A meta-analysis of chemokines in vitiligo: Recruiting immune cells towards melanocytes.

Chemokine research offers insightful information on the pathogenesis of cutaneous immune disorders, such as vitiligo. Compared to cytokines, the higher detectable levels of chemokines display promising potential as future disease biomarkers. Nonetheless, some published study results are contradictory, which can be attributed to patient characteristics and methodological differences. In this study, a meta-analysis was performed to compare chemokine expression in blood and skin samples from vitiligo patients versus healthy controls. Furthermore, the relationship between chemokine expression and disease activity was evaluated. Chemokine levels were investigated in 15 articles in the circulation and in 9 articles in vitiligo skin. Overall, some clear trends were observed. CXCR3 signaling by CXCL10 and CXCL9 has been confirmed by several reports, although CXCL10 showed more robust findings in blood samples. In this meta-analysis, CCL5, CXCL8, CXCL12, and CXCL16 levels were also significantly elevated. This indicates a complex immune pathway activation in vitiligo that overall supports a Th1-dominant response. Chemokines linked to the Th2 and Th17 pathways were less prevalent. Despite these findings, study protocols that examine a broader range of chemokines are encouraged, because current research is mostly focused on a small number of chemokines that were differentially expressed in previous studies.

IL-33-mediated activation of mast cells is involved in the progression of imiquimod-induced psoriasis-like dermatitis.

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis with an unclear pathogenesis. Mast cells (MCs) can serve as a bridge between innate and adaptive immunity and are involved in the regulation of the inflammatory state and immune homeostasis in diseases. MCs constitutively express interleukin-33 receptor T1/ST2 (IL-33R). IL-33 is a potent MCs activator that is actively secreted by keratinocytes in psoriasis. However, the regulatory role of MCs in psoriasis remains uncertain. Therefore, we hypothesised that IL-33 could promote MC activation to regulate psoriasis development. METHODS: We performed experiments on wild-type (WT) and MC-deficient (Kit Wsh/Wsh) mice, established psoriasis-like mouse models using imiquimod (IMQ), and performed RNA sequencing and transcriptomic analysis of skin lesions. Exogenous administration was performed using recombinant IL-33. Validation and evaluation were performed using PSI scoring, immunofluorescence, immunohistochemistry, and qPCR. RESULTS: We observed an upregulation in the number and activation of MCs in patients with psoriasis and in IMQ-induced psoriasis-like dermatitis. Deficiency of MCs ameliorates IMQ-induced psoriatic dermatitis at an early stage. IL-33 is increased and co-localized with MCs in the dermis of psoriasis-like lesions using immunofluorescence. Compared to WT mice, IMQ-induced KitWsh/Wsh mice demonstrated a delayed response to exogenous IL-33. CONCLUSIONS: MCs are activated by IL-33 in the early stages of psoriasis and exacerbate psoriasis-associated skin inflammation. The regulation of MC homeostasis may be a potential therapeutic strategy for psoriasis. Video Abstract.

Macrophage Biology in Human Granulomatous Skin Inflammation.

Cutaneous granulomatoses represent a heterogeneous group of diseases, which are defined by macrophage infiltration in the skin. Skin granuloma can be formed in the context of infectious and non-infectious conditions. Recent technological advances have deepened our understanding of the pathophysiology of granulomatous skin inflammation, and they provide novel insights into human tissue macrophage biology at the site of ongoing disease. Here, we discuss findings on macrophage immune function and metabolism derived from three prototypic cutaneous granulomatoses: granuloma annulare, sarcoidosis, and leprosy.

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study.

The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required.

MKP-1 Deficiency Exacerbates Skin Fibrosis in a Mouse Model of Scleroderma.

Scleroderma is a chronic fibrotic disease, where proinflammatory and profibrotic events precede collagen accumulation. MKP-1 [mitogen-activated protein kinase (MAPK) phosphatase-1] downregulates inflammatory MAPK pathways suppressing inflammation. MKP-1 also supports Th1 polarization, which could shift Th1/Th2 balance away from profibrotic Th2 profile prevalent in scleroderma. In the present study, we investigated the potential protective role of MKP-1 in scleroderma. We utilized bleomycin-induced dermal fibrosis model as a well-characterized experimental model of scleroderma. Dermal fibrosis and collagen deposition as well as the expression of inflammatory and profibrotic mediators were analyzed in the skin samples. Bleomycin-induced dermal thickness and lipodystrophy were increased in MKP-1-deficient mice. MKP-1 deficiency enhanced collagen accumulation and increased expression of collagens, 1A1 and 3A1, in the dermis. Bleomycin-treated skin from MKP-1-deficient mice also showed enhanced expression of inflammatory and profibrotic factors IL-6, TGF-ß1, fibronectin-1 and YKL-40, and chemokines MCP-1, MIP-1α and MIP-2, as compared to wild-type mice. The results show, for the first time, that MKP-1 protects from bleomycin-induced dermal fibrosis, suggesting that MKP-1 favorably modifies inflammation and fibrotic processes that drive the pathogenesis of scleroderma. Compounds enhancing the expression or activity of MKP-1 could thus prevent fibrotic processes in scleroderma and possess potential as a novel immunomodulative drug.

Imbalanced IL-1B and IL-18 Expression in Sézary Syndrome.

Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.

A Novel Hyaluronic Acid Matrix Ingredient with Regenerative, Anti-Aging and Antioxidant Capacity.

Hyaluronic acid (HA) and proteoglycans (such as dermatan sulphate (DS) and chondroitin sulphate (CS)) are the main components of the extracellular matrix of the skin, along with collagen and elastin. These components decrease with age, which implies a loss of skin moisture causing wrinkles, sagging and aging. Currently, the external and internal administration of effective ingredients that can reach the epidermis and dermis is the main alternative for combating skin aging. The objective of this work was to extract, characterise and evaluate the potential of an HA matrix ingredient to support anti-aging. The HA matrix was isolated and purified from rooster comb and characterised physicochemically and molecularly. In addition, its regenerative, anti-aging and antioxidant potential and intestinal absorption were evaluated. The results show that the HA matrix is composed of 67% HA, with an average molecular weight of 1.3 MDa; 12% sulphated glycosaminoglycans, including DS and CS; 17% protein, including collagen (10.4%); and water. The in vitro evaluation of the HA matrix's biological activity showed regenerative properties in both fibroblasts and keratinocytes, as well as moisturising, anti-aging and antioxidant effects. Furthermore, the results suggest that the HA matrix could be absorbed in the intestine, implying a potential oral as well as topical use for skin care, either as an ingredient in a nutraceutical or a cosmetic product.

Telocytes in Cutaneous Biology: A Reappraisal / Los telocitos en la biología cutánea: revaluación

The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions (AU)

Los telocitos (TC) son células intersticiales noveles que han sido subvaloradas durante mucho tiempo debido a su similitud histológica con otras células estromales. Los TC pueden separarse de las células estromales debido a sus distintas características inmunohistoquímicas, ultraestructurales y moleculares. A nivel funcional, los TC están implicados en la renovación tisular, el soporte mecánico y la modulación inmune. Dichas células están implicadas también en la transducción de señal, bien mediante sus interacciones directas con las células circundantes, o bien mediante la señalización paracrina, a través de las vesículas extracelulares. Los TC se ven dañados en ciertas situaciones inflamatorias y fibróticas tales como colitis ulcerosa, enfermedad de Crohn, fibrosis hepática, psoriasis y esclerosis sistémica. El trasplante de TC en el tejido dañado puede promover la regeneración tisular. Por tanto, mejorar los TC tisulares mediante trasplante o promoción de su supervivencia y crecimiento, utilizando medicaciones novedosas, representa una estrategia terapéutica innovadora para el futuro. En esta revisión abordamos diversos aspectos de los TC, incluyendo su origen, su distribución, sus características morfológicas y sus funciones. También tratamos la implicación de los TC cutáneos en el desarrollo de diversas situaciones patológicas (AU)

[Artículo traducido] Los telocitos en la biología cutánea: revaluación / Telocytes in Cutaneous Biology: A Reappraisal

Los telocitos (TC) son células intersticiales noveles que han sido subvaloradas durante mucho tiempo debido a su similitud histológica con otras células estromales. Los TC pueden separarse de las células estromales debido a sus distintas características inmunohistoquímicas, ultraestructurales y moleculares. A nivel funcional, los TC están implicados en la renovación tisular, el soporte mecánico y la modulación inmune. Dichas células están implicadas también en la transducción de señal, bien mediante sus interacciones directas con las células circundantes, o bien mediante la señalización paracrina, a través de las vesículas extracelulares. Los TC se ven dañados en ciertas situaciones inflamatorias y fibróticas tales como colitis ulcerosa, enfermedad de Crohn, fibrosis hepática, psoriasis y esclerosis sistémica. El trasplante de TC en el tejido dañado puede promover la regeneración tisular. Por tanto, mejorar los TC tisulares mediante trasplante o promoción de su supervivencia y crecimiento, utilizando medicaciones novedosas, representa una estrategia terapéutica innovadora para el futuro. En esta revisión abordamos diversos aspectos de los TC, incluyendo su origen, su distribución, sus características morfológicas y sus funciones. También tratamos la implicación de los TC cutáneos en el desarrollo de diversas situaciones patológicas (AU)

The telocytes (TCs) are novel interstitial cells that have been overlooked for a long time due to their histologic similarity to other stromal cells. TCs can be separated from the stromal cells based on their distinct immunohistochemical, ultrastructural, and molecular features. Functionally, TCs are involved in the tissue renewal, mechanical support, and immune modulation. These cells are also involved in the signal transduction either through their direct interactions with the neighboring cells or through the paracrine signaling via extracellular vesicles. TCs are damaged in several inflammatory and fibrotic conditions such as ulcerative colitis, Crohn's disease, hepatic fibrosis, psoriasis, and systemic sclerosis. The transplantation of TCs in the damaged tissue can promote tissue regeneration. Therefore, enhancing tissue TCs either by their transplantation or by promoting their survival and growth using novel medications represents novel therapeutic strategy in the future. In this review, we addressed several aspects of TCs including their origin, distribution, morphologic features, and functions. We also discussed their involvement of the cutaneous TCs in the development various pathologic conditions (AU)

Depilatory double-disc mouse model for evaluation of vesicant dermal injury pharmacotherapy countermeasures.

BACKGROUND: Sulfur mustard (SM) is a chemical warfare vesicant that severely injures exposed eyes, lungs, and skin. Mechlorethamine hydrochloride (NM) is widely used as an SM surrogate. This study aimed to develop a depilatory double-disc (DDD) NM skin burn model for investigating vesicant pharmacotherapy countermeasures. METHODS: Hair removal method (clipping only versus clipping followed by a depilatory), the effect of acetone in the vesicant administration vehicle, NM dose (0.5-20 µmol), vehicle volume (5-20 µl), and time course (0.5-21 days) were investigated using male and female CD-1 mice. Edema, an indicator of burn response, was assessed by biopsy skin weight. The ideal NM dose to induce partial-thickness burns was assessed by edema and histopathologic evaluation. The optimized DDD model was validated using an established reagent, NDH-4338, a cyclooxygenase, inducible nitric oxide synthase, and acetylcholinesterase inhibitor prodrug. RESULTS: Clipping/depilatory resulted in a 5-fold higher skin edematous response and was highly reproducible (18-fold lower %CV) compared to clipping alone. Acetone did not affect edema formation. Peak edema occurred 24-48 h after NM administration using optimized dosing methods and volume. Ideal partial-thickness burns were achieved with 5 µmol of NM and responded to treatment with NDH-4338. No differences in burn edematous responses were observed between males and females. CONCLUSION: A highly reproducible and sensitive partial-thickness skin burn model was developed for assessing vesicant pharmacotherapy countermeasures. This model provides clinically relevant wound severity and eliminates the need for organic solvents that induce changes to the skin barrier function.

Non­viral transfection methods optimized for miRNA delivery to human dermal fibroblasts.

Fibroblasts are beneficial model cells for in vitro studies and are frequently used in tissue engineering. A number of transfection reagents have been employed to deliver microRNAs (miRNAs/miRs) into cells for genetic manipulation. The present study aimed to establish an effective method of transient miRNA mimic transfection into human dermal fibroblasts. The experimental conditions included three different methods: Physical/mechanical nucleofection, and two lipid­based methods, Viromer® Blue and INTERFERin®. To evaluate the impact of these methods, cell viability and cytotoxicity assays were performed. The silencing effect of miR­302b­3p was revealed to alter the expression levels of its target gene carnitine O­octanoyltransferase (CROT) by reverse transcription­quantitative PCR. The present study showed that all selected non­viral transient transfection systems exhibited good efficiency. It was also confirmed that nucleofection, for which a 21.4­fold decrease in the expression of the CROT gene was observed 4 h after 50 nM hsa­miR­302b­3p transfection, was the most effective method. However, these results indicated that lipid­based reagents can maintain the silencing effect of miRNAs up to 72 h after transfection. In summary, these results indicated that nucleofection may be the optimal method for the transport of small miRNA mimics. However, lipid­based methods allow for the use of lower concentrations of miRNA and maintain longer­lasting effects.

Therapeutic effects of mesenchymal stem cells and their derivatives in common skin inflammatory diseases: Atopic dermatitis and psoriasis.

Chronic skin inflammatory diseases including atopic dermatitis (AD) and psoriasis have been considered uncontrolled inflammatory responses, which have usually troubled patients around the world. Moreover, the recent method to treat AD and psoriasis has been based on the inhibition, not regulation, of the abnormal inflammatory response, which can induce a number of side effects and drug resistance in long-term treatment. Mesenchymal stem/stromal cells (MSCs) and their derivatives have been widely used in immune diseases based on their regeneration, differentiation, and immunomodulation with few adverse effects, which makes MSCs a promising treatment for chronic skin inflammatory diseases. As a result, in this review, we aim to systematically discuss the therapeutic effects of various resources of MSCs, the application of preconditioning MSCs and engineering extracellular vesicles (EVs) in AD and psoriasis, and the clinical evaluation of the administration of MSCs and their derivatives, which can provide a comprehensive vision for the application of MSCs and their derivatives in future research and clinical treatment.

GFANet: Gated Fusion Attention Network for skin lesion segmentation.

Automatic segmentation of skin lesions is crucial for diagnosing and treating skin diseases. Although current medical image segmentation methods have significantly improved the results of skin lesion segmentation, the following major challenges still affect the segmentation performance: (i) segmentation targets have irregular shapes and diverse sizes and (ii) low contrast or blurred boundaries between lesions and background. To address these issues, this study proposes a Gated Fusion Attention Network (GFANet) which designs two progressive relation decoders to accurately segment skin lesions images. First, we use a Context Features Gated Fusion Decoder (CGFD) to fuse multiple levels of contextual features, and then a prediction result is generated as the initial guide map. Then, it is optimized by a prediction decoder consisting of a shape flow and a final Gated Convolution Fusion (GCF) module, where we iteratively use a set of Channel Reverse Attention (CRA) modules and GCF modules in the shape flow to combine the features of the current layer and the prediction results of the adjacent next layer to gradually extract boundary information. Finally, to speed up network convergence and improve segmentation accuracy, we use GCF to fuse low-level features from the encoder and the final output of the shape flow. To verify the effectiveness and advantages of the proposed GFANet, we conduct extensive experiments on four publicly available skin lesion datasets (International Skin Imaging Collaboration [ISIC] 2016, ISIC 2017, ISIC 2018, and PH2) and compare them with state-of-the-art methods. The experimental results show that the proposed GFANet achieves excellent segmentation performance in commonly used evaluation metrics, and the segmentation results are stable. The source code is available at https://github.com/ShiHanQ/GFANet.

A non-invasive wearable stress patch for real-time cortisol monitoring using a pseudoknot-assisted aptamer.

Stress is part of everyone's life and is exacerbated by traumatic events such as pandemics, disasters, violence, lifestyle changes, and health disorders. Chronic stress has many detrimental health effects and can even be life-threatening. Long-term stress monitoring outside of a hospital is often accomplished by measuring heart rate variability. While easy to measure, this digital biomarker has low specificity, greatly limiting its utility. To address this shortcoming, we report a non-invasive, wearable biomolecular sensor to monitor cortisol levels in sweat. Cortisol is a neuroendocrine hormone that regulates homeostasis as part of the stress pathway. Cortisol is detected using an electrochemical sensor functionalized with a pseudoknot-assisted aptamer and a flexible microfluidic sweat sampling system. The skin-worn microfluidic sampler provides rapid sweat collection while separating old and new sweat. The conformation-switching aptamer provides high specificity towards cortisol while being regenerable, allowing it to monitor temporal changes continuously. The aptamer was engineered to add a pseudoknot, restricting it to only two states, thus minimizing the background signal and enabling high sensitivity. An electrochemical pH sensor allows pH-corrected amperometric measurements. Device operation was demonstrated invitro with a broad linear dynamic range (1 pM - 1 µM) covering the physiological range and a sub-picomolar (0.2 pM) limit of detection in sweat. Real-time, on-body measurements were collected from human subjects using an induced stress protocol, demonstrating in-situ signal regeneration and the ability to detect dynamic cortisol fluctuations continuously for up to 90 min. The reported device has the potential to improve prognosis and enable personalized treatments.

Diagnostic aid to subepidermal calcified nodule with dermoscopy and reflectance confocal microscopy: a case report.

BACKGROUND: Subepidermal calcified nodule (SCN) is a type of calcinosis cutis that usually occurs in children. The lesions in the SCN resemble those of other skin diseases, such as pilomatrixoma, molluscum contagiosum, and juvenile xanthogranuloma, leading to a high rate of misdiagnoses. Noninvasive in vivo imaging techniques, represented by dermoscopy and reflectance confocal microscopy (RCM), have dramatically accelerated skin cancer research over the past decade, and their applications have greatly expanded into other skin disorders. However, the features of an SCN in dermoscopy and RCM have yet to be reported previously. Combining these novel approaches with conventional histopathological examinations is a promising method for increasing diagnostic accuracy. CASE PRESENTATION: We report on a case of SCN of the eyelid diagnosed with the aid of dermoscopy and RCM. A 14-year-old male patient who presented with a painless yellowish-white papule on his left upper eyelid was previously diagnosed with a common wart. Unfortunately, treatment with recombinant human interferon gel was not effective. To achieve a correct diagnosis, dermoscopy and RCM were performed. The former showed closely grouped multiple yellowish-white clods surrounded by linear vessels, and the latter exhibited hyperrefractile material nests at the dermal-epidermal junction level. The alternative diagnoses were, therefore, excluded because of in vivo characterizations. Subsequent surgical excision, histological examination, and von Kossa staining were performed. Pathology showed hyperkeratosis of the epidermis, a downward-directed basal-layer expansion, and small amorphous basophilic deposits scattered throughout the papillary dermis. The von Kossa staining confirmed calcium deposits in the lesion. An SCN was then diagnosed. During the 6-month follow-up, no relapse was observed. CONCLUSIONS: Patients with SCN could benefit from dermoscopy and RCM, which help achieve an accurate diagnosis. Clinicians should consider the possibility of an SCN for an adolescent patient with painless yellowish-white papules.

Reconstituting Cytoarchitecture and Function of Human Epithelial Tissues on an Open-Top Organ-Chip.

Nearly all human organs are lined with epithelial tissues, comprising one or multiple layers of tightly connected cells organized into three-dimensional (3D) structures. One of the main functions of epithelia is the formation of barriers that protect the underlining tissues against physical and chemical insults and infectious agents. In addition, epithelia mediate the transport of nutrients, hormones, and other signaling molecules, often creating biochemical gradients that guide cell positioning and compartmentalization within the organ. Owing to their central role in determining organ-structure and function, epithelia are important therapeutic targets for many human diseases that are not always captured by animal models. Besides the obvious species-to-species differences, conducting research studies on barrier function and transport properties of epithelia in animals is further compounded by the difficulty of accessing these tissues in a living system. While two-dimensional (2D) human cell cultures are useful for answering basic scientific questions, they often yield poor in vivo predictions. To overcome these limitations, in the last decade, a plethora of micro-engineered biomimetic platforms, known as organs-on-a-chip, have emerged as a promising alternative to traditional in vitro and animal testing. Here, we describe an Open-Top Organ-Chip (or Open-Top Chip), a platform designed for modeling organ-specific epithelial tissues, including skin, lungs, and the intestines. This chip offers new opportunities for reconstituting the multicellular architecture and function of epithelial tissues, including the capability to recreate a 3D stromal component by incorporating tissue-specific fibroblasts and endothelial cells within a mechanically active system. This Open-Top Chip provides an unprecedented tool for studying epithelial/mesenchymal and vascular interactions at multiple scales of resolution, from single cells to multi-layer tissue constructs, thus allowing molecular dissection of the intercellular crosstalk of epithelialized organs in health and disease.

Expression of Foxp3 in Fibromas and Fibrosarcomas of Skin and Subcutaneous Tissue in Dogs.

BACKGROUND/AIM: Foxp3 is a transcription factor responsible for the formation of T regulatory lymphocytes. Foxp3 expression can be associated with either neoplastic progression or regression. The aim of the study was to evaluate Foxp3 expression in soft tissue tumours (fibromas and fibrosarcomas) of skin and subcutaneous tissue in dogs and to describe its relationship with tumour malignancy grade. MATERIALS AND METHODS: The study was conducted on 71 skin and subcutaneous tumours including 31 fibromas and 40 fibrosarcomas. The samples underwent histological and immunohistochemical evaluation using anti-Foxp3, anti-Ki, and vimentin antibodies. RESULTS: Cytoplasmic expression of Foxp3 protein in the cutaneous and subcutaneous fibrosarcomas in dogs was confirmed. Moreover, a positive relationship between the expression of Foxp3 and tumour malignancy grade and between Foxp3 and Ki-67 expression was noted. CONCLUSION: A positive correlation between the Foxp3 expression intensity and malignancy grade suggests a significant role of Foxp3 in the carcinogenesis of skin and subcutaneous fibrosarcomas in dogs. Increased expression of Foxp3 may have a positive effect on the progression of cancer.

WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczema-like skin lesions, dry skin, severe itching, and recurrent recurrence. The whey acidic protein four-disulfide core domain gene WFDC12 is highly expressed in skin tissue and up-regulated in the skin lesions of AD patients, but its role and relevant mechanism in AD pathogenesis have not been studied yet. In this study, we found that the expression of WFDC12 was closely related to clinical symptoms of AD and the severity of AD-like lesions induced by DNFB in transgenic mice. WFDC12-overexpressing in the epidermis might promote the migration of skin-presenting cells to lymph nodes and increase Th cell infiltration. Meanwhile, the number and ratio of immune cells and mRNA levels of cytokines were significantly upregulated in transgenic mice. In addition, we found that ALOX12/15 gene expression was upregulated in the arachidonic acid metabolism pathway, and the corresponding metabolite accumulation was increased. The activity of epidermal serine hydrolase decreased and the accumulation of platelet-activating factor (PAF) increased in the epidermis of transgenic mice. Collectively, our data demonstrate that WFDC12 may contribute to the exacerbation of AD-like symptoms in DNFB-induced mouse model by enhancing arachidonic acid metabolism and PAF accumulation and that WFDC12 may be a potential therapeutic target for human atopic dermatitis.