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The stratum corneum (SC) forms the outermost layer of the skin, playing a critical role in preventing water loss and protecting against external biological and chemical threats. Approximately 90% of the SC consists of large, flat corneocytes, yet its barrier function primarily relies on the intercellular lipid matrix that surrounds these cells. Traditional methods for characterizing these lipids, such as Fourier transform infrared spectroscopy (FTIR), typically involve macroscopic analysis using attenuated total reflection (ATR) techniques. In this study, we introduce a novel approach for investigating SC samples at a microscopic level to gain detailed chemical insights and assess sample heterogeneity. Special emphasis is placed on advanced hyperspectral data pre-processing to ensure the accuracy and reliability of the results. We also evaluate methods for filtering out spectral data that significantly deviate from the mean and analyze the extracted mean spectra, the intensities of specific infrared peaks, and their ratios. The novelty of this work lies in its microscopic approach to analyzing the SC lipid matrix, diverging from the traditional macroscopic FTIR–ATR methods. By focusing on hyperspectral imaging and developing robust pre-processing techniques, this study provides more localized, high-resolution chemical insights. This microscopic perspective opens up the possibility of detecting subtle heterogeneities within the skin's lipid matrix, offering deeper, previously unattainable understanding of the SC's barrier function. Additionally, the exploration of spectral filtering methods enhances the precision of the analysis, paving the way for more refined and reliable investigations of skin structure and behavior in future research. [ABSTRACT FROM AUTHOR]

Changes in the expression of cornified envelope (CE) components are a hallmark of numerous pathological skin conditions and aging, underlying the importance of this stratum corneum structure in the homeostasis of the epidermal barrier. We performed a detailed characterisation of LCE6A, a member of the Late Cornified Envelope protein family. Immunohistochemical and immunoblot experiments confirmed that LCE6A is expressed late during epidermal differentiation. Crosslinking assays of recombinant LCE6A performed either in situ on human skin sections or in vitro demonstrated that LCE6A is indeed a substrate of transglutaminases and crosslinked to CEs. LCE6A‐derived peptides containing a glutamine‐lysine sequence retained these properties of the full‐length protein and reinforced the mechanical resistance of CE submitted to sonication. We designed P26, a LCE6A‐derived biomimetic peptide that similarly reinforced CE in vitro, and evaluated its protective properties ex vivo, on human skin explants, and in two double blind and vehicle‐controlled clinical trials. P26 was able to protect the skin from barrier disruption, to limit the damage resulting from a defective barrier, and could improve the signs of aging such as loss of skin firmness and increased skin roughness. Hence, our detailed characterisation of LCE6A as a component of the CE enabled us to develop a LCE6A‐derived peptide, biologically active with a new and original mode of action that could be of great interest as a cosmetic ingredient and a pharmacologic agent. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease associated with an impaired skin barrier. The skin barrier function is dependent on the extracellular lipid matrix which surrounds the corneocytes in the stratum corneum. Ceramides comprise essential components of this matrix. Alterations in the stratum corneum ceramide profile have been directly linked to barrier dysfunction and might be an underlying factor of the barrier impairment in psoriasis. In this study, we investigated the ceramide profile and barrier function in psoriasis. Lesional and non‐lesional skin of 26 patients and 10 healthy controls were analysed using in‐depth ceramide lipidomics by liquid chromatography‐mass spectrometry. Barrier function was assessed by measuring transepidermal water loss. Lesional skin showed a significant decrease in the abundance of total ceramides with significant alterations in the ceramide subclass composition compared to control and non‐lesional skin. Additionally, the percentage of monounsaturated ceramides was significantly increased, and the average ceramide chain length significantly decreased in lesional skin. Altogether, this resulted in a markedly different profile compared to controls for lesional skin, but not for non‐lesional skin. Importantly, the reduced barrier function in lesional psoriasis correlated to alterations in the ceramide profile, highlighting their interdependence. By assessing the parameters 2 weeks apart, we are able to highlight the reproducibility of these findings, which further affirms this connection. To conclude, we show that changes in the ceramide profile and barrier impairment are observed in, and limited to, lesional psoriatic skin. Their direct correlation provides a further mechanistic basis for the concomitantly observed impairment of barrier dysfunction. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune disorder characterized by epidermal melanocyte damage, with the typical clinical manifestation of white patches of skin. Keratinocytes, which work in concert with melanocytes to maintain the structural and functional integrity of the skin, are implicated in the progression of vitiligo. Recent studies have reported abnormal keratinocyte proliferation and epidermal thickening in some patients with vitiligo; however, the relationship between these changes and the clinical characteristics of vitiligo remains unclear. We assessed the changes in epidermal thickness in patients with vitiligo and their correlation with clinical characteristics. Compared to the non-lesional skins, the stratum corneum, viable epidermis, and full epidermis in the lesional skins were all significantly thicker. The thickness of the stratum corneum in the head, neck, and trunk was greatly lower than that in the extremities. The thickness of the stratum corneum in the sun-exposed area was higher than that in the sun-protected area, whereas the thickness of the viable epidermis decreased. In conclusion, our study found that the epidermis in the lesional skins of patients with vitiligo was significantly thickened, especially in the sun-exposed areas and extremities. [ABSTRACT FROM AUTHOR]

Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers – the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non‐invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full‐thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders. [ABSTRACT FROM AUTHOR]

Objective: Atopic dermatitis (AD) is characterized by compositional and structural changes to the skin at lesional sites. Alteration to the levels and organization of both protein and lipid components are associated with disease status and lead to impaired barrier and hydration. Corneodesmosin (CDSN) and the arrangement and length of the intercellular lipid lamellae (ICLL) are altered in disrupted skin states. The aim of this research was to profile the distribution of CDSN and the ICLL in the stratum corneum (SC) at lesional and non‐lesional sites in AD‐prone skin and to investigate the impact of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. Methods: An IRB‐approved study was conducted with participants with active AD. From a small subset of participants, tape strips were collected from lesional and non‐lesional sites on the arm, prior to and after twice daily application, over 4 weeks of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. Fluorescent antibody staining was used to investigate the distribution of CDSN. Transmission electron microscopy (TEM) was used to characterize the ICLL. Results: The distribution/coverage of CDSN was similar between lesional and non‐lesional sites at baseline; application of the lotion resulted in a more defined honeycomb/peripheral distribution. Normalized ICLL (nICLL) was lower in baseline samples from lesional sites relative to non‐lesional sites. Application of the lotion increased this parameter by the end of the study at all sites. Conclusion: The eczema calming lotion containing petroleum jelly, fatty acids and colloidal oatmeal provided changes in corneodesmosomal proteins distribution and ICLL, consistent with improvements in corneocyte maturation and improved barrier function in the skin of individuals with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Emollients plus are defined as topical formulations containing active ingredients with no pharmacological effect. They are designed to target multiple mechanisms in AD pathophysiology. The objective of the present study was to assess the efficacy of emollient plus medical device cream by performing a post-marketing surveillance study. It was carried out in cooperation with 88 members of the Polish Association for Atopic Diseases who were diagnosed with AD and voluntarily fulfilled the questionnaire after 14 days of product use. Additionally, the medical device underwent in vitro/ex vivo testing. Cytotoxicity was assessed by in vitro studies: direct MTT assay and indirect Agarose Overlay Assay. An ex vivo EpiDerm™ culture (EPI-200) was used to investigate the irritation potential, and culture medium was collected after 18 h of contact with the skin model to perform a flow cytometric for the analysis of inflammatory cytokines. A dermatological assessment with the local SCORAD was employed to confirm the efficacy of the cream. It was found that 86% of patients with AD observed an improvement in their skin condition during the two-week testing period. In vitro/ex vivo assays confirmed that the product is safe, non-irritant, and does not stimulate the production of proinflammatory cytokines. According to the local SCORAD, the symptoms of AD were alleviated. Moreover, preliminary studies indicated its efficacy in eliminating S. aureus on patients' skin. [ABSTRACT FROM AUTHOR]

The skin surface lipids (SSLs) film, composed of sebum and keratinocyte membrane lipids, is crucial to the barrier function of the stratum corneum (SC). The first part of this study investigated the impact of solar radiation on the SC based on a novel hydration and dehydration approach using Raman spectroscopy. The SSLs were found to absorb solar light, and thus participate to the protection of the skin surface. However, the protective function of the SSLs may be limited and is dependent to the heterogenous distribution of SSLs over the body surface. To ensure comprehensive protection, synergistic measures such as the application of solar filters are necessary. In this second part of the study, we have evaluated the limits of the protection capacity of SSLs and explored the protective action of a solar filters on both SSLs composition and the water hydration and dehydration kinetics in the SC. [ABSTRACT FROM AUTHOR]

[Display omitted] Ultraviolet B (UVB) radiation can compromise the functionality of the skin barrier through various mechanisms. We hypothesize that UVB induce photochemical alterations in the components of the outermost layer of the skin, known as the stratum corneum (SC), and modulate its antioxidative defense mechanisms. Catalase is a well-known antioxidative enzyme found in the SC where it acts to scavenge reactive oxygen species. However, a detailed characterization of acute UVB exposure on the activity of native catalase in the SC is lacking. Moreover, the effects of UVB irradiation on the molecular dynamics and organization of the SC keratin and lipid components remain unclear. Thus, the aim of this work is to characterize consequences of UVB exposure on the structural and antioxidative properties of catalase, as well as on the molecular and global properties of the SC matrix surrounding the enzyme. The effect of UVB irradiation on the catalase function is investigated by chronoamperometry with a skin covered oxygen electrode, which probes the activity of native catalase in the SC matrix. Circular dichroism is used to explore changes of the catalase secondary structure, and gel electrophoresis is used to detect fragmentation of the enzyme following the UVB exposure. UVB induced alterations of the SC molecular dynamics and structural features of the SC barrier, as well as its water sorption behavior, are investigated by a complementary set of techniques, including natural abundance 13C polarization transfer solid-state NMR, wide-angle X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, and dynamic vapor sorption microbalance. The findings show that UVB exposure impairs the antioxidative function of catalase by deactivating both native catalase in the SC matrix and lyophilized catalase. However, UVB radiation does not alter the secondary structure of the catalase nor induce any observable enzyme fragmentation, which otherwise could explain deactivation of its function. NMR measurements on SC samples show a subtle increase in the molecular mobility of the terminal segments of the SC lipids, accompanied by a decrease in the mobility of lipid chain trans-gauche conformers after high doses of UVB exposure. At the same time, the NMR data suggest increased rigidity of the polypeptide backbone of the keratin filaments, while the molecular mobility of amino acid residues in random coil domains of keratin remain unaffected by UVB irradiation. The FTIR data show a consistent decrease in absorbance associated with lipid bond vibrations, relative to the main protein bands. Collectively, the NMR and FTIR data suggest a small modification in the composition of fluid and solid phases of the SC lipid and protein components after UVB exposure, unrelated to the hydration capacity of the SC tissue. To conclude, UVB deactivation of catalase is anticipated to elevate oxidative stress of the SC, which, when coupled with subtle changes in the molecular characteristics of the SC, may compromise the overall skin health and elevate the likelihood of developing skin disorders. [ABSTRACT FROM AUTHOR]

Xerosis is a dermatological condition caused by genetic and/or environmental factors, characterized by excessive transepidermal water loss from the skin, which causes extreme dryness in those who suffer from it. For the purpose of this work, an aesthetic treatment was performed on a 13-year-old male patient from the city of Quito, Ecuador, who presented the characteristic signs and symptoms of an alteration called "X-linked ichthyosis." Specifically in this case, the treatment was performed on the upper extremities (arms), using only non-invasive techniques, performing a total of 13 sessions, where in each of them different equipment was used such as electroporator, galvanic current, brushing, ultrasonic palette and microdermabrasion; as well as active ingredients such as collagen, elastin, hyaluronic acid, ceramides, lactic acid, among others. Throughout the treatment, a photographic record was made, where the results can be seen with the naked eye; in addition, through a test using a physical method, it was possible to count the number of pieces of the stratum corneum that came off at the beginning and end of the treatment, obtaining an improvement of 76.47%. Based on all this, the protocol carried out presented extremely satisfactory results, demonstrating that despite being a condition of genetic origin, with the necessary treatment and care, a great improvement can be achieved and also improve the quality of life of those who suffer from this alteration. [ABSTRACT FROM AUTHOR]

The transdermal route is considered one of the most favourable routes of drug delivery over other conventional routes. The stratum corneum (SC) is the main barrier to the delivery of drugs by the transdermal route. Many strategies are employed to overcome SC barrier properties like lipid vesicles, permeation enhancers, physical methods, etc. The main objective of this research article was to explore and compare a few chemical penetration enhancers in combination with physical means like tape stripping and microneedle to enhance the transdermal permeation of caffeine. The transdermal gel of caffeine was prepared by dissolving the drug in distilled water containing various concentrations of chemical penetration enhancers, including Arlasolve DMI, ethanol, transcutol P and DMSO. Ex-vivo skin permeation and skin deposition studies were conducted on the transdermal gel alone and in combination with the microneedle or tape-stripping methods. The HPLC method analyzed the total amount of caffeine that permeated through the skin sample. The formulations containing Arlasolve DMI as a penetration enhancer showed the maximum drug penetration among all the penetration enhancers. A combination of microneedles with Arlasolve DMI showed the best skin permeation among all the methods tested. It was clear from the results that Arlasolve DMI would be a better option to use as a penetration enhancer in the dermatological formulations of caffeine in combination with a microneedle-based permeation enhancement method. [ABSTRACT FROM AUTHOR]

AbstractNanoemulsions are nano-sized particles, typically ranging from tens to hundreds of nanometers. These nanoemulsions possess various appealing properties, making them highly promising for various applications in pharmaceutics, foods, and cosmetics. These properties include their small size, which allows for a high surface area per unit volume, and their ability to disperse hydrophobic components and enhance absorption effectively. In the pharmaceutical industry, nanoemulsions have been developed to enhance the delivery of hydrophobic active ingredients. Macromolecular surfactants offer enhanced emulsion stability compared to conventional low-molecular surfactants. Enhanced stability is due to their slower desorption kinetics at the droplet interface, which reduces the risk of toxicity and skin irritation associated with the latter. This article presents a comprehensive investigation into the role of nanoemulsions in drug delivery. It commences by delineating various emulsion types and subsequently explores techniques for nanoemulsion preparation. Surfactants serve as pivotal components in both the production and stabilization of nanoemulsions. The review provides an encompassing overview of diverse surfactant types, encompassing small molecule variants, particle surfactants, phospholipids, peptides, and protein-based surfactants tailored for nanoemulsions. Additionally, it addresses nanoemulsion instability, elucidating strategies to mitigate instability challenges, and highlights the utilization of nanoemulsions in nanomedicine for effective drug delivery. This comprehensive overview aims to offer insights for researchers engaged in nanoemulsion-related studies and associated interdisciplinary fields. [ABSTRACT FROM AUTHOR]

The integumentary system, a vital organ, constitutes a multifaceted barrier against pathogens and environmental factors, crucial for maintaining homeostasis. Intrinsic and extrinsic factors can accelerate skin aging and compromise its homeostatic functions and solar rays, particularly ultraviolet (UV) radiation, pose a significant risk for skin cancer. Polyphenols are molecules that donate hydrogen or electrons, preventing the oxidation of substances, such as lipids, or the formation of inflammatory mediators by cyclooxygenase enzymes. This study explored the in vitro safety, by HET-CAM (hen's egg test on chorioallantoic membrane), and protective effects of polyphenols (chlorogenic acid, apigenin, kaempferol, and naringenin) against stratum corneum UV-induced lipid peroxidation using an innovative method, the HPLC-TBARS-EVSC (highperformance liquid chromatography-thiobarbituric acid reactive substances-ex vivo stratum corneum), and a stress test using methyl nicotinate and laser Doppler flowmetry to establish in vivo the samples' topical anti-inflammatory ability. An aqueous gel containing 0.1% w/w of each polyphenol was formulated using ammonium acryloyldimethyltaurate/VP copolymer. Through the utilization of the HET-CAM assay for in vitro safety assessment, chlorogenic acid, apigenin, kaempferol, and naringenin were classified as non-irritating active ingredients. This classification was based on their lack of adverse reactions within the vascularization of the chorioallantoic membrane. To assess the protective capabilities of four polyphenols against lipid peroxidation in the stratum corneum, the HPLC-TBARS-EVSC protocol was conducted. It was observed that only naringenin exhibited a significant reduction in epidermal lipoperoxidation, indicating superior anti-radical potential. Conversely, chlorogenic acid, apigenin, and kaempferol displayed a pro-oxidant profile under the specified test conditions. The laser Doppler flowmetry suggested the anti-inflammatory potential of naringenin, kaempferol, and chlorogenic acid, with naringenin showing superior efficacy involving all parameters quantified. Naringenin emerged as the only polyphenol capable of reducing the intensity of the inflammatory response induced by methyl nicotinate solution in the participants, compared to the blank gel and the untreated area. This comprehensive investigation underscores the diverse protective roles of polyphenols in skin health, emphasizing naringenin's notable anti-radical and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

The barrier function of the skin is primarily determined by its outermost layer, the Stratum Corneum (SC). The SC consists of corneocytes embedded in a lipid matrix composed mainly of ceramides, cholesterol, and free fatty acids in equimolar proportions and is organised in a complex lamellar structure with different periodicities and lateral packings. This matrix provides a diffusion pathway across the SC for bioactive compounds that are administered to the skin. In this regard, and as the skin administration route has grown in popularity, there has been an increase in the use of lipid mixtures that closely resemble the SC lipid matrix, either for a deeper biophysical understanding or for pharmaceutical and cosmetic purposes. This review focuses on a systematic analysis of the main outcomes of using lipid mixtures as SC lipid matrix models for pharmaceutical and cosmetic purposes. Thus, a methodical evaluation of the main outcomes based on the SC structure is performed, as well as the main recent developments in finding suitable new in vitro tools for permeation testing based on lipid models. [ABSTRACT FROM AUTHOR]

Background: To increase skin permeability, various transdermal delivery techniques have been developed. However, due to the stratum corneum as a skin barrier, transdermal delivery remains limited. Aims: In this study, we evaluated efficacy and safety of arc‐poration as a novel technique disrupting the stratum corneum. Results: Optical images and histological analysis using reconstituted human skin and porcine skin showed that the treatment of arc‐poration created micropores with an average diameter of approximately 100 μm only to the depth of the stratum corneum, but not viable epidermis. In addition, the Franz diffusion cell experiment using reconstituted human skin showed a remarkable increase in permeability following pretreatment with arc‐poration. Clinical results clearly demonstrated the enhancement of the skin‐improving effect of cosmetics by pretreatment of arc‐poration in terms of gloss, hydration, flakiness, texture, tone, tone evenness, and pigmentation of skin, without causing abnormal skin responses. The concentration of ozone and nitrogen oxides generated by arc‐poration was below the permissible value for the human body. Conclusions: Arc‐poration can increase skin permeability by creating stratum corneum‐specific micropores, which can enhance the skin‐improving effect of cosmetics without adverse responses. [ABSTRACT FROM AUTHOR]

Abstract Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers – the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non‐invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full‐thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders.

Autism spectrum disorder (ASD) is a common neurological disorder. Although the etiologies of ASD have been widely speculated, evidence also supports the pathogenic role of cutaneous inflammation in autism. The prevalence of ASD is higher in individuals with inflammatory dermatoses than in those without inflammatory diseases. Anti-inflammation therapy alleviates symptoms of ASD. Recent studies suggest a link between epidermal dysfunction and ASD. In the murine model, mice with ASD display epidermal dysfunction, accompanied by increased expression levels of proinflammatory cytokines in both the skin and the brain. Children with ASD, which develops in their early lifetime, also exhibit altered epidermal function. Interestingly, improvement in epidermal function alleviates some symptoms of ASD. This line of evidence suggests a pathogenic role of cutaneous dysfunction in ASD. Either an improvement in epidermal function or effective treatment of inflammatory dermatoses can be an alternative approach to the management of ASD. We summarize here the current evidence of the association between the skin and ASD.

Simple Summary: Our society is increasingly concerned about the well-being of animals like dolphins, which can be affected by life under professional human care or by anthropogenic disturbances in the wild. To better understand and improve their welfare, scientists are exploring new, non-invasive methods to study the response to stressors in these animals. This research introduces an approach for measuring the stress response by analysing cortisol from epidermis samples, a method that does not require invasive procedures. We developed and tested a reliable technique to extract and measure cortisol levels from the epidermis of common bottlenose dolphins and belugas. Our findings show that this method works well and is accurate, even with very small epidermis samples. We also found that the amount of stress hormones can vary depending on the individual animal but not necessarily where the body sample was taken. This study is a step forward in non-invasively studying and enhancing the welfare of cetaceans, offering insights into their stress levels in a way that is safer and more comfortable for them, which could ultimately lead to better care and conservation practices for these species. Society is showing a growing concern about the welfare of cetaceans in captivity as well as cetaceans in the wild threatened by anthropogenic disturbances. The study of the physiological stress response is increasingly being used to address cetacean conservation and welfare issues. Within it, a newly described technique of extracting cortisol from epidermal desquamation may serve as a non-invasive, more integrated measure of a cetacean's stress response and welfare. However, confounding factors are common when measuring glucocorticoid hormones. In this study, we validated a steroid hormone extraction protocol and the use of a commercial enzyme immunoassay (EIA) test to measure cortisol concentrations in common bottlenose dolphin (Tursiops truncatus) and beluga (Delphinapterus leucas) epidermal samples. Moreover, we examined the effect of sample mass and body location on cortisol concentrations. Validation tests (i.e., assay specificity, accuracy, precision, and sensitivity) suggested that the method was suitable for the quantification of cortisol concentrations. Cortisol was extracted from small samples (0.01 g), but the amount of cortisol detected and the variability between duplicate extractions increased as the sample mass decreased. In common bottlenose dolphins, epidermal skin cortisol concentrations did not vary significantly across body locations while there was a significant effect of the individual. Overall, we present a contribution towards advancing and standardizing epidermis hormone assessments in cetaceans. [ABSTRACT FROM AUTHOR]

Introduction: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). Methods: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. Results: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. Conclusion: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin. [ABSTRACT FROM AUTHOR]

We have developed a method to determine the limit of detection (LoD) for quantitative measurement of exogenous analytes in the outer layer of the human skin by in vivo confocal Raman spectroscopy. The method is in accordance with the guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use that have been adopted by regulatory authorities such as the American Food and Drug Administration and the European Medicines Agency. The method can be applied in silico so that the limit of detection can be assessed before starting a skin penetration study, for example, in areas of pharmaceutical formulation, pharmacokinetics, or toxicokinetics. This can significantly reduce the need for expensive and time-consuming feasibility studies. This paper describes the method to calculate this LoD as well as the experimental and methodological factors that can influence the calculation of the LoD. [ABSTRACT FROM AUTHOR]

Background: The stratum corneum (SC), the outermost layer of the skin epidermis, acts as an effective bi‐directional barrier, preventing water loss (inside–outside barrier) and entry of foreign substances (outside–inside barrier). Although transepidermal water loss (TEWL) is a widely‐used measure of barrier function, it represents only inside‐outside protection. Therefore, we aimed to establish a non‐invasive method for quantitative evaluation of the outside–inside barrier function and visually present a skin barrier model. Materials and methods: Skin barrier damage was induced by applying a closed patch of 1% sodium dodecyl sulfate to the forearms of eight participants; they were instructed to apply a barrier cream on a designated damaged area twice daily for 5 days. The SC barrier was evaluated by measuring TEWL and fluorescein sodium salt penetration rate before, immediately after, and 5 days after damage. The penetration rate was assessed using tape‐stripping (TS) technique and fluorescence microscopy. Results: The rates of fluorescein sodium salt penetration into the lower layers of SC differed significantly based on the degree of skin barrier damage. The correlation between penetration rate and TEWL was weak after two rounds of TS and became stronger after subsequent rounds. Five days after skin barrier damage, the penetration rate of all layers differed significantly between areas with and without the barrier cream application. Conclusion: Our findings demonstrated that the penetration rate was dependent on skin barrier conditions. The penetration rate and corresponding fluorescence images are suitable quantitative indicators that can visually represent skin barrier conditions. [ABSTRACT FROM AUTHOR]

Skin electroporation for drug delivery involves the application of Pulsed Electric Fields (PEFs) on the skin to disrupt its barrier function in a temporary and non-invasive manner, increasing the uptake of drugs. It represents a potential alternative to delivery methods that are invasive (e.g. injections) or limited. We have developed a drug delivery system comprising nanocomposite hydrogels which act as a reservoir for the drug and an electrode for applying electric pulses on the skin. In this study, we employed a multi-scale approach to investigate the drug delivery system on a mouse skin model, through electrical measurements, numerical modeling and fluorescence microscopy. The Electrical properties indicated a highly non-linear skin conductivity behavior and were used to fine-tune the simulations and study skin recovery after electroporation. Simulation of electric field distribution in the skin showed amplitudes in the range of reversible tissue electroporation (400–1200 V/cm), for 300 V PEF. Fluorescence microscopy revealed increased uptake of fluorescent molecules compared to the non-pulsed control. We reported two reversible electroporation domains for our configuration: (1) at 100 V PEF the first local transport regions appear in the extracellular lipids of the stratum corneum, demonstrated by a rapid increase in the skin's conductivity and an increased uptake of lucifer yellow, a small hydrophilic fluorophore and (2) at 300 V PEF, the first permeabilization of nucleated cells occurred, evidenced by the increased fluorescence of propidium iodide, a membrane-impermeable, DNA intercalating agent. Skin electroporation for transdermal drug delivery assessed by electrical measurements, numerical modeling and delivery of fluorescent molecules. [Display omitted] • Nanocomposite hydrogels function as drug reservoirs and electrodes. • Integrated electrical measurements, numerical modeling & molecule delivery. • Skin resistance drops with electric field strength. • Stratum corneum barrier disruption at 100 V. • Cell membrane permeabilization at 300 V in viable skin. [ABSTRACT FROM AUTHOR]

The epidermal differentiation complex (EDC) is a cluster of genes that encode protein components of the outermost layers of the epidermis in mammals, reptiles and birds. The development of the stratified epidermis from a single-layered ectoderm involves an embryo-specific superficial cell layer, the periderm. An additional layer, the subperiderm, develops in crocodilians and over scutate scales of birds. Here, we review the expression of EDC genes during embryonic development. Several EDC genes are expressed predominantly or exclusively in embryo-specific cell layers, whereas others are confined to the epidermal layers that are maintained in postnatal skin. The S100 fused-type proteins scaffoldin and trichohyalin are expressed in the avian and mammalian periderm, respectively. Scaffoldin forms the so-called periderm granules, which are histological markers of the periderm in birds. Epidermal differentiation cysteine-rich protein (EDCRP) and epidermal differentiation protein containing DPCC motifs (EDDM) are expressed in the avian subperiderm where they are supposed to undergo cross-linking via disulfide bonds. Furthermore, a histidine-rich epidermal differentiation protein and feather-type corneous beta-proteins, also known as beta-keratins, are expressed in the subperiderm. The accumulating evidence for roles of EDC genes in the development of the epidermis has implications on the evolutionary diversification of the skin in amniotes. [ABSTRACT FROM AUTHOR]

Background: The morphology and content of stratum corneum (SC) cells provide information on the physiological condition of the skin. Although the morphological and biochemical properties of the SC are known, no method is available to fully access and interpret this information. This study aimed to develop a method to comprehensively decode the physiological information of the skin, based on the SC. Therefore, we established a novel image analysis technique based on artificial intelligence (AI) and multivariate analysis to predict skin conditions. Materials and Methods: SC samples were collected from participants, imaged, and annotated. Nine biomarkers were measured in the samples using enzyme‐linked immunosorbent assay. The data were then used to teach machine‐learning models to recognize individual SC cell regions and estimate the levels of the nine biomarkers from the images. Skin physiological indicators (e.g., skin barrier function, facial analysis, and questionnaires) were measured or obtained from the participants. Multivariate analysis, including biomarker levels ​​and structural parameters of the SC as variables, was used to estimate these physiological indicators. Results: We established two machine‐learning models. The accuracy of recognition was assessed according to the average intersection over union (0.613), precision (0.953), recall (0.640), and F‐value (0.766). The predicted biomarker levels significantly correlated with the measured levels. Skin physiological indicators and questionnaire answers were predicted with strong correlations and correct answer rates. Conclusion: Various physiological skin conditions can be predicted from images of the SC using AI models and multivariate analysis. Our method is expected to be useful for dermatological treatment optimization. [ABSTRACT FROM AUTHOR]

Measuring skin hydration is important for dermatology research, cosmetic practice, and daily skincare; it provides valuable insight into skin assessment and predicts treatment outcomes. This study investigated the level of skin hydration on various parts of the body in female university students, utilizing corneometry for measurement. Demographic, water intake, skincare, and exercise habit data were collected. The highest hydration levels were on the face (n = 40), followed by cleavage skin (n = 42), neck skin (n = 48), and leg skin (n = 42). Differences were observed between the chin and forehead (106.06 ± 21.06 vs. 91.20 ± 26.68; p = 0.001) and the chin and cheek (106.06 ± 21.06 vs. 92.00 ± 27.63; p > 0.001). The differences in the hydration measurement results on cleavage were not significant (right clavicle 55.1 ± 12.93; left clavicle 51.84 ± 10.00; sternum 53.55 ± 16.3; p = 0.379). On the neck, the middle point exhibited the highest hydration (left 41.7 ± 11.3; middle 49.2 ± 12; right 47.2 ± 8.2; p > 0.001). The skin on the thigh was significantly drier than that on the shank (31.09 ± 6.89 vs. 33.54 ± 6.28; p = 0.008). Water consumption was positively associated with skin hydration and the amount of physical activity. We conclude that every skin area is characterized by different levels of hydration. Water intake and physical activity contribute to improved skin hydration. [ABSTRACT FROM AUTHOR]

Background: Tactile sensation plays a crucial role in object manipulation, communication, and even emotional well‐being. It has been reported that the deformability of skin (also described as skin compliance) that shows a large mechanical response to stimuli is associated with high tactile sensitivity. However, although the compliance of the stratum corneum, the outermost layer of skin, can change daily due to skin care and environmental factors, few studies have quantified the effect of the stratum corneum on tactile sensation. Aims: We investigated the changes in tactile sensitivity resulting from skin hydration and identified corresponding alterations in the compliance of the stratum corneum. Methods: A randomized controlled trial was conducted. Participants were randomly assigned to an intervention group (n = 20) that had a moisturizing cream applied to their cheeks or a control group (n = 19) that had Milli‐Q water applied to their cheeks. Tactile discrimination performance was assessed using psychophysical techniques before and after application. The water content, mechanical response characteristics, and penetration of PEG/PPG‐17/4 dimethyl ether from the cream in the stratum corneum were evaluated to identify hydration effects. Skin deformations occurring during tactile sensation were measured concurrently using a suction device employed for tactile stimulation. Results: Tactile sensitivity was increased in participants who had cream applied to the skin surface, while no significant change was observed in participants who received Milli‐Q water. The improved discrimination of tactile stimulus intensity was directly related to the magnitude of skin displacement. The higher water content of the stratum corneum due to cream application decreased the dynamic modulus of elasticity of the stratum corneum and increased the skin's extensibility in response to tactile stimuli. Conclusions: Hydrating the stratum corneum significantly enhances tactile sensitivity and is accompanied by an increase in skin extensibility, a factor in tactile intensity perception. The compliance of the thin stratum corneum layer plays a crucial role in tactile experiences that involve skin stretching. [ABSTRACT FROM AUTHOR]

The skin serves protective roles for internal organs and is responsible for maintaining homeostasis between the body and the environment. The outermost and most exposed part of the skin to environmental factors is the stratum corneum (SC). SC hydration and transepidermal water loss (TEWL) values provide information about the physiological state of the skin. Plant oils, owing to their chemical structure, possess moisturizing and protective functions. This study assessed the impact of a single application of drying oil (Rubus idaeus seed oil), semi-drying oil (Sesamum indicum seed oil), and nondrying oil (Cocos nucifera (coconut) oil) on specific skin characteristics in young, healthy women. Thirty-five female volunteers (age: 20.03 ± 1.69) participated in the study. Before commencing the investigation, a questionnaire survey on the subjective assessment of skin condition and a body composition test were conducted. Subsequently, each participant had three oils applied to nonoverlapping skin areas on the forearms. Skin characteristics were assessed before and 1 h after the oil application using specialized probes: a corneometer and a tewameter. An enhancement in skin hydration was evident after the application of each of the tested oils (p = 0.001). Raspberry oil demonstrated the most significant moisturizing effect, while coconut oil showed the weakest impact. Only raspberry seed oil (p = 0.012) resulted in a noteworthy decrease in TEWL. The initial skin condition did not correlate with the subjects' body composition, and the improvement induced by the application of the oils was not dependent on body weight, body water content, or BMI (body mass index). The applied vegetable oils positively influence the level of SC hydration. Improvement in barrier function, as measured by TEWL, was observed only for raspberry seed oil. [ABSTRACT FROM AUTHOR]

Epidermal development is responsible for the formation of the outermost layer of the skin, the epidermis. The establishment of the epidermal barrier is a critical aspect of mammalian development. Proper formation of the epidermis, which is composed of stratified squamous epithelial cells, is essential for the survival of terrestrial vertebrates because it acts as a crucial protective barrier against external threats such as pathogens, toxins, and physical trauma. In mammals, epidermal development begins from the embryonic surface ectoderm, which gives rise to the basal layer of the epidermis. This layer undergoes a series of complex processes that lead to the formation of subsequent layers, including the stratum intermedium, stratum spinosum, stratum granulosum, and stratum corneum. The stratum corneum, which is the topmost layer of the epidermis, is formed by corneoptosis, a specialized form of cell death. This process involves the transformation of epidermal keratinocytes in the granular layer into flattened dead cells, which constitute the protective barrier. In this review, we focus on the intricate mechanisms that drive the development and establishment of the mammalian epidermis to gain insight into the complex processes that govern this vital biological system. [ABSTRACT FROM AUTHOR]

The quantitative determination of topically applied substances in the skin is severely limited and represents a challenging task. The porcine skin ex vivo was topically treated with a gel containing caffeine (CF) and propylene glycol (PG), and depth‐resolved Raman spectra were recorded with two confocal Raman microscopes. We applied a novel tailored multivariate curve resolution‐alternating least squares method to the selected spectral regions (512–604 and 778–1148 cm−1) of gel‐treated skin and quantitatively determined the concentrations of CF and PG in the stratum corneum (SC). The highest concentration of CF (181 mg/cm3) was found at the surface, while PG (384 mg/cm3) was found at 10% SC depth, indicating the formation of a reservoir at the superficial SC. The concentrations of CF and PG decreased monotonically and reached the detection limit at ≈60% and ≈80% SC depth, respectively, indicating that neither permeate the SC. [ABSTRACT FROM AUTHOR]

Outdoor workers have increased risk of developing keratinocyte cancer due to accumulated skin damage resulting from chronic and excessive exposure to UVR. This study aims to identify potential noninvasive biomarkers to assess chronic UVR exposure. We analyzed stratum corneum biomarkers collected from 2 skin locations and 2 occupational groups with contrasting solar UVR exposure: the forehead and retroauricular skin among outdoor workers and indoor workers. Using a linear mixed model adjusting for age and skin phototype, we compared biomarkers between both skin sites in indoor and outdoor workers. We measured markers of the immune response and skin barrier, including cytokines, GFs, 15-hydroxyeicosatetraenoic acid, cis- and trans-urocanic acid, and corneocyte topography, indicated by circular nano objects. Differences between the 2 skin sites were found for cis-urocanic acid, total urocanic acid, IL-1α, IL-1RA, IL-1RA/IL-1α, IL-18, 15-hydroxyeicosatetraenoic acid, CCL4, and circular nano objects. The levels of cis-urocanic acid and CCL4 also differed between indoor and outdoor workers. These findings underscore changes in both immune response and skin barrier induced by UVR. They indicate the potential utility of stratum corneum biomarkers in detecting both chronic UVR exposure in occupational setting and aiding in the development of preventive measures.

The integumentary system, a vital organ, constitutes a multifaceted barrier against pathogens and environmental factors, crucial for maintaining homeostasis. Intrinsic and extrinsic factors can accelerate skin aging and compromise its homeostatic functions and solar rays, particularly ultraviolet (UV) radiation, pose a significant risk for skin cancer. Polyphenols are molecules that donate hydrogen or electrons, preventing the oxidation of substances, such as lipids, or the formation of inflammatory mediators by cyclooxygenase enzymes. This study explored the in vitro safety, by HET-CAM (hen’s egg test on chorioallantoic membrane), and protective effects of polyphenols (chlorogenic acid, apigenin, kaempferol, and naringenin) against stratum corneum UV-induced lipid peroxidation using an innovative method, the HPLC-TBARS-EVSC (high-performance liquid chromatography–thiobarbituric acid reactive substances–ex vivo stratum corneum), and a stress test using methyl nicotinate and laser Doppler flowmetry to establish in vivo the samples’ topical anti-inflammatory ability. An aqueous gel containing 0.1% w/w of each polyphenol was formulated using ammonium acryloyldimethyltaurate/VP copolymer. Through the utilization of the HET-CAM assay for in vitro safety assessment, chlorogenic acid, apigenin, kaempferol, and naringenin were classified as non-irritating active ingredients. This classification was based on their lack of adverse reactions within the vascularization of the chorioallantoic membrane. To assess the protective capabilities of four polyphenols against lipid peroxidation in the stratum corneum, the HPLC-TBARS-EVSC protocol was conducted. It was observed that only naringenin exhibited a significant reduction in epidermal lipoperoxidation, indicating superior anti-radical potential. Conversely, chlorogenic acid, apigenin, and kaempferol displayed a pro-oxidant profile under the specified test conditions. The laser Doppler flowmetry suggested the anti-inflammatory potential of naringenin, kaempferol, and chlorogenic acid, with naringenin showing superior efficacy involving all parameters quantified. Naringenin emerged as the only polyphenol capable of reducing the intensity of the inflammatory response induced by methyl nicotinate solution in the participants, compared to the blank gel and the untreated area. This comprehensive investigation underscores the diverse protective roles of polyphenols in skin health, emphasizing naringenin’s notable anti-radical and anti-inflammatory properties.

Abstract Background Despite its popularity, acceptability, and convenience, the oral route is not the classical route for the administration of all critical bioactives including lipophilic drugs, proteins, and peptides. Recent advances in drug delivery have identified the transdermal route as a compelling alternative channel for improved delivery of essential biomolecules due to the illuminating advantages derived from this route. In order to circumvent the poor permeation of the stratum corneum by transdermal patches, microneedles (MNs) technology, which combine the advantages of parenteral delivery using hypodermic needles and transdermal delivery, has been unveiled as a novel biomimetic technology for efficient and effective transport of payloads across the stratum corneum. Main body of abstract The concept of MNs was first documented by Chambers in 1921 when he reported some problems encountered during experimentation using Echinoderm eggs. Since the first patent recorded in 1976, there has been consistent interest and funding in development of MNs for various biomedical applications. MNs have been developed and classified based on their physical attributes and functional profiles into solid, coated, hollow, dissolvable, and swellable or hydrogel-based MNs. These devices are fabricated using advanced techniques like 3D bioprinting, laser methods, photolithography, and molding, and applying materials such as carbohydrates, silica, ceramics, metals, glass and polymers. MNs could be characterized based on their morphological, geometrical, surface, mechanical properties, biocompatibility, and permeability profiles. Evidences have shown that MNs could be commercialized for various clinical adaptations. The numerous biomedical applications of microneedles in drug, peptide, and protein delivery attest to the versatility and dynamic nature of the fabrication techniques, and the pliability of the formulation materials. In spite of the enormous potentials of MNs, extant literature has shown that MNs also have their own share of limitations like every novel technology designed for theranostic purposes. Short conclusion In this review, we have escalated discussions on the progress and advances made in the development and use of MNs by summarizing the benefits, limitations, fabrication techniques, fabrication materials, characterization methods, therapeutic applications, sterilization and stability considerations, safety and toxicological concerns, regulatory guidelines, and tips for successful commercialization of MNs.

Emollients plus are defined as topical formulations containing active ingredients with no pharmacological effect. They are designed to target multiple mechanisms in AD pathophysiology. The objective of the present study was to assess the efficacy of emollient plus medical device cream by performing a post-marketing surveillance study. It was carried out in cooperation with 88 members of the Polish Association for Atopic Diseases who were diagnosed with AD and voluntarily fulfilled the questionnaire after 14 days of product use. Additionally, the medical device underwent in vitro/ex vivo testing. Cytotoxicity was assessed by in vitro studies: direct MTT assay and indirect Agarose Overlay Assay. An ex vivo EpiDerm™ culture (EPI-200) was used to investigate the irritation potential, and culture medium was collected after 18 h of contact with the skin model to perform a flow cytometric for the analysis of inflammatory cytokines. A dermatological assessment with the local SCORAD was employed to confirm the efficacy of the cream. It was found that 86% of patients with AD observed an improvement in their skin condition during the two-week testing period. In vitro/ex vivo assays confirmed that the product is safe, non-irritant, and does not stimulate the production of proinflammatory cytokines. According to the local SCORAD, the symptoms of AD were alleviated. Moreover, preliminary studies indicated its efficacy in eliminating S. aureus on patients’ skin.

The barrier function of the skin is primarily determined by its outermost layer, the Stratum Corneum (SC). The SC consists of corneocytes embedded in a lipid matrix composed mainly of ceramides, cholesterol, and free fatty acids in equimolar proportions and is organised in a complex lamellar structure with different periodicities and lateral packings. This matrix provides a diffusion pathway across the SC for bioactive compounds that are administered to the skin. In this regard, and as the skin administration route has grown in popularity, there has been an increase in the use of lipid mixtures that closely resemble the SC lipid matrix, either for a deeper biophysical understanding or for pharmaceutical and cosmetic purposes. This review focuses on a systematic analysis of the main outcomes of using lipid mixtures as SC lipid matrix models for pharmaceutical and cosmetic purposes. Thus, a methodical evaluation of the main outcomes based on the SC structure is performed, as well as the main recent developments in finding suitable new in vitro tools for permeation testing based on lipid models.

Pressure ulcers (PUs) are chronic wounds that are detrimental to the quality of life of patients. Despite advances in monitoring skin changes, the structure and function of skin cells over the site of pressure ulcers are not fully understood. The present study aims to evaluate local changes in the properties of superficial corneocytes in category 1 PU sites sampled from a cohort of hospitalised patients. Cells were collected from a PU-compromised site and an adjacent control area and their topographical, maturation and mechanical properties were analysed. Corneocytes at the PU-compromised site were characterised by higher levels of immature cornified envelopes (p < 0.001) and greater amounts of desmoglein-1 (corneodesmosomal protein) (p < 0.001) compared to the adjacent control area. The cells at the control site presented the typical ridges-and-valleys topographical features of sacrum corneocytes. By contrast, the PU cells presented circular nano-objects at the cell surface, and, for some patients, the cell topography was deformed. CEs at the PU site were also smaller than at the control site. Although differences were not observed in the mechanical properties of the cells, those of the elderly patients were much softer compared with young subjects. This is the first study investigating the changes in corneocyte properties in category I pressure ulcers. Superficial cells at the PU sites showed altered topographical and maturation characteristics. Further studies are required to elucidate if these changes are a consequence of early loss of skin integrity or a result of mechanical and microclimate insults to the skin surface. • This is the first cohort study that has investigated the changes in the properties of corneocyte over category I PUs. • Superficial cells at the PU sites showed altered topographical and maturation characteristics. • Topographic features in the PU sites included the presence of circular nano-objects, as well as increased levels of desmoglein-1 in the central surface regions of the cells and an increase in the levels of immature cornified envelopes. [ABSTRACT FROM AUTHOR]

Background: Trajectories of stratum corneum (SC) lipid subclasses and their associations with infant atopic dermatitis (AD) are unclear. This study aimed to quantify the trajectories of 15 SC subclasses and carbon chain lengths and their associations with AD within 12 months. Methods: In total, 213 newborns were enrolled at birth with nonlesional skin samples collected from the inner forearm at birth, 42 days, 3, 6, and 12 months, respectively. Lesional skin samples were collected from 120 AD patients at clinic with the disease onset within the first year of life. Mass spectrometry was applied to assess relative contents of 12 ceramide (CER), three free fatty acid (FFA) subclasses, and average carbon chain length (CCL). AD incident within 1 year old was diagnosed by dermatologists according to UK criteria. Results: Sixty‐four (30.0%) cases of ADs occurred in the cohort. All SC lipid subclasses and CCLs, but EOP varied significantly during the first year. AD infants showed lower NP but higher NS, NH, AP, hydroxy FFA, and CCL of FFAs compared with nonaffected infants. After normalization by age, the differences remained and were more pronounced in lesional skin of clinical AD infants compared with non‐ADs. NS, NH, and CCL of FFAs in lesional skin of AD infants showed positive and significant correlations with the levels of transepidermal water loss at 3 month; some evidence supports a negative correlation for NP. Conclusions: We provide an overview of developmental trajectories of 15 CER and FFA subclasses across the first year of healthy infants and a link between the imbalance of some subclasses with the development of AD. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a common neurological disorder. Although the etiologies of ASD have been widely speculated, evidence also supports the pathogenic role of cutaneous inflammation in autism. The prevalence of ASD is higher in individuals with inflammatory dermatoses than in those without inflammatory diseases. Anti-inflammation therapy alleviates symptoms of ASD. Recent studies suggest a link between epidermal dysfunction and ASD. In the murine model, mice with ASD display epidermal dysfunction, accompanied by increased expression levels of proinflammatory cytokines in both the skin and the brain. Children with ASD, which develops in their early lifetime, also exhibit altered epidermal function. Interestingly, improvement in epidermal function alleviates some symptoms of ASD. This line of evidence suggests a pathogenic role of cutaneous dysfunction in ASD. Either an improvement in epidermal function or effective treatment of inflammatory dermatoses can be an alternative approach to the management of ASD. We summarize here the current evidence of the association between the skin and ASD. [ABSTRACT FROM AUTHOR]

Sinapic acid (SA) is a bioactive phenolic acid; its diverse properties are its anti-inflammatory, antioxidant, anticancer, and antibacterial activities. The bioactive compound SA is poorly soluble in water. Our goal was to formulate SA-transethosomes using thin-film hydration. The prepared formulations were examined for various parameters. In addition, the optimized formulation was evaluated for surface morphology, in-vitro penetration studies across the Strat M®, and its antioxidant activity. The optimized formulation (F5) exhibited 74.36% entrapment efficacy. The vesicle size, zeta potential, and polydispersity index were found to be 111.67 nm, −7.253 mV, and 0.240, respectively. The surface morphology showed smooth and spherical vesicles of SA-transethosomes. In addition, the prepared SA-transethosomes exhibited enhanced antioxidant activity. The SA-transethosomes demonstrated considerably greater penetration across the Strat M® membrane during the study. The flux of SA and SA-transethosomes through the Strat M® membrane was 1.03 ± 0.07 µg/cm2/h and 2.93 ± 0.16 µg/cm2/h. The enhancement ratio of SA-transethosomes was 2.86 ± 0.35 compared to the control. The SA-transethosomes are flexible nano-sized vesicles and are able to penetrate the entrapped drug in a higher concentration. Hence, it was concluded that SA-transethosome-based approaches have the potential to be useful for accentuating the penetrability of SA across the skin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dysfunction of the skin barrier plays a critical role in the initiation and progression of inflammatory skin diseases, such as atopic dermatitis and contact dermatitis. Epidermal biomarkers can aid in evaluating the functionality of the skin barrier and understanding the mechanisms that underlay its impairment. This narrative review provides an overview of recent studies on epidermal biomarkers associated with the function and integrity of the skin barrier, and their application in research on atopic dermatitis and contact dermatitis. The reviewed studies encompass a wide spectrum of molecular, morphological and biophysical biomarkers, mainly obtained from stratum corneum tape strips and biopsies. Lipids, natural moisturizing factors, and structural proteins are the most frequently reported molecular biomarkers. Additionally, corneocyte surface topography and elasticity show potential as biomarkers for assessing the physical barrier of the skin. In contact dermatitis studies, biomarkers are commonly employed to evaluate skin irritation and differentiate between irritant and allergic contact dermatitis. In atopic dermatitis, biomarkers are primarily utilized to identify differences between atopic and healthy skin, for predictive purposes, and monitoring response to therapies. While this overview identifies potential biomarkers for the skin barrier, their validation as epidermal biomarkers for atopic dermatitis and contact dermatitis has yet to be established. [ABSTRACT FROM AUTHOR]

Background: Lactic acid is a common active ingredient in many topical skincare products; however, measuring its delivery into the skin is challenging due to the presence of a large level of endogenous lactic acid. In this study, matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) was used to quantitatively and qualitatively measure the delivery of lactic acid into the skin from a range of topical skincare products. Materials and methods: Porcine skin samples were treated with various skincare products containing lactic acid. After 24 h, skin samples were sectioned and treated via H&E staining or prepared for MALDI‐MSI using chemical derivatization. Samples were then analyzed by MALDI‐MSI imaging to obtain lactic acid distribution in the entire skin section. Results: Due to the high level of endogenous lactic acid in the skin, a "triple isotope" of lactic acid (L‐Lactic acid‐13C3), was needed to provide full resolution from the skin's background signal with MALDI‐MSI. With this approach, the topically delivered lactic acid could be quantitatively and qualitatively analyzed from a variety of skincare products. Conclusions: The combination of L‐Lactic acid‐13C3 and MALDI‐MSI was successfully used to quantitatively and qualitatively measure the topical delivery of lactic acid from a variety of skincare products. This approach could be used in future work to better understand the mode of action of lactic acid as an active ingredient in skincare products. [ABSTRACT FROM AUTHOR]

The skin functions as a physical barrier and represents the first line of the innate immune system. There is increasing evidence that toll-like receptors (TLRs) are involved in the pathomechanisms of not only infectious diseases, but also noninfectious inflammatory diseases. Interestingly, it has been demonstrated that TLRs recognize both exogenous threats, e.g. bacteria and viruses, and endogenous danger signals related to inflammation, cell necrosis, or tissue damage. Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, which is associated with impaired skin barrier function, increased skin irritability to non-specific stimuli, and percutaneous sensitization. The impairment of skin barrier function in AD allows various stimuli, such as potential allergens and pathogens, to penetrate the skin and activate the innate immune system, including TLR signaling, which can lead to the development of adaptive immune reactions. In this review, I summarize the current understanding of the roles of TLR signaling in the pathogenesis of AD, with special emphasis on skin barrier function and inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: The skin barrier is the cornerstone of skin function. Evaluations of its morphological aspects, protein content and gene expression are necessary to study atopic dermatitis. Many human studies have assessed the presence of biomarkers in the skin of atopic patients. In dogs, previous biomarker studies have been performed using skin biopsies, which are invasive. This prospective blinded experimental pilot study aimed to evaluate the relevance of a noninvasive technique to extract information from the stratum corneum in dogs with the goal of facilitating future studies on atopic dermatitis. To evaluate the skin barrier, the stratum corneum (SC) must be isolated and extracted. Currently, skin biopsy is the gold standard method to investigate skin immunology and the presence of biomarkers in dogs. However, a standardized, non-invasive tool to exclusively remove the SC would be of great interest to study healthy and atopic dogs. In this study, we performed D-squames® tape stripping with standardized pressure on seven healthy beagle dogs. A control site was defined and then 25 strips, 50 strips and as many strips as needed to achieve a shiny appearance of the skin were performed on three different experimental sites. After stripping, blinded histopathological examination of a skin biopsy from each site was performed. The number of tape strips required for the skin to become shiny varied between individuals, with a mean of 40 (29–50) strips. There was no significant difference in SC depth between the control site and the site that underwent 25 tape strips. In contrast, the use of 50 strips removed almost all of the SC, with a mean remaining SC depth of 7.82 µm. These data suggest that this non-invasive method can effectively remove the SC, with individual variability, and that a shiny appearance of the skin after stripping can be used as an accurate marker of SC removal. [ABSTRACT FROM AUTHOR]

Society is showing a growing concern about the welfare of cetaceans in captivity as well as cetaceans in the wild threatened by anthropogenic disturbances. The study of the physiological stress response is increasingly being used to address cetacean conservation and welfare issues. Within it, a newly described technique of extracting cortisol from epidermal desquamation may serve as a non-invasive, more integrated measure of a cetacean’s stress response and welfare. However, confounding factors are common when measuring glucocorticoid hormones. In this study, we validated a steroid hormone extraction protocol and the use of a commercial enzyme immunoassay (EIA) test to measure cortisol concentrations in common bottlenose dolphin (Tursiops truncatus) and beluga (Delphinapterus leucas) epidermal samples. Moreover, we examined the effect of sample mass and body location on cortisol concentrations. Validation tests (i.e., assay specificity, accuracy, precision, and sensitivity) suggested that the method was suitable for the quantification of cortisol concentrations. Cortisol was extracted from small samples (0.01 g), but the amount of cortisol detected and the variability between duplicate extractions increased as the sample mass decreased. In common bottlenose dolphins, epidermal skin cortisol concentrations did not vary significantly across body locations while there was a significant effect of the individual. Overall, we present a contribution towards advancing and standardizing epidermis hormone assessments in cetaceans.