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Background: This review summarizes uses and new applications for dermatological research of in vitro culture models of human skin explants (HSEs). In the last decade, many innovations have appeared in the literature and an exponential number of studies have been recorded in various fields of application such as process culture engineering, stem cell extractions methodology, or cell-to-cell interaction studies under physiological and pathological conditions, wound-healing, and inflammation. Most studies also concerned pharmacology, cosmetology, and photobiology. However, these topics will not be considered in our review. Summary: A better understanding of the mechanisms driving intercellular relationships, at work in the maintenance of 3D tissue architectures has led to the improvement of cell culture techniques. Many papers have focused on the physiological ways that govern in vitro tissue maintenance of HSEs. The analysis of the necessary mechanical stress, intercellular and cell-matrix interactions, allows the maintenance and prolonged use of HSEs in culture for up to 15 days, regardless of the great variability of study protocols from one laboratory to another and in accordance with the objectives set. Because of their close similarities to fresh skin, HSEs are increasingly used to study skin barrier repair and wound healing physiology. Easy to use in co-culture, this model allows a better understanding of the connections and interactions between the peripheral nervous system, the skin and the immune system. The development of the concept of an integrated neuro-immuno-cutaneous system at work in skin physiology and pathology highlighted by this article represents one of the new technical challenges in the field of in vitro culture of HSE. This review of the literature also reveals the importance of using such models in pathology. As sources of stem cells, HSEs are the basis for the development of new tissue engineering models such as organoids or optical clearing tissues technology. This study identifies the main advances and cross-cutting issues in the use of HSE. [ABSTRACT FROM AUTHOR]

Introduction: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. Methods: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. Results: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. Conclusion: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism. [ABSTRACT FROM AUTHOR]

Background: Skin care is a basic, daily activity performed by formal and informal caregivers from birth until end of life. Skin care activities are influenced by different factors, e.g., culture, knowledge, industrial developments and marketing activities. Therefore, various preferences, traditions, and behaviors exist worldwide including skin care of neonates and infants. The objective of this scoping review was to obtain an overview about the evidence of skin care activities in neonates and infants. Studies from 2010 were eligible if the population was (skin) healthy neonates and infants; if the concept was skin care interventions; and if the context was at home, in a community setting, in a pediatric outpatient service, or in a hospital. We searched for the literature via OVID in MEDLINE and Embase, in the Cochrane Library, in trial registries and for gray literature. Summary: We identified 42 studies since 2010, which examined four main skin care interventions: bathing, wiping, washing, and topical application of leave-on products. Details of interventions were often not reported, and if they were, they were not comparable. The four skin care interventions focused on 13 different care goals, mainly prevention of skin diseases, maintaining skin barrier function, and improving (skin) health. We evaluated effects of skin care interventions using 57 different outcome domains; 39 of 57 were skin-related and 18 were not. Mostly, laboratory or instrumental measurements were used. Key Messages: Our scoping review identified four skin care interventions with a broad heterogeneity of product categories and application details. Studies in skin care interventions should include all relevant information about product category and application details to ensure comparability of study results. This would be helpful in developing recommendations for formal and informal caregivers. We identified 13 skin care goals. "Maintaining healthy skin/skin barrier function/skin barrier integrity," "prevention of atopic dermatitis," "cleansing," and "improving skin barrier function" were most often allocated to skin care interventions. There is substantial variability regarding outcome domains in skin care research. Our results support the need of developing core outcome sets in the field of skin care in healthy skin, especially in this age-group of neonates and infants. [ABSTRACT FROM AUTHOR]

The document titled "Acknowledgement to Reviewers" from the journal Skin Pharmacology & Physiology expresses gratitude to the reviewers who have supported the journal in 2024 by reviewing manuscripts. The names of the reviewers are not disclosed to maintain anonymity in the single-blind peer-review process. Reviewers are appreciated for their time, effort, and expertise in enhancing the quality of published manuscripts. Individual reviewers can claim a "Certificate of Review" through the journal's manuscript submission system. [Extracted from the article]

Introduction: Skin microbiome and skin physiology are important indicators of the epidermal homeostasis status. Stress models can reveal pathological conditions and modulating effects. Here we investigated the cutaneous microbiome in relation to skin physiology after mild tape stripping (TS) without treatment compared to two cosmetic leave-on lotions (pH 5.5 vs. pH 9.3) in 25 healthy volunteers. Methods: The microbiome was analyzed by 16S-rRNA-gene amplicon sequencing and put in relation to the following skin physiology parameter: epidermal barrier function (TEWA-Meter TM300), stratum corneum hydration (Corneometer CM 825), surface pH (pH-Meter), and skin erythema (Mexameter). Results: TS reduced the alpha diversity with a recovery over 7 days without treatment. Both lotions significantly accelerated the recovery of the alpha diversity already after 2 days with a slightly higher rate for the acidic lotion. After TS, the relative abundance of Proteobacteria was increased, whereas Actinobacteria were reduced. The relative abundances of typical skin-associated genera were reduced after TS. Taxa compositions returned to normal levels after 7 days in all treatment groups. An accelerated normalization could be observed with both lotions already after 2 days. A significant difference in skin pH was observed on day 2 and day 7 with an increased pH for the alkaline lotion. Both lotions induced an increase in stratum corneum hydration. Conclusion: The study proved the suitability of an experimental stress model in the assessment of skin surface microbiome in relation to skin physiology. Stratum corneum hydration increased significantly with both lotions already at day 2. Microbiome parameters (alpha diversity, mean relative taxa, abundance of selected genera) normalized over 2–7 days. The following mechanisms could be responsible for the accelerated normalization of the microbiome: (a) optimized hydration during the recovery phase, (b) the composition of the lotion, (c) the induced repair mechanism. Thus, the formulation has a positive effect on the stratum corneum hydration and subsequently on cutaneous microbiome and skin physiology. Furthermore, this eventually has implications on the modulation of exogenous stress-induced epidermal alterations. [ABSTRACT FROM AUTHOR]

Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate the effect of orally ingested collagen peptides (CPs) on skin condition and elucidate their mechanism of action. Methods: A randomized, placebo-controlled, double-blind trial was conducted in 99 healthy Japanese women, aged 35–50 years. The subjects were randomized into 3 groups (33 subjects/group) to receive 1 or 5 g of CP or placebo once daily for 12 weeks. Skin water content, transepidermal water loss (TEWL), skin elasticity, and skin thickness were evaluated before treatment and after 4, 8, and 12 weeks of treatment. The level of natural moisturizing factor (NMF) constituents in the stratum corneum (SC) was quantified before treatment and after 12 weeks of treatment. Results: Oral ingestion of CP increased the water content in the SC and epidermis and decreased TEWL. Furthermore, the NMF level in the SC was increased. However, skin elasticity and skin thickness remained unchanged. Conclusions: The improvement in skin water content following the oral ingestion of CP can be attributed to an increase in the level of NMF in the SC. Trial Registration: UMIN000030375 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: Skin is the interface between an organism and the external environment, and hence the stratum corneum (SC) is the first to withstand mechanical insults that, in certain conditions, may lead to integrity loss and the development of pressure ulcers. The SC comprises corneocytes, which are vital elements to its barrier function. These cells are differentiated dead keratinocytes, without organelles, composed of a cornified envelope and a keratin-filled interior, and connected by corneodesmosomes (CDs). Summary: The current review focusses on the relationship between the morphological, structural, and topographical features of corneocytes and their mechanical properties, to understand how they assist the SC in maintaining skin integrity and in responding to mechanical insults. Key Messages: Corneocytes create distinct regions in the SC: the inner SC is characterized by immature cells with a fragile cornified envelope and a uniform distribution of CDs; the upper SC has resilient cornified envelopes and a honeycomb distribution of CDs, with a greater surface area and a smaller thickness than cells from the inner layer. The literature indicates that this upward maturation process is one of the most important steps in the mechanical resistance and barrier function of the SC. The morphology of these cells is dependent on the body site: the surface area in non-exposed skin is about 1,000–1,200 μm2, while for exposed skin, for example, the cheek and forehead, is about 700–800 μm2. Corneocytes are stiff cells compared to other cellular types, for example, the Young's modulus of muscle and fibroblast cells is typically a few kPa, while that of corneocytes is reported to be about hundreds of MPa. Moreover, these skin cells have 2 distinct mechanical regions: the cornified envelope (100–250 MPa) and the keratin matrix (250–500 MPa). [ABSTRACT FROM AUTHOR]

Background: The lipid components and natural moisturizing factors (NMFs) of the stratum corneum (SC) are integral pieces of the self-regulating barrier strategy which comprises one of the most important functions of human skin and seems to be related to biomechanical responses of the SC. Objectives: This work presents the contributions of the lipid bilayers and NMFs to the barrier properties and mechanical responses of human SC. Methods: We performed 2 biomechanical experiments, substrate curvature testing and double cantilever beam cohesion measurements, on isolated human SC exposed to either water, a 1:1 mixture of acetone/ether, or a 1:1 mixture of chloroform/methanol for various durations. Results: We show that treating ex vivo SC with organic solvents results in lipid extraction which increases with duration of exposure. This extraction is tied to a remarkably linear increase in the levels and rates of biaxial stress development during drying/hydration cycles. This effect appears to be tied to the total amounts of lipids extracted. Furthermore, striking changes are seen in the intercellular cohesion properties of the tissue after solvent exposure. Interestingly, changes in drying stress profiles are not observed after treatment with water, which has been previously shown to remove NMFs from the tissue, and which therefore might be expected to induce changes in the drying behavior of the skin. However, changes in intercellular cohesion and the SC cohesion gradient are seen, suggesting impacts on the corneodesmosome protein binding junctions within the tissue. Conclusions: These results suggest that lipid loss causes marked increases in SC drying stresses, which may in turn contribute to changes in skin perception. NMF extraction may be important in vivo, but has remarkably little impact in isolated SC. [ABSTRACT FROM AUTHOR]

Introduction: Hyaluronan (HA) is a major component of the skin that exerts a variety of biological functions. Inter-α-trypsin inhibitor heavy chain (ITIH) proteins comprise a family of hyaladherins of which ITIH5 has recently been described in skin, where it plays a functional role in skin morphology and inflammatory skin diseases including allergic contact dermatitis (ACD). Objective: The current study focused on the ITIH5-HA interaction and its potential clinical and functional impact in extracellular matrix (ECM) stabilization. Methods: Studying the molecular effects of ITIH5 in skin, we established skin models comprising murine skin cells of Itih5 knockout mice and corresponding wild-type controls. In addition, human dermal fibroblasts with an ITIH5 knockdown as well as a murine recombinant Itih5 protein were established to examine the interaction between ITIH5 and HA using in vitro adhesion and HA degradation assays. To understand more precisely the role of ITIH5 in inflammatory skin diseases such as ACD, we generated ITIH5 knockout cells of the KeratinoSens® cell line. Results: Using murine skin models, ITIH5 knockdown fibroblasts, and a reactive oxygen species (ROS)-mediated HA degradation assay, we proved that ITIH5 binds to HA, thereby acting as a stabilizer of HA. Moreover, microarray profiling revealed the impact of ITIH5 on biological processes such as skin development and ECM homeostasis. Performing the in vitro KeratinoSens skin sensitization assay, we detected that ITIH5 decreases the sensitizing potential of moderate and strong contact sensitizers. Conclusion: Taken together, our experiments revealed that ITIH5 forms complexes with HA, thereby on the one hand stabilizing HA and facilitating the formation of ECM structures and on the other hand modulating inflammatory responses. [ABSTRACT FROM AUTHOR]

This review is the second part of a series which presents the state of the art in stratum corneum (SC) lipid matrix (LM) research in depth. In this part, the various hypothetical models which were developed to describe the structure and function of the SC LM as the skin's barrier will be discussed. New as well as a cumulative assortment of older results which change the view on the different models are considered to conclude how well the different models are holding up today. As a final conclusion, a model, factoring in as much of the known data as possible, is concluded, unifying the varying different models into one which can be developed further, as new results are found in the future. So far, the model is described with a single crystalline or gel-like phase with a certain amount of nanocrystallites of concentrated ceramides (CERs) and free fatty acids and more fluid nanodomains caused by a fluidizing effect of the cholesterol. These domains are dynamically resolved and reformed and do not impair the barrier function. The chain conformation is not completely clear yet; however, an equilibrium of fully extended and hairpin-folded CERs with ratios depending on the properties of each individual CER species is proposed as most likely. An overlapping middle layer as described for the tri-layer model in part I of this series would be present for both conformations. The macroscopic broad-narrow-broad layering, observed in electron micrographs, is explained by an external templating by the lipid envelope, and an internal templating by short and long lipid chains each preferentially show a homophilic association, forming thicker and thinner bilayers, respectively. The degree of influence of the very long ω-hydroxy-CERs is discussed as well. [ABSTRACT FROM AUTHOR]

Biomechanics of the skin is an important subject in skin research. It has been studied for many decades involving various technologies and methods to characterize and quantify mechanical properties of the skin under different in vivo conditions. The present EEMCO paper reviews the current rel-evant information, providing practical orientation to researchers dedicated to in vivo assessment of biomechanics of skin and its annexes. We discuss the available non-invasive instruments, including their principles and variables. A correspondence between the descriptors nomenclature proposed by Agache and the designation for the suction-based standard instruments is proposed. The addressed properties include skin softness/stiffness, firmness, elasticity, elastic and viscoelastic properties, extensibility, resilience, anisotropy, acoustical shock wave hardness, friction (in relation to topographic properties), thickness, fiber/stress mechanics (bending, cyclic, tensile, fatigue, or torsion), and hardness. We provide the relation of these properties to biomechanical descriptors and in some cases to SI units. Practical guidance for the proper use of these instruments, limitations, and possible interpretations are provided, while discussing the meaning of descriptive or "phenomenological" variables. For studies intended to quantify the effect of an intervention with regard to mechanical properties, we recommend a minimum of 30–40 participants, based on normal distribution of the data sets. Some important limitations are recognized, including the lack of standardization of procedures and calibration of instruments, which compromises the relevance and real nature of the descriptors/parameters obtained with these devices. The present work highlights an approach to a better practice and a science-supported biomechanical assessment of human skin, hair, and nails. [ABSTRACT FROM AUTHOR]

Aims: Among in vitro skin models, the scaffold-free skin equivalent (SFSE), without exogenous material, is interesting for pharmacotoxicological studies. Our aim was to adapt in vivo biophysical methods to study the structure, thickness, and extracellular matrix of our in vitro model without any chemical fixation needed as for histology. Methods: We evaluated 3 batches of SFSE and characterized them by histology, transmission electron microscopy (TEM), and immunofluorescence. In parallel, we investigated 3 biophysical methods classically used for in vivo evaluation, optical coherence tomography (OCT), and laser scanning microscopy (LSM) imaging devices as well as the cutometer suction to study the biomechanical properties. Results: OCT allowed the evaluation of SFSE total thickness and its different compartments. LSM has a greater resolution enabling an evaluation at the cell scale and the orientation of collagen fibers. The viscoelasticity measurement by cutometry was possible on our thin skin model and might be linked with mature collagen bundles visible in TEM and LSM and with elastic fibers seen in immunofluorescence. Conclusion: Our data demonstrated the simplicity and sensitivity of these different in vivo biophysical devices on our thin skin model. These noninvasive tools allow to study the morphology and the biomechanics of in vitro models. [ABSTRACT FROM AUTHOR]

The skin barrier function is mostly provided by the stratum corneum (SC), the uppermost layer of the epidermis. To noninvasively analyze the physiological properties of the skin barrier functionin vivo, it is important to determine the SC thickness. Confocal Raman microscopy (CRM) is widely used for this task. In the present in vivo study, a new method based on the determination of the DNA concentration profile using CRM is introduced for determining the SC thickness. The obtained SC thickness values are compared with those obtained using other CRM-based methods determining the water and lipid depth profiles. The obtained results show almost no significant differences in SC thickness for the utilized methods. Therefore, the results indicate that it is possible to calculate the SC thickness by using the DNA profile in the fingerprint region, which is comparable with the SC thickness calculated by the water depth profiles (ANOVA test p = 0.77) and the lipid depth profile (ANOVA test p = 0.74). This provides the possibility to measure the SC thickness by using the DNA profile, in case the water or lipid profile analyses are influenced by a topically applied formulation. The increase in DNA concentration in the superficial SC (0–2 µm) is related to the DNA presence in the microbiome of the skin, which was not present in the SC depth below 4 µm. [ABSTRACT FROM AUTHOR]

The pH of the skin is tightly regulated by endogenous buffering systems. We examined the influence of buffers of different pH and composition on skin barrier repair, pH, inflammation, and epidermal thickness/proliferation/differentiation. After tape-stripping in hairless mice buffers with pH 4–7 were applied in patch test chambers. After removal of the chambers, skin pH and transepidermal water loss (TEWL) were monitored for 24 h, and biopsies were taken for histology/immunohistology. Hairless mice showed a basal skin pH of about 5.8. Following barrier disruption and application of water, the pH increased by 0.6 units; increase in pH was reduced by the pH 4 glycolate buffer, unchanged by pH 4 citrate and pH 5.5 buffers, and even increased by the pH 7 buffer. pH 5.5, pH 4 citrate, and pH 4 glycolate buffers led to a slight, while the pH 7 buffer led to a significant increase in TEWL after barrier disruption compared to water. The pH 7 buffers led to a significant increase in epidermal thickness/proliferation/differentiation and inflammation after barrier disruption, whereas buffers with pH 4 and 5.5 caused a slight increase. In conclusion, only the pH 4 glycolate buffer significantly reduced the skin barrier disruption-related increase in skin pH. This was accompanied by only slight increase in epidermal thickness and inflammation compared to water. Application of the pH 7 buffer led to a significant increase in the skin pH, TEWL, epidermal thickness, and inflammation. The results are important for the formulation of topical products for effective acidification in pathological skin conditions. [ABSTRACT FROM AUTHOR]

Background: In addition to its role as a broad-spectrum imidazole antifungal drug, data from animal models as well as human clinical trials also demonstrated an anti-inflammatory efficacy of bifonazole (BFZ). In the histamine wheal test and after UV radiation, BFZ showed antiphlogistic effects that were comparable to those of hydrocortisone. However, the underlying molecular mechanisms of the anti-inflam-matory properties of BFZ are poorly understood. Methods: Performing an in vitro study we used full-thickness three-dimensional (3D) skin models containing macrophages as mediators of inflammation. We conducted two sets of experiments. In a first set we exposed our models to UVB irradiation to provoke an inflammation. A second approach used the addition of histamine into the culture medium. In both approaches, models were treated topically with a BFZ-containing ointment or a placebo ointment for 24 h, and then the effects were examined histologically as well as with microarray and quantitative real-time PCR analyses. Results: Histological examination showed that the BFZ-containing ointment reconstituted UVB- and histamine-mediated disorders within the skin models. Performing gene expression profiling in models that were treated with the BFZ-containing ointment after UVB irradiation, we detected an upregu-lation of differentiation markers (fillagrin, loricrin, and keratin 1), antimicrobial peptides (DEFB103A), and members of the cytochrome P450 family (CYP1A1 and CYP1B1) as well as a downregulation of genes that are involved in immune response (CCL22, CXCL12, CCL7, IRF1, ICAM1, TLR3, and RARRES3) and matrix metalloproteinases (MMP12 and MMP7). Models that were treated with the BFZ-containing ointment after histamine application showed an upregulation of members of the cytochrome P450 family (CAP1A1, CYP1B1, and CYP24A1) and a downregulation of immune response-associated genes (CXCL6, CXCL12, CCL8, IL6, and IL32). Conclusion: We present the first in vitro study showing anti-inflammatory effects of BFZ in human 3D skin models. To our knowledge, this is the first time that these effects could be translated from human clinical trials into an in vitro test system, allowing a more detailed examination of molecular mechanisms that were regulated by BFZ. [ABSTRACT FROM AUTHOR]

Background: About 50% of the sun's radiation arriving on earth is visible light (VIS). For a long time, its effects on human health have not been fully investigated. But recently, the influence of VIS has gained more attention, especially regarding skin physiology. Studies showed various effects, many of them harmful, comparable to UV radiation. As a result, there are now a few sunscreens commercially available which claim protection against VIS. The question of whether protection is necessary is still much discussed. Aims: The objective of this study was to develop an easy-to-perform high-energy visible (HEV) and low-end visible (LEV) light transmittance method to determine the direct VIS protection of sunscreens and other cosmetic samples. Furthermore, the influence of the brightness of the tested products on the HEV, LEV, and infrared A protection was investigated. Methods: An experimental setup consisting of a light source, a VIS-transmissible filter system, and a sensor unit was built to measure the direct VIS protection of sunscreens and other daily skin care products in two ranges of the VIS area. For a closer look, the brightness of the samples was evaluated by photometric assessment. Results/Conclusion: The experimental setup could be validated. It could be demonstrated for the first time that there is a strong positive linear correlation between transmittance and brightness of tinted sunscreen and daily skin care products with sunscreen properties in the HEV, LEV, and infrared A range. However, tinted samples worked best in the blue light region, and the higher the wavelength range, the lower the protection. [ABSTRACT FROM AUTHOR]

Background/Aims: Analysis of the relationship between the estradiol blood concentration and the skin moisture, pore width, discoloration and smoothness in differently aged women on the 5th and 25th days of the menstrual cycle. Methods: The study involved 57 women divided into 4 age groups. Measurements of skin moisture, pore width, discoloration and smoothness were performed using the Aramo SG Aram Huvis device. The estradiol serum concentration was determined by radioimmunoassay. Results: In the luteal phase of the cycle, facial skin moisture increases from 93.5% of the correct standard moisture index in the youngest to 115.5% in the oldest group. A positive correlation (r2 = 0.45) between estradiol concentration and skin moisture was observed on the 5th day of the cycle in 40- to 50-year-olds. For women on the 25th day of the menstruation cycle, estrogen concentration below the normal range was more beneficial for skin smoothness and pore width for the oldest group. The difference was not statistically significant (p > 0.05); how-ever, in the 40- to 50-year age group, skin smoothness was much better (43.5 ± 6.7%) for low estradiol while it was 37.5 ± 4.7% in the 20- to 29-year age group. Similarly, in the 40- to 50-year age group, skin pore width was much smaller (35.2 ± 15.7%) for low estradiol while it was 54.3 ± 28.8% in the 20- to 29-year age group. Conclusions: Skin moisture was related to the concentration of estradiol only in the oldest examined group of women regardless of the phase of menstrual cycle. In the 40- to 50-year-old group of women, the low level of estradiol on the 25th day of the cycle is better used to maintain a good facial skin appearance and has a positive influence not only on skin moisture, but also on pore width and skin smoothness. [ABSTRACT FROM AUTHOR]

Background: Skin reaction to spaceflight has not really been studied yet, although the skin has a very important barrier function to protect the body and can contribute to a more general understanding of physiology. It is proposed here to make a more thorough investigation of the skin during long-term spaceflight, using noninvasive techniques. Aims: The aim of the present Skin-B study is to investigate the kinetics and range of possible skin modifications during long-duration spaceflights and their recovery. Methods: In order to investigate the effect on skin physiological parameters during spaceflight, measurements were carried out on 6 astronauts with respect to skin hydration, transepidermal water loss/barrier function, and surface evaluation of the living skin in orbit. Additional measured parameters on the ground were skin elasticity, skin density and thickness, as well as microcirculation. Results: Data from the Skin-B subjects (n = 6) contradict the results obtained in the previous pilot study SkinCare (n = 1 subject). In the present study, no deterioration of the skin was found but rather an improvement in skin hydration and skin barrier function, and no changes or improvement in the appearance of the skin surface. Furthermore, the skin density and skin thickness as well as skin elasticity values were unchanged from pre-flight values. Conclusion: In conclusion, we found that spaceflight under present conditions has no negative impact on skin physiological parameters. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether the skin barrier function is impaired with regard to the pH value, water content, transepidermal water loss (TEWL), and the integrity of the stratum corneum, and whether the expression of caspase-14 is altered in moderate to severe chronic hand eczema (CHE).Methods: Thirty patients with moderate to severe CHE treated at our institute and 30 healthy volunteers were included in this study. The pH value, water content, TEWL, and the integrity of the stratum corneum were measured in all subjects.Results: Significantly increased pH value, decreased water content, elevated TEWL, and impaired integrity of the stratum corneum were observed in the lesional skin of CHE patients compared with the nonlesional skin of CHE patients and the normal skin of healthy volunteers. The expression of caspase-14 decreased in the lesional and nonlesional skin of CHE patients compared with the normal skin of healthy volunteers, especially prominent in the nonlesional skin. The mean optical density (OD) value of immunohistochemical staining for caspase-14 was significantly lower in the nonlesional skin than in the lesional skin and normal skin (p < 0.01 for both). Although the mean OD value was lower in the lesional skin than in the normal skin, the difference was not statistically significant (p > 0.05).Conclusion: Skin barrier dysfunction indeed occurs in CHE patients, which may be related to mechanisms associated with a downregulated expression of caspase-14. [ABSTRACT FROM AUTHOR]

Background/Aim: Inadequate fluid intake is assumed to be a trigger of water-loss dehydration, which is a major health risk in aged and geriatric populations. Thus, there is a need to search for easy to use diagnostic tests to identify dehydration. Our overall aim was to investigate whether skin barrier parameters could be used for predicting fluid intake and/or hydration status in geriatric patients. Methods: An explorative observational comparative study was conducted in a geriatric hospital including patients aged 65 years and older. We measured 3-day fluid intake, skin barrier parameters, Overall Dry Skin Score, serum osmolality, cognitive and functional health, and medications. Results: Forty patients were included (mean age 78.45 years and 65% women) with a mean fluid intake of 1,747 mL/day. 20% of the patients were dehydrated and 22.5% had an impending dehydration according to serum osmolality. Multivariate analysis suggested that skin surface pH and epidermal hydration at the face were associated with fluid intake. Serum osmolality was associated with epidermal hydration at the leg and skin surface pH at the face. Fluid intake was not correlated with serum osmolality. Diuretics were associated with high serum osmolality. Conclusions: Approximately half of the patients were diagnosed as being dehydrated according to osmolality, which is the current reference standard. However, there was no association with fluid intake, questioning the clinical relevance of this measure. Results indicate that single skin barrier parameters are poor markers for fluid intake or osmolality. Epidermal hydration might play a role but most probably in combination with other tests. [ABSTRACT FROM AUTHOR]

Background/Aims: Basophils have been reported to infiltrate skin lesions in various skin diseases, but not in systemic lupus erythematosus (SLE). This study investigated basophil infiltration in SLE and its mechanism. Methods: Twenty newly diagnosed SLE patients and twenty healthy controls were enrolled. Nine SLE patients underwent skin biopsies. Flow cytometric analysis the phenotype of peripheral basophils and their migration rate toward RANTES and MCP-1 were analyzed with the transwell culture system, also the expression of these two chemokines in skin tissue were analyzed with immunohistochemistry. Results: Increased activation and decreased numbers of peripheral basophils were observed in SLE patients compared with controls. Basophil migration into skin lesions of SLE patients were observed, but not in normal skin tissue. This migration was related to the upregulation of chemokine receptors CCR1 and CCR2 on basophils. In vitro studies showed that migration rate toward RANTES and MCP-1 increased significantly in basophils from SLE patients compared with those from controls. Consistently, high levels of RANTES and MCP-1 expression were observed in skin lesions from SLE patients but not in normal skin tissue. Conclusion: Basophil recruitment to skin lesions of SLE patients mediated by CCR1 and CCR2, which may contribute to tissue damage in SLE. [ABSTRACT FROM AUTHOR]

Background/Aims: Zinc (Zn) is an important microelement required by skin cells for a variety of biological processes. The role of Zn in melanocyte proliferation and homeostasis has to date not been investigated. Methods: Human dermal melanocytes were isolated from patients and their proliferative activity determined along with both total and labile Zn content. Subsequently, changes in proliferation as well as in Zn content were determined upon exposure of the dermal melanocytes to external Zn. Further in-depth analyses were undertaken aimed at measuring the expression of proliferation-related proteins (determined by immunoblotting and densitometry), as well as changes in mitochondrial biogenesis and membrane potential (assessed by fluorescence-based cellometry) along with endolysosomal activity (determined by spectrofluorimetrically-measured elevation in fluorescence of lysosomal-aimed nonfluorescent substrate). Results: Human skin melanocytes accumulate externally added Zn, a process which dose-dependently enhances their injury or proliferative activity. Enhanced proliferation is accompanied by an increased expression of the proteins AKT3, ERK1/2, c-MYC and CYCD. In addition, Zn-enriched melanocytes exhibit enhanced mitochondrial biogenesis, with individual mitochondria possessing stabilized mitochondrial membrane potential as well as showing elevated ATP and superoxide levels. Moreover, upon external exposure, Zn enters lysosomes/melanosomes, the activity of which is stimulated along with the process of autophagy. Conclusion: The determination of the unique Zn-dependent stimulation of melanocytes and in particular the enhancement of the cell's mitochondrial as well as lysosomal/ melanosomal activities may prove important in tracing the sequence of steps in the process of melanomagenesis. [ABSTRACT FROM AUTHOR]

The movement of water into and out of cells is a fundamental biological process that is essential for life. Such water movement not only regulates the activity of individual cells but also is responsible for the functioning of many organ systems and for maintaining whole body water balance. It had long been suspected that water movement across biological cell membranes was in some way enhanced or facilitated by pores or channels, but the search to identify these channels was long and tedious. As is often the case in science, the secret of the water channel was eventually discovered by chance in 1992 by Peter Agre and his colleagues at the Johns Hopkins University in Baltimore, who were working on red blood cell membrane proteins. This "first" water channel was originally named CHIP28 and is now known as aquaporin 1. Agre received the Nobel Prize in Chemistry in 2003 for this discovery. There are currently 13 known aquaporins in mammals, distributed in most tissues, but many more have been identified in lower organisms and in the plant kingdom. The involvement of aquaporins in processes such as urinary concentration and body fluid homeostasis, brain function, glandular secretion, skin hydration, male fertility, hearing, vision, and most important body functions that can be imagined are now all under intense scientific scrutiny. Moreover, defects in aquaporin function have been related to various disease conditions and pathological states. This brief review will discuss their background, discovery, and function in selected bodily processes, especially focusing on hydration. [ABSTRACT FROM AUTHOR]

Background: Glucosamine sulphate (GS) is essential in the biosynthesis of glycolipids, glycoproteins, glycosaminoglycans (GAGs), hyaluronate, and proteoglycans. Connective tissues primarily contain collagen and proteoglycans and play an important role in skin ageing. Objective: The objectives were to assess ex vivo the impact of GS on skin ageing parameters and in vivo the effect of GS on the skin physiology of mature healthy volunteers after oral intake. Methods: The impact of GS on skin ageing was assessed ex vivo via different immunohistochemical assays and histology and via a clinical study using biopsies. Modulation of selected skin physiology markers was assessed by real-time quantitative PCR on skin punch biopsies obtained from 8 healthy >50-year-old women having ingested GS 250 mg once daily for 8 weeks. Results: Ex vivo, GS significantly (all p = 0.02) increased the expression of CD44 and collagen type IV, the epidermis GAG level, and collagen type I synthesis. After 8 weeks of oral GS administration, a significantly increased expression was observed at the mRNA level for vimentin, fibromodulin, biglycan, xylosyl transferase, hyaluronan synthase, collagen types I and III, bone morphogenic protein-1, and decorin (all p = 0.05). Conclusion: Both experiments showed that GS has a positive effect on epidermal and dermal markers associated with age. [ABSTRACT FROM AUTHOR]

The article focuses on dermatonutrigenomics, considering the past, present, and future applications of nutrigenomics in dermatology. Topics discussed include the meaning of nutrigenomics, the rise of nutrigenomics during the early period of the the genome sequencing era, and the challenges and solutions with regards to nutrigenomics research.

Background: Therapeutic hypothermia is presumed to suppress inflammatory processes after perinatal asphyxia. In a previous study of neonatal hypoxic-ischemic encephalopathy (HIE) we found altered skin microcirculation in about a third of the infants after rewarming. We speculated whether this could be linked to increased inflammatory responses, such as high C-reactive protein (CRP). The present study further explored this question. Objective: The aim of this study was to explore the differences in skin microcirculation and its oxygen delivery ability during cooling and after rewarming in HIE infants with or without high CRP. Methods: A previously studied population of 28 HIE infants was divided into two subgroups depending on low or high CRP (repeated values above 30 mg/l for more than 24 h). The differences between the two groups regarding laser Doppler perfusion measurements (LDPMs), computer-assisted video microscopy and diffuse reflectance spectroscopies during cooling on days 1 and 3 and after rewarming on day 4 were assessed. Results: After rewarming, infants with high CRP showed significantly higher skin LDPM perfusion, lower functional vessel density and larger heterogeneity of capillary flow velocities as compared to infants with low CRP, while no such differences were found during cooling. Conclusion: Skin microcirculatory responses differed significantly after rewarming, but not during cooling, between asphyxiated neonates with or without high CRP. We speculate whether cooling influences the inflammatory skin microcirculatory response and the ability of oxygen delivery to the cells. Further studies are needed to investigate this as well as its applicability to other vascular beds in the body. [ABSTRACT FROM AUTHOR]

The present study assessed the possibility for the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]- octanoic acid (DCP-LA) as an antiaging compound for the skin by assaying senescence-associated β-galactosidase (SA- β-Gal), a biomarker of senescence and cell viability. The nitric oxide (NO) donor sodium nitroprusside (SNP) increased in SA-β-Gal-positive cells in cultured human fibroblasts and mouse keratinocytes, and DCP-LA significantly inhibited the effect of SNP. Moreover, SNP induced cell death in cultured mouse keratinocytes, and DCP-LA significantly prevented NO stress-induced death of keratinocytes. Taken together, these results indicate that DCP-LA exerts an antiaging action on the skin. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of the study was to elucidate the effect of sample preparation and microscope configuration on the results of confocal Raman microspectroscopic evaluation of the penetration of a pharmaceutical active into the skin (depth profiling). Methods: Pig ear skin and a hydrophilic formulation containing procaine HCl were used as a model system. The formulation was either left on the skin during the measurement, or was wiped off or washed off prior to the analysis. The microscope configuration was varied with respect to objectives and pinholes used. Results: Sample preparation and microscope configuration had a tremendous effect on the results of depth profiling. Regarding sample preparation, the best results could be observed when the formulation was washed off the skin prior to the analysis. Concerning microscope configuration, the use of a 40 × 0.6 numerical aperture (NA) objective in combination with a 25-µm pinhole or a 100 × 1.25 NA objective in combination with a 50-µm pinhole was found to be advantageous. Conclusion: Complete removal of the sample from the skin before the analysis was found to be crucial. A thorough analysis of the suitability of the chosen microscope configuration should be performed before acquiring concentration depth profiles. [ABSTRACT FROM AUTHOR]

Mechanical properties of expanded skin tissue are different from normal skin, which is dependent mainly on the structural and functional integrity of dermal collagen fibrils. In the present study, mechanical properties and surface topography of both expanded and nonexpanded skin collagen fibrils were evaluated. Anisotropic controlled rate self-inflating tissue expanders were placed beneath the skin of sheep's forelimbs. The tissue expanders gradually increased in height and reached equilibrium in 2 weeks. They were left in situ for another 2 weeks before explantation. Expanded and normal skin samples were surgically harvested from the sheep (n = 5). Young's modulus and surface topography of collagen fibrils were measured using an atomic force microscope. A surface topographic scan showed organized hierarchical structural levels: collagen molecules, fibrils and fibers. No significant difference was detected for the D-banding pattern: 63.5 ± 2.6 nm (normal skin) and 63.7 ± 2.7 nm (expanded skin). Fibrils from expanded tissues consisted of loosely packed collagen fibrils and the width of the fibrils was significantly narrower compared to those from normal skin: 153.9 ± 25.3 and 106.7 ± 28.5 nm, respectively. Young's modulus of the collagen fibrils in the expanded and normal skin was not statistically significant: 46.5 ± 19.4 and 35.2 ± 27.0 MPa, respectively. In conclusion, the anisotropic controlled rate self-inflating tissue expander produced a loosely packed collagen network and the fibrils exhibited similar Dbanding characteristics as the control group in a sheep model. However, the fibrils from the expanded skin were significantly narrower. The stiffness of the fibrils from the expanded skin was higher but it was not statistically different. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) radiation is the major environmental factor affecting functions of the skin. Compounds rich in polyphenols, such as Thymus vulgaris leaf extract and thymol, have been proposed for the prevention of UV-induced skin damage. We compared the acute effects induced by UVA and UVB rays on epidermal morphology and proliferation, cytotoxicity, and genotoxicity. Normal human skin explants were obtained from young healthy women (n = 7) after informed consent and cultured at the air-liquid interface overnight. After 24 h, the samples were divided in 2 groups: the former exposed to UVA (16 or 24 J/cm 2) and the latter irradiated with UVB (0.24 or 0.72 J/cm 2). One hour after the end of irradiation, supernatants were collected for evaluation of the lactate dehydrogenase activity. Twenty-four hours after UVB exposure, biopsies were processed for light and transmission electron microscopy analysis, proliferation, cytotoxicity, and genotoxicity. UVB and UVA rays induced early inhibition of cell proliferation and DNA damage compared to controls. In particular, UVB rays were always more cytotoxic and genotoxic than UVA ones. For this reason, we evaluated the effect of either T. vulgaris L. extract (1.82 µg/ml) or thymol (1 µg/ml) on all samples treated for 1 h before UVB irradiation. While Thymus had a protective action for all of the endpoints evaluated, the action of the extract was less. [ABSTRACT FROM AUTHOR]

Skin is commonly stored frozen and then thawed prior to use for in vitro permeation experiments. Does frozen storage of skin alter its barrier property? Numerous studies have found contradictory answers to this question. In this study, the steady-state flux and lag time of diethyl phthalate (DEP) were measured for fresh human skin and skin frozen at -85°C for 1, 2, 3, 6, 9, 12, and 18 months with 10% glycerol as a cryoprotective agent. No significant differences in steady-state flux were found between fresh and previously frozen samples (p = 0.6). For lag time, a significant (p = 0.002) difference was found among all groups, but comparisons with fresh skin were not significant. Does glycerol have a cryoprotective effect? The steady-state flux and lag time of DEP and caffeine were measured through human skin stored at -85°C for up to 12 months with and without 10% glycerol. No significant differences in steady-state flux or lag time were found between samples stored with or without glycerol for either DEP or caffeine (p ≥ 0.17). These findings support the use of frozen skin to measure the passive permeation of chemicals in studies unconcerned with viability and metabolism. Published by S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

Background: The formation of free radicals in human skin by solar ultraviolet radiation is considered to be the main reason for extrinsic skin aging. The antioxidants in human tissue represent an efficient protection system against the destructive action of these reactive free radicals. In this study, the parameters of the skin, epidermal thickness, stratum corneum moisture, elasticity and wrinkle volume, were determined before and after the treatment with antioxidant- or placebo-containing tablets and creams. Methods: The study included 5 groups of 15 volunteers each, who were treated for 2 months with antioxidant-containing or placebo tablets, creams or a combination of antioxidant-containing tablets and cream. The skin parameters were measured at time point 0 and at week 8 utilizing ultrasound for the determination of epidermal thickness, a corneometer for stratum corneum moisture measurements, skin profilometry for quantifying the wrinkle volume and a cutometer for determining the elasticity. Results: The verum cream had a positive influence on epidermal thickness, elasticity and skin moisture, but the verum tablets improved the epidermal thickness only. The combined application of verum tablets and creams led to a significant improvement of all investigated skin parameters, whereas the application of placebo tablets or cream did not influence any parameters. Conclusion: The topical and oral supplementation of antioxidants can be an instrument to improve several skin parameters and potentially counteract or decelerate the process of extrinsic skin aging. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The subject of oil penetration into the skin is controversially discussed in the scientific literature. Methods: Confocal Raman microscopy was used for analyzing oil penetration into the skin. The following methods were applied in the study: methods based on tracking specific peaks (method 1), the nonrestricted multiple least square fit (method 2), analyzing the lipid-to-keratin peak ratio using the perpendicular drop-down cutoff procedure (method 3), and the Gaussian function-based deconvolution procedure (method 4). Results: The results obtained using methods 1, 2 and 4 show that the investigated oils do not penetrate deeper than 11 µm into human and porcine skin. Petrolatum has a prominent swelling effect on the stratum corneum (32% in vivo, 28% ex vivo), while the other oils exhibit no significant swelling effect. By using method 3, the penetration profile of oils, and especially of petrolatum, into the skin was interpreted incorrectly for various reasons that are addressed herein below. Conclusion: Predominantly remaining in the uppermost corneocyte layers of the stratum corneum, topically applied oils do not reach the viable cells of the stratum spinosum. To exclude any possible mistakes when using the lipid-keratin Raman peak (2,820-3,030 cm-1), the penetration analysis should be performed using the Gaussian function-based deconvolution procedure. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Skin barrier function, confined to the stratum corneum, is traditionally evaluated using established, noninvasive biophysical methods like transepidermal water loss, capacitance and conductance. However, these methods neither measure skin molecular composition nor its structure, hindering the actual causes of skin barrier change or impairment. At the same time, confocal Raman microspectroscopy (CRS) can directly measure skin molecular composition and structure and has proven itself to be a powerful technique for biomolecular analysis. The aims of this literature review were to evaluate noninvasive biophysical methods in view of CRS and to outline a direction towards more specific and informative skin measurement methods. We address this by investigating, for the first time, the relation between in vivo assessment of the skin barrier using indirect biophysical methods and the actual skin composition and structure as given by CRS, and emphasize the high potential of CRS for dermatology and cosmetic sciences. CRS acceptance in these fields will require close collaboration between dermatologists, skin scientists and spectroscopy experts towards simplifying the technology and creating robust, rapid, easy-to-use and less expensive CRS applications. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

One of the known drawbacks of in vitro dermal absorption methods is their high interlaboratory variation. Although often attributed to biological skin differences, it has been shown that validation of other parameters such as temperature and stirring speed can reduce the high variability observed. The Organisation for Economic Co-operation and Development (OECD) and, at the EU level, the Scientific Committee on Consumer Safety (SCCS) have published guidance documents of how to perform these in vitro tests. For the parameter 'sample application' and 'adequate seal', it is indicated to apply the sample homogeneously and provide an adequate seal between the donor chamber and the membrane on which the sample is applied. Here, a simple and visual densitometer-based method is provided, which makes evaluation possible of any application protocol used. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Three evolutionary sources create 'primary' reactive oxygen species (ROS) and 'secondary' lipid oxygen species (LOS), forming the human body's 'free radical ground state'. We present evidence for the existence of a universal free radical threshold value (FRTV), defining the borderline between advantageous and adverse effects of free radicals observed above the free radical ground state. Based on standard vitamin D doses, the calculated amount of ∼3.5 × 1012 rad/mg ROS/LOS tissue represents the tolerated number of free radicals in skin tissue - defined as FRTV. By means of quantitative ESR x-band spectroscopy, the FRTV was experimentally verified using ex vivo human skin irradiated with ultraviolet + visible (UV + VIS), UVB + UVA and VIS light. In addition, we investigated whether this threshold is also existent in internal organs by extending our experiment to fresh porcine liver. Based on the determination of ROS/LOS below and above the FRTV, ROS > LOS was characterized as beneficial and LOS > ROS as deleterious to the organism, respectively. Results of the experiments using porcine liver confirmed the appearance of the FRTV at radical generation ∼3.5 × 1012 rad/mg. The relation ROS/LOS before and after the FRTV was consistent with the results determined for the skin. We conclude that the FRTV, theoretically calculated and experimentally confirmed, should be considered as a new 'universal body constant'. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. Objectives: Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1. Methods:Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product. Results: Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability. Conclusion: The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]