Skin Architecture Research Articles

Antibacterial and wound healing potential of biosynthesized zinc oxide nanoparticles against carbapenem-resistant Acinetobacter baumannii: an in vitro and in vivo study

Carbapenem-resistant Acinetobacter baumannii denotes a significant menace to public health, and it mandates an urgent development of new effective medications. Here, we aimed to estimate the efficiency of the zinc oxide nanoparticles (ZnO NP) biosynthesized from Arthrospira maxima (Spirulina) both in vitro and in vivo. Carbapenem-resistant A. baumannii isolates were collected, identified, tested for their antibiotic susceptibility, and then subjected to PCR to detect carbapenemase-producing genes. The most predominant carbapenemase resistance gene was blaKPC. The biosynthesized ZnO NP were characterized using UV, FTIR, XRD, SEM, and TEM. The prepared ZnO NP was then tested against A. baumannii isolates to determine the minimum inhibitory concentration (MIC), which ranged from 250 to 1000 μg/ml. Burn wound was persuaded in twenty rats and inoculated with carbapenem-resistant A. baumannii isolate. Rats were allocated into four groups: a negative control group, a positive control group treated with topical 0.9% saline, a test treatment group that received topical ZnO NP, and a standard treatment group. All groups received treatment for 15 consecutive days and then euthanized. Skin samples were harvested and then subjected to histopathological and immunochemical investigations. ZnO NP revealed a comparable antibacterial activity to colistin as it revealed a lower level of fibrosis, mature surface epithelization with keratinization, and restoration of the normal skin architecture. In addition, it significantly decreased the immunoreactivity of the studied inflammatory markers. Thus, ZnO NP synthesized by A. maxima could be considered a promising, safe, and biocompatible alternative to traditional antibiotics in the therapy of carbapenem-resistant A. baumannii infections.

Progress on three-dimensional visualizing skin architecture with multiple immunofluorescence staining and tissue-clearing approaches.

The skin forms the external covering of the body and is its largest organ, comprising many different cell types. Although the diversity of these cells has been widely studied with various histological methods, our understanding of skin architecture is mainly established on thin tissue sections, which restricted the information available to two dimensions. The development of innovative techniques to induce optical transparency ("clearing") in biological tissues has enabled researchers to visualize the three-dimensional reconstruction of intact organs and thick tissue sections at a cellular resolution. With the aid of tissue-clearing treatment, the labeled cutaneous nerve fibers and blood vessels can be followed for a longer distance on the thicker skin section or the whole mount skin under a fluorescence microscopy or a confocal microscopy. It is beneficial for demonstrating the morphological characteristics of nerve fibers and blood vessels themselves, as well as their spatial interconnection. In this review, we provide a brief summary of the literature on the use of tissue optical clearing methods and describe our experience of multiple fluorescent staining and tissue clearing approaches on thicker skin sections and whole-mount skin in our laboratory. Given the existing conventional methods, we expected to provide a more effective approach to comprehensively study skin architecture.

In vivo Antifungal Efficacy and Safety of Natural Compounds for Topical Treatment of Cutaneous Candidiasis

In vivo toxicity and antifungal therapeutic evaluation of selected natural compounds for topical applications was analyzed using standard methods. The natural compounds, blue vitriol, brimstone, trona, alum, palm ash and black stone were hygienically selected and purchased at a local market in southeastern Nigeria. The test organisms were isolated from high vaginal swab specimens obtained from cases of cutaneous candidiasis. The isolates were identified based on their morphological, physiological and molecular characteristics. The toxicological screening of the test samples was done using Draize’ skin irritancy test, Murine local lymph node assay (LLNA) and necropsy. The in vivo evaluation of antifungal activity of the solutions was done using eight-week-old albino rats weighing 120g – 150g. The animals were infected with the Candida isolates percutaneously; and treated using various formulations of the natural compounds. The skin sections were carefully observed for histopathological changes, before and after treatment. The total yeast counts of the infected skin tissues were also determined. The isolates include Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Draize’ skin test and Murine local lymph node assay showed no observable skin irritancy reaction (P>0.05). The normal skin architecture of the infected animals was restored after 5 days of treatment with the test samples; while the total yeast count decreased from 108 CFU/mL to 102 CFU/mL. The findings have revealed that natural compounds are effective as well as non-toxic topically, in treatment of cutaneous candidiasis.

Behavioral biometric optical tactile sensor for instantaneous decoupling of dynamic touch signals in real time

Decoupling dynamic touch signals in the optical tactile sensors is highly desired for behavioral tactile applications yet challenging because typical optical sensors mostly measure only static normal force and use imprecise multi-image averaging for dynamic force sensing. Here, we report a highly sensitive upconversion nanocrystals-based behavioral biometric optical tactile sensor that instantaneously and quantitatively decomposes dynamic touch signals into individual components of vertical normal and lateral shear force from a single image in real-time. By mimicking the sensory architecture of human skin, the unique luminescence signal obtained is axisymmetric for static normal forces and non-axisymmetric for dynamic shear forces. Our sensor demonstrates high spatio-temporal screening of small objects and recognizes fingerprints for authentication with high spatial-temporal resolution. Using a dynamic force discrimination machine learning framework, we realized a Braille-to-Speech translation system and a next-generation dynamic biometric recognition system for handwriting.

Paxbp1 Is Indispensable for the Maintenance of Epidermal Homeostasis

The mammalian epidermis is a structurally complex tissue that serves critical barrier functions, safeguarding the organism from the external milieu. The development of the epidermis is governed by sophisticated regulatory processes. However, the precise mechanism maintaining epidermal homeostasis remains incompletely elucidated. Recent studies have identified Paxbp1, an evolutionarily conserved protein, as being involved in the developmental regulation of various cells, tissues, and organs. Nonetheless, its role in skin development has not been explored. Here, we report that the targeted deletion of Paxbp1 in epidermal keratinocytes mediated by Keratin14-Cre leads to severe disruption in skin architecture. Mice deficient in Paxbp1 exhibited a substantially reduced epidermal thickness and pronounced separation at the dermo-epidermal junction upon birth. Mechanistically, we demonstrate that the absence of Paxbp1 hinders cellular proliferation, marked by a halt in cell cycle transition, suppressed gene expression of proliferation, and a compromised DNA replication pathway in basal keratinocytes, resulting in the thinning of the skin epidermis. Moreover, molecules and pathways associated with hemidesmosome assembly were impaired in Paxbp1-deficient keratinocytes, culminating in the detachment of the skin epidermal layer. Therefore, our study highlights an indispensable role of Paxbp1 in the maintenance of epidermal homeostasis.

A Novel Hybrid Injectable for Soft-tissue Augmentation: Analysis of Data and Practical Experience

Background: HA/CaHa (HArmonyCa, Allergan Aesthetics, an AbbVie Company) is a hybrid injectable filler developed for aesthetic purposes that contains calcium hydroxyapatite microspheres suspended in a hyaluronic acid gel. This review describes preclinical and clinical data, recommendations for use based on the primary author’s clinical experience, and case studies that illustrate implementation of product use recommendations and patient outcomes. Methods: Preclinical data on the lift capacity and tissue integration of the HA/CaHa hybrid injectable and clinical data on its safety, efficacy, and real-world use were extracted from poster presentations, published literature, manufacturer instructions for use, and proprietary data files. Case studies were presented based on clinical experience. Results: The HA component of HA/CaHa provides an immediate and noticeable filling and lifting effect, whereas CaHa microspheres result in neocollagenesis. In preclinical studies, HA/CaHa demonstrated higher lift capacity (P < 0.05) and faster tissue integration than a CaHa filler and led to collagen I gene and protein expression. Clinical studies showed clinical safety and effectiveness with high patient satisfaction. The most common adverse event was injection-site response. Clinician recommendations for achieving desired aesthetic results while minimizing or preventing adverse events are reviewed, including patient selection and assessment, treatment approaches based on face shape, injection technique, and postprocedure care. Conclusion: The novel hybrid injectable consisting of HA with incorporated CaHa microspheres in a single marketed product may help achieve aesthetic goals by immediately restoring volume and potentially improving skin architecture and soft-tissue quality over time.

Sub-acute dermal toxicity of Jatropha curcas Linn. leaf extract coated silver nanoparticles (SNPs) in wistar rats

The application of different nanoparticles is underway in the development of phyto-medicines. Silver nanoparticles (AgNPs) are commonly used as coating agents to treat various bacterial and viral diseases. Their safety and potential toxicity necessitate further research to explore the development of nanoparticles coated herbal drugs. The Azadirachta indica (neem) 5% leaf extract and silver nitrate was used to prepare the silver nanoparticles (SNPs) with the biological reduction (green synthesis) method [1]. The application of silver nanoparticles (SNPs) coated with J. carcus leaf extract (JcLE) on Wistar rats showed no adverse sign of toxicity on hematological parameters except an increase in the neutrophil count and increased in total erythrocyte count (TEC) on 28th day. Similarly, serum biochemical values exhibited an increase in aspartate aminotransferase (AST/SGOT) and alanine transaminase (ALT/SGPT) with JcLE-coated SNPs in treated groups. The histopathology revealed that there was no alteration in skin architecture, however, minimal alteration was observed in the liver and kidney with dilatation of the central vein and sinusoidal space, fatty change in the liver, multifocal necrobiotic changes, cystic degeneration and mild focal glomerular atrophy and hyaline cast in the lumen of tubules of kidney. It indicates the proper absorption and excretion of SNPs from the body. There was no significant effect on hematological parameters in the rats treated with J. curcas leaf extract-coated SNP. However, the serum biochemical analysis revealed a toxic effect on the kidney.

Enhanced wound healing activity of naturally derived Lagenaria siceraria seed oil binary nanoethosomal gel: formulation, characterization, in vitro/in vivo efficiency

BackgroundThe present study aims to enhance the wound healing potential of the seed oil (SO) of Lagenaria siceraria (Egyptian cultivar) via the preparation of SO-loaded binary nanoethosomal (SO-BNE) gels. SO-BNEs were prepared using 23 factorial design, characterized for vesicle size, zeta potential, polydispersity index, linoleic and oleic acid EE% for ensuring improved skin permeability. The L. siceraria SO, optimized SO-BNE gels (0.5% and 5%) and Mebo® were topically applied in full-thickness wounded rat model twice daily for 10 days.ResultsIn the SO-BNE gel groups, the normal appearance of the skin architecture and structure of the dermis was revealed. In addition, the levels of NRF2, TGF-β1 and FOXO1, collagen type I, SMA-α and MIP2 were significantly elevated. The wound healing potential of SO-BNE gels was proposed to be via suppression of oxidative stress and stimulation of skin regeneration biomarkers. Furthermore, the SO screening through GC/MS unveiled high percentages of unsaturated fatty acids. SO was also found to be nontoxic to human skin fibroblast cells; enhanced viability and migration rates at concentration of 50 g/mL by 99.76% and 75.9%, respectively.ConclusionThese findings demonstrate that the Lagenaria siceraria SO-loaded BNE gels represent a promising delivery for wound healing with enhanced release and bioavailability.

Identification of novel small molecule-based strategies of COL7A1 upregulation and readthrough activity for the treatment of recessive dystrophic epidermolysis bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disease caused by loss of function mutations in the gene coding for collagen VII (C7) due to deficient or absent C7 expression. This disrupts structural and functional skin architecture, leading to blistering, chronic wounds, inflammation, important systemic symptoms affecting the mouth, gastrointestinal tract, cornea, and kidney function, and an increased skin cancer risk. RDEB patients have an extremely poor quality of life and often die at an early age. A frequent class of mutations in RDEB is premature termination codons (PTC), which appear in homozygosity or compound heterozygosity with other mutations. RDEB has no cure and current therapies are mostly palliative. Using patient-derived keratinocytes and a library of 8273 small molecules and 20,160 microbial extracts evaluated in a phenotypic screening interrogating C7 levels, we identified three active chemical series. Two of these series had PTC readthrough activity, and one upregulated C7 mRNA, showing synergistic activity when combined with the reference readthrough molecule gentamicin. These compounds represent novel potential small molecule-based systemic strategies that could complement topical-based treatments for RDEB.

Engineering bi-layered skin-like nanopads with electrospun nanofibers and chitosan films for promoting fibroblast infiltration in tissue regeneration and wound healing

This study presents an innovative bi-layered three-dimensional skin-like nanopad (SLN) engineered for skin tissue regeneration. The SLN integrates a mechanically supportive polycaprolactone nanofibrous layer with a functional chitosan hydrogel film, mimicking natural skin. Our SLN exhibits superior flexibility, with a maximum elongation of 751.71 ± 125 % and exceptional porosity of 95 ± 4.5 %, ensuring effective exudate management due to its high water uptake capacity (4393 ± 72 %). FTIR analysis confirmed a distinctive fiber-hydrogel network within the SLN, which serves as a barrier against Staphylococcus aureus and Pseudomonas aeruginosa infiltration. In vitro cell viability assays with the human fibroblast have consistently demonstrated that 3D bi-layered SLN enhances fibroblast attachment, infiltration, and proliferation by 150 ± 20 %. In vivo studies in a rat model demonstrated significantly faster wound closure, with 60 % on day 7 and 87 % on day 10, compared to the 30 % and 60 % in controls, highlighting the efficacy of SLN. By mimicking the architecture of native skin, this biomimetic bi-layered SLN scaffold provides flexibility and support while accelerating in vivo wound closure by promoting fibroblast proliferation and infiltration. Customizable in size, depth, and shape, the engineered SLN has emerged as a promising platform for advanced wound care and tissue engineering.

DermoGAN: multi-task cycle generative adversarial networks for unsupervised automatic cell identification on in-vivo reflectance confocal microscopy images of the human epidermis.

Accurate identification of epidermal cells on reflectance confocal microscopy (RCM) images is important in the study of epidermal architecture and topology of both healthy and diseased skin. However, analysis of these images is currently done manually and therefore time-consuming and subject to human error and inter-expert interpretation. It is also hindered by low image quality due to noise and heterogeneity. We aimed to design an automated pipeline for the analysis of the epidermal structure from RCM images. Two attempts have been made at automatically localizing epidermal cells, called keratinocytes, on RCM images: the first is based on a rotationally symmetric error function mask, and the second on cell morphological features. Here, we propose a dual-task network to automatically identify keratinocytes on RCM images. Each task consists of a cycle generative adversarial network. The first task aims to translate real RCM images into binary images, thus learning the noise and texture model of RCM images, whereas the second task maps Gabor-filtered RCM images into binary images, learning the epidermal structure visible on RCM images. The combination of the two tasks allows one task to constrict the solution space of the other, thus improving overall results. We refine our cell identification by applying the pre-trained StarDist algorithm to detect star-convex shapes, thus closing any incomplete membranes and separating neighboring cells. The results are evaluated both on simulated data and manually annotated real RCM data. Accuracy is measured using recall and precision metrics, which is summarized as the -score. We demonstrate that the proposed fully unsupervised method successfully identifies keratinocytes on RCM images of the epidermis, with an accuracy on par with experts' cell identification, is not constrained by limited available annotated data, and can be extended to images acquired using various imaging techniques without retraining.

Development of mADM-collagen wound dressings for mimicking native skin architecture to enhance skin wound healing

Acellular dermal matrix (ADM) is one of the most promising scaffold materials due to its ability to retain natural extracellular matrix structure. Micronized acellular dermal matrix (mADM) was prepared with no intact cell nuclei and preserved growth factors by High Hydrostatic Pressure (HHP) approach. And mADM-collagen wound dressings were developed with different proportion of type I collagen and recombinant humanized type III collagen. The porous structure of the mADM-collagen wound dressings made them a good candidate for preventing excessive fluid accumulation, while the collagens with gel-like texture combined with mADM powder to form pasty texture wound dressing, which preserving the moisture at the wound site. Moreover, the paste texture of the mADM-collagen wound dressing was easy to reshape to conform any wound shapes and body contours. Furthermore, the resulted mADM-collagen wound dressings showed good biocompatibility by supporting fibroblasts adhesion and proliferation in vitro. Subsequently, a murine model of full-thickness skin wounds was employed to assess its effects on wound healing. Notably, mADM-75% Col-I exhibited superior effects throughout the wound healing process, specifically it promoted neovascularization, skin appendage growth and new skin regeneration. This formulation closely mimicked the collagen ratio found in healthy skin, facilitating the favorable wound repair. These results indicated the superior performance of this mADM-collagen wound dressing providing an optimal environment for wound healing.Graphical

Design, synthesis and anti-inflammatory assessment of certain substituted 1,2,4-triazoles bearing tetrahydroisoquinoline scaffold as COX 1/2-inhibitors

Aiming to discover effective and safe non-steroidal anti-inflammatory agents, a new set of 1,2,4-triazole tetrahydroisoquinoline hybrids 9a-g, 11a-g and 12a-g was synthesized and evaluated as inhibitors of COX-1 and COX-2. In order to overcome the adverse effects of highly selective COX-2 and non-selective COX-2 inhibitors, the compounds of this study were designed with the goal of obtaining moderately selective COX-2 inhibitors. In this study compounds 9e, 9g and 11f are the most effective derivatives against COX-2 with IC50 values 0.87, 1.27 and 0.58 µM, respectively which are better than or comparable to the standard drug celecoxib (IC50 = 0.82 µM) but with lower selectivity indices as required by our goal design. The results of the in vivo anti-inflammatory inhibition test revealed that compounds 9e, 9g and 11f displayed a higher significant anti-inflammatory activity than celecoxib at all-time intervals. In addition, these compounds significantly decreased the production of inflammatory mediators PGE-2, TNF-ɑ and IL-6. Compounds 9e, 9g and 11f had a safe gastric profile compared to indomethacin, also compound 11f (ulcerogenic index = 1.33) was less ulcerous than the safe celecoxib (ulcerogenic index = 3). Moreover, histopathological investigations revealed a normal architecture of both paw skin and gastric mucosa after oral treatment of rats with compound 11f. Furthermore, molecular docking studies were performed on COX-1 and COX-2 to study the binding pattern of compounds 9e, 9g and 11f on both isoenzymes.

Clinical use of lasers and energy-based devices in selected skin diseases

Introduction and purpose In recent years, there has been notable progress in the role of light-emitting technologies, including lasers and other energy-based devices, across various medical disciplines. Dermatology stands out as one of the prominent fields where laser treatments have gained significant popularity. In the clinical setting, a variety of laser types are utilized. A fundamental aspect of ensuring the safe use of laser devices involves comprehending their mechanisms at the tissue level. This knowledge enables practitioners to attain the desired outcomes effectively while minimizing the risk of complications. Lasers have demonstrated effectiveness in treating cutaneous vascular conditions because of their capacity to selectively target intravascular oxyhemoglobin. Rosacea, juvenile hemangioma, and port wine stains are among the vascular skin conditions for which laser therapy has shown notable success. Laser therapy is employed in treating hypertrophic scars, keloids, and acne scars because it facilitates the restructuring of the skin's architecture at the scar site, with the goal of minimizing its size and visibility. Laser therapy stands as the gold standard for removing tattoos. Materials and methods The methodology for conducting literature search involved utilizing medical subject headings terms to explore PubMed. Search terms included: “lasers”, “intense pulsed light”, “dermatology”, “rosacea”, “acne”, “scars”, “tattoo removal”. Conclusions Laser dermatological treatments are gaining popularity worldwide, driving new innovations and clinical applications. This review highlights the significant role and diverse clinical applications of lasers and intense pulsed light in dermatological practice. Improving the quality of skin in patients suffering from skin diseases can significantly increase their quality of life.

O22 Unravelling the pathophysiology of KLICK syndrome to identify therapeutically targetable pathways

Abstract Introduction and aims Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is an ultrarare genodermatosis associated with a homozygous pathogenic variant, c.-95delC in POMP, which encodes for proteasome maturation protein. Clinical manifestations include linear hyperkeratotic papules in the flexures, palmoplantar keratoderma and pseudoainhum. The pathophysiology of KLICK syndrome is poorly understood, resulting in nonspecific, limited treatment options. The aim of this work is to characterize KLICK syndrome at the cellular and molecular level, with the utilization of transcriptomic techniques for potential drug repurposing. Methods A lesional skin biopsy was obtained, following informed consent, from a 32-year-old female patient with KLICK syndrome. Histology and immunostaining were used to characterize the disrupted skin architecture. RNA sequencing was used to identify key dysregulated pathways and the L1000FWD reverse transcriptomics tool enabled the generation of a shortlist of potential therapeutics for KLICK syndrome. CRISPR editing techniques and induced pluripotent stem cell (iPSC) reprogramming Methods were used to generate cellular based models carrying the pathogenic POMP variant in order to support evaluation of the shortlisted therapeutic options. Results KLICK syndrome skin histology featured hyperkeratosis, hypergranulosis and delayed cellular flattening. Consistent with pathological features, pathway analysis of transcriptomic data revealed keratinocyte differentiation and epidermis development as key upregulated pathways in KLICK syndrome. Interestingly, the Panther pathway analysis tool suggested dysregulation in epidermal growth factor receptor (EGFR) signalling, and reverse transcriptomics identified erlotinib, an EGFR inhibitor, as a potential therapeutic treatment for KLICK syndrome. HaCaT keratinocytes were successfully edited using CRISPR-Cas9 to carry the KLICK patient POMP variant and a KLICK patient iPSC line was generated to support in vitro KLICK syndrome modelling. Conclusions KLICK syndrome is a hyperproliferative inflammatory skin disorder associated with a pathogenic variant in POMP. Reverse transcriptomics is a useful tool for shortlisting drugs with biologically relevant mechanisms of action with potential for treatment of rare genetic diseases such as KLICK syndrome.

Developing a gel-col heterogeneous network hydrogel scaffold for tissue-engineered skin with enhanced basement membrane formation

Tissue-engineered skin is constructed utilizing biocompatible matrix materials as scaffolds, and incorporating human epidermal keratinocytes (HEKs), dermal fibroblasts (HDFs), and bioactive molecules, addressing clinical issues such as skin graft rejection and donor scarcity. Conventional fabrication methods of tissue-engineered skin typically rely on homogeneous single-network scaffolds, which may not adequately address the distinct requirements of epidermal and dermal cells or the critical formation of the basement membrane, potentially impacting the development and functional integrity of the skin tissue. Cell culture studies employing GelMA hydrogels of varied concentrations have elucidated that epidermal cells exhibit increased viability on scaffolds with higher concentrations (15 %), whereas fibroblasts show increased proliferation within scaffolds of lower concentrations (5 %). Consequently, we have engineered a GelMA-collagen (Gel-Col) hydrogel scaffold with a heterogeneous network of dense and sparse matrices, conducive to the growth of both fibroblasts and epidermal cells. Culturing epidermal cells on this innovative scaffold, coupled with histological section staining, RT-PCR, and Western blot analyses, has demonstrated that the scaffold significantly enhances cellular adhesion and promotes the development of the epidermal basement membrane compared to single-network hydrogels. Mouse wound transplantation experiments have further confirmed the scaffold’s effectiveness in accelerating wound repair, supporting the development of the basement membrane, and enhancing epidermal regeneration. This research provides a reference for constructing tissue-engineered skin that more precisely emulates the intricate architecture and cellular dynamics of natural skin, propelling the advancement of tissue-engineered skin grafts in the clinical treatment of skin injuries.

Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress.

The new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib. hydrophobic Deucravacitinib was loaded into polyethylene glycol block-polypropylene sulphide (PEG-b-PPS) for transdermal delivery in the treatment of psoriasis. The oxidative stress model of HaCaT psoriasis was established by TNF-α and IL-17A in vitro. JC-1 assay, DCFH-DA staining and mtDNA copy number were utilized to assess mitochondrial function. 0.75% Carbopol®934 was incorporated into SPMs to produce hydrogels and Rhb was labeled to monitor penetration by Immunofluorescence. In vivo, we established IMQ-induced psoriatic model to evaluate therapeutic effect of Car@Deu@PEPS. Deu@PEPS exerted anti-psoriatic effects by restoring mitochondrial DNA copy number and mitochondrial membrane potential in HaCaT. In vivo, Car@Deu@PEPS supramolecular micelle hydrogels had longer retention time in the dermis in the IMQ-induced ROS microenvironment. Topical application of Car@Deu@PEPS significantly restored the normal epidermal architecture of psoriatic skin with abrogation of splenomegaly in the IMQ-induced psoriatic dermatitis model. Car@Deu@PEPS inhibited STAT3 signaling cascade with a corresponding decrease in the levels of the differentiation and proliferative markers Keratin 17 and Cyclin D1, respectively. Meanwhile, Car@Deu@PEPS alleviated IMQ-induced ROS generation and subsequent NLRP3 inflammasome-mediated pyroptosis. Deu@PEPS exerts prominent anti-inflammatory and anti-oxidative effects, which may offers a more patient-acceptable therapy with fewer adverse effects compared with oral deucravacitinib.

High-frequency photoacoustic and ultrasound imaging for skin evaluation: Pilot study for the assessment of a chemical burn.

Skin architecture and its underlying vascular structure could be used to assess the health status of skin. A non-invasive, high resolution and deep imaging modality able to visualize skin subcutaneous layers and vasculature structures could be useful for determining and characterizing skin disease and trauma. In this study, a multispectral high-frequency, linear array-based photoacoustic/ultrasound (PAUS) probe is developed and implemented for the imaging of rat skin in vivo. The study seeks to demonstrate the probe capabilities for visualizing the skin and its underlying structures, and for monitoring changes in skin structure and composition during a 5-day course of a chemical burn. We analayze composition of lipids, water, oxy-hemoglobin, and deoxy-hemoglobin (for determination of oxygen saturation) in the skin tissue. The study successfully demonstrated the high-frequency PAUS imaging probe was able to provide 3D images of the rat skin architecture, underlying vasculature structures, and oxygen saturation, water, lipids and total hemoglobin.

Spatial Mass Cytometry–Based Single-Cell Imaging Reveals a Disrupted Epithelial–Immune Axis in Prurigo Nodularis

Prurigo nodularis (PN) is a chronic, inflammatory skin condition that disproportionately affects African Americans and features intensely pruritic, hyperkeratotic nodules on the extremities and trunk. PN is understudied compared with other inflammatory skin diseases, with the spatial organization of the cutaneous infiltrate in PN yet to be characterized. In this work, we employ spatial imaging mass cytometry to visualize PN lesional skin inflammation and architecture with single-cell resolution through an unbiased machine learning approach. PN lesional skin has increased expression of caspase 3, NF-kB, and phosphorylated signal transducer and activator of transcription 3 compared with healthy skin. Keratinocytes in lesional skin are subdivided into CD14+CD33+, CD11c+, CD63+, and caspase 3-positive innate subpopulations. CD14+ macrophage populations expressing phosphorylated extracellular signal-regulated kinase 1/2 correlate positively with patient-reported itch (P= .006). Hierarchical clustering reveals a cluster of patients with PN with greater atopy, increased NF-kB+ signal transducer and activator of transcription 3-positive phosphorylated extracellular signal-regulated kinase 1/2-positive monocyte-derived myeloid dendritic cells, and increased vimentin expression (P < .05). Neighborhood analysis finds interactions between CD14+ macrophages, CD3+ T cells, monocyte-derived myeloid dendritic cells, and keratinocytes expressing innate immune markers. These findings highlight phosphorylated extracellular signal-regulated kinase-positive CD14+ macrophages as contributors to itch and suggest an epithelial-immune axis in PN pathogenesis.

A tricky singular papular peri‐cicatricial mammarian lesion

AbstractBreast cancer represents the most common malignancy in women worldwide. In most cases, metastasis is the leading cause of mortality. Early diagnosis is still challenging despite standardised, government‐led screening programs, but is crucial in achieving improved survival rates. Additionally, a deeper understanding of the metastatic potential of breast cancer is critical for developing therapeutic interventions to combat widespread disease. Cutaneous metastasis from underlying breast carcinoma is uncommon as the first manifestation of visceral malignancies and is commonly observed in advanced‐stage malignancies, often associated with poor prognosis, and a prompt, precise tissue diagnosis is mandatory. A high index of suspicion in oncologic patients is required to diagnose these lesions, as they can mimic benign skin manifestations and clinical findings may be subtle and going unnoticed. We report on a case of a 76‐year‐old female patient presenting to our non‐invasive diagnostic outpatient clinic with an unusual cutaneous presentation, as an early sign of locally advanced invasive ductal carcinoma breast cancer recurrence. The aim of our article is to underline the importance of the dermatologist in the multi‐disciplinary oncologic diagnostic process, including non‐invasive imaging evaluation of cutaneous lesions, especially insidious breast carcinomas. Dynamic optical coherence tomography (D‐OCT) is not routinely used due to its cost, therefore lesion's aspect has not been completely described, consequently, the correct evaluation of skin architecture appearance can add important information, especially in cutaneous oncology where it can help in early diagnosis or cancer recurrency. OCT may contribute to the detection of subclinical cutaneous manifestations of cancer or recurrence, in particular, when they are difficult to differentiate clinically from benign lesion. In the case we described, OCT of suspected lesion showed the loss of the DEJ with solid nests and irregular vessels.