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Summary: Daphniphyllum macropodum produces alkaloids that are structurally complex with polycyclic, stereochemically rich carbon skeletons. Understanding how these compounds are formed by the plant may enable exploration of their biological function and bioactivities.We employed multiple metabolomics techniques, including a workflow to annotate compounds in the absence of standards, to compare alkaloid content across plants and tissues.Different alkaloid structural types were found to have distinct distributions between genotypes, between tissues and within tissues. Alkaloid structural types also showed different isotope labelling enrichments that matched their biosynthetic relationships.The work suggests that mevalonate derived 30‐carbon alkaloids are formed in the phloem region before their conversion to 22‐carbon alkaloids which accumulate in the epidermis. This sets the stage for further investigation into the biosynthetic pathway. [ABSTRACT FROM AUTHOR]

Earthworms are fascinating animals capable of crawling and burrowing through various terrains using peristaltic motion and the directional friction response of their epidermis. Anisotropic anchoring governed by tiny appendages on their skin called setae is known to enhance the earthworm's locomotion. A multi‐material fabrication technique is employed to produce soft skins with bristles inspired by the earthworm epidermis and their setae. The effect of bristles arranged in triangular and square grids at two spatial densities on the locomotion capability of a simple soft crawling robot comprised of an extending soft actuator covered by the soft skin is investigated experimentally. The results suggest that the presence of bristles results in a rostral to caudal friction ratio of µR/µC > 1 with some variations across bristle arrangements and applied elongations. Doubling the number of bristles increases the robot's speed by a factor of 1.78 for the triangular grid while it is less pronounced for the rectangular grid with a small factor of 1.06. Additionally, it is observed that increasing the actuation stroke for the skin with the high‐density triangular grid, from 15% to 30%, elevates the speed from 0.5 to 0.9 mm s−1, but further increases in stroke to 45% may compromise the durability of the actuators with less gains in speed (1 mm s−1). Finally, it is demonstrated that a crawling robot equipped with soft skin can traverse both a linear and a curved channel. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs play essential roles in various physiological processes. They induce angiogenesis, promote wound healing, modulate immune responses, and serve as chemoattractants for immune cells. AMPs regulate the microbiome and combat microbial infections on the skin, lungs, and gastrointestinal tract. Produced in response to microbial signals, AMPs help maintain a balanced microbial community and provide a first line of defense against infection. In preterm infants, alterations in microbiome composition have been linked to various health outcomes, including sepsis, necrotizing enterocolitis, atopic dermatitis, and respiratory infections. Dysbiosis, or an imbalance in the microbiome, can alter AMP profiles and potentially lead to inflammation-mediated diseases such as chronic lung disease and obesity. In the following review, we summarize what is known about the vital role of AMPs as multifunctional peptides in protecting newborn infants against infections and modulating the microbiome and immune response. Understanding their roles in preterm infants and high-risk populations offers the potential for innovative approaches to disease prevention and treatment. [ABSTRACT FROM AUTHOR]

Summary: Leaf venation is a pivotal trait in the success of vascular plants. Whereas gymnosperms have single or sparsely branched parallel veins, angiosperms developed a hierarchical structure of veins that form a complex reticulum. Its physiological consequences are considered to have enabled angiosperms to dominate terrestrial ecosystems in the Late Cretaceous and Cenozoic.Although a hierarchical‐reticulate venation also occurs in some groups of extinct seed plants, it is unclear whether these are stem relatives of angiosperms or have evolved these traits in parallel. Here, we re‐examine the morphology of the enigmatic foliage taxon Furcula, a potential early Mesozoic angiosperm relative, and argue that its hierarchical vein network represents convergent evolution (in the Late Triassic) with flowering plants (which developed in the Early Cretaceous) based on details of vein architecture and the absence of angiosperm‐like stomata and guard cells.We suggest that its nearest relatives are Peltaspermales similar to Scytophyllum and Vittaephyllum, the latter being a genus that originated during the Late Triassic (Carnian) and shares a hierarchical vein system with Furcula.We further suggest that the evolution of hierarchical venation systems in the early Permian, the Late Triassic, and the Early Cretaceous represent 'natural experiments' that might help resolve the selective pressures enabling this trait to evolve. [ABSTRACT FROM AUTHOR]

The polygonal shape of cells in proliferating epithelia is a result of the tensile forces of the cytoskeletal cortex and packing geometry set by the cell cycle. In the larval Drosophila epidermis, two cell populations, histoblasts and larval epithelial cells, compete for space as they grow on a limited body surface. They do so in the absence of cell divisions. We report a striking morphological transition of histoblasts during larval development, where they change from a tensed network configuration with straight cell outlines at the level of adherens junctions to a highly folded morphology. The apical surface of histoblasts shrinks while their growing adherens junctions fold, forming deep lobules. Volume increase of growing histoblasts is accommodated basally, compensating for the shrinking apical area. The folded geometry of apical junctions resembles elastic buckling, and we show that the imbalance between the shrinkage of the apical domain of histoblasts and the continuous growth of junctions triggers buckling. Our model is supported by laser dissections and optical tweezer experiments together with computer simulations. Our analysis pinpoints the ability of histoblasts to store mechanical energy to a much greater extent than most other epithelial cell types investigated so far, while retaining the ability to dissipate stress on the hours time scale. Finally, we propose a possible mechanism for size regulation of histoblast apical size through the lateral pressure of the epidermis, driven by the growth of cells on a limited surface. Buckling effectively compacts histoblasts at their apical plane and may serve to avoid physical harm to these adult epidermis precursors during larval life. Our work indicates that in growing nondividing cells, compressive forces, instead of tension, may drive cell morphology. During the development of the larval Drosophila epidermis, histoblasts and epithelial cells compete for space as they grow and undergo morphological changes. This study shows that compressive forces play a key role in controlling the shape of histoblasts, leading to the buckling of their apical junctions and changing the morphology of the epidermis from straight to highly folded outlines. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers (Echis ocellatus and Bitis arietans) and cobras (Naja nigricollis and N. haje). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1β, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following E. ocellatus or N. nigricollis venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments. [ABSTRACT FROM AUTHOR]

Although not completely understood, the role of the Hedgehog-GLI (HH-GLI) signaling pathway in melanoma and epithelial skin tumors has been reported before. In this study, we confirmed in various melanoma cell line models that keratin 16 (KRT16) and S100 Calcium-Binding Protein A7 (S100A7) are transcriptional targets of GLI Family Zinc Finger (GLI) proteins. Besides their important role in protecting and maintaining the epidermal barrier, keratins are somehow tightly connected with the S100 family of proteins. We found that stronger expression of KRT16 indeed corresponds to stronger expression of S100A7 in our clinical melanoma samples. We also report a trend regarding staining of GLI1, which corresponds to stronger staining of GLI3, KRT16, and S100A7 proteins. The most interesting of our findings is that all the proteins are detected specifically in the epidermis overlying the tumor, but rarely in the tumor itself. The examined proteins were also not detected in the healthy epidermis at the edges of the sample, suggesting that the staining is specific to the epidermis overlaying the tumor mass. Of all proteins, only S100A7 demonstrated a statistically significant trend regarding tumor staging and staining intensity. Results from our clinical samples prove that immune infiltration is an important feature of melanoma. Pigmentophages and tumor-infiltrating lymphocytes (TIL) demonstrate a significant association with tumor stage, while mononuclear cells are equally present in all stages. For S100A7, we found an association between the number of TILs and staining intensity. Considering these new findings presented in our study, we suggest a more detailed examination of the possible role of the S100A7 protein as a biomarker in melanoma. [ABSTRACT FROM AUTHOR]

The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin‐related diseases in humans. Here, single‐cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The cross‐species comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis. Moreover, Phenome‐wide association study analysis revealed that the conserved genes between pigs and humans are strongly associated with human skin‐related diseases. In the epidermis, two lineage differentiation trajectories describe hair follicle (HF) morphogenesis and epidermal development. By comparing normal and hairless fetal pigs, it is found that the hair placode (Pc), the most characteristic initial structure in HFs, arises from progenitor‐like OGN+/UCHL1+ cells. These progenitors appear earlier in development than the previously described early Pc cells and exhibit abnormal proliferation and migration during differentiation in hairless pigs. The study provides a valuable resource for in‐depth insights into HF development, which may serve as a key reference atlas for studying human skin disease etiology using porcine models. [ABSTRACT FROM AUTHOR]

Transdermal transport can be challenging due to the difficulty in diffusing active substances through the outermost layer of the epidermis, as the primary function of the skin is to protect against the entry of exogenous compounds into the body. In addition, penetration of the epidermis for substances hydrophilic in nature and particles larger than 500 Da is highly limited due to the physiological properties and non-polar nature of its outermost layer, namely the stratum corneum. A solution to this problem can be the use of microneedles, which "bypass" the problematic epidermal layer by dispensing the active substance directly into the deeper layers of the skin. Microneedles can be obtained with various materials and come in different types. Of special interest are carriers based on biodegradable and biocompatible polymers, such as polysaccharides. Therefore, this paper reviews the latest literature on methods to obtain hyaluronic acid-based microneedles. It focuses on the current advancements in this field and consequently provides an opportunity to guide future research in this area. [ABSTRACT FROM AUTHOR]

Chinese plum (Prunus salicina Lindl.) originates from China and makes a large contribution to the global production of plums. The P. salicina 'Wushancuili' has a green coloration and high fruit quality and is economically important in eliminating poverty and protecting ecology in the Yangtze River Three Gorges Reservoir. However, rain-induced cracking (rain-cracking, literally skin cracking caused by rain) is a limitation to 'Wushancuili' fruit production and causes severe losses. This study reported a high-quality 'Wushancuili' genome assembly consisting of a 302.17-Mb sequence with eight pseudo-chromosomes and a contig N50 of 23.59 Mb through the combination of Illumina sequencing, Pacific Biosciences HiFi III sequencing, and high-throughput chromosome conformation capture technology. A total of 25 109 protein-coding genes are predicted and 54.17% of the genome is composed of repetitive sequences. 'Wushancuili' underwent a remarkable orthoselection during evolution. Gene identification revealed that loss-of-function in four core MYB10 genes results in the anthocyanin deficiency and absence of red color, revealing the green coloration due to the residual high chlorophyll in fruit skin. Besides, the occurrence of cracking is assumed to be closely associated with cell wall modification and frequently rain-induced pathogen enrichment through transcriptomic analysis. The loss of MYB10 genes might render fruit more susceptible to pathogen-mediated cracking by weakening the epidermal strength and reactive oxygen species (ROS) scavenging. Our findings provided fundamental knowledge regarding fruit coloration and rain-cracking and will facilitate genetic improvement and cultivation management in Chinese plums. [ABSTRACT FROM AUTHOR]

Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like herpes simplex and varicella zoster, and fungi-like Candida species appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result. Key Words: burn wound infections; biofilm; epidermis; hospital; opportunistic infection [ABSTRACT FROM AUTHOR]

Mangifera indica var Ataulfo is the main variety grown in the Soconusco region of Chiapas, Mexico and faces a decrease in firmness and weight loss due to hydrothermal treatment, in addition to non-uniform ripening and consequently a decrease in price as the harvest period lengthens. In order to improve the postharvest quality of the "Ataulfo" mango fruit, preharvest applications of aminoethoxyvinylglycine (AVG; ReTain®, a.i. 15%) were carried out in "La Norteña" with Phaeozem soil, 1500 mm of annual precipitation, and applications of agrochemicals, and in "Santa Cecilia" with Acrisol soil, 2500 mm of annual precipitation, and without agrochemicals. The treatments were: (1) Control, (2) One application 7 days before harvest (0.1 g L−1), (3) Two applications (14 days and 7 days before harvest, 0.2 g L−1) and (4) Three applications (21, 14 and 7 days before harvest, in total 0.3 g L−1), with completely randomized design in the laboratory. The results show contrasting differences between the evaluation sites, with lower weight loss (18.4%) and 3.1% more firmness in a drier climate and higher soil calcium content. The average firmness (N) on day 14 was 18.3 and with three applications of AVG it was 22.0. The °Brix at the end of the study in the control was 11.3 and on average with AVG applications it was 14.4. Three-time applications of AVG in preharvest delayed the weight loss with an increase in the maintenance of the firmness of the fruits. The weight of the fruit epidermis was lower with AVG applications, and increased with the number of applications. [ABSTRACT FROM AUTHOR]

The mammalian epidermis has evolved to protect the body in a dry environment. Genes of the epidermal differentiation complex (EDC), such as FLG (filaggrin), are implicated in the barrier function of the epidermis. Here, we investigated the molecular evolution of the EDC in sirenians (manatees and dugong), which have adapted to fully aquatic life, in comparison to the EDC of terrestrial mammals and aquatic mammals of the clade Cetacea (whales and dolphins). We show that the main subtypes of EDC genes are conserved or even duplicated, like late cornified envelope (LCE) genes of the dugong, whereas specific EDC genes have undergone inactivating mutations in sirenians. FLG contains premature stop codons in the dugong, and the ortholog of human CASP14 (caspase-14), which proteolytically processes filaggrin, is pseudogenized in the same species. As FLG and CASP14 have also been lost in whales, these mutations represent convergent evolution of skin barrier genes in different lineages of aquatic mammals. In contrast to the dugong, the manatee has retained functional FLG and CASP14 genes. FLG2 (filaggrin 2) is truncated in both species of sirenians investigated. We conclude that the land-to-water transition of sirenians was associated with modifications of the epidermal barrier at the molecular level. [ABSTRACT FROM AUTHOR]

Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin. [ABSTRACT FROM AUTHOR]

To address current challenges in effectively treating large skin defects caused by trauma in clinical medicine, the fabrication, and evaluation of a novel radially aligned nanofiber scaffold (RAS) with dual growth factor gradients is presented. These aligned nanofibers and the scaffold's spatial design provide many all‐around "highways" for cell migration from the edge of the wound to the center area. Besides, the chemotaxis induced by two growth factor gradients further promotes cell migration. Incorporating epidermal growth factor (EGF) aids in the proliferation and differentiation of basal layer cells in the epidermis, augmenting the scaffold's ability to promote epidermal regeneration. Concurrently, the scaffold‐bound vascular endothelial growth factor (VEGF) recruits vascular endothelial cells at the wound's center, resulting in angiogenesis and improving blood supply and nutrient delivery, which is critical for granulation tissue regeneration. The RAS+EGF+VEGF group demonstrates superior performance in wound immune regulation, wound closure, hair follicle regeneration, and ECM deposition and remodeling compared to other groups. This study highlights the promising potential of hierarchically assembled nanofiber scaffolds with dual growth factor gradients for wound repair and tissue regeneration applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aquaporin 3 (AQP3) channels are tetrameric membrane-bound channels that facilitate the transport of water and other small solutes across cell membranes in the skin. Decreased AQP3 expression is associated with skin dryness, skin aging, psoriasis, and delayed wound healing. Thus, our study focused on a novel combination based on Aloe barbadensis leaf extract and trimethylglycine for targeted AQP3 regulation in skin keratinocytes and deep skin moisturization. Firstly, a dose-finding cytotoxicity assay of the selected substances was performed with a 2,5-diphenyl-2H-tetrazolium bromide (MTT) indicator on HaCaT cells. The substances' ability to increase the amount of AQP3 in keratinocytes was evaluated in a keratinocyte cell culture by means of ELISA. Additionally, the deep skin hydration effect was confirmed in clinical research with healthy volunteers. According to the results, the maximum tolerated doses providing viability at 70% (MTDs) values for Aloe barbadensis leaf extract and trimethylglycine were 24.50% and 39.00%, respectively. Following the research and development, a complex based on Aloe barbadensis leaf extract and trimethylglycine in a 1:1 mass ratio exhibited a good cytotoxicity profile, with an MTDs value of 37.90%. Furthermore, it was shown that the combination had a clear synergetic effect and significantly increased AQP3 by up to 380% compared to the negative control and glyceryl glucoside (p < 0.001). It was clinically confirmed that the developed shower gel containing Aloe barbadensis leaf extract and trimethylglycine safely improved skin hydration after one use and over 28 days. Thus, this novel plant-based combination has promising potential for AQP3 regulation in the skin epidermis and a role in the development of dermatological drugs for the treatment of skin xerosis and atopic-related conditions. [ABSTRACT FROM AUTHOR]

Introduction: Vulvar lichen sclerosus (VLS) is a chronic progressive, lymphocyte-mediated inflammatory disease whose pathogenesis is complex and not fully elucidated. Aim: In the current study we have investigated for the first time the expression of interleukin-17 (IL-17) and S100A7 in lesional skin obtained from female individuals with histologically confirmed VLS. Material and methods: In our study we used skin biopsies obtained from female patients with histologically confirmed VLS (n = 20) and skin samples from healthy age- and gender-matched individuals (plastic surgery procedures) (n = 10) serving as controls. The tissue expressions of IL-17 and S100A7 were assessed with an immunohistochemical method. Results: The number of cells showing IL-17 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, IL-17 was expressed in the epidermis and by cells within the inflammatory infiltrate in the upper dermis. The number of cells showing S100A7 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, S100A7 was expressed by suprabasal keratinocytes in epidermis. S100A7 was also expressed by cells within the inflammatory infiltrate in the dermis. Conclusions: The results of our study may suggest the involvement of IL-17 and S100A7 in the pathogenesis of VLS. The better understanding of this disease may lead to the development of novel, effective therapeutic strategies e.g. using well-known biologics IL-17 inhibitors class. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bioinks play a fundamental role in skin bioprinting, dictating the printing fidelity, cell response, and function of bioprinted 3D constructs. However, the range of bioinks that support skin cells' function and aid in the bioprinting of 3D skin equivalents with tailorable properties and customized shapes is still limited. In this study, we describe a bioinspired design strategy for bioengineering double crosslinked pectin-based bioinks that recapitulate the mechanical properties and the presentation of cell-adhesive ligands and protease-sensitive domains of the dermal extracellular matrix, supporting the bioprinting of bilayer 3D skin models. Methacrylate-modified pectin was used as a base biomaterial enabling hydrogel formation via either chain-growth or step-growth photopolymerization and providing independent control over bioink rheology, as well as the mechanical and biochemical cues of cell environment. By tuning the concentrations of crosslinker and polymer in bioink formulation, dermal constructs were bioprinted with a physiologically relevant range of stiffnesses that resulted in strikingly site-specific differences in the morphology and spreading of dermal fibroblasts. We also demonstrated that the developed thiol-ene photo-clickable bioinks allow for the bioprinting of skin models of varying shapes that support dermis and epidermis reconstruction. Overall, the engineered bioinks expand the range of printable biomaterials for the extrusion bioprinting of 3D cell-laden hydrogels and provide a versatile platform to study the impact of material cues on cell fate, offering potential for in vitro skin modeling. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is an unusual skin tumor that has a significant rate of distant and local metastases. It is known that primary MCC of the eyelid usually occurs at the upper eyelid. Here we report an unusual case of MCC metastasis to the eyelid. A 63-year-old male was diagnosed with MCC three years earlier after initially presenting with a mass in his right thigh. After histopathological diagnosis, the patient received medical therapy. During treatment, he developed multiple distant metastases and a firm, purple, vascularized lesion on the upper eyelid. We confirmed the lesion was an eyelid metastasis of MCC by histopathological examination and imaging methods. This case shows that extraocular MCC can metastasize to the eyelids, particularly the upper eyelid, where primary periocular MCC usually appears. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex pathogenesis of radiation-induced skin injury. In this review, we summarize the latest findings on the complex pathogenesis of radiation dermatitis and correlate these with the clinical features of radiation-induced skin reactions. The current studies show that skin exposure to ionizing radiation induces cellular senescence in the epidermal keratinocytes. As part of their epithelial stress response, these senescent keratinocytes secrete pro-inflammatory mediators, thereby triggering skin inflammation. Keratinocyte-derived cytokines and chemokines modulate intercellular communication with the immune cells, activating skin-resident and recruiting skin-infiltrating immune cells within the epidermis and dermis, thereby orchestrating the inflammatory response to radiation-induced tissue damage. The increased expression of specific chemoattractant chemokines leads to increased recruitment of neutrophils into the irradiated skin, where they release cytotoxic granules that are responsible for the exacerbation of an inflammatory state. Moreover, the importance of IL-17-expressing γδ-T cells to the radiation-induced hyperproliferation of keratinocytes was demonstrated, leading to reactive hyperplasia of the epidermis. Radiation-induced, reactive hyperproliferation of the keratinocytes disturbs the fine-tuned keratinization and cornification processes, leading to structural dysfunction of the epidermal barrier. In summary, in response to ionizing radiation, epidermal keratinocytes have important structural and immunoregulatory barrier functions in the skin, coordinating interacting immune responses to eliminate radiation-induced damage and to initiate the healing process. [ABSTRACT FROM AUTHOR]

[Display omitted] Healable electronic skins, an essential component for future soft robotics, implantable bioelectronics, and smart wearable systems, necessitate self-healable and pliable materials that exhibit functionality at intricate interfaces. Although a plethora of self-healable materials have been developed, the fabrication of highly conformal biocompatible functional materials on complex biological surfaces remains a formidable challenge. Inspired by regenerative properties of skin, we present the self-assembled transfer-printable liquid metal epidermis (SALME), which possesses autonomous self-healing capabilities at the oil–water interface. SALME comprises a layer of surfactant-grafted liquid metal nanodroplets that spontaneously assemble at the oil–water interface within a few seconds. This unique self-assembly property facilitates rapid restoration (<10 s) of SALME following mechanical damage. In addition to its self-healing ability, SALME exhibits excellent shear resistance and can be seamlessly transferred to arbitrary hydrophilic/hydrophobic curved surfaces. The transferred SALME effectively preserves submicron-scale surface textures on biological substrates, thus displaying tremendous potential for future epidermal bioelectronics. [ABSTRACT FROM AUTHOR]

Rapid increase in body surface area of growing zebrafish larvae (Danio rario) is partially accomplished by asynthetic fission of superficial epithelial cells (SECs) of the skin. There are two cycles of this atypical form of cell division which is unaccompanied by DNA replication; resulting in cells with a variable DNA content. Here, electron microscopy of basal epithelium cells that give rise to these SECs in zebrafish larvae shows aggregation of mitochondria around the nucleus and the formation of nucleus–mitochondria membrane contact sites. Membrane aggregates appear in the lumen of the nuclear envelope at these sites of membrane contact in some cells, suggesting lipid turnover in this vicinity. As the epithelial cells mature and stratify, the mitochondria are engulfed by extensions arising from the nuclear envelope. The mitochondrial outer membrane fragments and mitochondria fuse with the nuclear envelope and parts of the endoplasmic reticulum. Other organelles, including the Golgi apparatus, progressively localize to a central region of the cell and lose their integrity. Thus, asynthetic fission is accompanied by an atypical pattern of organelle destruction and a prelude to this is the formation of nucleus–mitochondria membrane contact sites. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate secondary intention wound healing in the horse's limbs when treated with the synthetic epidermis spray (Novacika®, Cohesive S.A.S, France) or with a standard bandaging technique. Methods: Six Standardbred mares were included in the study. Four 2.5 x 2.5 cm full-thickness skin wounds were created on each thoracic limb. Two wounds were located on the dorsoproximal aspect of the cannon bone and the other two at the dorsoproximal aspect of the fetlock. Six hours after creation, wounds were randomly treated with synthetic epidermis spray or standard bandaging. The wounds were assessed every 4 days by gross visual assessment and using a 3D imaging camera. Analysis was performed with a 3D imaging application. Results: Out of 46 wounds, 22 showed exuberant granulation tissue and were part of the standard bandaging group. Whether the wounds were treated with synthetic epidermis spray or standard bandaging, the time for healing was the same. Conclusion: The synthetic epidermis spray studied in this model has allowed healing without the production of exuberant granulation tissue but did not reduce the median wound healing time compared to a standard bandaging technique. The synthetic epidermis spray is potentially an interesting alternative for the management of secondary intention wound healing of superficial and non-infected distal limb wounds in adult horses on economical and practical aspects. However, all statistical inference (p-values especially) must be interpreted with caution, given the size of the sample. [ABSTRACT FROM AUTHOR]

Saponin extract of Sapindus mukorossi Gaertn. (Vietnamese: Bo hon) has been of major interest in bio-detergent studies. In this work, we investigated the extraction parameters of the pericarp of S. mukorossi and evaluated potential of the extract as a bio-detergent. The results showed that extraction with 70% EtOH at a temperature of 80 °C, a powder to solvent ratio of 1:10, and 180 min duration, yielded the highest level of total saponin. The extract had a moisture content of 9.32% and a pH of 4.27-4.32, making it suitable for storage and use as a detergent. It also showed good foaming properties, with the stability of the foams maintained for more than 2 hours. Additionally, the extract did not cause dermal irritation in rabbit skin and showed inhibitory action against Escherichia coli at a concentration of 100 mg/mL. These findings provide practical indications for the application of the extract of S. mukorossi as a bio-detergent. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the Krt14 gene, and indirect effects via pathogenic mutation in the KLHL24 gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. We report one severe case of EBS with mottled pigmentation arising from the Met119Thr pathogenic variant in KRT14, another case involving a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management. [ABSTRACT FROM AUTHOR]

A presence of tumor zones within biological tissues can be defined during the analysis of the skin surface temperature. This research is devoted to mathematical simulation of the time-dependent bio-heat transfer in tissues under a tumor influence. The one-dimensional partial differential equation of the Pennes model has been used for description of bio-heat transfer within the biological tissue with five layers, namely, epidermis, papillary dermis, reticular dermis, subcutaneous adipose tissue, and a muscle layer. The formulated boundary-value problem has been solved using the developed in-house computational code based on the finite difference schemes. The developed numerical algorithm has been verified using analytical and numerical solutions of other authors for the simpler test problem. As a result of this study, the temperature distributions have been obtained for the tissue in the presence of tumor zones in different layers of the skin. The influence of five layers of skin on the temperature distribution has been investigated, and the dependence for the skin surface temperature on the tumor zone location has been obtained. The obtained outcomes illustrate the effectiveness of this technique of cancer diagnosis and identify the optimal parameters for its application. Thus, this work represents an important step in the development of cancer diagnosis methods using thermography. The results obtained can be used to improve the accuracy of diagnosis and develop new treatment methods. [ABSTRACT FROM AUTHOR]

The microtubule motor dynein is critical for the assembly and positioning of mitotic spindles. In Caenorhabditis elegans , these dynein functions have been extensively studied in the early embryo but remain poorly explored in other developmental contexts. Here, we use a hypomorphic dynein mutant to investigate the motor's contribution to asymmetric stem cell–like divisions in the larval epidermis. Live imaging of seam cell divisions that precede formation of the seam syncytium shows that mutant cells properly assemble but frequently misorient their spindle. Misoriented divisions misplace daughter cells from the seam cell row, generate anucleate compartments due to aberrant cytokinesis, and disrupt asymmetric cell fate inheritance. Consequently, the seam becomes disorganized and populated with extra cells that have lost seam identity, leading to fatal epidermal rupture. We show that dynein orients the spindle through the cortical GOA-1Gα–LIN-5NuMA pathway by directing the migration of prophase centrosomes along the anterior–posterior axis. Spindle misorientation in the dynein mutant can be partially rescued by elongating cells, implying that dynein-dependent force generation and cell shape jointly promote correct asymmetric division of epithelial stem cells. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor environment is the place where the tumor resides implying that it might evolve in the role of disease progression, particularly in the phase of tumor dissemination. For cutaneous melanoma, in the early phase of disease advancement, the microenvironment is confined to the epidermal compartment since the dermo-epidermal basement membrane prevents dermal invasion. Here, poorly aggressive melanoma cells gain the aggressiveness necessary for disease progression. After dermo-epidermal membrane breakdown, the melanoma cells progressively lose keratinocyte control and engage in unusual partnerships mainly with dermal fibroblasts. Melanoma progression is a multistep evolution from a common melanocytic nevus through a radial superficial growth phase, the invasive vertical growth phase finally leading to metastatic dissemination into distant organs. Melanoma aggressiveness largely depends on the propensity to metastasize, which means the capacity to escape from the physiological microenvironment since tissue damage due to primary melanoma lesions is generally modest. Physiologically, epidermal melanocytes are attached to the basement membrane, and their adhesion/migration is under the control of surrounding keratinocytes. Thus, the epidermal compartment represents the first microenvironment responsible for melanoma spread. This complex process involves cell–cell contact and a broad range of secreted bioactive molecules. Invasion, or at the beginning of the microinvasion, implies the breakdown of the dermo-epidermal basement membrane followed by the migration of neoplastic melanocytic cells in the superficial papillary dermis. Correspondingly, several experimental evidences documented the structural and functional rearrangement of the entire tissue surrounding neoplasm that in some way reflects the atypia of tumor cells. Lastly, the microenvironment must support the proliferation and survival of melanocytes outside the normal epidermal–melanin units. This task presumably is mostly delegated to fibroblasts and ultimately to the self-autonomous capacity of melanoma cells. This review will discuss remodeling that occurs in the epidermis during melanoma formation as well as skin changes that occur independently of melanocytic hyperproliferation having possible pro-tumoral features. [ABSTRACT FROM AUTHOR]

Human skin comprises multiple hierarchical layers that perform various functions such as protection, sensing, and structural support. Developing electronic skin (E‐skin) with similar properties has broad implications in health monitoring, prosthetics, and soft robotics. While previous efforts have predominantly concentrated on sensory capabilities, this study introduces a hierarchical polymer system that not only structurally resembles the epidermis‐dermis bilayer structure of skin but also encompasses sensing functions. The system comprises a polymeric hydrogel, representing the "dermis", and a superimposed nanoporous polymer film, forming the "epidermis". Within the film, interconnected nanoparticles mimic the arrangement of interlocked corneocytes within the epidermis. The fabrication process employs a robust in situ interfacial precipitation polymerization of specific water‐soluble monomers that become insoluble during polymerization. This process yields a hybrid layer establishing a durable interface between the film and hydrogel. Beyond the structural mimicry, this hierarchical structure offers functionalities resembling human skin, which includes (1) water loss protection of hydrogel by tailoring the hydrophobicity of the upper polymer film; (2) tactile sensing capability via self‐powered triboelectric nanogenerators; (3) built‐in gold nanowire‐based resistive sensor toward temperature and pressure sensing. This hierarchical polymeric approach represents a potent strategy to replicate both the structure and functions of human skin in synthetic designs. [ABSTRACT FROM AUTHOR]

The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient's skin upon minimal mechanical stress. Causal for this severe condition are genetic mutations in genes, leading to the functional impairment, reduction, or absence of the encoded protein within the skin's basement membrane zone connecting the epidermis to the underlying dermis. The major burden of affected families justifies the development of long-lasting and curative therapies operating at the genomic level. The landscape of causal therapies for EB is steadily expanding due to recent breakthroughs in the gene therapy field, providing promising outcomes for patients suffering from this severe disease. Currently, two gene therapeutic approaches show promise for EB. The clinically more advanced gene replacement strategy was successfully applied in severe EB forms, leading to a ground-breaking in vivo gene therapy product named beremagene geperpavec (B-VEC) recently approved from the US Food and Drug Administration (FDA). In addition, the continuous innovations in both designer nucleases and gene editing technologies enable the efficient and potentially safe repair of mutations in EB in a potentially permanent manner, inspiring researchers in the field to define and reach new milestones in the therapy of EB. [ABSTRACT FROM AUTHOR]

Melanin, the most abundant skin chromophore, is produced by melanocytes and is one of the key components responsible for mediating the skin's response to ultraviolet radiation (UVR). Because of its antioxidant, radical scavenging, and broadband UV absorbing properties, melanin reduces the penetration of UVR into the nuclei of keratinocytes. Despite its long-established photoprotective role, there is evidence that melanin may also induce oxidative DNA damage in keratinocytes after UV exposure and therefore be involved in the development of melanoma. The present work aimed at evaluating the dependence of UV-induced DNA damage on melanin content and distribution, using reconstructed human epidermis (RHE) models. Tanned and light RHE were irradiated with a 233 nm UV-C LED source at 60 mJ/cm2 and a UV lamp at 3 mJ/cm2. Higher UV-mediated free radicals and DNA damage were detected in tanned RHE with significantly higher melanin content than in light RHE. The melanin distribution in the individual models can explain the lack of photoprotection. Fluorescence lifetime-based analysis and Fontana–Masson staining revealed a non-homogeneous distribution and absence of perinuclear melanin in the tanned RHE compared to the in vivo situation in humans. Extracellularly dispersed epidermal melanin interferes with photoprotection of the keratinocytes. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) is among the major air pollutants suspended in the atmosphere. PM2.5 has a particle size of 2.5 µm; it is known to cause inflammation, especially in the respiratory tract and skin. Since the skin acts a primary barrier against harmful environmental substances that may enter the body, it is highly exposed to PM2.5 present in the environment. However, the adverse health effects of PM2.5 exposure on human skin have not been accurately examined due to the lack of a system that exposes human epidermal tissue to the actual environmental concentration of PM2.5. In this study, we developed an air-liquid interface exposure system for exposing cultured human 3D epidermis and cornea to PM2.5 collected through cyclonic separation. PM2.5 suspension was nebulized in an acrylic chamber, and the resulting mist was pumped through a diffusion dryer into a glass exposure chamber. A particle counter was connected to the exposure chamber to continuously measure the spatial mass concentration of PM. Human 3D epidermis was cultured in the exposure chamber. Exposure of the human 3D epidermis to PM aerosol increased interleukin-8 release into the media around 50 µg/m3. Mass concentrations above 100 µg/m3 caused cell death. Furthermore, a human corneal model showed similar responses against PM2.5 exposure as 3D epidermis. The air-liquid interface exposure system developed in this study is considered useful for evaluating the health effects induced by environmental PM2.5 and can be used as an alternative to experiments involving actual human or animals. [ABSTRACT FROM AUTHOR]

Although various hair health medicines have been developed and are used today, additional safe and effective natural hair growth therapies still need to be developed. Nephelium lappaceum var. pallens (Hiern) Leenh. extract (NLE) reportedly exhibits anticancer, antidiabetic, and antioxidant effects, which could be linked to androgenic processes; however, there are no reports of its effects on testosterone (TS)-inhibited hair growth. The present study investigated the effects of NLE on TS-induced inhibition of hair growth in C57BL/6 mice and human follicular dermal papilla cells. Oral administration of NLE restored hair growth that was suppressed following subcutaneous injection of TS more effectively than finasteride, a drug used for treating hair loss. Histological analysis demonstrated that oral NLE administration increased the number and diameter of hair follicles in the dorsal skin of C57BL/6 mice. In addition, western blot and immunofluorescence assays showed that the oral NLE administration restored TS-induced suppression of cyclin D1, proliferating cell nuclear antigen, and loricrin expression in the skin cells of the mice. Finally, TS suppression of cell proliferation in human follicular dermal papilla cells was significantly reversed by NLE pretreatment. The results suggest that NLE is a promising nutraceutical for hair growth because it promotes hair growth in androgenetic alopecia-like models. [ABSTRACT FROM AUTHOR]

Prostaglandin E2 (PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2 secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin-Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors, we demonstrate that calcium transients in a single cell cause PGE2-mediated radial spread of PKA activation (RSPA) in neighboring cells. By in vivo imaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2 discharge in response to the increasing cytoplasmic Ca2+ concentrations. The cell density of MDCK cells correlated with the frequencies of calcium transients and the following RSPA. The extracellular signal-regulated kinase (ERK) activation also enhanced the frequency of RSPA in MDCK and in vivo. Thus, the PGE2 discharge is regulated temporally by calcium transients and ERK activity. [ABSTRACT FROM AUTHOR]

Background: Recognizing Langerhans cell histiocytosis (LCH) might be a challenge due to its rarity. Reflectance confocal microscopy (RCM) and dermoscopy were emergent promising non‐invasive technique as auxiliary tools in diagnosis of different skin conditions. However, the RCM and dermoscopic features of LCH had been less investigated. To reveal the common RCM and dermoscopic features of LCH. Materials and methods: Forty cases of LCH were retrospectively analyzed according to age, locations, clinical, RCM, and dermoscopic features from September 2016 to December 2022. To reveal the differences and common in clinical, RCM, and dermoscopic features that occur in different anatomic location. Results: In the study, sites of predilection include the trunk 31/40 (77.5%), extremity 21/40 (52.5%), face 14/40 (35%), scalp 11/40 (27.5%), vulvar 4/40 (10%), and nail 2/40 (5%). All LCHs had the common RCM features. There were significant differences in clinical and dermoscopic features for age and lesion anatomic site. The common dermoscopic features for scalp, face, trunk, and extremity were the erythematous scaly rash, purplish‐red globules or patches, scar‐like streaks with ectatic vessels. While the features for nail LCH were purpuric striae, onycholysis and purulent scaly rash, and the erosive erythematous plaque and purulent scaly rash for vulvar LCH. The common RCM features of all LCH showed a focal highly reflective dense image in the surface keratin layer, epidermis architectural disarray, obscuration of dermo‐epidermal junction, numerous polygonal, large, medium reflective, short dendrites cells in the epidermis, and dermis. All LCH involving the vulvar and nail did not manifest skin lesions. Conclusion: RCM and dermoscopy showed promising value for diagnosis and differentiation of LCH. [ABSTRACT FROM AUTHOR]

Background: Seborrheic keratosis (SK) is a skin condition affecting the keratinocytes. Although various treatment options are available, the need for a simpler topical treatment approach is unmet. Hydrogen peroxide (HP) acts by forming free radicals and initiates apoptosis in cells. Aims and Objectives: The aim of this study was to evaluate the safety and efficacy of 30% HP in SK. Materials and Methods: This study was conducted on patients attending the Dermatology, Venereology, and Leprology at MGM Hospital attached to Kakatiya Medical College, Warangal and Government Medical College Mahabubabad, Telangana, during the period from December 2019 to May 2021. In total, 80 adult patients with SKs were enrolled. The study was approved by the Research Ethics Committee of the MGM Hospital attached to Kakatiya Medical College. This is a prospective and interventional study. Eighty patients will be treated with 30% of HP topically. A photographic record of the pre- and post-treatment appearance of lesions was maintained. Physician's lesion assessment (PLA) score was evaluated on day 15th and 106th day after treatment. Local skin reactions (LSRs) were divided into mild, moderate, and severe categories. LSR was observed immediately after 2 weeks and 106 days of treatment. Results: Most of the patients were of middle to elderly age group. SK lesions were most common seen over the head and trunk. The dermatosis papulosa nigra variant was the most common. PLA 0 was observed by day 15 in some patients after application. Of 30% HP, faster healing rates were observed in lesions over the face, and middle aged. Conclusion: About 30% HP is a promising option for the treatment of SK. [ABSTRACT FROM AUTHOR]

The epidermis serves many vital roles, including protecting the body from external influences and healing eventual injuries. It is maintained by an incredibly complex and perfectly coordinated keratinization process. In this process, desquamation is essential for the differentiation of epidermal basal progenitor cells into enucleated corneocytes, which subsequently desquamate through programmed death. Numerous factors control keratinocyte differentiation: epidermal growth factor, transforming growth factor-α, keratinocyte growth factor, interleukins IL-1-β and IL-6, elevated vitamin A levels, and changes in Ca2+ concentration. The backbone of the keratinocyte transformation process from mitotically active basal cells into fully differentiated, enucleated corneocytes is the expression of specific proteins and the creation of a Ca2+ and pH gradient at precise locations within the epidermis. Skin keratinization disorders (histologically characterized predominantly by dyskeratosis, parakeratosis, and hyperkeratosis) may be categorized into three groups: defects in the α-helical rod pattern, defects outside the α-helical rod domain, and disorders of keratin-associated proteins. Understanding the process of keratinization is essential for the pathogenesis of many dermatological diseases because improper desquamation and epidermopoiesis/keratinization (due to genetic mutations of factors or due to immune pathological processes) can lead to various conditions (ichthyoses, palmoplantar keratodermas, psoriasis, pityriasis rubra pilaris, epidermolytic hyperkeratosis, and others). [ABSTRACT FROM AUTHOR]

Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology. [ABSTRACT FROM AUTHOR]

Encyclia is the second-largest genus in the neotropical subtribe Laeliinae (Orchidaceae) and has more than 150 species, which are characterized by fairly consistent flower morphology. Its taxonomy and species boundaries, however, seem to be still under debate. In the present study, we first examined the lip micromorphology of 61 species of Encyclia sensu stricto. We correlated our results with external flower morphology and phylogenetic analyses performed on a combined dataset that included both nuclear (ITS, Xdh, PhyC) and plastid markers (ycf1, rpl32, and trnL-trnF). Phylogenetic reconstruction showed that Encyclia sensu stricto species form a coherent, monophyletic group. However, it is difficult to determine the relationships between the different groups within one larger clade. The groups all form distinct lineages that evolved from a common ancestor. The UPGMA cluster analysis for the seven qualitative micromorphological features clearly divides the genus into two main groups, the larger of which is further subdivided into two subgroups. None of these, however, overlap with any of the phylogeographic units distinguished in previously published papers or in presented article. It is worth noting that the groups resulting from the UPGMA analysis cannot be defined by macromorphological features. The pattern of similarities between species, taking into account both macro- and micromorphological features, is eminently mosaic in nature, and only a multifaceted approach can explain this enigmatic group. [ABSTRACT FROM AUTHOR]

Nowadays, modern ultrasound machines and high-frequency transducers allow us to accurately assess the superficial soft tissues of the human body. In this sense, sonographic evaluation of the skin and related pathologies is progressively growing in the pertinent literature. To the best of our knowledge, a standardized sonographic protocol focused on the assessment of pathological skin scars is still lacking. As such, the main purpose of the present study was to propose a technical guide to sonographically assess skin scars in the daily practice of clinicians—starting from knowledge on their histopathological features. In order to standardize the ultrasound examination, a superficial-to-deep, layer-by-layer approach has been proposed to optimize its reproducibility and to promote a common language among the different healthcare providers. [ABSTRACT FROM AUTHOR]

In the skin, repeated incidents of ischemia followed by reperfusion can result in the breakdown of the skin and the formation of a pressure ulcer. Here we gently applied paired magnets to the backs of mice to cause ischemia for 1.5 h and then removed them to allow reperfusion. The sterile inflammatory response generated within 4 h causes a stage 1 pressure ulcer with an elevation of the gap junction protein Cx43 in the epidermis. If this process is repeated the insult will result in a more severe stage 2 pressure ulcer with a breakdown of the epidermis 2–3 days later. After a single pinch, the elevation of Cx43 in the epidermis is associated with the inflammatory response with an increased number of neutrophils, HMGB1 (marker of necrosis) and RIP3 (responsible for necroptosis). Delivering Cx43 specific antisense oligonucleotides sub-dermally after a single insult, was able to significantly reduce the elevation of epidermal Cx43 protein expression and reduce the number of neutrophils and prevent the elevation of HMGB1 and RIP3. In a double pinch model, the Cx43 antisense treatment was able to reduce the level of inflammation, necroptosis, and the extent of tissue damage and progression to an open wound. This approach may be useful in reducing the progression of stage 1 pressure ulcers to stage 2. [ABSTRACT FROM AUTHOR]

Keratinocytes are one of the primary cells affected by psoriasis inflammation. Our study aimed to delve deeper into their morphology, transcriptome, and epigenome changes in response to psoriasis-like inflammation. We created a novel cytokine mixture to mimic mild and severe psoriasis-like inflammatory conditions in cultured keratinocytes. Upon induction of inflammation, we observed that the keratinocytes exhibited a mesenchymal-like phenotype, further confirmed by increased VIM mRNA expression and results obtained from confocal microscopy. We performed RNA sequencing to achieve a more global view, revealing 858 and 6987 DEGs in mildly and severely inflamed keratinocytes, respectively. Surprisingly, we found that the transcriptome of mildly inflamed keratinocytes more closely mimicked that of the psoriatic epidermis transcriptome than the severely inflamed keratinocytes. Genes involved in the IL-17 pathway were a major contributor to the similarities of the transcriptomes between mildly inflamed KCs and psoriatic epidermis. Mild and severe inflammation led to the gene regulation of epigenetic modifiers such as HATs, HDACs, DNMTs, and TETs. Immunofluorescence staining revealed distinct 5-hmC patterns in inflamed versus control keratinocytes, and consistently low 5-mC intensity in both groups. However, the global DNA methylation assay detected a tendency of decreased 5-mC levels in inflamed keratinocytes versus controls. This study emphasizes how inflammation severity affects the transcriptomic similarity of keratinocytes to psoriatic epidermis and proves dynamic epigenetic regulation and adaptive morphological changes in inflamed keratinocytes. [ABSTRACT FROM AUTHOR]

Simple Summary: Epithelial ovarian cancer (EOC) is the fifth-leading cause of cancer-related deaths in women worldwide and the most lethal gynecologic malignancy. Seventy-five percent of patients are diagnosed at an advanced stage, accompanied by extensive pelvic and abdominal metastases, and thus have a poor prognosis. We first screened for critical genes in EOC in the GEO database. LLGL2 was upregulated in ovarian cancer tissue, while low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients, implying that LLGL2 may function as a tumor suppressor gene. Our data demonstrated that overexpression of LLGL2 inhibited the ovarian cancer cell migration and invasion abilities in vivo and in vitro. Mechanistically, LLGL2 altered the intracellular localization and function of ACTN1 by interacting with ACTN1 and regulating cytoskeleton remodeling to inhibit the invasion and metastasis of ovarian cancer cells. Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells. [ABSTRACT FROM AUTHOR]

The uc.291 transcript controls keratinocytes differentiation by physical interaction with ACTL6A and subsequent induction of transcription of the genes belonging to the epidermal differentiation complex (EDC). Uc.291 is also implicated in the dedifferentiation phenotype seen in poorly differentiated cutaneous squamous cell carcinomas. Here, we would like to investigate the contribution of uc.291 to the unbalanced differentiation state of keratinocytes observed in hyperproliferative skin disorders, e. g., psoriasis. Psoriasis is a multifactorial inflammatory disease, caused by alteration of keratinocytes homeostasis. The imbalanced differentiation state, triggered by the infiltration of immune cells, represents one of the events responsible for this pathology. In the present work, we explore the role of uc.291 and its interactor ACTL6A in psoriasis skin, using quantitative real-time PCR (RT-qPCR), immunohistochemistry and bioinformatic analysis of publicly available datasets. Our data suggest that the expression of the uc.291 and of EDC genes loricrin and filaggrin (LOR, FLG) is reduced in lesional skin compared to nonlesional skin of psoriatic patients; conversely, the mRNA and protein level of ACTL6A are up-regulated. Furthermore, we provide evidence that the expression of uc.291, FLG and LOR is reduced, while ACTL6A mRNA is up-regulated, in an in vitro psoriasis-like model obtained by treating differentiated keratinocytes with interleukin 22 (IL-22). Furthermore, analysis of a publicly available dataset of human epidermal keratinocytes treated with IL-22 (GSE7216) confirmed our in vitro results. Taken together, our data reveal a novel role of uc.291 and its functional axis with ACTL6A in psoriasis disorder and a proof of concept that biological inhibition of this molecular axis could have a potential pharmacological effect against psoriasis and, in general, in skin diseases with a suppressed differentiation programme. [ABSTRACT FROM AUTHOR]

Triclosan is an anti-microbial chemical incorporated into products that are applied to the skin of healthcare workers. Exposure to triclosan has previously been shown to be associated with allergic disease in humans and impact the immune responses in animal models. Additionally, studies have shown that exposure to triclosan dermally activates the NLRP3 inflammasome and disrupts the skin barrier integrity in mice. The skin is the largest organ of the body and plays an important role as a physical barrier and regulator of the immune system. Alterations in the barrier and immune regulatory functions of the skin have been demonstrated to increase the risk of sensitization and development of allergic disease. In this study, the impact of triclosan exposure on the skin barrier and keratinocyte function was investigated using a model of reconstructed human epidermis. The apical surface of reconstructed human epidermis was exposed to triclosan (0.05-0.2%) once for 6, 24, or 48 h or daily for 5 consecutive days. Exposure to triclosan increased epidermal permeability and altered the expression of genes involved in formation of the skin barrier. Additionally, exposure to triclosan altered the expression patterns of several cytokines and growth factors. Together, these results suggest that exposure to triclosan impacts skin barrier integrity and function of human keratinocytes and suggests that these alterations may impact immune regulation. [ABSTRACT FROM AUTHOR]