Quantitative Analysis and Molecular Docking Simulation of Flavonols from Eruca sativa Mill. and Their Effect on Skin Barrier Function.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Infant lung function and early skin barrier impairment in the development of asthma at age 3 years.

BACKGROUND: Largely unexplored, we investigated if lower lung function, impaired skin barrier function by transepidermal water loss (TEWL), eczema, and filaggrin (FLG) mutations in infancy were associated with asthma in early childhood. METHODS: From the factorially designed randomized controlled intervention study PreventADALL, we evaluated 1337/2394 children from all randomization groups with information on asthma at age 3 years, and at age 3 months either lung function, TEWL, eczema, and/or FLG mutations. Lower lung function was defined as the time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) <0.25, and skin barrier impairment as a high TEWL >9.50 g/m2 /h. Eczema was clinically observed, and DNA genotyped for FLG mutations. Asthma was defined as asthma-like symptoms (≥3 episodes of bronchial obstruction) between age 2-3 years as well as a history of doctor-diagnosed asthma and/or asthma medication use. Associations were analyzed in logistic regression models, presented with adjusted ORs (aOR) and 95% confidence intervals (CI). RESULTS: Lower lung function and skin barrier impairment were associated with asthma in general; aOR (95% CI) 5.4 (2.1, 13.7) and 1.6 (1.1, 2.5), while eczema and FLG mutations were associated with asthma in children with atopic dermatitis or allergic sensitization only. Stratifying for sex, the risk of asthma was only increased in boys with lower lung function; aOR (95% CI) 7.7 (2.5, 23.6), and in girls with FLG mutations; aOR (95% CI) 3.5 (1.5, 8.2). CONCLUSION: Lower lung function and impaired skin barrier function in infancy may increase the risk of asthma at age 3 years.

Lipidomics Reveals the Effects of Detergents on Skin Surface Lipids in Young Adults.

BACKGROUND: Detergent is a chemical product commonly used in people's daily life. Contact with detergent solutions can damage the human skin barrier and cause skin diseases. Skin surface lipids (SSLs) play a decisive role in skin barrier function. This study aimed to observe the changes of SSLs in young adults after exposure to detergent solutions to explore the underlying mechanism of skin barrier function damage. METHODS: A self-controlled study on youth adults was conducted in Zhengzhou, China, in November 2020. The study lasted for a total of 1 week, and skin barrier function was assessed by trans-epidermal water loss (TEWL) values. The changes of SSLs before and after exposure to the detergent with subjects were measured using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry. RESULTS: The skin barrier function of subjects' hands was impaired after exposure to detergent (TEWL value increased, p < 0.001). A total of 520 SSLs were detected, divided into 6 main categories. The average relative abundance of these 6 major lipids decreased after exposure. Sphingolipids (mainly ceramides), free fatty acids (mainly long-chain fatty acids), cholesterol lipids, and glycerophospholipids are the most severely damaged lipids. CONCLUSION: Detergent solutions can damage the skin barrier function and SSLs of young hands; interventions targeting SSLs to eliminate detergent damage to human skin may be of value.

Driving adult tissue repair via re-engagement of a pathway required for fetal healing.

Fetal cutaneous wound closure and repair differ from that in adulthood. In this work, we identify an oxidant stress sensor protein, nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), that is abundantly expressed in normal fetal epidermis (and required for fetal wound closure), though not in adult epidermis, but is variably re-induced upon adult tissue wounding. NPGPx is a direct target of the miR-29 family. Following injury, abundance of miR-29 is lowered, permitting a prompt increase in NPGPx transcripts and protein expression in adult wound-edge tissue. NPGPx expression was required to mediate increased keratinocyte migration induced by miR-29 inhibition in vitro and in vivo. Increased NPGPx expression induced increased SOX2 expression and ß-catenin nuclear localization in keratinocytes. Augmenting physiologic NPGPx expression via experimentally induced miR-29 suppression, using cutaneous tissue nanotransfection or targeted lipid nanoparticle delivery of anti-sense oligonucleotides, proved to be sufficient to overcome the deleterious effects of diabetes on this specific pathway to enhance tissue repair.

Functional properties and skin care effects of sodium trehalose sulfate.

BACKGROUND: It is known that heparinoid, a mucopolysaccharide polysulfate, is effective in improving rough skin and promoting blood circulation as medicines for diseased areas. However, heparinoid has a molecular weight of more than 5000 and cannot penetrate healthy stratum corneum. OBJECTIVE: We tested the efficacy of sulfated oligosaccharides with a molecular weight of less than 2000 on the human skin barrier function and moisturizing function. METHODS: We measured the transepidermal water loss (TEWL) of a three-dimensional human epidermis model cultured for 3 days after topical application of sulfated oligosaccharides, then observed the effects on TEWL suppression. The mRNA levels of proteins involved in intercellular lipid transport and storage in the stratum corneum, and moisture retention were measured using RT-qPCR. RESULTS: An increase in the mRNA levels of the ATP-binding cassette subfamily A member 12 (ABCA12), which transports lipids into stratum granulosum, was confirmed. Increases were also observed in the mRNA levels of filaggrin (FLG), which is involved in the generation of natural moisturizing factors, and of caspase-14, calpain-1 and bleomycin hydrolase, which are involved in the degradation of FLG. Antibody staining confirmed that the application of sodium trehalose sulfate to 3D model skin resulted in more ABCA12, ceramide, transglutaminase1, and FLG than those in controls. In a randomized, placebo-controlled, double-blind study, participants with low stratum corneum water content applied a lotion and emulsion containing sodium trehalose sulfate to their faces for 4 weeks. Sodium trehalose sulfate decreased the TEWL and increased the stratum corneum water content. CONCLUSION: These results suggest that cosmetics containing sodium trehalose sulfate act on the epidermis by increasing barrier factors and moisturizing factors, thereby ameliorating dry skin.

Efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate for improving sensitive skin symptoms.

BACKGROUND: Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management. AIM: To evaluate the efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate as an optimal care for facial sensitive skin. METHODS: A total of 110 participants (64 in group A and 46 in group B) with facial sensitive skin applied the cream twice daily for 28 days. Group A evaluated their sensitive skin, product efficacy, and product use experience at D0 (15 min), D1, D14, and D28. In group B, skin barrier function-related indicators were measured at baseline and on D1, D7, D14, and D28. Dermatologists evaluated tolerance for all participants. RESULTS: After 28 days of use, in group A, 100% of participants reported mildness and comfort with product use. Participants demonstrated significant improvements in skin barrier function-related indicators, including increased stratum corneum moisture content, reduced erythema index, elevated sebum content, decreased trans-epidermal water loss, and diminished skin redness parameter a* value (all p < 0.05). Dermatologist evaluations revealed excellent tolerance among all participants. CONCLUSION: The panthenol-enriched cream with prebiotics and probiotic lysate exhibited substantial clinical efficacy in ameliorating facial sensitive skin conditions, coupled with a high safety profile.

Quantitative skin surface hydration measurement by visible optical image processing: A pilot study.

BACKGROUND: Skin barrier function is significantly impacted by skin moisture. Most non-invasive evaluation techniques to measure skin surface hydration relying on its electrical properties, which are limited in scope and have unstable operations. Applying image processing for skin hydration assessment is uncommon, with an emphasis on skin-capacitive pictures and near-infrared images in general, which demand a certain spectrum. As a result, there is an increasing need for wide-area skin hydration evaluation and mapping. OBJECTIVE: The study aims to propose a quantitative evaluation algorithm for skin surface hydration from visible-light images. MATERIALS AND METHODS: Three devices were applied to measure skin hydration: skin image capture device and two recognized commercial skin devices. A digital image processing system creates a new index, called GVR, to symbolize skin surface moisture. The CLAHE algorithm was applied to enhance the contrast of skin image, and after calculating it with the monochrome image, the skin reflectance image was segmented. The GVR was estimated using the values of the individual sites and the entire skin. The correlation coefficient between the three methods was examined using statistical analysis to assess the performance of GVR. RESULTS: Skin hydration estimated from visible-light images is influenced by the entire facial structure in addition to specific areas. The electrical and visible image evaluations showed a strong association with a significant difference. CONCLUSION: It was discovered that reflecting measures from visible images provide a quick and efficient way to quantify the moisture of the skin's surface.

Atopic Dermatitis: Disease Background and Risk Factors.

Multiple risk factors have been associated with the development of atopic dermatitis (AD). Recent advances in understanding the role of genetics in this disease have been made, with discovery of the filaggrin (FLG) gene as the most notable so far. In addition to FLG gene mutations as a risk factor for AD, a positive family history of atopic or allergic disease in either parent has been shown to confer a greater risk of developing AD. Atopic dermatitis usually presents early in life and is thought to represent the initial step in the "atopic march," which is characterized by the development of other atopic diseases later in life such as asthma, allergic rhinitis, and/or rhinoconjunctivitis, food allergies, and hay fever. Other comorbid diseases that have been associated with AD include increase risk of viral and bacterial skin infections, neuropsychiatric diseases such as attention-deficit hyperactivity disorders (ADHD), and autistic spectrum disorder (ASD). Patients with AD have also been found to have worse sleep quality overall compared to patients without AD. In this chapter, we will discuss the risk factors associated with development of atopic dermatitis as well as the most commonly reported comorbidities in patients with this disease.

Effects of 1,3-propanediol associated, or not, with butylene glycol and/or glycerol on skin hydration and skin barrier function.

OBJECTIVE: This study aimed to assess the effect of 1,3-propanediol at different concentrations (5%, 10%, or 15%), either applied alone or in combination with butylene glycol (BG) (5%) and/or glycerol (5%), on skin hydration and skin barrier function. The measurements were conducted using capacitance to determine skin hydration and trans epidermal water loss (TEWL) rates to evaluate skin barrier function. METHODS: A total of 30 healthy female subjects participated in the study. Capacitance and TEWL measurements were conducted at multiple time points, including before application and at 15 min, 2 and 8 h after the humectants were applied to the forearms of the subjects. All the subjects provided written informed consent. RESULTS: The 1,3-propanediol in all concentrations and in all combinations (with BG and/or glycerol) increased skin hydration and improved skin barrier function 15 min, 2 and 8 h after application. Glycerol increased the hydration performance of 1,3-propanediol. The application of 1,3-propanediol at a concentration of 15%, either alone or in combination with other humectants, reduced the TEWL to a greater extent than lower concentrations of 1,3-propanediol. Furthermore, the addition of glycerol to 1,3-propanediol 15% improved the skin barrier and reduced TEWL when compared with 1,3-propanediol alone and with the combination of 1,3-propanediol + BG. CONCLUSION: The humectants significantly improved skin hydration and reduced TEWL throughout the 8-h time course. The increase in 1,3-propanediol concentration, as well as its combination with glycerol, provided a greater benefit to the skin, improving both hydration and the skin barrier function.

OBJECTIF: Cette étude visait à évaluer l'effet sur l'hydratation de la peau et la fonction de barrière cutanée du 1,3-propanediol à différentes concentrations (5 %, 10 % ou 15 %), appliqué seul ou en association avec du butylène glycol (5 %) et/ou du glycérol (5 %). Les mesures ont été effectuées à l'aide de la capacitance pour déterminer l'hydratation de la peau et les taux de perte d'eau transépidermique (Trans Epidermal Water Loss, TEWL) pour évaluer la fonction de barrière cutanée. MÉTHODES: Au total, 30 sujets de sexe féminin en bonne santé ont participé à l'étude. Les mesures de la capacitance et de la TEWL ont été effectuées à plusieurs moments, y compris avant l'application, 15 minutes, 2 heures et 8 heures après l'application des produits humectant sur les avant-bras des sujets. Tous les sujets ont fourni un consentement éclairé écrit. RÉSULTATS: Le 1,3-propanediol, à toutes les concentrations et dans toutes les associations (avec le butylène glycol et/ou le glycérol), a augmenté l'hydratation de la peau et amélioré la fonction de barrière cutanée à 15 minutes, 2 heures et 8 heures après l'application. Le glycérol a augmenté les performances d'hydratation du 1,3-propanediol. L'application de 1,3-propanediol à une concentration de 15 %, seul ou en association avec d'autres produits humectant, a réduit la TEWL dans une plus grande mesure que des concentrations inférieures de 1,3-propanediol. En outre, l'ajout de glycérol au 1,3-propanediol 15 % a amélioré la barrière cutanée et réduit la TEWL par rapport au 1,3-propanediol seul et à l'association 1,3-propanediol + butylène glycol. CONCLUSION: Les produits humectant ont significativement amélioré l'hydratation de la peau et réduit la TEWL tout au long des 8 heures. L'augmentation de la concentration de 1,3-propanediol, ainsi que son association avec le glycérol, ont apporté un plus grand bénéfice à la peau, améliorant à la fois l'hydratation et la fonction de barrière cutanée.

A modified protocol for studying filaggrin degradation using a reconstructed human epidermis model under low and high humidity.

BACKGROUND: Filaggrin (FLG) is an essential protein that plays a vital role in maintaining skin barrier function and moisture levels, allowing the skin to adapt to dry environments. However, the precise temporal dynamics of FLG metabolism in the human epidermis remain poorly understood, and suitable tools to study these time-dependent effects are currently lacking. OBJECTIVE: To investigate the molecular mechanisms and time course of FLG metabolism and skin barrier function under high- and low-humidity conditions, utilizing a reconstructed epidermis model. METHODS: EpiSkin specimens cultured under humid or dry conditions for varying durations (2-48 h) were compared by assessing FLG degradation and skin barrier formation using immunofluorescence staining and western blotting. RESULTS: Under conditions of low humidity, the proteolysis of FLG in EpiSkin increased between 4 and 12 h and was accompanied by elevated levels of cysteine-aspartic protease (caspase)-14. The expression of peptidyl arginine deiminase 1 and calpain 1 also increased at 4 h. However, after 24 h, the expression of these three FLG-degrading proteins significantly decreased. Conversely, the levels of pyrrolidone-5-carboxylic acid and urocanic acid initially decreased at 2 h and then increased between 12 and 24 h. Additionally, the expression of skin barrier proteins, such as FLG, transglutaminase 5, loricrin and zonula occludens-1, decreased starting from 12 h. Notably, epidermal cell viability and activity were also inhibited. CONCLUSION: We propose a reliable and ethical model to study the temporal dynamics of FLG metabolism and its role in skin barrier function. Using a commercially reconstructed epidermis to mimic dry skin formation obviates the need for animal and human testing.

CONTEXTE: la filaggrine (FLG) est une protéine essentielle qui joue un rôle vital dans le maintien de la fonction de barrière cutanée et des taux d'humidité, permettant à la peau de s'adapter aux environnements secs. Cependant, la dynamique temporelle précise du métabolisme de la FLG dans l'épiderme humain reste mal comprise, et des outils appropriés pour étudier ces effets dépendant du temps font actuellement défaut. OBJECTIF: étudier les mécanismes moléculaires et l'évolution dans le temps du métabolisme de la FLG et de la fonction de barrière cutanée en milieux à humidité élevée et faible, en utilisant un modèle d'épiderme reconstruit. MÉTHODES: les échantillons EpiSkin cultivés en milieux humides ou secs pendant des durées variables (2 à 48 h) ont été comparés en évaluant la dégradation de la FLG et la formation d'une barrière cutanée à l'aide d'une coloration par immunofluorescence et d'un Western blot. RÉSULTATS: en milieux à faible humidité, la protéolyse de la FLG dans EpiSkin a augmenté entre 4 et 12 h et s'est accompagnée de taux élevés de cystéine­protéase aspartique (caspase)­14. L'expression du peptidyl arginine déiminase 1 et de la calpaïne 1 a également augmenté à 4 h. Cependant, après 24 h, l'expression de ces trois protéines de dégradation de la FLG a significativement diminué. Inversément, les taux d'acide pyrrolidone­5­carboxylique et d'acide urocanique ont initialement diminué au bout de 2 h, puis ont augmenté entre 12 et 24 h. En outre, l'expression des protéines de la barrière cutanée, telles que la FLG, la transglutaminase 5, la loricrine et le zonula occludens­1, a diminué à partir de 12 h. Notamment, la viabilité et l'activité des cellules épidermiques ont également été inhibées. CONCLUSION: nous proposons un modèle fiable et éthique pour étudier la dynamique temporelle du métabolisme de la FLG et son rôle dans la fonction de barrière cutanée. L'utilisation d'un épiderme reconstitué commercialement pour imiter la formation d'une peau sèche élimine la nécessité de réaliser des examens sur des animaux et des humains.

Preventive effects of dietary fucoxanthin on ultraviolet A induced photoaging in hairless mice.

BACKGROUND: Repeated exposure to ultraviolet A (UVA) irradiation, which can penetrate the epidermis and reach the dermis, is one of the major causes of skin photoaging. Photoaged skin is characterized clinically by generalized wrinkling, a dry and loose appearance, and seborrheic keratoses, along with skin barrier dysfunction. Fucoxanthin, a xanthophyll carotenoid with a specific allenic bond and 5,6-monoepoxide in its structure, has been found to serve various functions as a food supplement. In the present study, the protective effects of orally administered fucoxanthin at relatively low concentrations (0.001% and 0.01%) against UVA induced photoaging were evaluated in vivo using hairless mice. RESULTS: Oral supplementation of 0.001% fucoxanthin was sufficient for its metabolites to accumulate in the skin, thereby inhibiting pathological changes induced by UVA irradiation, including impaired skin barrier function and accelerated wrinkle formation. Analysis of gene expression revealed that dietary fucoxanthin exerted antiphotoaging effects, possibly by modulating natural moisturizing factor (NMF) synthesis, desquamation, and ceramide composition in the epidermis, and by inhibiting the UVA induced degradation of collagen fibers and inflammation in the dermis. CONCLUSION: Taken together, our data indicate the potential application of dietary fucoxanthin as a novel ingredient in nutricosmetics for skin care against photoaging. © 2024 Society of Chemical Industry.

Effects of consecutive bed bathing with weak versus ordinary pressure on skin barrier recovery of hospitalised older adults: A within-person randomised controlled trial.

AIM: Wiping pressure (WP [mmHg]) during bed baths is essential to maintain skin integrity and care quality for older adults. However, effects of different wiping pressures on skin barrier recovery over multiple days remain unclear. This study evaluated and compared the effects of consecutive bed bathing with weak pressure and that with ordinary pressure on skin barrier recovery of hospitalised older adults. METHODS: This within-person, randomised, controlled trial involved 254 forearms (127 patients) and was conducted at a general hospital. Forearms were blinded and randomly assigned a site and sequence of two bed bathing sessions: wiping three times with weak (10≤WP<20) and ordinary pressure (20≤WP<30) once per day for 2 consecutive days. The skin barrier was assessed daily based on transepidermal water loss (TEWL) and stratum corneum hydration (SCH) before and 15 min after the interventions. Dry skin was assessed using the overall dry skin score. RESULTS: A linear mixed model showed that the time courses of TEWL and SCH differed significantly between groups. Impaired skin barrier function caused by ordinary pressure on the first day did not recover to baseline values the next day, whereas weak pressure did not cause significant changes. During subgroup analyses, TEWL of patients with dry skin was more likely to increase with ordinary pressure. CONCLUSIONS: Despite decreased skin barrier recovery experienced by older adults, our findings suggest the safety of weak pressure and highlight the importance of WP during bed baths. Weak pressure is particularly desirable for patients with dry skin. TRIAL REGISTRATION: UMIN000048838.

Film-Forming, Moisturizing, and Sensory Properties of a Cosmetic Formulation Containing Tara Gum and Brazilian Berry Extracts.

The development of cosmetic formulations with moisturizing and film-forming properties has been very important to help keep skin physiology and protection. In this context, this study aimed to develop a cosmetic formulation containing Tara gum and Brazilian berry extract and evaluate its physical-mechanical, film-forming, and sensory properties. A gel formulation was developed based on Tara gum added to Plinia cauliflora extract and was characterized by its spreadability profile and sensory properties. A clinical study was carried out with ten participants to evaluate the skin microrelief, stratum corneum water content, transepidermal water loss (TEWL), and skin morphological characteristics by reflectance confocal microscopy (RCM) before and after 2 h of application of the formulations. The formulation with Brazilian berry significantly decreased the work of shear parameter, which can be correlated with improved spreadability in the sensory analysis. The clinical study showed that both formulations improved skin hydration and reduced the TEWL. The RCM imaging analysis showed the visible film on the skin surface, a decrease in the size of furrows, an increase in the reflectance of the interkeratinocytes, and reflectance of the stratum corneum for both formulations. These results were more pronounced for the formulation containing Brazilian berry. The Tara gum in the gel formulation promoted the formation and visualization of a polymeric net on the stratum corneum surface, demonstrated by the images obtained from RCM. However, the formulation added with the Brazilian berry extract improved the skin microrelief, honeycomb pattern of the epidermis, and skin hydration in deeper layers of the epidermis.

Vitamin D and wound healing: Assessing skin barrier function and implications for chloasma treatment.

Chloasma, which is distinguished by irregularities in the pigmentation of skin, poses substantial challenge in the field of dermatology. The regulatory influence of vitamin D on the functions of skin cells implies that it may have the capacity to effectively treat chloasma and promote wound healing. To assess the efficacy of vitamin D in chloasma treatment and its impact on the function of skin barrier during the process of wound healing. The research spanned from April 2022 to September 2023, in Shanghai, China, examined 480 individuals who had been diagnosed with chloasma. A double-blind, placebo-controlled clinical trial was utilized to evaluate effectiveness of topical vitamin D3 in treatment of chloasma. Concurrently, randomized control trial investigated the effects of ingested vitamin D3 supplements on the process of wound healing. Transepidermal water loss (TEWL), chloasma severity score changes, wound size reduction and skin hydration levels were critical performance indicators. Statistically, the severity scores of chloasma decreased significantly in the vitamin D treatment group at 3 and 6 months compared with the placebo (p < 0.05). The Vitamin D group exhibited superior wound healing outcomes, including more substantial reduction in lesion size and enhanced skin barrier function, as evidenced by increased skin hydration and decreased TEWL (p < 0.05). Vitamin D substantially mitigated the severity of chloasma and has beneficial effect on wound healing and integrity of the skin barrier. Based on the results obtained, vitamin D exhibited promise as a therapeutic intervention in the field of dermatology, specifically in treatment of chloasma and promotion of wound recovery.

Topical dexpanthenol effects on physiological parameters of the stratum corneum by Confocal Raman Microspectroscopy.

BACKGROUND: Topical use of dexpanthenol presents well-established moisturizing properties and maintenance and repair of the skin barrier function, however, its exact action mechanisms are not completely elucidated. In this context, Confocal Raman Microspectroscopy is an optical method that enables non-invasive and non-destructive in vivo analysis with the sensitive acquisition of molecular changes in different skin layers. Herein, the aim was to evaluate the effects of topical dexpanthenol on the components and physiological parameters of the stratum corneum (SC). MATERIALS AND METHODS: Ten healthy female subjects underwent skin evaluation by means of a Confocal Raman Spectrometer Skin Analyzer 3510. Spectral data were obtained from the skin of the anterior forearm region, before and 2 h after applying a cosmetic formulation containing or not containing 5% dexpanthenol. RESULTS: Semiquantitative analysis of the natural moisturizing factor showed a significant decrease in content after 2 h of topical dexpanthenol application, while the analysis of the lamellar organization of intercellular lipids and the secondary structure of keratin showed a significant increase in hexagonal organization of lipids at the first half of the SC and a significant increase in ß-pleated sheet conformation of keratin. CONCLUSION: Effects of topical dexpanthenol on SC suggest a contribution in increasing fluidity of both lipidic and protein components of the SC and are compatible with dexpanthenol activity in maintaining adequate physiological conditions and preventing transepidermal water loss. This study also contributes to the elucidation of action mechanisms and other concurrent biochemical processes.

Quantitative evaluation of skin barrier function using water evaporation time related to transepidermal water loss.

BACKGROUND: Transepidermal water loss (TEWL) is often used as an index for skin barrier function. The skin barrier tester, SBT-100 (Rousette Strategy Inc), measures the TEWL, water evaporation time, and time constant by contacting the skin and diffusing water into the closing measurement chamber. However, the relationship between the TEWL and time constant has not been sufficiently investigated. This study involved analyzing the underlying measurement principle and obtaining data through two experiments. MATERIALS AND METHODS: The TEWL and time constant were measured using SBT-100. Experiment 1 produced a simple simulation model for continuous water evaporation from the skin using a moisture-permeable film. In experiment 2, four skin sites of 43 healthy volunteers were examined from May to September 2018. RESULTS: In experiment 1, the TEWL increased and time constant decreased, following an increase in humidity in the external environment. Both parameters demonstrated significant negative correlation (drying: ρ = -0.832, p < 0.001). For the 43 healthy volunteers who participated in experiment 2, their TEWL increased and time constant decreased in summer. For all skin measurement sites, both data demonstrated significant negative correlation (forehead: ρ = -0.909, p < 0.001; back of the left hand: ρ = -0.829, p < 0.001; left lateral elbow: ρ = -0.896, p < 0.001; left lateral malleolus: ρ = -0.865, p < 0.001). CONCLUSION: Results indicated that the time constant is significantly correlated with TEWL. Furthermore, the time constant can be used as a parameter for evaluating skin barrier function.

Evaluation of a Novel Skin Emollient Cream on Skin Lipidome and Lipid Organization.

INTRODUCTION: The stratum corneum (SC) matrix is composed of free fatty acids, cholesterol, and ceramides (CERs), which play a key role in the skin barrier function. Changes in the composition and content of skin lipids will affect the function of the skin barrier. The effect of a glycerol/petrolatum-based emollient (G/P-emollient) cream on the lipid profiles of isolated ex vivo human SC and the SC of a reconstructed human epidermis (RHE) model was measured. METHODS: The spatial organization of the cream and the isolated SC intercellular matrix were studied using X-ray diffraction. The inter-bilayer distances in the multi-lamellar lipid structures and lattice type were analyzed using small-angle X-ray scattering and wide-angle X-ray scattering (WAXS), respectively. Lipidomic analysis using shotgun lipidomics was performed on RHE models to quantify CER classes and chain lengths. This technology enables the analysis of thousands of lipids in a single biological sample. RESULTS: The crystallized components of the cream are lipids, which were mainly packed in orthorhombic lattices, as well as hexagonal lattices and were similar to the SC structure. The cream penetrated the SC but did not alter the WAXS profile. It increased the amount of higher carbon number CERs (>42 carbons) and decreased lower carbon number CERs (<42 carbons). All chain length of CERs and acyl-CER classes (CER EOS, EOH, EOP, EOdS) were increased as the total CER classes. A decrease of the CER C34 for hydroxylated and non-hydroxylated CERs was also observed. The cream altered the S and P CER forms (increased the NP/NS and AP/AS ratios), indicating it could reduce the relative feedback mechanism observed in inflammatory pathologies, for example, atopic dermatitis. The cream increased CER NP, which is decreased in dry skin. CONCLUSION: G/P-emollient cream may be beneficial for skin pathologies by modifying SC lipids, balancing CER levels and ratios, and improving the barrier function. Importantly, the cream structure mimics that of the SC and penetrated the lower SC layers without compromising its lamellar structure.

Coffea arabica Extract Attenuates Atopic Dermatitis-like Skin Lesions by Regulating NLRP3 Inflammasome Expression and Skin Barrier Functions.

Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation and anti-inflammation effects of Coffea arabica extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1ß and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.

Atopic Dermatitis: Molecular Alterations between Lesional and Non-Lesional Skin Determined Noninvasively by In Vivo Confocal Raman Microspectroscopy.

Atopic dermatitis (AD)/atopic eczema is a chronic relapsing inflammatory skin disease affecting nearly 14% of the adult population. An important pathogenetic pillar in AD is the disrupted skin barrier function (SBF). The atopic stratum corneum (SC) has been examined using several methods, including Raman microspectroscopy, yet so far, there is no depth-dependent analysis over the entire SC thickness. Therefore, we recruited 21 AD patients (9 female, 12 male) and compared the lesional (LAS) with non-lesional atopic skin (nLAS) in vivo with confocal Raman microspectroscopy. Our results demonstrated decreased total intercellular lipid and carotenoid concentrations, as well as a shift towards decreased orthorhombic lateral lipid organisation in LAS. Further, we observed a lower concentration of natural moisturising factor (NMF) and a trend towards increased strongly bound and decreased weakly bound water in LAS. Finally, LAS showed an altered secondary and tertiary keratin structure, demonstrating a more folded keratin state than nLAS. The obtained results are discussed in comparison with healthy skin and yield detailed insights into the atopic SC structure. LAS clearly shows molecular alterations at certain SC depths compared with nLAS which imply a reduced SBF. A thorough understanding of these alterations provides useful information on the aetiology of AD and for the development/control of targeted topical therapies.

Calcitriol, an Active Form of Vitamin D3, Mitigates Skin Barrier Dysfunction in Atopic Dermatitis NC/Nga Mice.

Atopic dermatitis and psoriasis are prevalent chronic inflammatory skin diseases that are characterized by dysfunctional skin barriers and substantially impact patients' quality of life. Vitamin D3 regulates immune responses and keratinocyte differentiation and improves psoriasis symptoms; however, its effects on atopic dermatitis remain unclear. Here, we investigated the effects of calcitriol, an active form of vitamin D3, on an NC/Nga mouse model of atopic dermatitis. We observed that the topical application of calcitriol decreased the dermatitis scores and epidermal thickness of NC/Nga mice with atopic dermatitis compared to untreated mice. In addition, both stratum corneum barrier function as assessed by the measurement of transepidermal water loss and tight junction barrier function as evaluated by biotin tracer permeability assay were improved following calcitriol treatment. Moreover, calcitriol treatment reversed the decrease in the expression of skin barrier-related proteins and decreased the expression of inflammatory cytokines such as interleukin (IL)-13 and IL-33 in mice with atopic dermatitis. These findings suggest that the topical application of calcitriol might improve the symptoms of atopic dermatitis by repairing the dysfunctional epidermal and tight junction barriers. Our results suggest that calcitriol might be a viable therapeutic agent for the treatment of atopic dermatitis in addition to psoriasis.