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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]

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]

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]

[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]

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]

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]

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.

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]

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.

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.

IntroductionThe removal of unwanted hair is a widespread grooming practice adopted by both males and females. Although many depilatory techniques are now available, shaving remains the most common, despite its propensity to irritate skin. Current techniques to investigate the impact of shaving regimes on skin health rely on costly and lengthy clinical trials, which hinge on recruitment of human volunteers and can require invasive biopsies to elucidate cellular and molecular-level changes.MethodsWell-characterised human skin equivalent technology was combined with a commonplace dermatological technique of tape stripping, to remove cellular material from the uppermost layer of the skin (stratum corneum). This method of exfoliation recapitulated aspects of razor-based shaving in vitro, offering a robust and standardised in vitro method to study inflammatory processes such as those invoked by grooming practices.ResultsTape strip insult induced inflammatory changes in the skin equivalent such as: increased epidermal proliferation, epidermal thickening, increased cytokine production and impaired barrier function. These changes paralleled effects seen with a single dry razor pass, correlated with the number of tape strips removed, and were attenuated by pre-application of shaving foam, or post-application of moisturisation.DiscussionTape strip removal is a common dermatological technique, in this study we demonstrate a novel application of tape stripping, to mimic barrier damage and inflammation associated with a dry shave. We validate this method, comparing it to razor-based shaving in vitro and demonstrate the propensity of suitable shave- and skin-care formulations to mitigate damage. This provides a novel methodology to examine grooming associated damage and a platform for screening potential skin care formulations.

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 non-infectious 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.

In this study, we determined partition (Ksc/m) and diffusion (Dsc) coefficients of five different polycyclic aromatic hydrocarbons (PAH) migrating from squalane into and through the stratum corneum (s.c.) layer of the skin. Carcinogenic PAH have previously been detected in numerous polymer-based consumer products, especially those dyed with carbon black. Upon dermal contact with these products, PAH may penetrate into and through the viable layers of the skin by passing the s.c. and thus may become bioavailable. Squalane, a frequent ingredient in cosmetics, has also been used as a polymer surrogate matrix in previous studies. Ksc/m and Dsc are relevant parameters for risk assessment because they allow estimating the potential of a substance to become bioavailable upon dermal exposure. We developed an analytical method involving incubation of pigskin with naphthalene, anthracene, pyrene, benzo[a]pyrene and dibenzo[a,h]pyrene in Franz diffusion cell assays under quasi-infinite dose conditions. PAH were subsequently quantified within individual s.c. layers by gas chromatography coupled to tandem mass spectrometry. The resulting PAH depth profiles in the s.c. were fitted to a solution of Fick’s second law of diffusion, yielding Ksc/m and Dsc. The decadic logarithm logKsc/m ranged from −0.43 to +0.69 and showed a trend to higher values for PAH with higher molecular masses. Dsc, on the other hand, was similar for the four higher molecular mass PAH but about 4.6-fold lower than for naphthalene. Moreover, our data suggests that the s.c./viable epidermis boundary layer represents the most relevant barrier for the skin penetration of higher molecular mass PAH. Finally, we empirically derived a mathematical description of the concentration depth profiles that better fits our data. We correlated the resulting parameters to substance specific constants such as the logarithmic octanol-water partition coefficient logP, Ksc/m and the removal rate at the s.c./viable epidermis boundary layer.

The outermost layer of the epidermis, the stratum corneum (SC), ensures protection against harmful xenobiotics, and alterations in its lipidic matrix composition are related to several cutaneous dysfunctions. The skin barrier function is usually attributed to ceramides, but the role of free fatty acids, such as stearic acid, has been increasingly acknowledged. This research work aimed to develop solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) based on stearic acid and glyceryl distearate, in order to explore the potential of these materials as the basis of lipid nanoparticles. Different blends of stearic acid, Precirol® ATO 5, Capryol® 90 and Tween® 80 were probed to prepare SLN and NLC. These lipid nanoparticles were further characterised according to particle size, polydispersity index (PDI), pH, and viscosity. Accelerated and long-term stability tests were also performed for 90 days, as well as in vivo assays to evaluate safety and efficacy. Overall, most nanoparticles showed interesting properties for topical application if they had sizes less than 300 nm, PDI below 0.3, pH compatible with skin and viscosity lower than 5 mPa.s. In long-term stability studies, the SLN_2 and NLC_2 formulations stood out, as they remained stable over time. In vivo biocompatibility tests conducted in human volunteers showed no negative impact of the formulations when applied openly or under occlusion. Efficacy studies with the most stable nanoparticles made of Precirol® ATO 5 showed an increase in skin hydration. The nanoparticles developed in this study have shown potential to be used for cosmetic purposes, and the blend of lipids provided good biocompatibility and moisturising properties. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microphase transitions of lipid-assembled monolayers (LAMs) were observed in the presence of two new types of ceramides. • LAMs were fabricated by Langmuir-Blodgett assembly of intercellular lipids with ultra-long chain ceramide or 1-O-acylceramide. • We verified that ceramides were involved in LAM formation to strengthen the skin barrier function. Intercellular lipid lamellae, consisting of ceramide, cholesterol, and free fatty acids, are the primary pathways for substances in the stratum corneum (SC). The microphase transition of lipid-assembled monolayers (LAMs), mimicking an initial layer of the SC, would be affected by new types of ceramides: ceramide with ultra-long chain (CULC) and 1-O-acylceramide (CENP) with three chains in different direction. The LAMs were fabricated with varying the mixing ratio of CULC (or CENP) against base ceramide via Langmuir-Blodgett assembly. Surface pressure-area isotherms and elastic modulus-surface pressure plots were obtained to characterize π-dependent microphase transitions. The surface morphology of LAMs was observed by atomic force microscopy. The CULCs favored lateral lipid packing, and the CENPs hindered the lateral lipid packing by lying alignment, which was due to their different molecular structures and conformations. The sporadic clusters and empty spaces in the LAMs with CULC were presumably due to the short-range interactions and self-entanglements of ultra-long alkyl chains following the freely jointed chain model, respectively, which was not noticeably observed in the neat LAM films and the LAM films with CENP. The addition of surfactants disrupted the lateral packing of lipids, thus weakening the LAM elasticity. These findings allowed us to understand the role of CULC and CENP in the lipid assemblies and microphase transition behaviors in an initial layer of SC. [ABSTRACT FROM AUTHOR]

Imaging-based evaluation of lipids in the stratum corneum by label-free stimulated Raman scattering microscopy Keywords: barrier; intercellular lipids; label-free; noninvasive; stimulated Raman scattering microscopy; stratum corneum EN barrier intercellular lipids label-free noninvasive stimulated Raman scattering microscopy stratum corneum 1 5 5 06/28/23 20230601 NES 230601 B Dear Editor, b The stratum corneum (SC) plays an important role as a barrier against the external environment. White bars represent skin without acetone treatment, and black bars represent skin with acetone treatment. As we reported previously,[9] cell morphology in the SC could be visualized by using SRS microscopy, and polygonal cells were observed in the SC (dashed lines in Figure 1(B)). [Extracted from the article]

Studying skin barrier function is central to our understanding of many skin disorders. The past decade has seen a surge of skin barrier related investigative work. Genetic, biochemical and cell biology experiments have added much evidence to the importance of the barrier in disease pathogenesis of a variety of disorders including ichthyosis, atopic dermatitis and psoriasis. However, functional assays prove ever more important to demonstrate relevance of any of these findings. A paper published by Monash and Blank 60 years ago describes a stress test of the skin barrier, measuring skin barrier recovery, a functional test of tremendous implications. This seminal paper has not been cited for almost 15 years, time to acknowledge its critical importance and to review the relevance of this method today.

Transdermal drug delivery plays a significant part in the drug delivery system when compared to other routes of drug administration. The function of the stratum corneum (SC) is a barrier. Recently, numerous methods have been thrived to improve the perforation of drugs across the skin. The most effective method is to use enhancers since these agents enhance skin permeability. Natural penetration enhancers like essential oils demonstrate higher enhancement activity and are more widely accepted than synthetic penetration enhancers. High potential in the expansion and interaction with the SC intercellular lipids has led to an increasing interest in these oils as penetration enhancers. This article gives an overview of a few essential oils, including their mode of action and important parameters for permeation improvement. The present work can provide essential oils as alternative enhancers, and this could be useful in transdermal administration.

Seble Mesfin,1 Mekbeb Afework,2 Dereje Bikila,3 Alemayehu Tessema,4 Midekso Sento1 1Department of Biomedical Science, Adama Comprehensive Specialized Hospital Medical College, Adama, Eastern Ethiopia; 2Department of Anatomy, School of Medicine, College of Health science, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Nursing, Arsi University College of Health Science, Assela, Ethiopia; 4Department of Pediatrics, Adama Comprehensive specialized Hospital Medical College, Adama, Eastern EthiopiaCorrespondence: Seble Mesfin; Mekbeb Afework, Tel +983501666 ; +911411285, Email seblemesfin87@gmail.com; m.afework@yahoo.comBackground: Vernix caseosa is a complex proteolipid material synthesized partly by fetal sebaceous glands during the last trimester of pregnancy. Understanding the structure and function of newborn skin is crucial for determining optimal thermal support, infection control, and skin moisturization. So far, in Ethiopia, there is no research done related to the distribution of vernix caseosa and associated factors on newborn skin. Doing such research could give awareness about factors associated with the distribution of vernix caseosa on newborns’ skin and to take necessary protective measures for those that may be affected.Objective: The objective of this study is to assess the distribution of vernix caseosa and associated factors among newborns delivered at Adama Comprehensive Specialized Hospital Medical College from November to December 1, 2021.Methodology: Hospital-based cross-sectional study design was conducted from November to December 1, 2021 at Adama Comprehensive Specialized Hospital Medical College (ACSHMC). Four hundred twenty-two eligible newborns were selected by a systematic sampling method. Data were collected by four data collectors by using a pretested questionnaire. The distribution of vernix caseosa on the different regions of the neonate was assessed, by exposing their whole body for a minute. Data entry was done by EPI data version 4.6 and analyzed by using SPSS version 25. A logistic regression of P-value of < 0.25 during bivariate and P < 0.05 during multivariate analysis at a 95% confidence level was considered statistically significant.Results: Out of 422 study participants 231 (54.7%) with 95% CI (49.8, 59.8) babies had vernix caseosa. Being primiparous with (AOR = 1.9, PV = 0.013, 95% CI: 1.141, 2.92), being multiparous with (AOR = 1.98, PV = 0.04, CI: 1.29, 3.225), being females with (AOR = 2.1, PV = 0.001, CI: 1.39, 3.18), being preterm with (AOR = 2.98, PV = 0.036, 95% CI: 1.08, 10.72), non-diseased newborns with (AOR = 1.6, PV = 0.046, 95% CI: 1.07, 2.7) were identified as associated factors for the distribution of vernix caseosa on the newborn skin.Conclusion: This study showed that the distribution of vernix caseosa on the skin of the newborns was associated with parity, sex, gestational age, and absence of disease.Keywords: epidermal barrier, stratum corneum, vernix caseosa

Abstract Background Transdermal drug delivery is one of the most widely used drug administration routes, which offer several advantages over other routes of drug delivery. The apical layer of the skin called the stratum corneum is the most dominant obstacle in the transdermal drug delivery, which restricts the passage of drugs across the skin. Considerable strategies have been applied to enhance the rate of permeation across the epithelial cells; however, the most widely used strategy is the use of sorption boosters, also known as permeation enhancers. Main body Terpenes were considered as efficient skin permeation enhancers and are generally recognized as safe as per Food and Drug Administration. Terpenes improve the permeability of drugs either by destructing the stratum corneum’s tightly packed lipid framework, excessive diffusivity of drug in cell membrane or by rampant drug partitioning into epithelial cells. Various vesicular systems have been developed and utilized for the transdermal delivery of many drugs. Invasomes are one such novel vesicular system developed which are composed of phospholipids, ethanol and terpenes. The combined presence of ethanol and terpenes provides exceptional flexibility to the vesicles and improves the permeation across the barrier offered due to the stratum corneum as both ethanol and terpenes act as permeation enhancers. Therefore, utilization of invasomes as carriers to facilitate higher rate of drug permeation through the skin can be a very useful approach to improve transdermal drug delivery of a drug. Conclusion The paper focuses on a broad updated view of terpenes as effective permeation enhancers and invasomes along with their applications in the pharmaceutical formulations.

Background The skin barrier is important in the pathogenesis of atopic dermatitis and stratum corneum lipids have a critical role. Skin surface lipids have been largely overlooked but also contribute to barrier function. An untargeted approach was used to compare the skin surface lipids from atopic and non-atopic West Highland White terrier dogs (WHWT). Objectives The primary hypothesis was that a difference in the lipidome would exist. The secondary hypothesis was that affected and unaffected skin lipids would differ. Animals and methods This prospective, cross-sectional, case-controlled study included thirty-nine privately owned WHWTs. Dogs were assigned to one of four disease status groups based on strict criteria. Samples for lipid analysis were collected from the skin surface of unaffected and affected sites. Lipid analysis was by untargeted liquid chromatography/mass spectrometry and utilised lipid identification software packages. Principle component analysis (PCA) and partial least-squares discriminant analysis (sPLS-DA) statistical methods analysed the association between the relative lipid abundance and disease status and affected and unaffected skin. Results Samples for lipid analysis found 421 lipid soluble features of which ten lipids were positively identified. Statistical analysis could not distinguish between non-atopic and atopic dogs but did reveal a statistically significant difference in the lipid profiles from affected and non-affected skin irrespective of disease status. Conclusions A large array of unidentified lipids from the skin surface were found with a difference between affected and unaffected skin unrelated to disease status. Investigation into the lipidome of the skin surface is an emerging area of research with clinical and therapeutic applications.

[Display omitted] Nanoplastics are mainly generated from the decomposition of plastic waste and artificial production and have attracted much attention due to their wide distribution in the environment and the potential risk for humans. As the largest organ of the human body, the skin is inevitably in contact with nanoplastics. Stratum corneum is the first barrier when the skin is exposed to nanoplastics. However, little is known about the interactions between nanoplastics and stratum corneum. Here, the effects of particle size and surface functionalization (amino-modified and carboxy-modified) of polystyrene nanoplastics on the stratum corneum models were studied by Langmuir monolayer and molecular dynamics simulations. An equimolar mixture of ceramide/cholesterol/free fatty acid was used to mimic stratum corneum intercellular lipids. The Langmuir monolayer studies demonstrated that the larger size and surface functionalization of polystyrene nanoplastics significantly reduced the stability of stratum corneum lipid monolayer in a concentration-dependent fashion. Simulation results elucidated that functionalized polystyrene oligomers had a stronger interaction with lipid components of the stratum corneum model membrane. The cell experiments also indicated that functionalized polystyrene nanoplastics, especially for amino-modified polystyrene nanoplastics, had significant cytotoxicity on normal human dermal fibroblast cells. Our results provide fundamental information and the basis for a deeper understanding of the health risks of nanoplastics to humans. [ABSTRACT FROM AUTHOR]

Natural moisturizing factor (NMF) includes several compounds in the stratum corneum (SC), among them, urocanic acid (UCA). Ultraviolet (UV) exposure turns the trans-UCA of the SC into its cis isomer. We investigated the impact of a topical emollient emulsion treatment on the UCA isomers of the SC exposed to artificial UV stress. Aliquots of emollient emulsion were applied in healthy subjects for 2 h on delimited areas of the volar forearm, then, the SC was removed by tape stripping. Tapes were irradiated in a solar simulator chamber and a high performance liquid chromatograph was used to quantify UCA isomers from stripped SC extract. The amount of both UCA isomers were almost twice higher in the SC treated with the emollient emulsion. We also observed that the UV irradiation elevated the amount of the cis/trans UCA ratio on the SC (non-treated and treated), suggesting that the emollient sample was not able to avoid the UCA isomerization. The in vivo tests corroborated with the UCA data obtained ex vivo, since we found an increase in the superficial skin hydration with respective reduction of the TEWL, probably occurring by the occlusion performed by the emollient emulsion containing 15.0% w/w of caprylic/capric triglyceride. [ABSTRACT FROM AUTHOR]

[Display omitted] The main function of a membrane is to control the exchange of matter between the surrounding regions. As such, accurate modeling of membranes is important to properly describe their properties. In many cases in both biological systems and technical applications, the membranes are composite structures where transport properties may vary between the different sub-regions of the membrane. In this work we develop a method based on Mesh analysis that is asymptotically exact and can describe diffusion in composite membrane structures. We do this by first reformulating a generalized Fick's law to include the effects from activity coefficient, diffusion coefficient, and solubility using a single condensed parameter. We then use the derived theory and Mesh analysis to, in essence, retrieve a finite element method approach. The calculated examples are based on a membrane structure that reassembles that of the brick and mortar structure of stratum corneum, the upper layer of our skin. Resulting concentration profiles from this procedure are then compared to experimental results for the distribution of different probes within intact stratum corneum, showing good agreement. Based on the derived approach we further investigate the impact from a gradient in the fluidity of the stratum corneum mortar lipids across the membrane, and find that it is substantial. We also show that anisotropic organisation of the lipid mortar can have large impact on the effective permeability compared to isotropic mortar lipids. Finally, we examine the effects of corneocyte swelling, and their lateral arrangement in the membrane on the overall membrane permeability. [ABSTRACT FROM AUTHOR]

The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main subclasses in the SC lipid matrix are ceramides (CER), cholesterol, and free fatty acids. In inflammatory skin diseases, such as atopic dermatitis and psoriasis, the SC lipid composition is modulated compared to the composition in healthy SC. One of the main alterations is the molar ratio between the concentration of CER N-(tetracosanoyl)-sphingosine (CER NS) and CER N-(tetracosanoyl)-phytosphingosine (CER NP), which correlated with an impaired skin barrier function. In the present study, we investigated the impact of varying the CER NS:CER NP ratios on the lipid organization, lipid arrangement, and barrier functionality in SC lipid model systems. The results indicate that a higher CER NS:CER NP ratio as observed in diseased skin did not alter the lipid organization or lipid arrangement in the long periodicity phase encountered in SC. The trans-epidermal water loss, an indication of the barrier functionality, was significantly higher for the CER NS:CER NP 2:1 model (mimicking the ratio in inflammatory skin diseases) compared to the CER NS:CER NP 1:2 ratio (in healthy skin). These findings provide a more detailed insight into the lipid organization in both healthy and diseased skin and suggest that in vivo the molar ratio between CER NS:CER NP contributes to barrier impairment as well but might not be the main factor.

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.

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.