Recognizing Latinos’ range of skin pigment and phototypes to enhance skin cancer prevention

Latinos in the United States may have the mistaken assumption that their natural pigmentation protects them from developing skin cancer that, effectively, serves as a barrier to Latinos receiving education in primary and secondary prevention of skin cancer. Latino adults of Mexican or Puerto Rican heritage attending community health fairs in the greater Chicago area responded to a culturally informed and sensitive measure for sunburn and tan, which was previously adapted to capture skin irritation with tenderness from the sun occurring in darker skin types (n = 350). By self‐reported responses and spectrophotometry assessment of constitutive pigmentation, adapted Fitzpatrick skin types (FST) ranged from skin type I–IV in the Mexican American participants and from II to V in the Puerto Rican participants. The objectively measured proportion of adapted FST II skin type was greater than commonly perceived and demonstrated that many Latinos do indeed have sun‐sensitive skin.     

Interactions of betulinic acid with xenobiotic metabolizing and antioxidative enzymes in DMBA-treated Sprague Dawley female rats

Cancer chemoprevention is related to classical epidemiology and involves the use of agents that inhibit, delay, or reverse the carcinogenesis that occurs as a result of accumulation of mutations and increased proliferation. Betulinic acid is known for its cytotoxic effects against a panel of cancer cell lines. In the present study, interactions of betulinic acid (BA) with xenobiotic metabolizing enzymes including mixed function oxidases (cytochrome b5, P420, P450, NADPH cytochrome P450 reductase, and NADH cytochrome b5 reductase), phase II enzymes (GST, DT-diaphorase, γ-glutamyl transpeptidase), LDH, antioxidative enzymes (glutathione reductase, SOD, catalase, ascorbate peroxidase, and guaiacol peroxidase), and lipid peroxidation are studied alone as well as in the presence of 7,12 dimethylbenzanthracene (DMBA)—a potent carcinogen using Sprague Dawley female rats. The effect of BA on reduced glutathione content and protein content is also taken into consideration. It has been found that administration of BA decreased the level of mixed function oxidases that are involved in the conversion of carcinogen to electrophile, elevated the level of phase II enzymes which participated in the removal of electrophiles by sulfation, conjugation etc. It has been found that BA effectively removed or neutralized the reactive species by the action of phase II enzymes and such an effect was reflected from the specific activities of antioxidative enzymes which were found to be lower as compared to positive control (DMBA-treated group) and in some cases even that of untreated control. BA was also found to have a pronounced effect in protecting the animals from lipid peroxidation as evident from the reduced levels of TBARS, conjugated diene, and lipid hydroperoxide formation. This study highlights the role of BA in modulating the activities of xenobiotic and antioxidative enzymes that have putative roles in cancer initiation and proliferation.     

Analysis of relation between skin elasticity and the entropy of skin image using near‐infrared and visible light sources

Skin elasticity has been regarded as one of the main indicators of skin condition. Current measurement devices for skin elasticity are mostly expensive for home‐use and should contact the skin surface. As a first step to develop improved methods, we focus on the relation between skin elasticity and the entropy of skin images. Reduced skin elasticity causes wrinkles. It spreads frequency components and increases their randomness in the frequency domain. The randomness is quantified as entropy, which is a measure of the disorder of a system in physics. Therefore, skin elasticity is expected to have a negative relation with entropy. This tendency can be improved by applying penetration depth characteristics according to the wavelength of light. From cheeks and forehead of 12 Korean adults, skin images are acquired with three different light sources (470 nm, 870 nm and broadband light) and skin elasticity is measured. The root mean square error between the measured data and the fitted model is “0.27” (870 nm), “0.49” (broadband light) and “1.42” (470 nm). Furthermore, the results are analyzed by classifying by sex, age and measurement area. This study demonstrates the possibility of developing noncontact home‐use devices to measure skin elasticity in the future.     

MicroRNAs对动物皮肤和毛发发育调控作用的研究进展

MicroRNAs是近年来发现的一类由19-25个核苷酸组成的非编码单链小RNA分子,它们通过与靶基因mRNA3’UTR结合抑制靶基因的翻译,在转录后水平调控基因表达.MicroRNAs参与了包括细胞分化、增殖和凋亡及免疫系统应答在内的一系列发育调控和生物学过程.最近研究发现MicroRNAs在多种哺乳动物皮肤中均表达,并参与了哺乳动物皮肤及毛发发育的调控过程,这些都为研究这个新颖的调控因子在干细胞生物学和发育生物学中的功能奠定了基础.本文综述了近年来MicroRNAs对哺乳动物皮肤和毛发发育调控作用的研究状况.     

Molecular analysis of the prevalent microbiota of human male and female forehead skin compared to forearm skin and the influence of make-up

Aims: To compare the bacterial diversity of two different ecological regions including human forehead, human forearm and to estimate the influence of make‐up. Methods and Results: Twenty‐two swab‐scraped skin samples were analysed by profiling bacterial 16S rRNA genes using PCR‐based sequencing of randomly selected clones. Of the 1056 clones analysed, 67 genera and 133 species‐level operational taxonomic units (SLOTUs) belonging to eight phyla were identified. A core set of bacterial taxa was found in all samples, including Actinobacteria, Firmicutes, and Proteobacteria, but pronounced intra‐ and interpersonal variation in bacterial community composition was observed. Only 4·48% of the genera and 1·50% of the SLOTUs were found in all 11 subjects. In contrast to the highly diverse microbiota of the forearm skin, the forehead skin microbiota represented a small‐scale ecosystem with a few genera found in all individuals. The use of make‐up, including foundation and powder, significantly enlarged the community diversity on the forehead skin. Conclusions: Our study confirmed the presence of a highly diverse microbiota of the human skin as described recently. In contrast to forearm skin, gender does not seem to have much influence on the microbial community of the forehead skin. However, the use of make‐up was associated with a remarkable increase in the bacterial diversity. Significance and Impact of the Study: This study enhances our knowledge about the highly complex microbiota of the human skin and demonstrates for the first time the significant effect of make‐up on the bacterial diversity of the forehead skin.     

The CCN1 (CYR61) protein promotes skin growth by enhancing epithelial‐mesenchymal transition during skin expansion

The skin expansion technique is widely used to induce skin growth for large‐scale skin deformity reconstruction. However, the capacity for skin expansion is limited and searching for ways to improve the expansion efficiency is a challenge. In this study, we aimed to explore the possible mechanism of skin expansion and to find a potential therapeutic target on promoting skin growth. We conducted weighted gene coexpression network analysis (WGCNA) of microarray data generated from rat skin expansion and found CCN1 (CYR61) to be the central hub gene related to epithelial‐mesenchymal transition (EMT). CCN1 up‐regulation was confirmed in human and rat expanded skin and also in mechanically stretched rat keratinocytes, together with acquired mesenchymal phenotype. After CCN1 stimulation on keratinocytes, cell proliferation was promoted and partial EMT was induced by activating β‐catenin pathway. Treatment of CCN1 protein could significantly increase the flap thickness, improve the blood supply and restore the structure in a rat model of skin expansion, whereas inhibition of CCN1 through shRNA interference could dramatically reduce the efficiency of skin expansion. Our findings demonstrate that CCN1 plays a crucial role in skin expansion and that CCN1 may serve as a potential therapeutic target to promote skin growth and improve the efficiency of skin expansion.     

The role of human immortal skin keratinocytes-acellular dermal matrix scaffold in skin repair and regeneration

In this study, we aimed to investigate the phenotypic characteristics of human immortal skin keratinocytes (HaCaT) cells and the role of acellular dermal matrix (ADM) in coculture system of HaCaT cells and ADM. Flow cytometry was used to examine the cluster of differentiation (CD) makers of HaCaT cells. Apoptosis analysis was applied to detect the apoptosis rate of HaCaT cells. Morphological observation of ADM isolated from the reticular layer of Sprague-Dawley rat dermis was utilized to evaluate the morphological structure of ADM. Methylthiazolyl tetrazolium (MTT) assay and morphological experiments were further used to confirm the scaffold role of ADM in HaCaT cells. A wound-healing mice model accompanied by HaCaT-ADM scaffold transplantation was performed to further verify the function of HaCaT-ADM scaffold. Our results showed that CD71, CD49f, K19, and CD29 were highly expressed in HaCaT cells, and the percentage of apoptosis cells was significantly increased, which represented that HaCaT cells had much stronger capacities of adhesion and proliferation than normal human keratinocytes. Additionally, the morphological structure of ADM presented many natural microbores, which made cells rapidly grow on ADM. The results exhibited that the HaCaT cells indeed promptly proliferate on ADM and easily grow into the microbores of ADM. Finally, an in vivo experiment further confirmed that the transplantation of the HaCaT-ADM scaffold into the dorsal skin of a wound-healing mice model could gradually repair the injured wound. Thus, these findings indicated that HaCaT cells might be as seed cells to develop skin tissue engineering and the HaCaT-ADM scaffold might be a better candidate to promote skin repair and regeneration.     

人造生物皮肤

由活细胞和生物相容性材料制成的人造生物皮肤是第一种获得ＦＤＡ批准的组织工程产品,它们在治疗严重烧伤病人和顽固性溃疡病人具有很好的疗效。本综述了人造生物皮肤的特点、制备方法和作用机理,并介绍了一些组织工程皮肤产品。     

Ultrastructural analysis between fetal and adult wound healing process of marsupial opossum skin

The opossum delivers a newborn baby equivalent to tremature fetus state by postpregnancy. The peculiarity is advantageous for studies of fetus, because operations to take out fetus from the uterus of a mother are not necessary. When mammalian skin is wounded by full-thickness excision, fetal and adult wound healing processes differ. Fetal-type wound healing does not leave a scar. However, studies of how the fetal wound healing process differs in detail from the adult type are not advanced. We first observed the normal skin development of the gray short-tailed opossum (Monodelphis domestica) using an electron microscope. As for normal skin, an epidermis became multi-layered, and thickened from birth through to 7 days after birth. The quantity of extracellular matrix of the dermis increased thereafter, and several types of cells were found in the dermis. To examine the wound healing, we used material from a 1 day-old newborn baby, and from another 15 days after birth, and compared the wound healing style morphologically. Differences in the constitution of cells and fine structures of the skin were observed, it was obviously suggested that change in the wound healing style from fetal-type to adult-type occurred between 1 to 15 days after birth.     

Artificial skin in perspective: concepts and applications

Skin, the largest organ of the human body, is organized into an elaborate layered structure consisting mainly of the outermost epidermis and the underlying dermis. A subcutaneous adipose-storing hypodermis layer and various appendages such as hair follicles, sweat glands, sebaceous glands, nerves, lymphatics, and blood vessels are also present in the skin. These multiple components of the skin ensure survival by carrying out critical functions such as protection, thermoregulation, excretion, absorption, metabolic functions, sensation, evaporation management, and aesthetics. The study of how these biological functions are performed is critical to our understanding of basic skin biology such as regulation of pigmentation and wound repair. Impairment of any of these functions may lead to pathogenic alterations, including skin cancers. Therefore, the development of genetically controlled and well characterized skin models can have important implications, not only for scientists and physicians, but also for manufacturers, consumers, governing regulatory boards and animal welfare organizations. As cells making up human skin tissue grow within an organized three-dimensional (3D) matrix surrounded by neighboring cells, standard monolayer (2D) cell cultures do not recapitulate the physiological architecture of the skin. Several types of human skin recombinants, also called artificial skin, that provide this critical 3D structure have now been reconstructed in vitro. This review contemplates the use of these organotypic skin models in different applications, including substitutes to animal testing.     

Stem cell recovering effect of copper‐free GHK in skin

The peptide Gly‐His‐Lys (GHK) is a naturally occurring copper(II)‐chelating motifs in human serum and cerebrospinal fluid. In industry, GHK (with or without copper) is used to make hair and skin care products. Copper‐GHK plays a physiological role in the process of wound healing and tissue repair by stimulating collagen synthesis in fibroblasts. We also reported that copper‐GHK promotes the survival of basal stem cells in the skin. However, the effects of copper‐free GHK (GHK) have not been investigated well. In this study, the effects of GHK were studied using cultured normal human keratinocytes and skin equivalent (SE) models. In monolayer cultured keratinocytes, GHK increased the proliferation of keratinocytes. When GHK was added during the culture of SE models, the basal cells became more cuboidal than control model. In addition, there was linear and intense staining of α6 and β1 integrin along the basement membrane. The number of p63 and proliferating cell nuclear antigen positive cells was also significantly increased in GHK‐treated SEs than in control SEs. Western blot and slide culture experiment showed that GHK increased the expression of integrin by keratinocytes. All these results showed that GHK increased the stemness and proliferative potential of epidermal basal cells, which is associated with increased expression of integrin. In conclusion, copper‐free GHK showed similar effects with copper‐GHK. Thus, it can be said that copper‐free GHK can be used in industry to obtain the effects of copper‐GHK in vivo. Further study is necessary to explore the relationship between copper‐free GHK and copper‐GHK. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Environmental pollutants and skin cancer

We are increasingly exposed to environmental pollution. Pollutants can be inhaled, ingested or come into contact with the skin depending on the form in which they occur. On metabolization, activation, or accumulation, pollutants can become extremely toxic for the vital organs and this is often related to a strong genotoxic effect. Since the skin acts as a barrier between the organism and the environment, it is frequently directly exposed to pollution. It is very often degraded by polluting agents and acts as an inlet toward other tissues. Numerous studies in man recognize and demonstrate the carcinogenic power of certain pollutants in the digestive and respiratory tracts. The "pollutants" that react most specifically with the skin are: ultraviolet radiation, polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene), volatile organic compounds (e.g., benzene), heavy metals, and ozone. Ultraviolet radiation, a "physical" pollutant, has been described as being the factor responsible for most skin cancers in man. The genotoxicity of UV light is well documented (type of lesion or mutation, etc.) and its carcinogenic effect is clearly demonstratedin vivo in man. A few epidemiological studies describe the carcinogenicity of certain pollutants such as arsenic or lead on the skin. However, most of the evidence for the role of pollutants in skin cancers comes fromin vivo animal studies or fromin vitro studies (e.g., PAHs). In this report, different studies are presented to illustrate the research strategies developed to investigate the mechanism of action of "chemical" pollutants and their potential role in human skin pathology. All the study models and the associated techniques of investigation are tools for a better understanding and thus more efficient prevention of the deleterious effects caused by the environment. This revised version was published online in August 2006 with corrections to the Cover Date.     

Optimisation of skin phototype classification

Understanding individuals' skin pigmentation and photosensitivity is important in judging risk of skin cancer and response to certain treatment modalities. However, individuals with darkly pigmented skin are poorly represented in the widely used Fitzpatrick skin phototype (FST) system. Moreover, the FST system is prone to misuse, as it relies on subjective patient and clinician assessment of skin type, and does not clearly differentiate pigmentation from photosensitivity. By evaluating the key literature surrounding the FST system, its criticisms and proposed alternatives, this review serves to understand how skin phototype classification can be optimised.     

Nestin‐expressing interfollicular blood vessel network contributes to skin transplant survival and wound healing

Using nestin‐driven green fluorescent protein (ND‐GFP) transgenic mice, we previously demonstrated an inter‐hair‐follicle blood vessel network that expresses ND‐GFP and appears to originate from ND‐GFP expressing hair‐follicle stem cells. We report here that angiogenesis of transplanted skin or healing wounds originates from this ND‐GFP‐expressing microvasculature network. ND‐GFP‐expressing blood vessels were visualized growing from the ND‐GFP‐expressing hair‐follicle stem cell area and re‐establishing the dermal microvasculature network after skin transplantation or wound healing. When the ND‐GFP stem cell area from the vibrissa (whisker) from ND‐GFP mice was transplanted to transgenic mice ubiquitously expressing RFP, we observed chimeric ND‐GFP‐RFP blood vessels, suggesting the joining of inter‐follicular blood vessel networks from the transplant and host. These observations suggest that the inter‐hair‐follicle blood‐vessel network contributes to skin transplant survival and wound healing. J. Cell. Biochem. 110: 80–86, 2010. © 2010 Wiley‐Liss, Inc.     

A novel composition for in vitro and in vivo regeneration of skin and connective tissues

The particular combination of polydeoxyribonucleotides, l-carnitine, calcium ions, proteolytic enzyme and other ingredients acts in a synergetic way in the regeneration of skin and connective tissues. This new formulation of active principles was tested in vitro as a cell and tissue culture medium and in vivo for various preparations in support of tissue regeneration. In vitro, the new blend allowed the maintenance of skin biopsies for more than 1 year in eutrophic conditions. Immunocytochemical analyses of fibroblasts isolated from these biopsies confirmed a significant increase of the epidermal and connective wound-healing markers such as collagen type I, collagen type IV, cytokeratin 1 (CK1), CK5, CK10 and CK14 versus controls. To examine the effects of the new compound in vivo, we studied impaired wound healing in genetically diabetic db/db mice. At day 18, diabetic mice treated with the new composition showed 100% closure of wounds and faster healing than mice treated with the other solutions. This complex of vital continuity factors or life-keeping factors could be used as a tissue-preserving solution or a cosmetic/drug/medical device to accelerate wound healing in the treatment of patients with deficient wound repair to promote the regeneration of cutaneous and connective tissues (injuries-wound, dermatitis) and prevent the recurrent relapses.     

Exercise‐stimulated interleukin‐15 is controlled by AMPK and regulates skin metabolism and aging

Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle‐to‐skin signaling occurs. We demonstrate that endurance exercise attenuates age‐associated changes to skin in humans and mice and identify exercise‐induced IL‐15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL‐15 expression in part through skeletal muscle AMP‐activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL‐15 therapy mimics some of the anti‐aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low‐dose IL‐15 therapy may prove to be a beneficial strategy to attenuate skin aging.     

Reflection and penetration depth of millimeter waves in murine skin

Millimeter (mm) wave reflectivity was used to determine murine skin permittivity. Reflection was measured in anesthetized Swiss Webster and SKH1-hairless mice in the 37-74 GHz frequency range. Two skin models were tested. Model 1 was a single homogeneous skin layer. Model 2 included four skin layers: (1) the stratum corneum, (2) the viable epidermis plus dermis, (3) fat layer, and (4) muscle which had infinite thickness. We accepted that the permittivity of skin in the mm wave frequency range results from the permittivity of cutaneous free water which is described by the Debye equation. Using Fresnel equations for reflection we determined the skin parameters best fitting to the reflection data and derived the permittivity of skin layers. The permittivity data were further used to calculate the power density and specific absorption rate profiles, and the penetration depth of mm waves in the skin. In both murine models, mm waves penetrate deep enough into tissue to reach muscle. In human skin, mm waves are mostly absorbed within the skin. Therefore, when extrapolating the effects of mm waves found in animals to humans, it is important to take into account the possible involvement of muscle in animal effects.     

CYLD regulates keratinocyte differentiation and skin cancer progression in humans

CYLD is a gene mutated in familial cylindromatosis and related diseases, leading to the development of skin appendages tumors. Although the deubiquitinase CYLD is a skin tumor suppressor, its role in skin physiology is unknown. Using skin organotypic cultures as experimental model to mimic human skin, we have found that CYLD acts as a regulator of epidermal differentiation in humans through the JNK signaling pathway. We have determined the requirement of CYLD for the maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We show that CYLD overexpression increases keratinocyte differentiation while CYLD loss of function impairs epidermal differentiation. In addition, we describe the important role of CYLD in the control of human non-melanoma skin cancer progression. Our results show the reversion of the malignancy of human squamous cell carcinomas that express increased levels of CYLD, while its functional inhibition enhances the aggressiveness of these tumors which progress toward spindle cell carcinomas. We have found that the mechanisms through which CYLD regulates skin cancer progression include the control of tumor differentiation, angiogenesis and cell survival. These findings of the role of CYLD in human skin cancer prognosis make our results relevant from a therapeutic point of view, and open new avenues for exploring novel cancer therapies.