Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices.

Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.

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

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

The decline in cellular iron is crucial for differentiation in keratinocytes.

Iron is a vital metal for most biological functions in tissues, and its concentration is exquisitely regulated at the cellular level. During the process of differentiation, keratinocytes in the epidermis undergo a noticeable reduction in iron content. Conversely, psoriatic lesions, characterized by disruptions in epidermal differentiation, frequently reveal an excessive accumulation of iron within keratinocytes that have undergone differentiation. In this study, we clarified the significance of attenuated cellular iron content in the intricate course of epidermal differentiation. We illustrated this phenomenon through the utilization of hinokitiol, an iron chelator derived from the heartwood of Taiwanese hinoki, which forcibly delivers iron into cells independent of the intrinsic iron-regulation systems. While primary cultured keratinocytes readily succumbed to necrotic cell death by this iron chelator, mild administration of the hinokitiol-iron complex modestly disrupts the process of differentiation in these cells. Notably, keratinocyte model cells HaCaT and anaplastic skin rudiments exhibit remarkable resilience against the cytotoxic impact of hinokitiol, and the potent artificial influx of iron explains a suppressive effect selectively on epidermal differentiation. Moreover, the augmentation of iron content induced by the overexpression of divalent metal transporter 1 culminates in the inhibition of differentiation in HaCaT cells. Consequently, the diminution in cellular iron content emerges as an important determinant influencing the trajectory of keratinocyte differentiation.

Influence of cosmetic foundation cream on skin condition during treadmill exercise.

BACKGROUND: There is a growing trend of individuals wearing cosmetics while participating in physical activities. Nonetheless, there remains a need for further understanding regarding the effects of makeup on the facial epidermis during exercise, given the existing knowledge gaps. PURPOSE: This study aimed to evaluate the effects of a cosmetic foundation cream on skin conditions during physical activity. METHODS: Forty-three healthy college students, 20 males (26.3 ± 1.5 years) and 23 females (23.1 ± 1.0 years), were enrolled in this study. Foundation cream was applied to participants on half of the face in two different areas (MT: makeup T zone and MU: makeup U zone). The other half of the face served as internal control (T: non-makeup T zone and U: non-makeup U zones). Skin levels of moisture, elasticity, pore, sebum, and oil were measured using a skin analysis device (Aramhuvis, Gyeonggi, Republic of Korea) before and after a 20-min treadmill exercise. Paired t-test and independent t-test were performed for skin condition measurements at pre- and postexercise. RESULTS: The skin moisture levels in both the T and MT significantly increased after exercise (p < 0.05) (pre-T: 24.5 ± 1.3, post-T: 38.5 ± 3.5 and pre-MT: 18.7 ± 0.7, post-MT: 40.4 ± 4.8). Elasticity also significantly improved in both the T and MT (p < 0.05) (pre-T: 25.6 ± 1.3, post-T: 41.5 ± 3.5 and pre-MT: 20.0 ± 0.9, post-MT: 41.7 ± 3.7). The size of the pores in the T zone observed a significant increase after exercise (p < 0.05) (pre-T: 41.7 ± 2.1, post-T: 47.8 ± 2.4). The sebum levels in the T zone exhibited a reduction following physical activity, whereas there was a notable increase in sebum levels in the makeup zones (p < 0.05) (pre-MT: 2.4 ± 0.7, post-MT:4.2 ± 0.8 and pre MU 1.8 ± 0.34, post MU 4.9 ± 0.9). The oil level was increased in the non-makeup zones (pre-T: 6.1 ± 1.4, post-T: 11.8 ± 2.0 and pre-U: 7.3 ± 1.5, post-U: 11.9 ± 1.9; p < 0.05) and decreased in the makeup zones (pre-MT: 13.3 ± 1.9, post-MT: 7.4 ± 2.3 and pre-MU: 22.1 ± 2.4, post-MU: 3.2 ± 1.0; p < 0.05). CONCLUSIONS: The findings suggest that using foundation cream during aerobic exercise can reduce skin oil, causing dryness. Additionally, makeup can clog pores and increase sebum production. Therefore, wearing makeup may not be recommended for people with dry skin conditions based on the results of the current study. This research offers important insights to the public, encouraging them to consider the possible consequences of using makeup while exercising.

Epidermal barrier function in dry, flaky and sensitive skin: A narrative review.

The stratum corneum (SC)-the outermost layer of the epidermis-is the principal permeability and protective barrier of the skin. Different components of the SC, including corneocytes, natural moisturizing factor, a variety of enzymes and their inhibitors, antimicrobial peptides and lipids, work interactively to maintain barrier function. The main barrier properties of the SC are the limitation of water loss and the prevention of infection and contact with potentially harmful exogenous factors. Although the SC functions consistently as a protective barrier throughout the body, variations in functions and morphology occur across body sites with age and skin type. Healthy SC function also depends on the interplay between the chemosensory barrier, the skin's microbiome and the innate immune system. Dysregulation of SC barrier function can lead to the development of skin disorders, such as dry, flaky or sensitive skin, but the complete underlying pathophysiology of these are not fully understood. This review provides insight into the current literature and emerging themes related to epidermal barrier changes that occur in the context of dry, flaky and sensitive skin. Additional studies are needed to further elucidate the underlying aetiology of dry, flaky and sensitive skin and to provide tailored treatment.

Age-dependent changes in epidermal architecture explored using an automated image analysis algorithm on in vivo reflectance confocal microscopy images.

BACKGROUND: Reflectance confocal microscopy (RCM) allows for real-time in vivo visualization of the epidermis at the cellular level noninvasively. Parameters relating to tissue architecture can be extracted from RCM images, however, analysis of such images requires manual identification of cells to derive these parameters, which can be time-consuming and subject to human error, highlighting the need for an automated cell identification method. METHODS: First, the region-of-interest (ROI) containing cells needs to be identified, followed by the identification of individual cells within the ROI. To perform this task, we use successive applications of Sato and Gabor filters. The final step is post-processing improvement of cell detection and removal of size outliers. The proposed algorithm is evaluated on manually annotated real data. It is then applied to 5345 images to study the evolution of epidermal architecture in children and adults. The images were acquired on the volar forearm of healthy children (3 months to 10 years) and women (25-80 years), and on the volar forearm and cheek of women (40-80 years). Following the identification of cell locations, parameters such as cell area, cell perimeter, and cell density are calculated, as well as the probability distribution of the number of nearest neighbors per cell. The thicknesses of the Stratum Corneum and supra-papillary epidermis are also calculated using a hybrid deep-learning method. RESULTS: Epidermal keratinocytes are significantly larger (area and perimeter) in the granular layer than in the spinous layer and they get progressively larger with a child's age. Skin continues to mature dynamically during adulthood, as keratinocyte size continues to increase with age on both the cheeks and volar forearm, but the topology and cell aspect ratio remain unchanged across different epidermal layers, body sites, and age. Stratum Corneum and supra-papillary epidermis thicknesses increase with age, at a faster rate in children than in adults. CONCLUSIONS: The proposed methodology can be applied to large datasets to automate image analysis and the calculation of parameters relevant to skin physiology. These data validate the dynamic nature of skin maturation during childhood and skin aging in adulthood.

Polarity in skin development and cancer.

The epidermis is a stratified squamous epithelium that forms the outermost layer of the skin. Its primary function is to act as a barrier, keeping pathogens and toxins out and moisture in. This physiological role has necessitated major differences in the organization and polarity of the tissue as compared to simple epithelia. We discuss four aspects of polarity in the epidermis - the distinctive polarities of basal progenitor cells as well as differentiated granular cells, the polarity of adhesions and the cytoskeleton across the tissue as keratinocytes differentiate, and the planar cell polarity of the tissue. These distinctive polarities are essential for the morphogenesis and the function of the epidermis and have also been implicated in regulating tumor formation.

Transepidermal water loss and stratum corneum hydration in forearm versus hand palm.

BACKGROUND: Skin measurements of transepidermal water loss (TEWL) and stratum corneum hydration (SCH) reflect different aspects of skin physiology. Since epidermal water loss depends on epidermal-to-air water vapor gradients, a possible quantitative relationship between TEWL and SCH may exist. This investigation's purpose was to test the possible TEWL-SCH relationship. MATERIALS AND METHODS: SCH and TEWL were measured noninvasively on forearm and palmer thenar eminence (hand) in 40 young adults (20 males) along with total body fat percentage (FAT) via bioimpedance. RESULTS: A significant positive nonlinear correlation (p < 0.001) was detected between SCH and TEWL in hands of the male cohort that occurred when SCH exceeded a threshold level. This threshold level was not exceeded in male or female forearms and forearms did not display a SCH-TEWL correlation. There was a weak inverse dependence of TEWL on FAT on both forearm and hand (p < 0.05), but no SCH-FAT relationship was observed. TEWL values on the forearm and hand were moderately correlated with each other (p = 0.002) but SCH values were not. CONCLUSION: The findings clarify the relationship between forearm and palmer hydration and TEWL values, and their relationship to total body fat percentages in young healthy adults. The significant correlation between palmer stratum corneum hydration and palmer TEWL that was discovered in the male but not the female cohort suggests a threshold hydration level for which TEWL depends both on skin barrier function and stratum corneum hydration. This implies that conditions with increased SCH may in part account for elevated TEWL values.

Quantitative morphometric analysis of intrinsic and extrinsic skin ageing in individuals with Fitzpatrick skin types II-III.

Skin ageing is an intricate physiological process affected by intrinsic and extrinsic factors. There is a demand to understand how the skin changes with age and photoexposure in individuals with Fitzpatrick skin types I-III due to accelerated photoageing and the risk of cutaneous malignancies. To assess the structural impact of intrinsic and extrinsic ageing, we analysed 14 skin parameters from the photoprotected buttock and photoexposed dorsal forearm of young and ageing females with Fitzpatrick skin types II-III (n = 20) using histomorphic techniques. Whilst the minimum viable epidermis (Emin ) remained constant (Q > 0.05), the maximum viable epidermis (Emax ) was decreased by both age and photoexposure (Q ≤ 0.05), which suggests that differences in epidermal thickness are attributed to changes in the dermal-epidermal junction (DEJ). Changes in Emax were not affected by epidermal cell proliferation. For the first time, we investigated the basal keratinocyte morphology with age and photoexposure. Basal keratinocytes had an increased cell size, cellular height and a more columnar phenotype in photoexposed sites of young and ageing individuals (Q ≤ 0.05), however no significant differences were observed with age. Some of the most striking changes were observed in the DEJ, and a decrease in the interdigitation index was observed with both age and photoexposure (Q ≤ 0.001), accompanied by a decreased height of rête ridges and dermal papilla. Interestingly, young photoexposed skin was comparable to ageing skin across many parameters, and we hypothesise that this is due to accelerated photoageing. This study highlights the importance of skin care education and photoprotection from an early age.

Compromised skin barrier induced by prolonged face mask usage during the COVID-19 pandemic and its remedy with proper moisturization.

BACKGROUND: Prolonged face mask usage, a daily practice for the public due to the COVID-19 pandemic, creates high levels of humidity underneath the mask, which may cause unexpected skin concerns. OBJECTIVE: To investigate the impact of repeated mask usage on the face by comparing skin properties inside and outside of the mask-covered areas. METHODS: A double-blinded, randomized, split-face clinical study was conducted with 21 healthy female participants who wore face masks at least 6 h every day for 1 week, with one side of their face treated with a moisturizer three times daily. On day 8, after 5 h of wearing the mask, skin properties (sebum, hydration, and trans-epidermal water loss [TEWL]) were evaluated at 15, 60, and 120 min post-mask removal, followed by barrier disruption and recovery assessment. RESULTS: Mask usage weakened stratum corneum (SC) on facial skin compared to uncovered areas, including reduced SC hydration (p < 0.02 at 15 min) and increased TEWL in response to tape stripping challenge (p < 0.03 after stripping). In addition, sebum production also increased after mask removal (p < 0.01 at 15 min). Notably, a daily moisturizer mitigated these effects by increasing SC hydration (p < 0.001) and improving SC resilience against barrier disruption. CONCLUSION: Daily prolonged usage of a facial mask, essential due to the COVID-19 situation, generated a high-humidity microenvironment and led to compromised SC, which was revealed by a barrier challenge technique. Moreover, proper facial moisturization may help to maintain skin homeostasis and prevent the barrier impairment caused by repeated mask usage.

Sensory axons induce epithelial lipid microdomain remodeling and determine the distribution of junctions in the epidermis.

Epithelial cell properties are determined by the polarized distribution of membrane lipids, the cytoskeleton, and adhesive junctions. Epithelia are often profusely innervated, but little work has addressed how neurites affect epithelial organization. We previously found that basal keratinocytes in the zebrafish epidermis enclose axons in ensheathment channels sealed by autotypic junctions. Here we characterized how axons remodel cell membranes, the cytoskeleton, and junctions in basal keratinocytes. At the apical surface of basal keratinocytes, axons organized lipid microdomains quantitatively enriched in reporters for PI(4,5)P2 and liquid-ordered (Lo) membranes. Lipid microdomains supported the formation of cadherin-enriched, F-actin protrusions, which wrapped around axons, likely initiating ensheathment. In the absence of axons, cadherin-enriched microdomains formed on basal cells but did not organize into contiguous domains. Instead, these isolated domains formed heterotypic junctions with periderm cells, a distinct epithelial cell type. Thus, axon endings dramatically remodel polarized epithelial components and regulate epidermal adhesion.

A comprehensive comparison of facial skin hydration based on capacitance and conductance measurements in Chinese women.

OBJECTIVES: The aim of this study was to compare the data of conductance and capacitance measurements of facial skin hydration and to evaluate and discuss the advantages and disadvantages of the different approaches. METHODS: We measured skin capacitance (Corneometer® CM 825) and skin conductance (Skicon-200EX®) on 30 pre-defined facial sites of 125 Chinese women, resulting in 3750 readings per device. The data were analysed and compared, and continuous colour maps were generated on a 3D avatar for capacitance, conductance, relative difference (Δ%) and correlation (R-value) by interpolating between the individual readings and converting the values to colours. This visualization allows a better interpretation of the results. RESULTS: The complexity of facial skin hydration is revealed by this approach. The similarities and discrepancies in the facial hydration maps are clearly apparent. Due to the superiority of the Skicon in measuring high hydration levels, differences in skin hydration were evident on the forehead compared with the Corneometer maps, which may be related to the more superficial measurement of the Skicon within the stratum corneum. Conversely, a greater understanding of the complexity of facial skin hydration in the nasolabial fold was obvious when using the Corneometer. The best congruence between the instruments was found at two specific but separated facial areas, one around the inner eye region and the other one on a line between the nasolabial sulcus and the oblique, lateral jaw. Interestingly, the data were not normally distributed for both instruments and they had opposite skews. All facial clusters were statistically different from each other (p < 0.001), except the cheek and jaw for the Skicon. Larger than expected percentage coefficients of variance were found for the Corneometer on some facial sites that might be explainable by differences in stratum corneum physiology and biochemistry. Corneometer values of 48 AU and Skicon values of 132 µS were taken as the cutoff for normally hydrated facial skin. CONCLUSIONS: Both devices have their advantages and disadvantages suggesting that bio-instrumental measurement of skin hydration is actually more complicated than commonly thought and that the different facial zones and the use of multiple instrumentation have not been adequately considered.

OBJECTIFS: L'objectif de cette étude était de comparer des données issues de mesures d'hydratation de la peau du visage par conductance et capacité électrique, et d'évaluer et discuter les avantages et désavantages de ces différentes approches. METHODES: La capacité électrique de la peau (Corneometer® CM 825) et saconductance (Skicon-200EX®) ont été mesurées en 30 points pré-définis du visage de 125 femmes chinoises, menant ainsi à 3750 mesures par appareil. Les données ont été analysées et comparées, puis transposées visuellement sur avatar 3D via la création de cartographies continues de couleur par conversion de chaque valeur en une coordonnée de couleur et interpolation colorielle entre les différents points. Des cartographies de capacité électrique, de conductance ainsi que celle de la différence relative (Δ%) et de corrélation (R-value) ont été générées, ces visualisations permettant de mieux interpréter les résultats. RESULTS: Cette étude a mis en lumière la complexité de l'hydratation de la peau du visage. Les similarités et différences entre les cartographies d'hydratation faciale apparaissent clairement. Du fait de la supériorité du Skicon pour la mesure de hauts taux d'hydratation, des différences sont clairement visualisées entre les cartographies d'hydratation des deux appareils au niveau du front, et pourraient être dues à une mesure plus superficielle au sein du stratum corneum avec le Skicon. A l'inverse, l'utilisation du Corneometer permet une bien meilleure compréhension de la complexité de l'hydratation de la peau au niveau du sillon nasogénien. Les appareils montrent les résultats les plus similaires au niveau de deux zones spécifiques et séparées du visage, une au niveau du coin interne de l'œil et l'autre sur une ligne séparant le sillon nasolabial et l'oblique latéral de la machoire. Il est intéressant de noter que les distributions des données ne suivent pas une loi normale, pour aucun des deux appareils, et présentent des biais de distribution opposés. Tous les résultats obtenus au niveau des clusters faciaux étudiés montrent des différences statistiquement significatives entre eux (p⟨0.001), à l'exception de la joue et de la mâchoire, avec le Skicon. Des pourcentages de coefficients de variation plus élevés qu'attendus ont été obtenus avec le Corneometer en certaines zones du visage, qui pourraient être expliqués par des différences physiologiques et biochimiques du stratum corneum. Des valeurs de 48 UA avec le Corneometer et de 132 µS avec le Skicon ont été retenues comme valeurs seuil d'une peau du visage normalement hydratée. CONCLUSIONS: Les deux appareils montrent des avantages et désavantages, suggérant que la mesure bio-instrumentale de l'hydratation cutanée du visage est en réalité plus compliquée que communément admise et qu'une approche multiinstrumentale n'a pas été suffisamment considérée à ce jour pour appréhender les différentes zones du visages.

Multiscale modelling of desquamation in the interfollicular epidermis.

Maintenance of epidermal thickness is critical to the barrier function of the skin. Decreased tissue thickness, specifically in the stratum corneum (the outermost layer of the tissue), causes discomfort and inflammation, and is related to several severe diseases of the tissue. In order to maintain both stratum corneum thickness and overall tissue thickness it is necessary for the system to balance cell proliferation and cell loss. Cell proliferation in the epidermis occurs in the basal layer and causes constant upwards movement in the tissue. Cell loss occurs when dead cells at the top of the tissue are lost to the environment through a process called desquamation. Desquamation is thought to occur through a gradual reduction in adhesion between cells, due to the cleaving of adhesion proteins by enzymes, in the stratum corneum. In this paper we will investigate combining a (mass action) subcellular model of desquamation with a three dimensional (cell centre based) multicellular model of the interfollicular epidermis to better understand maintenance of epidermal thickness. Specifically, our aim is to determine if a hypothesised biological model for the degradation of cell-cell adhesion, from the literature, is sufficient to maintain a steady state tissue thickness. These investigations show the model is able to provide a consistent rate of cell loss in the multicellular model. This loss balances proliferation, and hence maintains a homeostatic tissue thickness. Moreover, we find that multiple proliferative cell populations in the basal layer can be represented by a single proliferative cell population, simplifying investigations with this model. The model is used to investigate a disorder (Netherton Syndrome) which disrupts desquamation. The model shows how biochemical changes can cause disruptions to the tissue, resulting in a reduced tissue thickness and consequently diminishing the protective role of the tissue. A hypothetical treatment result is also investigated: we compare the cases of a partially effective homogeneous treatment (where all cells partially recover) and a totally effective heterogeneous treatment (in which a proportion of the cells totally recover) with the aim to determine the difference in the response of the tissue to these different scenarios. Results show an increased benefit to corneum thickness from the heterogeneous treatment over the homogeneous treatment.

Dynamic regulation of human epidermal differentiation by adhesive and mechanical forces.

The interfollicular epidermis is the multilayered epithelium that forms the outer layer of the skin. It is maintained by stem cells that are attached to a basement membrane, which lies on top of the underlying connective tissue, the dermis. Cells undergo terminal differentiation as they detach from the basement membrane and move toward the outer epidermal surface. Over time, many of the molecular regulators of this process have been identified. It is now is clear that these pathways also receive critical input from the physical properties of the tissue. In this review, we describe how changes in these factors regulate differentiation and how new insights from single cell RNA sequencing could provide validation or challenge to the existing experimental models.

Looking at Interleukin-22 from a New Dermatological Perspective: From Epidermal Homeostasis to Its Role in Chronic Skin Diseases.

Twenty years after the cloning, characterization, and identification of interleukin (IL)-22 in 2000, the precise biological role of this cytokine in healthy and unhealthy skin is not completely known. The aim of this review is to provide an overview on the recent knowledge available in literature about the origin, sources, targets, molecular mechanism of action, and clinical issues regarding IL-22. Last but not least, recent experimental evidence obtained in a 3D model of organotypic culture of normal human skin highlights its homeostatic role and will be discussed in detail, as personal observations. As most of the data concerning IL-22 immunomodulating activity are obtained from mouse models, this work offers a new perspective on its clinical role. The hypothesis herein advanced is that IL-22 profoundly affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.

Sub-epidermal moisture assessment as a prompt for clinical action in treatment of pressure ulcers in at-risk hospital patients.

OBJECTIVE: This study assesses anonymous patient-level data on the use of sub-epidermal moisture (SEM) assessment technology as a tool in the prevention of pressure ulceration in at-risk hospital patients. METHOD: The relationship between technology-generated prompts for clinical action (patient turning, application of pressure redistributing equipment, heel protection or cream) and consequent clinical action was evaluated using data cross-tabulations (using data aggregated over multiple anatomical sites); in a multilevel model with patients clustered within wards, clustered in turn within hospitals, and controlling for additional patient- and institution-level factors; and using receiver operating characteristic (ROC) analyses of anatomy-specific data. The ability of the SEM assessment technology to detect deep and early-stage pressure ulcers/injuries on specific anatomical areas of a patient's body on admission, earlier than visual and tactile skin tissue assessments (STA), was assessed. RESULTS: A total of 15,574 patient assessments ('cases') were reported on 1995 patients. Most incidences of nurse action were in response to a prompt from SEM assessments (4944/5494; 90.0%). An SEM delta (Δ)≥0.6 resulted in nurse action in 4944/13,071 cases (37.8%). The multilevel model revealed strong evidence that SEM Δ prompts were significantly associated with nurse action (p<0.001; adjusted odds ratio: 1.99). CONCLUSION: In this study, SEM assessment technology effectively prompted nurse action moreso than skin reddening diagnosed via trained clinician judgement and STAs. While baseline responses of nurses' actions remained low, with or without SEM Δ prompts, findings verified the 'clinical utility' of SEM assessment technology as an objective prompt for early clinical action over and above existing mechanisms.

Regeneration of collagen fibrils at the papillary dermis by reconstructing basement membrane at the dermal-epidermal junction.

The epidermal basement membrane deteriorates with aging. We previously reported that basement membrane reconstruction not only serves to maintain epidermal stem/progenitor cells in the epidermis, but also increases collagen fibrils in the papillary dermis. Here, we investigated the mechanism of the latter action. Collagen fibrils in the papillary dermis were increased in organotypic human skin culture treated with matrix metalloproteinase and heparinase inhibitors. The expression levels of COL5A1 and COL1A1 genes (encoding collagen type V α 1 chain and collagen type I α 1 chain, respectively) were increased in fibroblasts cultured with conditioned medium from a skin equivalent model cultured with the inhibitors and in keratinocytes cultured on laminin-511 E8 fragment-coated plates. We then examined cytokine expression, and found that the inhibitors increased the expression of PDGF-BB (platelet-derived growth factor consisting of two B subunits) in epidermis. Expression of COL5A1 and COL1A1 genes was increased in cultured fibroblasts stimulated with PDGF-BB. Further, the bifunctional inhibitor hydroxyethyl imidazolidinone (HEI) increased skin elasticity and the thickness of the papillary dermis in the skin equivalent. Taken together, our data suggests that reconstructing the basement membrane promotes secretion of PDGF-BB by epidermal keratinocytes, leading to increased collagen expression at the papillary dermis.

Vasculature atrophy causes a stiffened microenvironment that augments epidermal stem cell differentiation in aged skin.

Stem cell loss causes tissue deterioration associated with aging. The accumulation of genomic and oxidative stress-induced DNA damage is an intrinsic cue for stem cell loss1,2; however, whether there is an external microenvironmental cue that triggers stem cell loss remains unclear. Here we report that the involution of skin vasculature causes dermal stiffening that augments the differentiation and hemidesmosome fragility of interfollicular epidermal stem cells (IFESCs) in aged mouse skin. Aging-related IFESC dysregulation occurs in plantar and tail skin, and is correlated with prolonged calcium influx, which is contributed by the mechanoresponsive ion channel Piezo1 (ref. 3). Epidermal deletion of Piezo1 ameliorated IFESC dysregulation in aged skin, whereas Piezo1 activation augmented IFESC differentiation and hemidesmosome fragility in young mice. The dermis stiffened with age, which was accompanied by dermal vasculature atrophy. Conversely, induction of the dermal vasculature softened the dermis and ameliorated IFESC dysregulation in aged skin. Single-cell RNA sequencing of dermal fibroblasts identified an aging-associated anti-angiogenetic secretory molecule, pentraxin 3 (ref. 4), which caused dermal sclerotization and IFESC dysregulation in aged skin. Our findings show that the vasculature softens the microenvironment for stem cell maintenance and provide a potential mechanobiology-based therapeutic strategy against skin disorders in aging.

How many skin barriers haveth we: Percutaneous egression of ions?

INTRODUCTION: Skin provides critical barrier properties that enable terrestrial life. Myriad research has focused on the "water barrier" to transepidermal water loss (TEWL) despite there being a multitude of skin barrier properties. We asked what other barrier properties may have been overlooked and compiled data demonstrating the "electrolyte barrier" to be of potential clinical relevance. METHODS: A literature search was conducted through PubMed, Embase, Google Scholar, and Web of Science databases for the following keywords: "transepidermal" or "epidermal" or "cutaneous" or "skin" or "percutaneous" and "ion" or "sodium" or "chloride" or "potassium" or "electrolyte" and "flux" or "egression." Textbooks at the University of California, San Francisco were also hand reviewed. Experimental studies quantifying in vivo or ex vivo percutaneous egression of ions in response to human skin barrier perturbation were included. RESULTS: Experimental damage to skin, mostly by tape-stripping, frequently induced increased ion flux rates through the epidermis, in addition to increases in TEWL values. Interestingly, barrier perturbation did not always result in a concomitant rise in TEWL and transepidermal ion flux rates, such as in delipidization, indicating a distinction between the two barriers. CONCLUSION: Quantifying the percutaneous egression of ions in response to physical or chemical alterations may offer additional data that are not to be captured with TEWL studies exclusively. Continued efforts should be made to: (1) advance this technique as a method of assessing skin status and (2) enhance our understanding of other barriers and mechanisms.