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Elevated amounts of reactive oxygen species (ROS) including hydrogen peroxide (H 2 O 2 ) are observed in the epidermis in different skin disorders. Thus, epidermal sensing of H 2 O 2 should be useful to monitor the progression of skin pathologies. We have evaluated epidermal sensing of H 2 O 2 in vitro, by visualising H 2 O 2 permeation through the skin. Skin membranes were mounted in Franz cells, and a suspension of Prussian white microparticles was deposited on the stratum corneum face of the skin. Upon H 2 O 2 permeation, Prussian white was oxidised to Prussian blue, resulting in a pattern of blue dots. Comparison of skin surface images with the dot patterns revealed that about 74% of the blue dots were associated with hair shafts. The degree of the Prussian white to Prussian blue conversion strongly correlated with the reciprocal resistance of the skin membranes. Together, the results demonstrate that hair follicles are the major pathways of H 2 O 2 transdermal penetration. The study recommends that the development of H 2 O 2 monitoring on skin should aim for pathway-specific epidermal sensing, allowing micrometre resolution to detect and quantify this ROS biomarker at hair follicles.Graphical abstract.

To better understand the influence of ultraviolet (UV) irradiation on the initial steps of skin carcinogenesis, we examine patches of labeled keratinocytes as a proxy for clones in the interfollicular epidermis (IFE) and measure their size variation upon UVB irradiation. Multicolor lineage tracing reveals that in chronically irradiated skin, patches near hair follicles (HFs) increase in size, whereas those far from follicles do not change. This is explained by proliferation of basal epidermal cells within 60 μm of HF openings. Upon interruption of UVB, patch size near HFs regresses significantly. These anatomical differences in proliferative behavior have significant consequences for the cell of origin of basal cell carcinomas (BCCs). Indeed, a UV-inducible murine BCC model shows that BCC patches are more frequent, larger, and more invasive near HFs. These findings have major implications for the prevention of field cancerization in the epidermis., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Upon wounding, multiple stem cell populations in the hair follicle (HF) and interfollicular epidermis (IFE) converge at the site of injury. Although these cells can contribute permanently to the regenerating epithelium, it remains unclear whether these contributions vary among cells originating from diverse compartments in the skin. By comparing the fates of several keratinocyte lineages, we observed here an initial decrease in both HF- and IFE-derived cells within the transient acanthotic layers of the regenerating epithelium. At the same time, the relative abundance of early-arriving IFE-derived cells specifically in the wound basal layer declined as later-arriving HF-derived cells entered the site of injury. Although laggard bulge-derived cells were typically constrained at the regenerative periphery, these cells persisted in the wound basal layer. Finally, suppressing Notch enabled IFE-derived cells to out-compete HF-derived cells. Taken together, these findings indicate that IFE-, HF- and bulge-derived cells make distinct contributions to regeneration over time. Furthermore, we speculate that extrinsic, non-genetic factors such as spatial constraint, distance from the wound, and basal versus suprabasal position may largely determine whether a cell ultimately persists.

Objective: Outer root sheath (ORS) cells of human hair follicles are a readily available, non-invasive source of keratinocytes for epidermis reconstruction. The aim of this study was to characterize a model of epidermis reconstructed from ORS cells (ORS-derived model) and to evaluate its reproducibility, in comparison with native human skin and two marketed reconstructed skin models (model A, Episkin(®) and model B, Skinethic(®) )., Methods: Cell morphology and tissue architecture of the three models were analysed histologically and proliferation and differentiation marker expression by immunohistochemistry and mRNA quantification., Results: All models displayed the same general epidermal architecture as native epidermis, but with a thicker stratum corneum in models A and B. Compared with native epidermis, Ki67 was correctly localized in epidermal basal cells in all models, as K10 in suprabasal layers. In all skin models, transglutaminase 1 (TGM1) was prematurely expressed in suprabasal layers. However, this expression was only observed from the upper stratum spinosum in the ORS-derived model. In this model, filaggrin and loricrin were correctly located in the stratum granulosum. Filaggrin, involucrin, loricrin and TGM1 mRNAs (markers of keratinocyte terminal differentiation) were transcriptionally expressed in all models. In the ORS-derived model, transcriptional expression level was similar to that of native skin., Conclusion: ORS cell-based reconstructed epidermis is a valid and reproducible model for human epidermis and it may be used to evaluate the effects of active substances and cosmetic formulations., (© 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Background: A precise balance between the proliferation and differentiation of epidermal progenitors is required to achieve the barrier function during the development of epidermis. During the entire process of skin development, the newly formed basal layer cells divide, differentiate, and migrate outward to the surface of the skin, which is tightly regulated by a series of events related to cell cycle progression. The CRL4DTL complex (Cullin 4 RING ligase, in association with the substrate receptor DTL) has long emerged as a master regulator in various cellular processes, which mediates the degradation of key cell cycle proteins. However, the roles of DTL in regulating epidermal morphogenesis during skin development remain unclear. Results: We showed that DTL deficiency in epidermal progenitor cells leads to defects in epidermal stratification and loss of hair follicles accompanied by reduced epidermal progenitor cells and disturbed cell cycle progression during skin development. Transcriptome analysis revealed that p53 pathway is activated in DTL‐depleted epidermal progenitor cells. The apoptosis of epidermal cells showed in DTL deficiency mice is rescued by the absence of p53, but the proliferation and differentiation defects were p53‐independent. Conclusion: Our findings indicate that DTL plays a vital role in epidermal malformation during skin development. Key Findings: Loss of DTL in developing skin leads to defects in epidermal stratification.DTL prevents activation of p53 pathway in developing epidermal progenitors.DTL regulates the proliferation and differentiation of epidermal progenitor cells through a p53‐independent way. [ABSTRACT FROM AUTHOR]

Terminal differentiation of epithelial cells is critical for the barrier function of the skin, the growth of skin appendages, such as hair and nails, and the development of the skin of amniotes. Here, we present the hypothesis that the differentiation of cells in the embryonic periderm shares characteristic features with the differentiation of epithelial cells that support the morphogenesis of cornified skin appendages during postnatal life. The periderm prevents aberrant fusion of adjacent epithelial sites during early skin development. It is shed off when keratinocytes of the epidermis form the cornified layer, the stratum corneum. A similar role is played by epithelia that ensheath cornifying skin appendages until they disintegrate to allow the separation of the mature part of the skin appendage from the adjacent tissue. These epithelia, exemplified by the inner root sheath of hair follicles and the epithelia close to the free edge of nails or claws, are referred to as scaffolding epithelia. The periderm and scaffolding epithelia are similar with regard to their transient functions in separating tissues and the conserved expression of trichohyalin and trichohyalin-like genes in mammals and birds. Thus, we propose that parts of the peridermal differentiation program were coopted to a new postnatal function during the evolution of cornified skin appendages in amniotes. [Display omitted] • The periderm prevents adhesion of adjacent stratified epithelia during development • Cornified skin appendages require scaffolding epithelia for morphogenesis • The inner root sheath of the hair follicle is an example a scaffolding epithelium • Scaffoldin is a marker of the periderm and scaffolding epithelia of birds • Trichohyalin is the mammalian homolog of scaffoldin [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]

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: Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents. The radiation destroys the repair mechanism, resulting in delayed or prolonged wound healing. It still lacks an effective therapeutic strategy currently. OBJECTIVE: To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury, which are designed to be antibacteria, promoted healing and analgesics. METHODS: Using levofloxacin, fibroin and lidocaine hydrochloride as raw materials, 3D bioprinting technology was applied to prepare the multifunctional wound dressing. (1) The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and incubated at 37 °C overnight to detect the diameter of the antibacterial zone. (2) 40 Kunming mice were randomly divided into trauma group, radiation and trauma model group, treatment group and positive drug group, with 10 mice in each group. Mice in the radiation and trauma model group, treatment group and positive drug group were irradiated by 60Co gamma rays. After 1 hour of radiation, a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups. Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group. Trethanolamine cream was applied to the wounds of the positive drug group. Multifunctional dressing was applied to the wounds of the treatment group. The dressing was changed every 2 days, and the treatment was continued for 14 days. Wound healing rate and serum interleukin-6 level were measured at 3, 7 and 14 days after wound modeling. 14 days after the wound modeling, the skin tissue of the wound was obtained and received hematoxylin-eosin staining, Masson staining and cytokeratin-14 immunohistochemical staining. RESULTS AND CONCLUSION: (1) 3D-printed multifunctional wound dressing had good antibacterial activity. The antibacterial zone diameters against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were (4.15±0.09), (4.18±0.23) and (4.35±0.13) cm, respectively. (2) With the extension of modeling time, the wound healed gradually. The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3, 7 and 14 days after modeling (P < 0.01, P < 0.001). The wound healing rate of the treatment group was higher than that of the positive drug group. With the extension of modeling time, the serum interleukin level of mice increased first and then decreased. The serum interleukin level in the treatment group at 3, 7 and 14 days after modeling was lower than that in the radiation and trauma model group. Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group, and the dermal collagen fibers were densely arranged. The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group. In the treatment group, normal skin mucosal tissue was observed, the epidermis was arranged closely, and the sweat glands, hair follicles and dermal collagen fibers were arranged regularly. In the positive drug group, the arrangement of epidermal layer was tight, and the arrangement of sweat glands, hair follicles and dermal collagen fibers was regular. Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups (P < 0.01, P < 0.001). (3) The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia, anti-infection and promoting healing. [ABSTRACT FROM AUTHOR]

The skin is the largest organ in the human body and serves various functions, including mechanical protection and mechanosensation. Yet, even though skin's biomechanics are attributed to two main layers—epidermis and dermis—computational models have often treated this tissue as a thin homogeneous material or, when considering multiple layers, have ignored the most prominent heterogeneities of skin seen at the mesoscale. Here, we create finite element models of representative volume elements (RVEs) of skin, including the three-dimensional variation of the interface between the epidermis and dermis as well as considering the presence of hair follicles. The sinusoidal interface, which approximates the anatomical features known as Rete ridges, does not affect the homogenized mechanical response of the RVE but contributes to stress concentration, particularly at the valleys of the Rete ridges. The stress profile is three-dimensional due to the skin's anisotropy, leading to high-stress bands connecting the valleys of the Rete ridges through one type of saddle point. The peaks of the Rete ridges and the other class of saddle points of the sinusoidal surface form a second set of low-stress bands under equi-biaxial loading. Another prominent feature of the heterogeneous stress pattern is a switch in the stress jump across the interface, which becomes lower with respect to the flat interface at increasing deformations. These features are seen in both tension and shear loading. The RVE with the hair follicle showed strains concentrating at the epidermis adjacent to the hair follicle, the epithelial tissue surrounding the hair right below the epidermis, and the bulb or base region of the hair follicle. The regions of strain concentration near the hair follicle in equi-biaxial and shear loading align with the presence of distinct mechanoreceptors in the skin, except for the bulb or base region. This study highlights the importance of skin heterogeneities, particularly its potential mechanophysiological role in the sense of touch and the prevention of skin delamination. [ABSTRACT FROM AUTHOR]

Skin perceives and reacts to external mechanical forces to create resistance against the external environment. Excessive or inappropriate stimuli of pressure may lead to cellular alterations of the skin and the development of both benign and malignant skin disorders. We conducted a comprehensive literature review to delve into the pressure-induced and aggravated skin disorders and their underlying pressure-related mechanisms. Dysregulated mechanical responses of the skin give rise to local inflammation, ischemia, necrosis, proliferation, hyperkeratosis, impaired regeneration, atrophy, or other injurious reactions, resulting in various disease entities. The use of personal devices, activities, occupations, weight bearing, and even unintentional object contact and postures are potential scenarios that account for the development of pressure-related skin disorders. The spectrum of these skin disorders may involve the epidermis (keratinocytes and melanocytes), hair follicles, eccrine glands, nail apparatuses, dermis (fibroblasts, mast cells, and vasculature), subcutis, and fascia. Clarifying the clinical context of each patient and recognizing how pressure at the cellular and tissue levels leads to skin lesions can enhance our comprehension of pressure-related skin disorders to attain better management. [ABSTRACT FROM AUTHOR]

The mammalian skin and its appendages depend on tightly coordinated differentiation of epithelial cells. Epidermal growth factor receptor (EGFR) pathway substrate 8 (EPS8) like 1 (EPS8L1) is enriched in the epidermis among human tissues and has also been detected in the epidermis of lizards. Here, we show by the analysis of single-cell RNA-sequencing data that EPS8L1 mRNA is co-expressed with filaggrin and loricrin in terminally differentiated human epidermal keratinocytes. Comparative genomics indicated that EPS8L1 is conserved in all main clades of mammals, whereas the orthologous gene has been lost in birds. Using a polyclonal antibody against EPS8L1, we performed an immunohistochemical screening of skin from diverse mammalian species and immuno-electron microscopy of human skin. EPS8L1 was detected predominantly in the granular layer of the epidermis in monotremes, marsupial, and placental mammals. The labeling was partly associated with cell membranes, and it was evident along the perimeter of keratinocytes at the transition with the cornified layer of the epidermis, similar to involucrin distribution. Basal, spinous, and the fully mature cornified layers lacked immunolabeling of EPS8L1. In addition to the epidermis, the hair follicle inner root sheath (IRS) was immunolabeled. Both epidermal granular layer and IRS contribute to the barrier function of the skin, suggesting that EPS8L1 is involved in the regulation of these barriers. [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]

The present study examined whether sweat glands are present in the skin of sub-Antarctic fur seals, Arctocephalus tropicalis, using standard histological procedures and light microscopy. Aspects of the microanatomy and histology of skin were described to elucidate structure and function. Sweat glands were present both in the furred areas of the body trunk, as well as in naked skin areas of the flippers. The density of the apocrine sweat glands appeared higher in fur-covered areas than in naked areas, while the size of sweat glands was similar amongst naked and fur-covered skin. The superficial position of sweat glands in the dermis of naked skin areas and the large, coiled, tubular nature of the secretory portion seem to indicate sweat gland activity in contrast to the deep lying, narrow sweat glands in fur-covered areas. [ABSTRACT FROM AUTHOR]

The planar cell polarity (PCP) pathway collectively orients cells with respect to a body axis. Hair follicles of the murine epidermis provide a striking readout of PCP activity in their uniform alignment across the skin. Here, we characterize, from the molecular to tissue-scale, PCP establishment in the rosette fancy mouse, a natural variant with posterior-specific whorls in its fur, to understand how epidermal polarity is coordinated across the tissue. We find that rosette hair follicles emerge with reversed orientations specifically in the posterior region, creating a mirror image of epidermal polarity. The rosette trait is associated with a missense mutation in the core PCP gene Fzd6, which alters a consensus site for N-linked glycosylation, inhibiting its membrane localization. Unexpectedly, the Fzd6 trafficking defect does not block asymmetric localization of the other PCP proteins. Rather, the normally uniform axis of PCP asymmetry rotates where the PCP-directed cell movements that orient follicles are reversed, suggesting the PCP axis rotates 180°. Collectively, our multiscale analysis of epidermal polarity reveals PCP patterning can be regionally decoupled to produce posterior whorls in the rosette fancy mouse. [ABSTRACT FROM AUTHOR]

Purpose: In animals, the appropriate levels of Enhancer of zeste homolog 2 (EZH2), a well-established epigenetic regulator, are essential for the embryonic development of skin and appendages. We aimed to explore the EZH2 expression patterns in the skin of human fetuses and compare them with adults. Materials and Methods: We performed EZH2 immunohistochemical staining in skin samples from the scalp region of 67 fetuses and from the farthest surgical margin of the lip wedge resection, where no lesions were found, of 23 adults. EZH2 scores were evaluated according to the literature. Results: Epidermal (r = - 0.528), dermal (rs = - 0.509), and hair follicle (r = - 0.576) EZH2 scores were inversely correlated with gestational age. Epidermal and hair follicle EZH2 scores were significantly higher in adults compared to fetuses. There were significant and positive correlations between epidermal, dermal, and hair follicle EZH2 scores among fetuses and adults. Conclusion: Lower levels of EZH2 may be necessary for final cutaneous differentiation and maturation before birth. Our findings may have a therapeutic impact on cutaneous disorders with differentiation defects, chronic wounds, and alopecias. [ABSTRACT FROM AUTHOR]

All living jawed vertebrates possess teeth or did so ancestrally. Integumental surface also includes the cornea. Conversely, no other anatomical feature differentiates the clades so readily as skin appendages do, multicellular glands in amphibians, hair follicle/gland complexes in mammals, feathers in birds, and the different types of scales. Tooth-like scales are characteristic of chondrichthyans, while mineralized dermal scales are characteristic of bony fishes. Corneous epidermal scales might have appeared twice, in squamates, and on feet in avian lineages, but posteriorly to feathers. In contrast to the other skin appendages, the origin of multicellular glands of amphibians has never been addressed. In the seventies, pioneering dermal–epidermal recombination between chick, mouse and lizard embryos showed that: (1) the clade type of the appendage is determined by the epidermis; (2) their morphogenesis requires two groups of dermal messages, first for primordia formation, second for appendage final architecture; (3) the early messages were conserved during amniotes evolution. Molecular biology studies that have identified the involved pathways, extending those data to teeth and dermal scales, suggest that the different vertebrate skin appendages evolved in parallel from a shared placode/dermal cells unit, present in a common toothed ancestor, c.a. 420 mya. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a poor prognosis and an unknown cell of origin. Proffered cells of origin include epithelial stem cells of the hair follicle or interfollicular epidermis, dermal stem cells and pro/pre‐ or pre‐B cells. MCC has also been proposed to have more than one cell of origin and indeed to represent more than one type of carcinoma, currently grouped together due to phenotypic similarities. We explored the heterogeneous nature of MCC by studying the most variably expressed genes with the goal of identifying gene expression patterns that are either clinically relevant or have implications regarding the cell(s) of origin. We performed RNA sequencing on primary tumor samples from 102 patients and identified the top 200 most variably expressed genes. These genes and the tumor samples were hierarchically clustered based on their expression. The functions of three gene clusters exhibiting clearly divergent expression between samples were studied by cross‐referencing the lists of genes with online databases. High expression of a gene cluster related to embryonic developmental processes and low expression of a gene cluster related to neuroendocrine processes distinguished Merkel cell polyomavirus (MCPyV)‐negative tumors from MCPyV‐positive tumors. Furthermore, two prognostically relevant subgroups of MCPyV‐positive MCC were identified based on dichotomic expression of genes related to epidermal structures and processes. We identified three distinct molecular subgroups of MCC with prognostic relevance. We propose that the dichotomic expression of epidermis‐related genes might reflect both an epidermal and a nonepidermal origin for MCPyV‐positive MCC. [ABSTRACT FROM AUTHOR]

In this review, the histological structures of the skin are summarized for fundamental knowledge for toxicological assessment. The skin is composed of epidermis, dermis, subcutaneous tissue, and associated adnexa. In the epidermis, keratinocytes comprise four layers, and three other cell types, besides keratinocytes, play various roles. Epidermal thickness varies with species and body site. In addition, it can be affected by tissue preparation procedures, which can render toxicity assessments difficult. Bulge stem cells are the origin of sebaceous glands, epidermal basal layer, and hair follicle formation, and they play an important role in the maintenance of the basic structure of the skin. Stem cells and appendages formed from stem cells sometimes become toxic targets, and it is useful to study the origins of the hair follicle/hair cycle to interpret their toxicity. Irritant contact dermatitis and allergic contact dermatitis are the main adverse reactions in topical application studies. The mechanism involves direct chemical irritation of the skin, and histologically, epidermal necrosis and accompanying inflammatory cell infiltration. In allergic contact dermatitis, an inflammatory reaction and intercellular or intracellular edema, histologically represented by lymphocytic infiltration of the epidermis and dermis, are observed. Regional and species differences exist in the dermal absorption of compounds, and differences in the thickness of the stratum corneum substantially contribute to these differences. Learning the basic structures, functions, and possible artifacts will contribute to the evaluation of skin toxicity by topical and systemic applications. [ABSTRACT FROM AUTHOR]

Background: Transcription factor lymphoid enhancer‐binding factor 1 (LEF1) is a downstream mediator of the Wnt/β‐catenin signaling pathway. It is expressed in dermal papilla and surrounding cells in the hair follicle, promoting cell proliferation, and differentiation. Results: Here, we report that LEF1 is also expressed all through the hair cycle in the terminal Schwann cells (TSCs), a component of the lanceolate complex located at the isthmus. The timing of LEF1 appearance at the isthmus coincides with that of hair follicle innervation. LEF1 is not found at the isthmus in the aberrant hair follicles in nude mice. Instead, LEF1 in TSCs is found in the de novo hair follicles reconstituted on nude mice by stem cells chamber graft assay. Cutaneous denervation experiment demonstrates that the LEF1 expression in TSCs is independent of nerve endings. At last, LEF1 expression in the interfollicular epidermis during the early stage of skin development is significantly suppressed in transgenic mice with T‐cell factor 3 (TCF3) overexpression. Conclusion: We reveal the expression dynamics of LEF1 in skin during development and hair cycle. LEF1 expression in TSCs indicates that the LEF1/Wnt signal might help to establish a niche at the isthmus region for the lanceolate complex, the bulge stem cells and other neighboring cells. Key Findings: LEF1 is expressed in the terminal Schwann cells (TSCs) surrounding the hair follicle isthmus.LEF1 expression in TSCs is independent of nerve endings.LEF1 expression in the interfollicular epidermis is suppressed by overexpression of TCF3.LEF1+ TSCs might constitute a Wnt‐active niche at the isthmus region. [ABSTRACT FROM AUTHOR]

The skin is the largest organ of the body and consists of an epidermis, dermis and subcutaneous adipose tissue. The skin surface area is often stated to be about 1.8 to 2 m2 and represents our interface with the environment; however, when one considers that microorganisms live in the hair follicles and can enter sweat ducts, the area that interacts with this aspect of the environment becomes about 25–30 m2. Although all layers of the skin, including the adipose tissue, participate in antimicrobial defense, this review will focus mainly on the role of the antimicrobial factors in the epidermis and at the skin surface. The outermost layer of the epidermis, the stratum corneum, is physically tough and chemically inert which protects against numerous environmental stresses. It provides a permeability barrier which is attributable to lipids in the intercellular spaces between the corneocytes. In addition to the permeability barrier, there is an innate antimicrobial barrier at the skin surface which involves antimicrobial lipids, peptides and proteins. The skin surface has a low surface pH and is poor in certain nutrients, which limits the range of microorganisms that can survive there. Melanin and trans-urocanic acid provide protection from UV radiation, and Langerhans cells in the epidermis are poised to monitor the local environment and to trigger an immune response as needed. Each of these protective barriers will be discussed. [ABSTRACT FROM AUTHOR]

The cross-linking of structural proteins is critical for establishing the mechanical stability of the epithelial compartments of the skin and skin appendages. The introduction of isopeptide bonds between glutamine and lysine residues depends on catalysis by transglutaminases and represents the main protein cross-linking mechanism besides the formation of disulfide bonds. Here, we used a fluorescent labeling protocol to localize the activity of transglutaminases on thin sections of the integument and its appendages in mammals and birds. In human tissues, transglutaminase activity was detected in the granular layer of the epidermis, suprabasal layers of the gingival epithelium, the duct of sweat glands, hair follicles and the nail matrix. In the skin appendages of chickens, transglutaminase activity was present in the claw matrix, the feather follicle sheath, the feather sheath and in differentiating keratinocytes of feather barb ridges. During chicken embryogenesis, active transglutaminase was found in the cornifying epidermis, the periderm and the subperiderm. Transglutaminase activity was also detected in the filiform papillae on the tongue of mice and in conical papillae on the tongue of chickens. In summary, our study reveals that transglutaminase activities are widely distributed in integumentary structures and suggests that transglutamination contributes to the cornification of hard skin appendages such as nails and feathers. [ABSTRACT FROM AUTHOR]

Copyright of Vlaams Diergeneeskundig Tijdschrift is the property of Ghent University, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Skin is largely composed of an epidermis that overlies a supporting dermis. Recent advancements in our understanding of how diverse groups of dermal fibroblasts regulate epidermal and hair follicle growth and differentiation have been fueled by tools capable of resolving molecular heterogeneity at a single-cell level. Fibroblast heterogeneity can be traced back to their developmental origin before their segregation into spatially distinct fibroblast subtypes. The mechanisms that drive this lineage diversification during development are being unraveled, with studies showing that both large- and small-scale positional signals play important roles during dermal development. Here, we first delineate what is known about the origins of the dermis and the central role of Wnt/ß-catenin signaling in its specification across anatomical locations. We then discuss how one of the first morphologically recognizable fibroblast subtypes, the hair follicle dermal condensate lineage, emerges. Leveraging the natural variation of skin and its appendages between species and between different anatomical locations, these collective studies have identified shared and divergent factors that contribute to the extraordinary diversity of skin. [ABSTRACT FROM AUTHOR]

A definite identification of epidermal stem cells is not known and the mechanism of epidermal differentiation is not fully understood. Toward both of these quests, considerable information is available from the research on lineage tracing and clonal growth analysis in the basal layer of the epidermis, on the hair follicle and the interfollicular epidermal stem cells, and on Wnt signaling along with its role in the developmental patterning and cell differentiation. In this paper, literature on the aforementioned research has been collated and analyzed. In addition, models of the basal layer cellular composition and the epidermal differentiation have been presented. [ABSTRACT FROM AUTHOR]

Xenotransplantation of human skin to mice with immunodeficiency is one of the most adequate models for studying the mechanisms of regeneration and, thus, it opens up broad prospects for research in the fields of modern cell biology and regenerative medicine. The full-thickness skin strip xenotransplantation model developed in our laboratory allowed us to describe the dynamics of restoration of the human dermis and subcutaneous adipose tissue. Expression and activation of YAP1 protein during regeneration of epidermis, hair follicles (HF), and papillary dermis (PD) was investigated, on the basis of which assumptions were made about the nature of some cellular and molecular processes during the regeneration of human skin. [ABSTRACT FROM AUTHOR]

Hair follicles regenerate periodically by spontaneously undergoing cycles of growth, regression, and relative quiescence. During the hair cycle, follicle stem cells residing in a specialized niche remain quiescent, and they are stimulated to proliferate throughout the growth phase of the hair follicle. Although cell cycle regulators play a prominent role during the activation of hair follicle stem cells, the identity and the role of these regulators have not been confirmed. Herein, we reported that stem cells located in the bulge region of the HF (BuSCs) express high levels of cyclin‐dependent kinase 4 (CDK4) through the quiescent phase of the hair cycle. Using gain‐ and loss‐of‐function studies, we have determined that the CDK4 protein level affects the number of BuSCs. Transgenic expression of CDK4 in the bulge region of the hair follicles reduces the number of BuSCs, whereas CDK4 ablation resulted in an increasing number of BuSCs. These results suggest that deregulation of CDK4 protein levels contributes to distorting the self‐renewal/proliferation balance and, in turn, altering the number of BuSCs. [ABSTRACT FROM AUTHOR]

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To establish the optimal amount of nutrients in the diets required for the pregnant sheep, in the conditions of the distant-mountain keeping of the North Caucasus in 2018, after tupping, 120 Tushin ewes were selected for the third lambing, which were divided into four groups 30 heads each. Ewes of the control group received a food ration prepared in accordance with the standards of the All-Russian Research Institute of Animal Husbandry (VIZH) (2003). The ration of the second, third and fourth groups of ewes was increased in total nutritional value by 10%, 15% and 20%, respectively, compared with the diet of the control group. The study of skin structure was carried out using prepa-rations made from pregnant ewe skin samples taken from five heads from each group. It was found that, depending on the season of the year and severity, the skin of the experimental ewes underwent significant changes: the thickness of the skin and its layers decreased, the activity of sweat and se-baceous glands decreased, the hair follicles and the diameter of the collagen fiber bundles de-creased in size. The greatest decrease in these parameters occurred in the skin of ewes that were pregnant and received a diet prepared in accordance with the VIZH standards (17.1%). Similar chang-es occurred in the thickness of the epidermis, pilar and reticular layers. The smallest decrease in the thickness of the skin and its layers occurred in the group of ewes under high feeding conditions. The study of horizontal sections of the skin of the experimental groups of ewes showed that the level of feeding during the lambing period did not affect the number of follicles in the hair group. In the groups of ewes that received an increased level of feeding, the number of follicles per unit of skin area decreased by 8.0-13.9%, which is associated with an increase in body condition and, according-ly, an increase in skin area.

The current case report presents a case of non‐thymoma‐associated exfoliative dermatitis in an 8‐year‐old European Shorthair female cat. The animal displayed extensive alopecia and excessive peeling of the epidermis. There were no other apparent disorders, except for the skin lesions. Roentgenographic and sonographic examinations, complete blood count and blood serum chemistry analyses, and skin biopsy were performed. The histopathological investigation revealed hyperkeratosis of the epidermis and the infiltration of lymphocytes and macrophages at the dermal‐epidermal junction around the hair follicles and sebaceous glands. Moreover, edema of the basal layer and melanin migration from the epidermis to the dermis were observed. The patient underwent treatment with immunosuppressive doses of prednisolone, antibiotic therapy, and baths in anti‐seborrheic shampoos and displayed resolution. However, recurrence was observed after one month. Consequently, the patient received cyclosporine A, in addition to the aforementioned treatment and the lesions resolved without relapse. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) are a source of nutrients and growth factors, which support the proliferation and growth of keratinocytes as well as promoting the induction of new hair follicles and maintenance of hair growth. The protection from reactive oxygen species (ROS) and the promotion of angiogenesis are considered two of the basal mechanisms to preserve the growth of the hair follicle. In this study, a noncrosslinked hyaluronic acid (HA) filler (HYDRO DELUXE BIO, Matex Lab S.p.A.) containing several amino acids was tested with in vitro assays on human follicle dermal papilla cells (HFDPCs). The experiments were carried out to investigate the possible protection against oxidative stress and the ability to increase the vascular endothelial growth factor (VEGF) release. The results demonstrated the restoration of cell viability against UVB-induced cytotoxicity and an increase in the VEGF secretion. These data demonstrate the capability of the product to modulate human dermal papilla cells, suggesting a future use in mesotherapy, a minimally invasive local intradermal therapy (LIT), after further clinical investigations. [ABSTRACT FROM AUTHOR]

In the present study, we compare between the skin in the local rabbits and wild rabbits, samples obtain from flank region. The study revealed basic structure of skin formed by epidermis where covered by stratified keratinized squamous epithelial and arrange into rows of cells. The second layer was dermis which consists of two regions, superficial papillary and reticular deepest region; there was no clear demarcation between these layers, but presence of dense irregular connective tissues. There were two type of hairs follicle primary and secondary. The primary follicles in local rabbits consist of 3 primary and cluster of secondary follicles while in wild rabbit the follicular of hair consist of central hair follicle and surrounded by secondary smaller follicles. The ratio of secondary to primary hair follicles was lesser in local than wild rabbit, besides thickness of epidermis in local more than wild rabbit, also high density of collagen and elastic fibers in local than wild rabbits. [ABSTRACT FROM AUTHOR]

• Melanosomes are concentrated in the basal keratinocytes for localized protection. • Regional distribution of melanosomes correlates with their selective transfer. • Regional distribution of melanosomes correlates with their differential degradation. Human skin is a highly efficient self-renewing barrier that is critical to withstanding environmental insults. Undifferentiated keratinocyte stem cells reside in the basal layer of the epidermis and in hair follicles that continuously give rise to progenies ensuring epidermal turnover and renewal. Ultraviolet (UV) radiation is a proven cause of skin keratinocyte cancers, which preferentially occur at sun-exposed areas of the skin. Fortunately, melanocytes produce melanin that is packaged in specific organelles (termed melanosomes) that are then delivered to nearby keratinocytes, endowing the recipient cells with photoprotection. It has long been thought that melanosome transfer takes place stochastically from melanocytes to keratinocytes via an as-yet-unrecognized manner. However, recent studies have indicated that melanosomes are distributed regionally in the basal layer of the skin, affording localized intensive photoprotection for progenitor keratinocytes and stem cells that reside in the microenvironment of the basal epidermis. In this review, we summarize current knowledge about molecular and cellular mechanisms that are responsible for the selective transfer and exclusive degradation of melanosomes in the epidermis, emphasizing implications for skin carcinogenesis. [ABSTRACT FROM AUTHOR]

Epsilon toxin (ETX) is a key pathogenic factor of C. perfringens type B and D, causing fatal enterotoxemia in sheep and goats. Excessive production of ETX increases intestinal permeability; its entrance into the bloodstream leads to severe edema in organs such as the brain and kidneys. At present, very few cell lines are known to be sensitive to ETX, with the most sensitive cell model for in vitro research being the MDCK cell line. Recently, more tissue-derived cell lines have been shown to be sensitive to ETX, but the mechanism of cytotoxicity remains unknown. Herein, for the first time, we aimed to evaluate the effects of ETX on HaCaT keratinocytes and human epidermal keratinocytes (HEKa). In addition, the median lethal dose of subcutaneous injection of ETX in mice was 109 ng/kg. At this dose, ETX rapidly entered the blood circulation, causing hemorrhage and edema in the brain and kidneys. ETX also increased the expression of aquaporin 3 in the muscle layer and hair follicles of the skin. We further showed the presence of the MAL protein in HaCaT keratinocytes and HEKa and skin tissues, supporting the hypothesis that it is a key element in the mechanism of cytotoxicity of ETX. In conclusion, skin cell lines were used for the first time as a model for studying the toxic effects of ETX, which will help elucidate the cytotoxicity induced by ETX and the related molecular mechanisms. [Display omitted] • Clostridium perfringens epsilon toxin formed toxin pores and oligomers in HaCaT and human epidermal keratinocytes. • Clostridium perfringens epsilon toxin lead to ATP depletion and the death of HaCaT and human epidermal keratinocytes. • Clostridium perfringens epsilon toxin increased the aquaporin 3 expression in the muscle layer and hair follicles. • Keratinocytes and skin tissues expressed MAL, which colocalized with Clostridium perfringens epsilon toxin. [ABSTRACT FROM AUTHOR]

Keratinocytes and melanocytes live in the epidermis, which is considered to be a very good environment for both. Therefore, any change in this regard will affect the function of both of them. Keratinocytes form the main bulk of the epidermis and are the only melanin storage as the dendrites of the basal melanocytes run between keratinocytes and gift melanin granules to surrounding keratinocytes. Consequently, any immunoinflammatory reaction in the epidermis will influence the function of both of them. Recent evidence has shown that psoriasis, pityriasis alba, and vitiligo are closely related diseases and might reflect one etiopathogenesis initially targeting the hair follicles and then extending into the epidermis proper. Hence, the three diseases form one condition: the so-called PPV triad. Consequently, the objective of the following work is to show how these three skin problems are closely related clinically, immunologically, and pathologically, thus constituting the PPV triad. [ABSTRACT FROM AUTHOR]

The development of complex stratified epithelial barriers in mammals is initiated from single-layered epithelia. How stratification is initiated and fueled are still open questions. Previous studies on skin epidermal stratification suggested a central role for perpendicular/asymmetric cell division orientation of the basal keratinocyte progenitors. Here, we use centrosomes, that organize the mitotic spindle, to test whether cell division orientation and stratification are linked. Genetically ablating centrosomes from the developing epidermis leads to the activation of the p53-, 53BP1- and USP28-dependent mitotic surveillance pathway causing a thinner epidermis and hair follicle arrest. The centrosome/p53-double mutant keratinocyte progenitors significantly alter their division orientation in the later stages without majorly affecting epidermal differentiation. Together with time-lapse imaging and tissue growth dynamics measurements, the data suggest that the first and major phase of epidermal development is boosted by high proliferation rates in both basal and suprabasally-committed keratinocytes as well as cell delamination, whereas the second phase maybe uncoupled from the division orientation of the basal progenitors. The data provide insights for tissue homeostasis and hyperproliferative diseases that may recapitulate developmental programs. How the developing skin epidermis is transformed from a simple single-layered epithelium to a complex and stratified barrier is still an open question. Here, the authors provide a model based on high proliferation and delamination of the keratinocyte progenitors that support the stratification process. [ABSTRACT FROM AUTHOR]

Objective: In human skin, melanocytes and melanoblasts are mostly located in the epidermis in addition to hair follicles. In hairy skin such as mouse skin, the inter‐follicular epidermis is generally flat. In contrast, in human skin, the epidermis is wavy and possesses well‐developed rete ridges. It is not well understood what difference exists in cell function between melanocytes present in the inter‐rete ridge and those in the rete ridge. To clarify this problem, we first tried to determine the melanocyte and melanoblast populations per unit area of epidermis both in the rete ridge and inter‐rete ridge epidermis. Methods: Thirty‐eight samples from normal skin sites of 28 patients (14 males and 14 females) aged from 5 to 76 years were fixed and processed to dopa and combined dopa‐premelanin reactions. The numbers of cells positive to the dopa (melanocytes) and combined dopa‐premelanin (melanoblasts and melanocytes) reactions were scored. Results: The average melanocyte population/0.1 mm2 of the inter‐rete ridge was 74 cells, whereas that of the rete ridge was 147 cells. Moreover, the average melanoblast population/0.1 mm2 in the inter‐rete ridge was 43 cells, whereas that of the rete ridge was 131 cells. The melanoblast population in the rete ridge differed between female and male, but the melanocyte populations in the rete ridge and inter‐rete ridge and the melanoblast population in the inter‐rete ridge did not differ between female and male. However, no age difference in the melanocyte and melanoblast populations was observed between the rete ridge and inter‐rete ridge. Conclusion: Human epidermal melanocytes and melanoblasts in the rete ridge exist more numerously than in the inter‐rete ridge. [ABSTRACT FROM AUTHOR]

Culturing skin cells outside of the body has been a cornerstone of dermatological investigation for many years; however, human skin equivalent systems typically lack the full complexity of native skin. Notably, skin appendages, such as hair follicles and sweat glands, remain a challenge to generate or maintain in cell cultures and reconstruct in damaged skin. Recent work from our lab has demonstrated methods for generating appendage‐bearing skin tissue—known as skin organoids—from pluripotent stem cells. Here, we will summarize this work and other related works, and then discuss the potential future applications of skin organoids in dermatological research. [ABSTRACT FROM AUTHOR]

The emergence of hair is a defining event during mammalian skin development, but the cellular mechanisms leading to the opening of the hair follicle canal remain poorly characterized. Our previous studies have shown that early hair buds possess a central column of differentiated keratinocytes expressing Keratin 79 (K79), which marks the future hair follicle opening. Here, we report that during late embryogenesis and early postnatal development, K79+ cells at the distal tips of these columns downregulate E‐cadherin, change shape, recede and undergo cell death. These changes likely occur independently of sebaceous glands and the growing hair shaft, and serve to create an orifice for hair to subsequently emerge. Defects in this process may underlie phenomena such as ingrown hair or may potentially contribute to upper hair follicle pathologies including acne, hidradenitis suppurativa and infundibular cysts. [ABSTRACT FROM AUTHOR]

The hair follicle is a classical model for studying epithelial–mesenchymal interactions. Given the critical role of fibroblast growth factor 8 (Fgf8) in embryonic development, we generated a mouse model that overexpresses Fgf8 specifically in the epidermis. Interestingly, these mutant mice exhibited stunted, smaller bodies and severe hypotrichosis. Histological analysis showed that the hair follicles in the mutants were arrested at stage 2 of hair development. The density of hair follicles in the mutant mice was also lower compared to that in the control mice. Overexpression of Fgf8 inhibited the proliferation of epidermal cells and simultaneously promoted apoptosis, leading to the arrest of hair follicle development. Further analysis showed that sonic hedgehog (Shh) and bone morphogenetic protein 4 (Bmp4) were downregulated and upregulated, respectively. To summarize, our study demonstrates that FGF signalling plays an important role in the regulation of hair follicle development. [ABSTRACT FROM AUTHOR]

This study was conducted on skin samples from New Zealand white rabbits during the period E15 days prenatal to E25. to investigate the histomorphological development of the skin, hair follicle, Sebaceous glands. Early in the fetal life (E15) the epidermis is in the form of simple squamous epithelium or stratified Nonkeratinized squamous epithelium of two or more layers, depending on the region studied, while the dermis is in the form of loose connective tissue composed of mesenchymal cells in a loose and irregular shape. (E20) prenatal, the epidermis is stratified squamous epithelium non-keratinized composed of more than three layers including the periderm, the intermediate layer and the basal layer in all regions, except Fingered hand and foot that appearance keratinized squamous. the cells of the mesoderm begin to condense under the basal layer, indicating the beginning of the formation of hairs placodes. Stratification became evident in(E25) of prenatal with a marked keratinized and extension of hair follicles in the dermis, accompanied by the beginning of the development of sebaceous glands in the form of a group of cells. During our study of the development of the skin of the New Zealand rabbit before birth, we could not notice any sweat glands in the examined skin samples. [ABSTRACT FROM AUTHOR]

Xenotransplantation of skin transplants from humans to animals with immunodeficiency is one of the most successful models for studying human tissues in normal and pathological conditions. The main limitation of this approach is the size of the graft; the lower part of the dermis and subcutaneous fat is missing in skin explants with an area of more than 10 × 10 mm, and full-layer xenografts rarely exceed the size of 3 × 3 mm. This study shows that transplantation of 15 × 5 mm full-layer strips ensures successful integration and preservation of all skin structures: the epidermis, dermal part, blood vessels, hair follicles, and sebaceous and sweat glands. Hair follicles in the grafts reproduce the cycle of physiological regeneration. This model is suitable for studying the regeneration of hair follicles, glands, interfollicular epidermis, and other skin structures. [ABSTRACT FROM AUTHOR]

In the case of insufficient attention of the breeder to sheep selection according to wool uniformity, a fairly large group of animals with wool unequal in length and fineness within the staple and along the fleece appears in the herd. The breeder's excessive enthusiasm for wool uniformity in the fleece leads to the weakening of the sheep's body composition and decreased vigor. The Republic of North Ossetia-Alania, research was carried out in 2019-2020. The geographic location of the farm: Northern latitude: 43.175598. Eastern longitude: 44.295621 and 412 meters above sea level. For the experiment, 10 fine-wooled mongrel winter lambing double-toothed gimmers were selected according to the principle of pairs-analogs. In the spring before shearing, samples of wool and skin on the upper part of the neck, shoulder, back, rump, thigh, flank, shoulder blade, and belly were taken from 14-month-old test double-toothed gimmers. Based on the studies carried out, one can make the following conclusions: - despite the wool homogeneity in the fleece, within different topographic areas, sheep skin has an unequal thickness and structure, which largely determines the coat quality; - the thickest skin in the test sheep was found along the back line. From the back to the flanks, the thickness of the skin decreases. The thinnest skin was on the belly; - on thicker skin, a longer and thicker coat grows, on thinner skin, a shorter and thinner coat grows; - with a change in the wool fiber density, the epidermis thickness changes. The thicker the coat, the thinner the epidermis, the thicker the epidermis, the more scanty the coat; - within different skin topographic areas, the PFs (primary follicles) and SFs (secondary follicles) depth and the ratio of these values are different, which affects the evenness of wool equal in length and untrue wool. The rump, neck, shoulder, and thigh had the maximal PF/SF depth ratio. The same topographic areas were characterized by lesser wool uniformity in length and fineness. [ABSTRACT FROM AUTHOR]

The mammalian skin is equipped with a highly dynamic stratified epithelium. The maintenance and regeneration of this epithelium is supported by basally located keratinocytes, which display stem cell properties, including lifelong proliferative potential and the ability to undergo diverse differentiation trajectories. Keratinocytes support not just the surface of the skin, called the epidermis, but also a range of ectodermal structures including hair follicles, sebaceous glands, and sweat glands. Recent studies have shed light on the hitherto underappreciated heterogeneity of keratinocytes by employing state-of-the-art imaging technologies and single-cell genomic approaches. In this mini review, we highlight major recent discoveries that illuminate the dynamics and cellular mechanisms that govern keratinocyte differentiation in the live mammalian skin and discuss the broader implications of these findings for our understanding of epithelial and stem cell biology in general. [ABSTRACT FROM AUTHOR]

Nerve endings and terminal Schwann cells (TSCs) specifically and densely surround hair follicle at isthmus area, forming a neuromuscular‐junction‐like structure called lanceolate complex. The interplay between neuronal components and epidermis in this specialized structure enables hair to properly sense complex stimuli from environments. However, how nerves precisely attach to and innervate this specific region during development remains to be elucidated. Here, we demonstrate that SEMA3C, a secreted protein member of semaphorin family responsible for axonal guidance, is localized right below sebaceous gland and in close approximation with nerve endings and TSCs processes all through the entire hair cycle. SEMA3C protein is deposited outside of epithelial cells and its expression is independent on the presence of nerve endings/TSCs. SEMA3C is also found in portions of dermal papilla at growth phase. The tight spatial association of SEMA3C with lanceolate complex suggests that it might play roles in establishment and/or maintenance of the lanceolate complex in hair follicle. [ABSTRACT FROM AUTHOR]

IFAP syndrome is a rare genetic disorder characterized by ichthyosis follicularis, atrichia, and photophobia. Previous research found that mutations in MBTPS2 , encoding site-2-protease (S2P), underlie X-linked IFAP syndrome. The present report describes the identification via whole-exome sequencing of three heterozygous mutations in SREBF1 in 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. SREBF1 encodes sterol regulatory element-binding protein 1 (SREBP1), which promotes the transcription of lipogenes involved in the biosynthesis of fatty acids and cholesterols. This process requires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucleus where it binds to sterol regulatory elements (SRE). The three detected SREBF1 mutations caused substitution or deletion of residues 527, 528, and 530, which are crucial for S1P cleavage. In vitro investigation of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of the transcriptionally active form of SREBP1. As a result, SREBP1 variants exhibited significantly lower transcriptional activity compared to the wild-type, as demonstrated via luciferase reporter assay. RNA sequencing of the scalp skin from IFAP-affected individuals revealed a dramatic reduction in transcript levels of low-density lipoprotein receptor (LDLR) and of keratin genes known to be expressed in the outer root sheath of hair follicles. An increased rate of in situ keratinocyte apoptosis, which might contribute to skin hyperkeratosis and hypotrichosis, was also detected in scalp samples from affected individuals. Together with previous research, the present findings suggest that SREBP signaling plays an essential role in epidermal differentiation, skin barrier formation, hair growth, and eye function. [ABSTRACT FROM AUTHOR]

Nowadays, there is a great attention to the plasma applications in medicine. Not only does cold atmospheric pressure plasma provide a therapeutic opportunity to control redox-based processes, it is also an innovative method in rejuvenation. Given the current interest in new methods of rejuvenation, we aimed to introduce a novel pulsed nitrogen plasma torch with potential use in rejuvenation. We investigated production of reactive species at different pulse energy by spectroscopy and also measured nitric oxide and O2 concentration and evaluated the flame temperature. Fifteen Wistar rats were divided into three groups based on the applied energy settings; the skin of the animals was processed with plasma. For quantitative evaluation of dermis, epidermis and hair follicles (to confirm the effects of this technique on rejuvenation), skin biopsies were taken from both unexposed and treated areas. The spectroscopy results showed the presence of nitric oxide in plasma and the concentration was suitable for dermatological applications. A significant increase was observed in epidermal thickness, fibroblast cell proliferation and collagenesis (P < 0.05). Interestingly, plasma led to a temporary increase in the diameter of primary and secondary hair follicles compared to the controls. The results confirmed the positive effects of this pulsed nitrogen plasma torch on rejuvenation and also revealed a new possible aspect of cold plasma; its effect on hair follicles as a promising area in the treatment of alopecia that requires further clinical and molecular studies. [ABSTRACT FROM AUTHOR]

• Spinal cord injury (SCI) leads to irreversible motor and sensory disabilities. • We studied the effects of Ast + EPI-NCSCs combination on SCI in rat. • Ast and EPI-NCSCs treatments improved motor function following SCI. • Combination therapy had better effect on behavioral function after SCI. • Ast + EPI-NCSCs prevented neural damages via mitochondrial biogenesis activation. Spinal cord injury (SCI), a multifactorial disease, can lead to irreversible motor and sensory disabilities. Cell therapy in combination with pharmacological agents can be a promising approach to attenuate SCI damages. Epidermal neural crest stem cells (EPI-NCSCs) extracted from bulge hair follicle in adults are attractive candidates due to the possibility of autologous transplantation. This study evaluated the effect of EPI-NCSCs combined with astaxanthin (Ast), a potent antioxidant, on damages induced by SCI. Male rats were treated with Ast (0.2 mM) and EPI-NCSCs (106/10 μl PBS) alone and combined together after SCI contusion. Motor function was assessed by Basso, Beattie and Bresnahan (BBB) test on days 1, 3, 7, 14, 21, 28, 35 and 42 post-injury. Motor neurons number and myelin level were evaluated on days 14 and 42 using Nissl and Luxol Fast Blue staining. The gene expression of mitochondrial biogenesis involved factors (PGC1α, NRF1 and TFAM) was measured by qPCR. All treatments improved motor function, with the highest BBB score in Ast + Cell compared to Ast and Cell. Decreased motor neurons number and myelin level following SCI, were increased by Ast, Cell and Ast + Cell, but combination therapy significantly had a better effect. We observed reduction in PGC1α, NRF1, and TFAM expression in spinal tissue after SCI, and treatment with Cell and Ast + Cell significantly restored NRF1 and TFAM mRNA levels. These results suggested that Ast in combination with EPI-NCSCs has better effects on behavioral dysfunction, motor neuron loss and demyelination after SCI. These protective effects may be attributed to mitochondrial biogenesis activation. [ABSTRACT FROM AUTHOR]