Functional properties and skin care effects of sodium trehalose sulfate.

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

The protective effect of a new absorbent incontinence design against an alkaline pH challenge on the epidermal barrier.

BACKGROUND: Incontinence-associated dermatitis (IAD) is one of the most common complications of incontinence. Improved diaper designs can minimize the occurrence of IAD. PURPOSE: To develop a novel diaper design to minimize the damaging effects of incontinence on the epidermal barrier. METHODS: An optimized diaper design was tested for surface dryness (ie, rewet), maintenance of a skin-adapted surface pH of 5.5, and ability to protect epidermal barrier function from an alkaline pH 10.7 challenge. RESULTS: The diapers released a mean (standard deviation [SD]) of 1.2 (0.2) mg/cm2 of solution under pressure after the first loading and a mean of 2.9 (1.7) mg/cm2 after the second loading. The surface pH remained between 4.5 and 5.5 over 5 hours. In healthy skin, transepidermal water loss (TEWL) increased by a mean of 3.43 (4.67) g/m2/h after the alkaline urine solution challenge with the new diaper design versus a mean of 8.38 (5.67) g/m2/h with a cellulose patch (P < .001) as a control. The mean erythema readings were 1.18 (1.30) g/m2/h for the new design and 2.56 (1.25) g/m2/h for the cellulose patches (P < .001). CONCLUSION: The new diaper design minimizes rewetting, maintains an acidic surface, and protects the epidermal barrier against an alkaline pH challenge. This design may help prevent IAD.

Epidermal retinol dehydrogenases cyclically regulate stem cell markers and clock genes and influence hair composition.

The hair follicle (HF) is a self-renewing adult miniorgan that undergoes drastic metabolic and morphological changes during precisely timed cyclic organogenesis. The HF cycle is known to be regulated by steroid hormones, growth factors and circadian clock genes. Recent data also suggest a role for a vitamin A derivative, all-trans-retinoic acid (ATRA), the activating ligand of transcription factors, retinoic acid receptors, in the regulation of the HF cycle. Here we demonstrate that ATRA signaling cycles during HF regeneration and this pattern is disrupted by genetic deletion of epidermal retinol dehydrogenases 2 (RDHE2, SDR16C5) and RDHE2-similar (RDHE2S, SDR16C6) that catalyze the rate-limiting step in ATRA biosynthesis. Deletion of RDHEs results in accelerated anagen to catagen and telogen to anagen transitions, altered HF composition, reduced levels of HF stem cell markers, and dysregulated circadian clock gene expression, suggesting a broad role of RDHEs in coordinating multiple signaling pathways.

Pressure-Insensitive Epidermal Thickness of Fingertip Skin for Optical Image Encryption.

In this study, an internal fingerprint-guided epidermal thickness of fingertip skin is proposed for optical image encryption based on optical coherence tomography (OCT) combined with U-Net architecture of a convolutional neural network (CNN). The epidermal thickness of fingertip skin is calculated by the distance between the upper and lower boundaries of the epidermal layer in cross-sectional optical coherence tomography (OCT) images, which is segmented using CNN, and the internal fingerprint at the epidermis-dermis junction (DEJ) is extracted based on the maximum intensity projection (MIP) algorithm. The experimental results indicate that the internal fingerprint-guided epidermal thickness is insensitive to pressure due to normal correlation coefficients and the encryption process between epidermal thickness maps of fingertip skin under different pressures. In addition, the result of the numerical simulation demonstrates the feasibility and security of the encryption scheme by structural similarity index matrix (SSIM) analysis between the original image and the recovered image with the correct and error keys decryption, respectively. The robustness is analyzed based on the SSIM value in three aspects: different pressures, noise attacks, and data loss. Key randomness is valid by the gray histograms, and the average correlation coefficients of adjacent pixelated values in three directions and the average entropy were calculated. This study suggests that the epidermal thickness of fingertip skin could be seen as important biometric information for information encryption.

Evaluation of linear dermatoses by reflectance confocal microscopy in children.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

The retinoid X receptor has a critical role in synthetic rexinoid-induced increase in cellular all-trans-retinoic acid.

Rexinoids are agonists of nuclear rexinoid X receptors (RXR) that heterodimerize with other nuclear receptors to regulate gene transcription. A number of selective RXR agonists have been developed for clinical use but their application has been hampered by the unwanted side effects associated with the use of rexinoids and a limited understanding of their mechanisms of action across different cell types. Our previous studies showed that treatment of organotypic human epidermis with the low toxicity UAB30 and UAB110 rexinoids resulted in increased steady-state levels of all-trans-retinoic acid (ATRA), the obligatory ligand of the RXR-RAR heterodimers. Here, we investigated the molecular mechanism underlying the increase in ATRA levels using a dominant negative RXRα that lacks the activation function 2 (AF-2) domain. The results demonstrated that overexpression of dnRXRα in human organotypic epidermis markedly reduced signaling by resident ATRA, suggesting the existence of endogenous RXR ligand, diminished the biological effects of UAB30 and UAB110 on epidermis morphology and gene expression, and nearly abolished the rexinoid-induced increase in ATRA levels. Global transcriptome analysis of dnRXRα-rafts in comparison to empty vector-transduced rafts showed that over 95% of the differentially expressed genes in rexinoid-treated rafts constitute direct or indirect ATRA-regulated genes. Thus, the biological effects of UAB30 and UAB110 are mediated through the AF-2 domain of RXRα with minimal side effects in human epidermis. As ATRA levels are known to be reduced in certain epithelial pathologies, treatment with UAB30 and UAB110 may represent a promising therapy for normalizing the endogenous ATRA concentration and signaling in epithelial tissues.

Safety of Prolonged Exposure of Human Skin to Aqueous Ozone in a Test Hand Hygiene Model.

AIMS: This research assessed the safety of aqueous ozone (AO) on human skin after multiple exposures for up to 40 hours. METHODS AND RESULTS: Full thickness recombinant human skin (EpiDerm FT, EFT-400) was exposed to AO for 7 seconds per minute for the first 6 minutes of each hour, repeated hourly over four time periods (4, 10, 20 and 40 hours). An MTT assay assessed viability of skin cells after exposure, compared to incubator control, negative control and vehicle control (distilled water). No significant difference in tissue viability was found between the AO condition and any of the control conditions through 20 hours of exposures. At 40 hours of exposure, tissue viability was lower in the AO group when compared with negative control (p = 0.030) but not the other controls. CONCLUSIONS: The current study supports further consideration of repeated application of AO on human skin, such as for hand hygiene. IMPACT STATEMENT: The present research is the first well-controlled in vitro study assessing the cytotoxicity of repeated exposures of AO on a full-thickness human skin model. This information helps to inform the evaluation of AO as a potential alternative for hand and wound antisepsis.

Hydradermabrasion through the lens of Line-Field Confocal Optical Coherence Tomography.

BACKGROUND: Hydradermabrasion, also known as "HydraFacial," is an exfoliative cosmetic procedure for skin rejuvenation that has gained popularity. Despite its increasing popularity, clinical studies validating its efficacy with non-invasive assessment of histological changes to the skin, are scarce. In this study, we used Line-Field Confocal Optical Coherence Tomography (LC-OCT), an optical imaging device, to non-invasively visualize microscopic changes to skin anatomy after hydradermabrasion treatment. MATERIALS/METHODS: Eight volunteers (Fitzpatrick skin types II-V) were recruited for this study. Images, using LC-OCT (DeepLive, DAMAE medical) were obtained before and after hydradermabrasion and at 2 weeks post-treatment. A commercially available hydradermabrasion device was utilized to perform the dermabrasion. RESULTS: In the epidermis, initially, a decrease in the average thickness of the stratum corneum, from 9.42 to 6.67 µm was visualized in LC-OCT images after hydradermabrasion. However, at 2 weeks of follow-up, the average stratum corneum thickness was 9.75 µm, resulting in an overall increase in the average thickness after treatment. Improved homogenization of the stratum corneum and decreased number of undulations in the epidermis post-treatment were also visualized. In all the subjects, the superficial dermis appeared stretched, which returned to baseline by the 2-week follow-up. At the 2-week follow-up, there were no visible differences in the quality and quantity of collagen fibers in the dermis. CONCLUSION: In our study, LC-OCT images of the epidermis and dermis demonstrated microscopic features of skin rejuvenation when treated with hydradermabrasion. Thus, not only highlighting the efficacy of hydradermabrasion but also the potential of LC-OCT to serve as a tool for visualizing the microscopic effects of cosmetic procedures on skin anatomy.

Molecular control of cellulosic fin morphogenesis in ascidians.

BACKGROUND: The tunicates form a group of filter-feeding marine animals closely related to vertebrates. They share with them a number of features such as a notochord and a dorsal neural tube in the tadpole larvae of ascidians, one of the three groups that make tunicates. However, a number of typical chordate characters have been lost in different branches of tunicates, a diverse and fast-evolving phylum. Consequently, the tunic, a sort of exoskeleton made of extracellular material including cellulose secreted by the epidermis, is the unifying character defining the tunicate phylum. In the larva of ascidians, the tunic differentiates in the tail into a median fin (with dorsal and ventral extended blades) and a caudal fin. RESULTS: Here we have performed experiments in the ascidian Phallusia mammillata to address the molecular control of tunic 3D morphogenesis. We have demonstrated that the tail epidermis medio-lateral patterning essential for peripheral nervous system specification also controls tunic elongation into fins. More specifically, when tail epidermis midline identity was abolished by BMP signaling inhibition, or CRISPR/Cas9 inactivation of the transcription factor coding genes Msx or Klf1/2/4/17, median fin did not form. We postulated that this genetic program should regulate effectors of tunic secretion. We thus analyzed the expression and regulation in different ascidian species of two genes acquired by horizontal gene transfer (HGT) from bacteria, CesA coding for a cellulose synthase and Gh6 coding for a cellulase. We have uncovered an unexpected dynamic history of these genes in tunicates and high levels of variability in gene expression and regulation among ascidians. Although, in Phallusia, Gh6 has a regionalized expression in the epidermis compatible with an involvement in fin elongation, our functional studies indicate a minor function during caudal fin formation only. CONCLUSIONS: Our study constitutes an important step in the study of the integration of HGT-acquired genes into developmental networks and a cellulose-based morphogenesis of extracellular material in animals.

Bioengineered MSCCxcr2 transdifferentiated keratinocyte-like cell-derived organoid potentiates skin regeneration through ERK1/2 and STAT3 signaling in diabetic wound.

Skin regeneration is severely compromised in diabetic foot ulcers. Allogeneic mesenchymal stem cell (MSC) transplantation is limited due to the poor engraftment, mitogenic, and differentiation potential in the harsh wound microenvironment. Thus, to improve the efficacy of cell therapy, the chemokine receptor Cxcr2 was overexpressed in MSCs (MSCCxcr2). CXCL2/CXCR2 axis induction led to the enhanced proliferation of MSCs through the activation of STAT3 and ERK1/2 signaling. Transcriptional upregulation of FGFR2IIIb (KGF Receptor) promoter by the activated STAT3 and ERK1/2 suggested trans-differentiation of MSCs into keratinocytes. These stable MSCCxcr2 in 2D and 3D (spheroid) cell cultures efficiently transdifferentiated into keratinocyte-like cells (KLCs). An in vivo therapeutic potential of MSCCxcr2 transplantation and its keratinocyte-specific cell fate was observed by accelerated skin tissue regeneration in an excisional splinting wound healing murine model of streptozotocin-induced type 1 diabetes. Finally, 3D skin organoids generated using MSCCxcr2-derived KLCs upon grafting in a relatively avascular and non-healing wounds of type 2 diabetic db/db transgenic old mice resulted in a significant enhancement in the rate of wound closure by increased epithelialization (epidermal layer) and endothelialization (dermal layer). Our findings emphasize the therapeutic role of the CXCL2/CXCR2 axis in inducing trans-differentiation of the MSCs toward KLCs through the activation of ERK1/2 and STAT3 signaling and enhanced skin regeneration potential of 3D organoids grafting in chronic diabetic wounds.

Culture insert device with perfusable microchannels enhancesin vitroskin model development and barrier function assessment.

The ever-stricter regulations on animal experiments in the field of cosmetic testing have prompted a surge in skin-related research with a special focus on recapitulation of thein vivoskin structurein vitro. In vitrohuman skin models are seen as an important tool for skin research, which in recent years attracted a lot of attention and effort, with researchers moving from the simplest 2-layered models (dermis with epidermis) to models that incorporate other vital skin structures such as hypodermis, vascular structures, and skin appendages. In this study, we designed a microfluidic device with a reverse flange-shaped anchor that allows culturing of anin vitroskin model in a conventional 6-well plate and assessing its barrier function without transferring the skin model to another device or using additional contraptions. Perfusion of the skin model through vascular-like channels improved the morphogenesis of the epidermis compared with skin models cultured under static conditions. This also allowed us to assess the percutaneous penetration of the tested caffeine permeation and vascular absorption, which is one of the key metrics for systemic drug exposure evaluation.

Noninvasive evaluation of the skin barrier in reconstructed human epidermis using speckle analysis: Correlation with Raman microspectroscopy.

BACKGROUND: Reconstructed epidermis models, obtained from 3D keratinocytes culture, have gained significant prominence as prototypes for safety and efficacy testing in skin research. To effectively evaluate these models, it is essential to perform molecular and functional characterization. The skin's barrier function is one of the essential aspects of the epidermis that needs to be assessed. A noninvasive method is thus required for the evaluation of the skin barrier in these models. With this perspective, the aim of this feasibility study is to apply the speckle technique for the assessment of the skin barrier in the Reconstructed Human Epidermis (RHE). MATERIALS AND METHODS: Speckle analysis as well as Raman microspectroscopy were performed on RHE samples at two maturation days, D17 and D20. RESULTS: Between D17 and D20, our study showed an increase in various Raman parameters, including stratum corneum percentage, lateral lipid packing, lipid-to-protein ratio, and protein secondary structure. Furthermore, the degree of light polarization and the speckle grain size also increased over this period. CONCLUSION: The speckle technique proved to be effective for evaluating the skin barrier in Reconstructed Human Epidermis (RHE) models. Comparison with Raman validates this approach and provides comprehensive molecular and functional characterization of reconstructive skin models.

Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier.

BACKGROUND: Natural products are often friendly and can be used on children's skin after systematic and careful research. Therefore, in this study, the Royal Oji Complex (ROC), a product with natural ingredients, was used to study their effectiveness on keratinocytes taken from the skin of children from 0 to 3 years old. METHOD: Normal human epidermal keratinocytes and tissue-isolated keratinocytes (TIKC) from young donors were treated with three different concentrations of ROC: 0.1, 1, and 10 ppm. The mRNA expression of the epidermal barrier's essential genes, such as hyaluronic acid synthase 3 (Has3), involucrin (IVL), loricrin (LOR), and claudin-1 (CLD1) was investigated using qRT-PCR. Ceramide content was measured by ELISA, with retinoic acid (R.A.) and amarogentin (AMA) serving as positive controls. RESULTS: ROC significantly elevated HAS3 gene expression in HEKn cells, especially at 10 ppm, indicating potential advantages for skin hydration in young infants. IVL increased at first but decreased as ROC concentrations increased. LOR was upregulated at lower ROC concentrations but reduced at higher doses. CLD1 gene expression increased considerably in HEKn but reduced with increasing ROC doses. Ceramide concentration increased somewhat but not significantly at 10 ppm. CONCLUSION: ROC shows potential in altering keratinocyte gene expression, with unique responses in HEKn and TIKC from young donors. While changes in ceramide content were insignificant, these results help to comprehend ROC's multiple effects on young children's skin.

A Protocol for the Automated Assessment of Cutaneous Pathology in a Mouse Model of Hemichannel Dysfunction.

In this chapter, we provide detailed instructions to perform quantitative reflectance imaging in a mouse model of a rare epidermal disorder caused by hyperactive connexin 26 hemichannels. Reflectance imaging is a versatile and powerful tool in dermatology, offering noninvasive, high-resolution insights into skin pathology, which is essential for both clinical practice and research. This approach offers several advantages and applications. Unlike traditional biopsy, reflectance imaging is noninvasive, allowing for real-time, in vivo examination of the skin. This is particularly valuable for monitoring chronic conditions or assessing the efficacy of treatments over time, enabling the detailed examination of skin morphology. This is crucial for identifying features of skin diseases such as cancers, inflammatory conditions, and infections. In therapeutic applications, reflectance imaging can be used to monitor the response of skin lesions to treatments. It can help in identifying the most representative area of a lesion for biopsy, thereby increasing the diagnostic accuracy. Reflectance imaging can also be used to diagnose and monitor inflammatory skin diseases, like psoriasis and eczema, by visualizing changes in skin structure and cellular infiltration. As the technology becomes more accessible, it has potential in telemedicine, allowing for remote diagnosis and monitoring of skin conditions. In academic settings, reflectance imaging can be a powerful research tool, enabling the study of skin pathology and the effects of novel treatments, including the development of monoclonal antibodies for therapeutic applications.

Natural Moisturizing Factor-Enriched Formulations Compared to a Ceramide-Based Cream.

BACKGROUND: We aimed to investigate the effects of 2 ceramide plus natural moisturizing factor-enriched formulations compared to a ceramide-based cream on skin moisturization. METHODS: Two double-blinded comparative studies were conducted, which enrolled 35 (n=29 females, n=6 males) and 33 (n=21 females, n=12 males) participants, respectively. Participants applied ceramide plus natural moisturizer cream or ceramide-based cream (study 1) or applied ceramide plus natural moisturizing factor lotion or ceramide-based cream (study 2) to each of their lower legs for 10 days with a 5-day regression period (no moisturizer applied). Skin hydration by corneometry after bilateral application was conducted once daily for each leg in both groups.   Results: An increase in corneometer units vs baseline for the ceramide plus natural moisturizing factor-enriched cream and natural moisturizing factor-enriched lotion were greater than the increase vs baseline for the ceramide-based cream at days 10 and 15; with an overall statistical significance in favor of the ceramide plus natural moisturizing factor-enriched formulations at day 10.  Conclusions: The marked improvement in skin moisturization following utilization of the ceramide plus natural moisturizing  factor-enriched cream and lotion compared to the ceramide-based cream can be attributed to the inherent properties of the natural moisturizing factors. These properties are known to maintain the humectancy and intercellular lipid membrane of the stratum corneum, which directly improves the permeability barrier function of human skin in reducing transepidermal water loss. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8172.

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.

Dermal stiffness governs the topography of the epidermis and the underlying basement membrane in young and old human skin.

The epidermis is a stratified epithelium that forms the outer layer of the skin. It is composed primarily of keratinocytes and is constantly renewed by the proliferation of stem cells and their progeny that undergo terminal differentiation as they leave the basal layer and migrate to the skin surface. Basal keratinocytes rest on a basement membrane composed of an extracellular matrix that controls their fate via integrin-mediated focal adhesions and hemidesmosomes which are critical elements of the epidermal barrier and promote its regenerative capabilities. The distribution of basal cells with optimal activity provides the basement membrane with its characteristic undulating shape; this configuration disappears with age, leading to epidermal weakness. In this study, we present an in-depth imaging analysis of basal keratinocyte anchorage in samples of human skin from participants across the age spectrum. Our findings reveal that skin aging is associated with the depletion of hemidesmosomes that provide crucial support for stem cell maintenance; their depletion correlates with the loss of the characteristic basement membrane structure. Atomic force microscopy studies of skin and in vitro experiments revealed that the increase in tissue stiffness observed with aging triggers mechanical signals that alter the basement membrane structure and reduce the extent of basal keratinocyte anchorage, forcing them to differentiate. Genomic analysis revealed that epidermal aging was associated with mechanical induction of the transcription factor Krüppel-like factor 4. The altered mechanical properties of tissue being a new hallmark of aging, our work opens new avenues for the development of skin rejuvenation strategies.

Cellular patterning and cyto-architectural organization of the skin of electric catfish (Malapterurus electricus, Siluriformes) with a particular emphasis on its ampullary electroreceptor.

The functional morphology of the skin of Malapteruridae is presumably evolved to cope with a diversified range of ambient physiological, environmental, and behavioral conditions. Herein, we firstly characterized the microstructures and intriguing patterning of the skin of twelve adult electric catfish (Malapterurus electricus, Malapteruridae) using histological, histochemical, immunofluorescent, and ELISA standard methodology. The skin comprises three sequentially-oriented layers: the epidermis, dermis, and hypodermis with a significantly increased thickness of the former. The epidermis contains four types of cells: the surface epithelial cells, mucous cells, granular cells, and club cells. We defined distinctive ampullary electroreceptors in the outer epidermis that possess flask-shaped sensory crypt containing electroreceptor cells together with vertical collagen rods. Dermis and hypodermis are composed of connective tissue; however, the former is much more coarse and dense with comparable reactivity for Masson-Goldner trichrome (MT). Placing our data in the context of the limited body of previous work, we showed subtle changes in the expression of mucin subunits together with cytoskeletal fractions of collagens, myosin, F-actin, keratins, and tubulins. Taken as a whole, our results convincingly showed that the skin of M. electricus shares some structural similarities to other Siluriformes, however, it has some functional modifications that are implicated in protection, defense, and foraging behavior.

TCR signaling and cellular metabolism regulate the capacity of murine epidermal γδ T cells to rapidly produce IL-13 but not IFN-γ.

Resident epidermal T cells of murine skin, called dendritic epidermal T cells (DETCs), express an invariant γδ TCR that recognizes an unidentified self-ligand expressed on epidermal keratinocytes. Although their fetal thymic precursors are preprogrammed to produce IFN-γ, DETCs in the adult epidermis rapidly produce IL-13 but not IFN-γ early after activation. Here, we show that preprogrammed IFN-γ-producing DETC precursors differentiate into rapid IL-13 producers in the perinatal epidermis. The addition of various inhibitors of signaling pathways downstream of TCR to the in vitro differentiation model of neonatal DETCs revealed that TCR signaling through the p38 MAPK pathway is essential for the functional differentiation of neonatal DETCs. Constitutive TCR signaling at steady state was also shown to be needed for the maintenance of the rapid IL-13-producing capacity of adult DETCs because in vivo treatment with the p38 MAPK inhibitor decreased adult DETCs with the rapid IL-13-producing capacity. Adult DETCs under steady-state conditions had lower glycolytic capacity than proliferating neonatal DETCs. TCR stimulation of adult DETCs induced high glycolytic capacity and IFN-γ production during the late phase of activation. Inhibition of glycolysis decreased IFN-γ but not IL-13 production by adult DETCs during the late phase of activation. These results demonstrate that TCR signaling promotes the differentiation of IL-13-producing DETCs in the perinatal epidermis and is needed for maintaining the rapid IL-13-producing capacity of adult DETCs. The low glycolytic capacity of adult DETCs at steady state also regulates the rapid IL-13 response and delayed IFN-γ production after activation.

Unraveling the skin; a comprehensive review of atopic dermatitis, current understanding, and approaches.

Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease characterized by red pruritic skin lesions, xerosis, ichthyosis, and skin pain. Among the social impacts of atopic dermatitis are difficulties and detachment in relationships and social stigmatization. Additionally, atopic dermatitis is known to cause sleep disturbance, anxiety, hyperactivity, and depression. Although the pathological process behind atopic dermatitis is not fully known, it appears to be a combination of epidermal barrier dysfunction and immune dysregulation. Skin is the largest organ of the human body which acts as a mechanical barrier to toxins and UV light and a natural barrier against water loss. Both functions face significant challenges due to atopic dermatitis. The list of factors that can potentially trigger or contribute to atopic dermatitis is extensive, ranging from genetic factors, family history, dietary choices, immune triggers, and environmental factors. Consequently, prevention, early clinical diagnosis, and effective treatment may be the only resolutions to combat this burdensome disease. Ensuring safe and targeted drug delivery to the skin layers, without reaching the systemic circulation is a promising option raised by nano-delivery systems in dermatology. In this review, we explored the current understanding and approaches of atopic dermatitis and outlined a range of the most recent therapeutics and dosage forms brought by nanotechnology. This review was conducted using PubMed, Google Scholar, and ScienceDirect databases.