Human Skin Diseases Research Articles

Risk Factor Profile and Quality of Life of Psoriasis Vulgaris

Background: Psoriasis is an autoimmune human skin disease. It is a chronic and recurrent lesion characterized by erythema patches with well-defined borders with rough, multi-layered, and transparent scales with a significant negative impact on patients' quality of life. Several risk factors for psoriasis can decrease patient’ quality of life. Purpose: To determine the risk factor profile and quality of life of psoriasis patients at the dermatology and venereology outpatient clinic at Dr. Soetomo General Academic Hospital Surabaya. Methods: This was a cross-sectional study involving new and control psoriasis patients. Their risk factors were evaluated using questionnaires, and their quality of life was measured using the DLQI questionnaires. The data was collected at the Dermatology and Venereology outpatient unit Dr. Soetomo General Academic Hospital Surabaya. Result: Of the 24 patients, the biggest risk factor for psoriasis patients was trauma/ Koebner phenomenon, as reported in 15 patients (62.5%), and 11 patients’ (45.8%) quality of life was affected. Conclusion: Trauma was the largest risk factor for psoriasis, and psoriasis has significantly affected patient’ quality of life.

Expert System for Diagnosing Human Skin Diseases Using Web-Based Naïve Bayes Method

Skin disease is a disease that often found in tropical countries like Indonesia. According to the survey, skin disease is the third of the ten most outpatient diseases. Lack of public knowledge about skin diseases and how to prevent and treat them can cause a person to develop acute skin diseases. The purpose of this research is to create an expert system application for diagnosis of human skin diseases using the web-based naïve Bayes method. With expert system, it hoped that human skin diseases can be detected early and can minimize the occurrence of more dangerous diseases. The calculation in this expert system uses the naïve Bayes method. This expert system makes diagnosis by analyzing input of symptoms experienced by patient and then processing it using certain rules according the expert knowledge that has been stored in the knowledge base. The result of this research is to build an expert system for diagnosing human skin diseases using website-based naïve Bayes. The results of the system trial of 20 respondents were the website could provide diagnosis results based on the inputted rules and could diagnose skin diseases properly. This website can used as an alternative use of technology so it can be used to diagnose skin diseases quickly, precisely and accurately. So in the future the handling of skin diseases can be faster and more efficient.

Atopic Dermatitis in Domestic Animals: What Our Current Understanding Is and How This Applies to Clinical Practice.

Atopic dermatitis is a clinical syndrome that affects both people and animals. Dogs closely mimic the complexity of the human skin disease, and much progress has been made in recent years in terms of our understanding of the role of skin impairment and the identification of new treatments. Cats and horses also develop atopic syndromes which include both cutaneous and respiratory signs, yet studies in these species are lagging. It is now recognized that atopic dermatitis is not a single disease but a multifaceted clinical syndrome with different pathways in various subgroups of patients. Appreciating this complexity is clinically relevant as we develop more targeted treatments which may work well in some patients but not in others. Different phenotypes of atopic dermatitis have been described in dogs, and it is possible that phenotypes related to breed and age may exist in other animals similar to how they are described in people. The awareness of different mechanisms of disease leads to the desire to correlate different phenotypes with specific biomarkers and responses to treatment. In this review, the current understanding and updated information on atopic syndrome in animals are described, highlighting opportunities for further studies in the future.

Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases

Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.

Pengembangan Sistem Pakar Berbasis Android untuk Menentukan Obat Generik pada Penyakit Kulit Menggunakan Metode Forward Chaining

Skin disease can be suffered by all people and ages as a common disease. In general treatment for people with skin diseases is by consulting to medical experts and asking for a medicine prescription. However, by utilizing current communication technology, sufferers are able to get good information about skin diseases. The expert system for the diagnosis of skin diseases has been done before. However, the expert system is built based on web and desktop, so it is less flexible in use, moreover in supporting self assistance for the skin disease sufferer. Therefore, this study aims to develop an Android-based expert system that can help diagnose skin diseases in humans as well as provide recommendations of generic medicine as first aid. The expert system developed by implementing the Forward Chaining (FC) method as an inference technique. This research was conducted in five phases, namely data collection, analysis system, design system, implementation, and testing. The knowledge base in this expert system includes 39 types of skin diseases, 83 symptoms, 16 types of generic drugs, 150 lines rules of skin disease diagnosis, and 39 lines recommendations of generic drug.

Human pluripotent stem cells: An alternative for 3D in vitro modelling of skin disease

To effectively study the skin and its pathology, various platforms have been used to date, with in vitro 3D skin models being considered the future gold standard. These models have generally been engineered from primary cell lines. However, their short life span leading to the use of various donors, imposes issues with genetic variation. Human pluripotent stem cell (hPSC)-technology holds great prospects as an alternative to the use of primary cell lines to study the pathophysiology of human skin diseases. This is due to their potential to generate an unlimited number of genetically identical skin models that closely mimic the complexity of in vivo human skin. During the past decade, researchers have therefore started to use human embryonic and induced pluripotent stem cells (hESC/iPSC) to derive skin resident-like cells and components. These have subsequently been used to engineer hPSC-derived 3D skin models. In this review, we focus on the advantages, recent developments, and future perspectives in using hPSCs as an alternative cell source for modelling human skin diseases in vitro.

Designing a multi-epitope vaccine against Mycobacteroides abscessus by pangenome-reverse vaccinology

Mycobacteroides abscessus (Previously Mycobacterium abscessus) is an emerging microorganism of the newly defined genera Mycobacteroides that causes mainly skin and tissue diseases in humans. The recent availability of total 34 fully sequenced genomes of different strains belonging to this species has provided an opportunity to utilize this genomics data to gain novel insights and guide the development of specific antimicrobial therapies. In the present study, we collected collectively 34 complete genome sequences of M. abscessus from the NCBI GenBank database. Pangenome analysis was conducted on these genomes to understand the genetic diversity and to obtain proteins associated with its core genome. These core proteins were then subjected to various subtractive filters to identify potential antigenic targets that were subjected to multi-epitope vaccine design. Our analysis projected the open pangenome of M. abscessus containing 3443 core genes. After applying various stepwise filtration steps on the core proteins, a total of four potential antigenic targets were identified. Utilizing their constituent CD4 and CD8 T-cell epitopes, a multi-epitope based subunit vaccine was computationally designed. Sequence-based analysis as well as structural characterization revealed the immunological effectiveness of this designed vaccine. Further molecular docking, molecular dynamics simulation and binding free energy estimation with Toll-like receptor 2 indicated strong structural associations of the vaccine with the immune receptor. The promising results are encouraging and need to be validated by additional wet laboratory studies for confirmation.

Generation of a Simplified Three-Dimensional Skin-on-a-chip Model in a Micromachined Microfluidic Platform.

This work presents a new, cost-effective, and reliable microfluidic platform with the potential to generate complex multilayered tissues. As a proof of concept, a simplified and undifferentiated human skin containing a dermal (stromal) and an epidermal (epithelial) compartment has been modelled. To accomplish this, a versatile and robust, vinyl-based device divided into two chambers has been developed, overcoming some of the drawbacks present in microfluidic devices based on polydimethylsiloxane (PDMS) for biomedical applications, such as the use of expensive and specialized equipment or the absorption of small, hydrophobic molecules and proteins. Moreover, a new method based on parallel flow was developed, enabling the in situ deposition of both the dermal and epidermal compartments. The skin construct consists of a fibrin matrix containing human primary fibroblasts and a monolayer of immortalized keratinocytes seeded on top, which is subsequently maintained under dynamic culture conditions. This new microfluidic platform opens the possibility to model human skin diseases and extrapolate the method to generate other complex tissues.

Daily Lifestyle and Cutaneous Malignancies.

Daily lifestyle is a fundamental part of human life and its influence accumulates daily in the human body. We observe that a good daily lifestyle has a beneficial impact on our health; however, the actual effects of individual daily lifestyle factors on human skin diseases, especially skin cancers, have not been summarized. In this review, we focused on the influence of daily lifestyle on the development of skin cancer and described the detailed molecular mechanisms of the development or regulation of cutaneous malignancies. Several daily lifestyle factors, such as circadian rhythm disruption, smoking, alcohol, fatty acids, dietary fiber, obesity, and ultraviolet light, are known to be associated with the risk of cutaneous malignancies, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Although the influence of some daily lifestyles on the risk of skin cancers is controversial, this review provides us a better understanding of the relationship between daily lifestyle factors and skin cancers.

Itch in Atopic Dermatitis - What Is New?

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

ScRNA-seq of Rashes Shows Recurrent Downregulation of the RNA-binding protein ZFP36L2, Revealing Its Role In Mediating Human T cell Cytokine Repression

Abstract The mechanisms driving inflammatory disease are incompletely understood. We performed single-cell RNA-seq on immune cells isolated from 24 human inflammatory skin disease samples of atopic dermatitis, psoriasis, and lichen planus and identified the RNA-binding protein ZFP36L2 as a recurrently repressed transcript in T cells (log FC = −0.85; adjPval < 0.001). CRISPR/Cas9-mediated disruption of ZFP36L2 in unstimulated primary human T cells resulted in a greater than 5-fold induction of inflammatory cytokines (e.g. TNF-α (p = 0.008), GM-CSF, (p = 0.002), IFN-γ (p = 0.030), and IL-13 (p = 0.044)), with minimal effect in stimulated T cells. This greater effect prior to stimulation suggests a role for ZFP36L2 in repressing the onset of inflammation. Consistent with this, temporal analysis of ZFP36L2 and cytokine T cell response to inflammatory stimuli displays ZFP36L2 transcript downregulation prior to induction of cytokine transcripts. These results reveal a previously unknown early, central regulatory role for ZFP36L2 in human inflammation and cutaneous disease, suggesting a potential target for therapeutic exploitation.

Exploring Mycosporine-Like Amino Acids (MAAs) as Safe and Natural Protective Agents against UV-Induced Skin Damage.

Prolonged exposure to harmful ultraviolet radiation (UVR) can induce many chronic or acute skin disorders in humans. To protect themselves, many people have started to apply cosmetic products containing UV-screening chemicals alone or together with physical sunblocks, mainly based on titanium–dioxide (TiO2) or zinc-oxide (ZnO2). However, it has now been shown that the use of chemical and physical sunblocks is not safe for long-term application, so searches for the novel, natural UV-screening compounds derived from plants or bacteria are gaining attention. Certain photosynthetic organisms such as algae and cyanobacteria have evolved to cope with exposure to UVR by producing mycosporine-like amino acids (MAAs). These are promising substitutes for chemical sunscreens containing commercially available sunblock filters. The use of biopolymers such as chitosan for joining MAAs together or with MAA-Np (nanoparticles) conjugates will provide stability to MAAs similar to the mixing of chemical and physical sunscreens. This review critically describes UV-induced skin damage, problems associated with the use of chemical and physical sunscreens, cyanobacteria as a source of MAAs, the abundance of MAAs and their biotechnological applications. We also narrate the effectiveness and application of MAAs and MAA conjugates on skin cell lines.

The Translational Relevance of Human Circulating Memory Cutaneous Lymphocyte-Associated Antigen Positive T Cells in Inflammatory Skin Disorders.

Circulating memory T cells are heterogeneous in their tissue tropism. The skin-seeking T cell subset expresses the cutaneous lymphocyte-associated antigen (CLA) on their surface. CLA+ memory T cells not only migrate from blood to skin but also recirculate between blood and skin. Studying CLA+ memory T cells in cutaneous diseases has allowed a better understanding of immune-inflammatory mechanisms that take place. The analysis of the phenotypical features of these cells, their antigen specificity, cytokine production profile, and changes in relationship to clinical status and therapies among other characteristics have led to the concept that they constitute peripheral cellular biomarkers in T cell-mediated cutaneous conditions. CLA+ memory T cells are of relevance in the pathogenesis of several cutaneous diseases, such as psoriasis (PSO), atopic dermatitis, vitiligo, and drug-induced allergic reactions, to name a few. The interaction of circulating CLA+ T cells with skin-resident cells has been investigated in different ex vivo coculture models made out of clinical samples. Interestingly, microbes that are present in the skin or related with human skin diseases are preferentially recognized by CLA+ T cells. Thus, the interaction of Streptococcus pyogenes with CLA+ T cells in PSO is providing novel concepts that help to understand disease immunopathogenesis. The goal of this review is to present latest results in the field of CLA+ T cells in T cell-mediated inflammatory skin diseases and their translational relevance for human immunodermatology.

IL-1 Family Antagonists in Mouse and Human Skin Inflammation.

Interleukin (IL)-1 family cytokines initiate inflammatory responses, and shape innate and adaptive immunity. They play important roles in host defense, but excessive immune activation can also lead to the development of chronic inflammatory diseases. Dysregulated IL-1 family signaling is observed in a variety of skin disorders. In particular, IL-1 family cytokines have been linked to the pathogenesis of psoriasis and atopic dermatitis. The biological activity of pro-inflammatory IL-1 family agonists is controlled by the natural receptor antagonists IL-1Ra and IL-36Ra, as well as by the regulatory cytokines IL-37 and IL-38. These four anti-inflammatory IL-1 family members are constitutively and highly expressed at steady state in the epidermis, where keratinocytes are a major producing cell type. In this review, we provide an overview of the current knowledge concerning their regulatory roles in skin biology and inflammation and their therapeutic potential in human inflammatory skin diseases. We further highlight some common misunderstandings and less well-known observations, which persist in the field despite recent extensive interest for these cytokines.

Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions.

The microbiome plays an important role in a wide variety of skin disorders. Not only is the skin microbiome altered, but also surprisingly many skin diseases are accompanied by an altered gut microbiome. The microbiome is a key regulator for the immune system, as it aims to maintain homeostasis by communicating with tissues and organs in a bidirectional manner. Hence, dysbiosis in the skin and/or gut microbiome is associated with an altered immune response, promoting the development of skin diseases, such as atopic dermatitis, psoriasis, acne vulgaris, dandruff, and even skin cancer. Here, we focus on the associations between the microbiome, diet, metabolites, and immune responses in skin pathologies. This review describes an exhaustive list of common skin conditions with associated dysbiosis in the skin microbiome as well as the current body of evidence on gut microbiome dysbiosis, dietary links, and their interplay with skin conditions. An enhanced understanding of the local skin and gut microbiome including the underlying mechanisms is necessary to shed light on the microbial involvement in human skin diseases and to develop new therapeutic approaches.

Multiomics Integration in Skin Diseases with Alterations in Notch Signaling Pathway: PlatOMICs Phase 1 Deployment.

The high volume of information produced in the age of omics was and still is an important step to understanding several pathological processes, providing the enlightenment of complex molecular networks and the identification of molecular targets associated with many diseases. Despite these remarkable scientific advances, the majority of the results are disconnected and divergent, making their use limited. Skin diseases with alterations in the Notch signaling pathway were extensively studied during the omics era. In the GWAS Catalog, considering only studies on genomics association (GWAS), several works were deposited, some of which with divergent results. In addition, there are thousands of scientific articles available about these skin diseases. In our study, we focused our attention on skin diseases characterized by the impairment of Notch signaling, this pathway being of pivotal importance in the context of epithelial disorders. We considered the pathologies of five human skin diseases, Hidradenitis Suppurativa, Dowling Degos Disease, Adams–Oliver Syndrome, Psoriasis, and Atopic Dermatitis, in which the molecular alterations in the Notch signaling pathway have been reported. To this end, we started developing a new multiomics platform, PlatOMICs, to integrate and re-analyze omics information, searching for the molecular interactions involved in the pathogenesis of skin diseases with alterations in the Notch signaling pathway.

Pd Nanoparticle Adsorption ZnO Nanorods for Enhancing Photodetector UV-Sensing Performance

Ultraviolet (UV) detection is an important index, as UV rays can cause skin diseases in humans. To enhance the performance of UV photodetectors, we fabricated palladium nanoparticles(Pd NPs) modified ZnO nanorods. The surface morphology is observed by using transmission electron microscopy and transmission electron microscopy. The crystal structure is analysed by using X-ray diffraction. The optical property is investigated by using photoluminescence spectra. The I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dark</sub> of the ZnO and Pd/ZnO samples was 5.05 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-8</sup> and 2.24 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-9</sup> A when a 1 V bias was applied. On the other hand, the I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">photo</sub> of the ZnO and Pd/ZnO samples was 2.56 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> and 4.38 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> A when the sample is illuminated UV light (365 nm). The current ratio of I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">photo</sub> /I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dark</sub> for the ZnO and Pd/ZnO samples was 50.8 and 1960, respectively. The enhanced performance of the Pd NPs can produce a strong electric field after light is absorbed via the localised surface plasmon resonance effect.

Human skin ringworm detection using wavelet and curvelet transforms: a comparative study

The common human skin disease called ringworm is investigated in the light of computer vision. Two distinct methodologies are developed for its detection. The first methodology implements three-level multi-wavelet decomposition of the skin images and subsequent evaluation of the approximation and detail subband energies which act as the texture characterising features. The second methodology incorporates the curvelet to segment the circular protrusion of the skin images especially with ringworms followed by statistical texture investigation by grey-level co-occurrence matrix (GLCM). After feature extraction by both the methodologies, binary classifier called the support vector machine (SVM) recognises the images as ringworm with detection accuracy of around 87% and 80% for the first and second methodologies respectively. In addition, the performance indexing parameters of SVM classification like sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) which are not previously addressed are evaluated. Both the methodologies are comprehensively demonstrated and compared to select the better one. The selected method is then compared with the available technique and commented upon.

Light and Skin.

Sunlight comprises radiation of different wavelengths, of which UVA and UVB are most important with respect to human skin diseases. Next to erythema, edema, and sunburns, UV radiation causes skin cancer. UV radiation of any wavelength is now considered as a class I carcinogen to humans. The mutagenic effects of UV radiation depend on DNA damage following direct absorption by nuclear DNA, resulting in cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts that, if not repaired by nucleotide excision repair pathway, result in characteristic UV signature mutations (C→T or CC→TT transition). In addition, increased formation of reactive oxygen species by UV exposure may cause formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine leading to T→G transversion. In addition, UV radiation has been shown to induce a number of immune modulations that largely result in local and potentially also in systemic immunosuppression, which may not only impair control of dysplastic and neoplastic skin lesions but also affect immuno-pathological and infectious skin diseases. Recent find-ings have shown that ambient doses of high-energy visible light, beyond the UV range, may also cause damage to human skin.

Human skin ringworm detection using wavelet and curvelet transforms: a comparative study

The common human skin disease called ringworm is investigated in the light of computer vision. Two distinct methodologies are developed for its detection. The first methodology implements three-level multi-wavelet decomposition of the skin images and subsequent evaluation of the approximation and detail subband energies which act as the texture characterising features. The second methodology incorporates the curvelet to segment the circular protrusion of the skin images especially with ringworms followed by statistical texture investigation by grey-level co-occurrence matrix (GLCM). After feature extraction by both the methodologies, binary classifier called the support vector machine (SVM) recognises the images as ringworm with detection accuracy of around 87% and 80% for the first and second methodologies respectively. In addition, the performance indexing parameters of SVM classification like sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) which are not previously addressed are evaluated. Both the methodologies are comprehensively demonstrated and compared to select the better one. The selected method is then compared with the available technique and commented upon.