Substantial evidence for the rhododendrol-induced generation of hydroxyl radicals that causes melanocyte cytotoxicity and induces chemical leukoderma.

Background: Rhododendrol (4-(4-hydroxyphenyl)-2-butanol) has been used as a lightening/whitening cosmetic but was recently reported to induce leukoderma. Although rhododendrol has been shown to be transformed by tyrosinase to hydroxyl-rhododendrol, which is cytotoxic to melanocytes, its detailed mechanism of action including the involvement of reactive oxygen species is not clearly understood.

Objective: To confirm the relationship of hydroxyl radical generation to melanocyte cytotoxicity induced by rhododendrol, this study was performed.

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs).

Variation in Hsp70-1A Expression Contributes to Skin Color Diversity.

The wide range in human skin color results from varying levels of the pigment melanin. Genetic mechanisms underlying coloration differences have been explored, but identified genes do not account for all variation seen in the skin color spectrum. Post-transcriptional and post-translational regulation of factors that determine skin color, including melanin synthesis in epidermal melanocytes, melanosome transfer to keratinocytes, and melanosome degradation, is also critical for pigmentation.

Developmental Changes in Neonatal and Infant Skin Structures During the First 6 Months: In Vivo Observation.

Background/objectives: Developmental changes of structures in neonatal and infant skin have not been well characterized. The purpose of this study was to clarify changes in skin structures during neonatal and infant growth in vivo.

Methods: Fifteen healthy, full-term neonates (seven girls, eight boys) were studied.

t-Flavanone Improves the Male Pattern of Hair Loss by Enhancing Hair-Anchoring Strength: A Randomized, Double-Blind, Placebo-Controlled Study.

Introduction: trans-3,4'-Dimethyl-3-hydroxyflavanone (t-flavanone) is a derivative of astilbin that actively stimulates hair growth. The aim of the present study was to identify the mechanisms of action of t-flavanone on hair growth.

Methods: A double-blind usage test was performed with healthy volunteers who had androgenic alopecia (AGA).

Cooperation of endothelin-1 signaling with melanosomes plays a role in developing and/or maintaining human skin hyperpigmentation.

Skin hyperpigmentation is characterized by increased melanin synthesis and deposition that can cause significant psychosocial and psychological distress. Although several cytokine-receptor signaling cascades contribute to the formation of ultraviolet B-induced cutaneous hyperpigmentation, their possible involvement in other types of skin hyperpigmentation has never been clearly addressed. Since our continuous studies using skin specimens from more than 30 subjects with ethnic skin diversity emphasized a consistent augmentation in the expression of endothelin-1 (ET-1) and its receptor (Endothelin B receptor, ET-B) in hyperpigmented lesions, including senile lentigos (SLs), the precise function of ET-1 signaling was investigated in the present study.

Angular-type furocoumarins from the roots of Angelica atropurpurea and their inhibitory activity on the NFAT signal transduction pathway.

One new (1) and two known angular-type (2,3) furocoumarins, isoarchangelicin (1), archangelicin (2), and 2'-angeloyl-3'-isovaleryl vaginate (3), were isolated from the roots of Angelica atropurpurea. The structure of the new compound was established on the basis of one- and two-dimensional NMR spectra and other spectroscopic studies. The inhibitory activity of these three compounds and a deacylated form of archangelicin (4) on the nuclear factor of activated T cells (NFAT) signal transduction pathway was tested by NFAT-responsive luciferase reporter gene assay in cultured cells.

Depigmentation caused by application of the active brightening material, rhododendrol, is related to tyrosinase activity at a certain threshold.

Background: Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, rhododendrol.

Objective: To investigate the mechanism underlying the depigmentation caused by rhododendrol-containing cosmetics, this study was performed.

Effects of IGF-binding protein 5 in dysregulating the shape of human hair.

The hair follicle has a unique dynamic property to cyclically regenerate throughout life. Despite significant progress in hair structure and hair shape determination using animal models, the mechanisms controlling the architecture and the shape of the human hair remain largely unexplored. In this study, comparison of the genetic expression of several human genes, especially those involved in growth, development, and differentiation, between Caucasian curly hair and naturally straight hair was performed.

Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses.

Although human skin fibroblast (HSF) elastase has been characterized as a membrane-bound metalloproteinase, little is known about its structure, amino acid sequence, and encoding gene. As there are similarities in the molecular weights and inhibitory profiles of HSF elastase and neprilysin (neutral endopeptidase 24.11 (NEP)), in this study we tested the hypothesis that they are identical using immunoprecipitation and transfection methods.

Development of a new evaluation method for cheek sagging using a Moire 3D analysis system.

Background/aims: Facial sagging becomes progressively noticeable with aging. Previously developed methods to study facial sagging measure the shape of sagging skin, evaluate skin properties such as elasticity or flexibility or visually score the degree of sagging using a photo scale. However, the practical use of these methods has shortcomings and is thus limited to advanced levels of sagging.

Development of a novel method to measure the elastic properties of skin including subcutaneous tissue: new age-related parameters and scope of application.

Background/purpose: We have developed a new apparatus to measure the elastic properties of skin without contact using an air blown technique.

Methods: Real-time measurements of skin movement induced by air blown on the surface were measured at various times. We investigated age-related changes in the displacement of the skin surface caused by air using various parameters.

trans-3,4'-Dimethyl-3-hydroxyflavanone, a hair growth enhancing active component, decreases active transforming growth factor beta2 (TGF-beta2) through control of urokinase-type plasminogen activator (uPA) on the surface of keratinocytes.

trans-3,4'-Dimethyl-3-hydroxyflavanone (t-flavanone) is a synthetic compound with hair growth enhancing activity that is effective against male pattern alopecia. t-Flavanone was designed as a derivative of astilbin, the active hair growth enhancing component of Hypericum perforatum extracts. This study was designed to elucidate the mechanism of hair growth enhancement by t-flavanone.

The characteristics of aromatase deficient hairless mice indicate important roles of extragonadal estrogen in the skin.

The roles of extragonadal estrogen in the skin are poorly understood, due to the lack of proper animal models. We examined the skin phenotypes of aromatase-knockout hairless (ArKO) mice and wild-type hairless (WT) mice, both of which were obtained through crossbreeding of Ar+/- mice and hairless mice. Differences in the skins of ArKO and WT mice were compared with those of ovariectomized (OVX) and control (Sham) mice.

Crucial role of fibroblast integrins alpha2 and beta1 in maintaining the structural and mechanical properties of the skin.

Background: In vivo functions of integrins in dermis have been investigated using several types of genetically integrin deficient mice. However, there are few studies to clarify actual in vivo functions of integrins in the dermis using normal type animals.

Objective: We investigated the actual in vivo functions of integrins in maintaining structural and mechanical properties in the normal skin by means of blocking interactions between fibroblasts and the extracellular matrix (ECM).

A horse chestnut extract, which induces contraction forces in fibroblasts, is a potent anti-aging ingredient.

Contraction forces generated by non-muscle cells, such as fibroblasts, play important roles in determining cell morphology, vasoconstriction, and/or wound healing. We have searched among various plant extracts for ingredients that generate cell contraction forces using fibroblast-populated collagen gels. Using that model, we found that an extract of horse chestnuts (Aesculus hippocastanum) is able to generate such contraction forces in fibroblasts.

Horse chestnut extract induces contraction force generation in fibroblasts through activation of Rho/Rho kinase.

Contraction forces generated by non-muscle cells such as fibroblasts play important roles in determining cell morphology, vasoconstriction, and/or wound healing. However, few factors that induce cell contraction forces are known, such as lysophosphatidic acid and thrombin. Our study analyzed various plant extracts for ingredients that induce generation of cell contraction forces in fibroblasts populating collagen gels.

Inhibition of ultraviolet-B-induced wrinkle formation by an elastase-inhibiting herbal extract: implication for the mechanism underlying elastase-associated wrinkles.

Background: Previously, we have demonstrated that fibroblast-derived elastase plays an essential role in the increased three-dimensional tortuosity of elastic fibers, contributing to the loss of skin elasticity in UV-B-exposed skin. This decrease in skin elasticity is closely associated with the formation of wrinkles induced by UV exposure.

Objective: To further clarify the role of elastase in the formation of wrinkles induced by UV exposure, we assessed the effects of an extract of Zingiber officinale (L.

The effect of sunscreen on skin elastase activity induced by ultraviolet-A irradiation.

It has been reported that application of sunscreens prevents the photoaging of skin in animal models and in humans. We irradiated the dorsal skin of hairless mice with ultraviolet-A (UVA), and investigated the effects of sunscreens on skin elastase activity and on skin properties. Six-week-old female HR/ICR hairless mice were used in these experiments.

The formation of wrinkles caused by transition of keratin intermediate filaments after repetitive UVB exposure.

It has been reported that the formation of wrinkles involves changes in the elastic properties of the dermis due to the denaturation of elastic fibers. Several studies have shown that the hydration condition of the stratum corneum is also important in wrinkle formation. It is, however, still unclear how the stratum corneum contributes to wrinkle formation.

Comparison of age-related changes in wrinkling and sagging of the skin in Caucasian females and in Japanese females.

We compared age-related changes in wrinkles in eight areas of facial skin (forehead, glabella, upper eyelid, corner of the eye, lower eyelid, nasolabial groove, cheek, and corner of the mouth) and sagging in the subzygomatic area of Caucasian females and of Japanese females. The subjects studied included 85 healthy Caucasian females (ages 20-69 years) living in Cincinnati in the U.S.

A study of diurnal variation in wrinkles on the human face.

We recently evaluated diurnal variations in facial skin elasticity and thickness and reported a decrease in skin thickness and an increase in skin elasticity in the afternoon compared with the morning. This phenomenon may be associated with the effect of gravity on dermal fluids. There have been no reports on the diurnal variation in wrinkles on the face, and we now describe such a study.