Epidermal stem cells: skin surveillance and clinical perspective.

The skin epidermis is continually influenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels epidermal renovation and hair regeneration with powerful self-renewal ability, as well as keeping diverse signals that direct their activity under surveillance with quick response. The importance of epidermal stem cells in wound healing and immune-related skin conditions has been increasingly recognized, and their potential for clinical applications is attracting attention. In this review, we delve into recent advancements and the various physiological and psychological factors that govern distinct epidermal stem cell populations, including psychological stress, mechanical forces, chronic aging, and circadian rhythm, as well as providing an overview of current methodological approaches. Furthermore, we discuss the pathogenic role of epidermal stem cells in immune-related skin disorders and their potential clinical applications.

Efficacy in patients with EGFR-positive non-small-cell lung cancer treated with dacomitinib who had skin adverse events: post hoc analyses from ARCHER 1050.

Aim: We investigated association between skin adverse events (AEs) and efficacy with dacomitinib in patients with EGFR-positive non-small-cell lung cancer (NSCLC).Methods: Post hoc analyses from ARCHER 1050 evaluated efficacy in patients who did and did not experience grade ≥2 skin AEs with dacomitinib. Landmark analyses were performed at 3 and 6 months.Results: In patients who had skin AEs (72.2%) vs. those who did not (27.7%), median progression-free survival was 16.0 vs. 9.2 months, median overall survival (OS) was 37.7 vs. 21.6 months, and objective response rate was 80.2 vs. 61.5%; OS was improved at 3 and 6 months landmark analyses.Conclusion: Presence of grade ≥2 skin AEs was associated with numerically improved efficacy and represents a valuable biomarker of treatment outcome with dacomitinib in patients with advanced NSCLC.Clinical Trial Registration: NCT01774721 (ClinicalTrials.gov).

The ARCHER 1050 study assessed how the drugs called dacomitinib and gefitinib affected people with non-small-cell lung cancer (NSCLC) who had mutations in the EGFR gene. In this study, people who were treated with dacomitinib lived longer without their cancer getting worse than people who were treated with gefitinib. Skin adverse reactions were higher in people who were treated with dacomitinib than gefitinib. In this follow-up analysis, researchers wanted to see if the treatment effect of dacomitinib was different between people who had skin adverse reactions and people who did not have skin adverse reactions after treatment with dacomitinib. The results from this analysis showed that after treatment with dacomitinib, half of the people who had skin adverse reactions lived for 16.0 months, and half of the people who did not have skin adverse reactions lived for 9.2 months without their cancer getting worse. This study also showed that half of the people who had skin adverse reactions lived for 37.7 months, and half of the people who did not have skin adverse reactions lived for 21.6 months. In summary, the results from this study showed that the treatment effect of dacomitinib was better in people who had skin adverse reactions after treatment with dacomitinib. Therefore, skin adverse reactions can be a marker of better treatment effect in people with NSCLC who had mutations in the EGFR gene when treated with dacomitinib.

[Translated article] Congenital and Hereditary Nail Disease.

Nail disorders in newborns can show independently or as components of systemic illnesses or genodermatoses. The examination of these abnormalities is complex and sometimes challenging. However, familiarity with these disorders can significantly contribute to uncovering potential underlying conditions. This review includes the physiological nail changes seen within the first few months of life, such as Beau's lines, onychoschizia, koilonychia, congenital nail fold hypertrophy of the first digit, and onychocryptosis. This review also focuses on the most relevant congenital disorders reported and how to perform differential diagnosis. Finally, this review highlights those hereditary diseases in which nail involvement is crucial for diagnosis, such as nail-patella syndrome, congenital pachyonychia, or congenital dyskeratosis, among others.

Autosomal dominant genodermatoses in adults being heralded by superimposed skin lesions in children.

In autosomal dominant skin disorders, pronounced mosaic involvement may sometimes occur in the neonate, originating in a heterozygous embryo from early loss of heterozygosity, probably during the first week after fertilization. In biallelic phenotypes, such overlaying mosaic involvement may coexist with disseminated mosaicism, for example, in neurofibromatosis or tuberous sclerosis. In other phenotypes, however, classical nonsegmental involvement tends to appear much later, which is why the superimposed mosaic is a heralding feature. In Brooke-Spiegler syndrome (eccrine cylindromatosis), a large pedigree documented a 5-year-old boy with multiple, congenital small eccrine cylindromas along the lines of Blaschko. Disseminated cylindromas were absent because they usually appear in adulthood. ̶ In Hornstein-Knickenberg syndrome, an affected woman had an 8-year-old son with a nevus comedonicus-like lesion exemplifying a forerunner of the syndrome. ("Birt-Hogg-Dubé syndrome" represents a nonsyndromic type of hereditary perifollicular fibromas.) In glomangiomatosis, neonatal superimposed mosaicism is a heralding feature because disseminated lesions appear during puberty or adulthood. Linear porokeratosis is a harbinger of disseminated porokeratosis that develops 30 or 40 years later. ̶ Cases of superimposed linear Darier disease were forerunners of nonsegmental manifestation. ̶ In a case of Hailey-Hailey disease, neonatal mosaic lesions heralded nonsegmental involvement that began 22 years later.

Secretome of human umbilical cord mesenchymal stem cell maintains skin homeostasis by regulating multiple skin physiological function.

Skin is the largest organ in the body and the first defense to resist various diseases and external stimuli that easily cause infection and inflammation. Aseptic inflammation, barrier damage, and foreign aid pressure induce the destruction and damage to the skin microenvironment. Subsequently, it destroys the skin's physiological function, leading to the maintenance and circulation of steady-state imbalance and aggravating the process of skin disorders. Our study evaluated the therapeutic potential of the secretome of human umbilical cord mesenchymal stem cells (UC-CM) for dermatological diseases in adult human skin cells, ex vivo skin tissue, and a 3D skin model. Our data suggested several advantages of UC-CM due to (1) their low cytotoxicity and sensitization properties; (2) their anti-inflammatory capacity for treating inflammatory chronic cutaneous diseases; (3) their enhanced capacity of the skin barrier for treating abnormal barrier metabolism; and (4) their positive impact on restoring skin homeostasis due to effective regulation ability of skin physiological function including cell apoptosis, detoxification, and anti-aging. We thus envisage that the possibility of harnessing the therapeutic potential of UC-CM might benefit patients suffering from inflammatory skin disorders such as atopic dermatitis, acne, and psoriasis.

Pain Management in Dermatology.

BACKGROUND: The dermatologist has to deal with many situations where the patient feels pain and must therefore know how to manage it. SUMMARY: The aim of this review was to explore the treatments available to manage pain in dermatology in different circumstances, with an emphasis on pharmacological and non-pharmacological interventions specifically studied in dermatology.

miRNAs, Mesenchymal Stromal Cells and Major Neoplastic and Inflammatory Skin Diseases: A Page Being Written: A Systematic Review.

Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.

Generating Functional and Highly Proliferative Melanocytes Derived from Human Pluripotent Stem Cells: A Promising Tool for Biotherapeutic Approaches to Treat Skin Pigmentation Disorders.

Melanocytes are essential for skin homeostasis and protection, and their loss or misfunction leads to a wide spectrum of diseases. Cell therapy utilizing autologous melanocytes has been used for years as an adjunct treatment for hypopigmentary disorders such as vitiligo. However, these approaches are hindered by the poor proliferative capacity of melanocytes obtained from skin biopsies. Recent advances in the field of human pluripotent stem cells have fueled the prospect of generating melanocytes. Here, we have developed a well-characterized method to produce a pure and homogenous population of functional and proliferative melanocytes. The genetic stability and potential transformation of melanocytes from pluripotent stem cells have been evaluated over time during the in vitro culture process. Thanks to transcriptomic analysis, the molecular signatures all along the differentiation protocol have been characterized, providing a solid basis for standardizing the protocol. Altogether, our results promise meaningful, broadly applicable, and longer-lasting advances for pigmentation disorders and open perspectives for innovative biotherapies for pigment disorders.

The Anti-Acne Potential and Chemical Composition of Knautia drymeia Heuff. and Knautia macedonica Griseb Extracts.

The treatment of acne and other seborrheic diseases has arisen as a significant clinical challenge due to the increasing appearance of multi-drug resistant pathogens and a high frequency of recurrent lesions. Taking into consideration the fact that some Knautia species are valuable curatives in skin diseases in traditional medicine, we assumed that the thus far unstudied species K. drymeia and K. macedonica may be a source of active substances used in skin diseases. The purpose of this study was to evaluate the antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities of their extracts and fractions. An LC-MS analysis revealed the presence of 47 compounds belonging to flavonoids and phenolic acids in both species while the GC-MS procedure allowed for the identification mainly sugar derivatives, phytosterols, and fatty acids and their esters. The ethanol as well as methanol-acetone-water (3:1:1) extracts of K. drymeia (KDE and KDM) exhibited great ability to scavenge free radicals and good capacity to inhibit cyclooxygenase-1, cyclooxygenase-2, and lipoxygenase. Moreover, they had the most favorable low minimal inhibitory concentration values against acne strains, and importantly, they were non-toxic toward normal skin fibroblasts. In conclusion, K. drymeia extracts seem to be promising and safe agents for further biomedical applications.

Topical foam as a promising carrier system for active pharmaceutical ingredients: review of clinical studies.

Skin disorders are preferentially treated by topical administration of medicines or cosmetics because of the possibility of local action. However, a great concern is the delivery of topical actives with effective penetration through the stratum corneum to ensure the desired effect. Considering the search for a carrier system that allows the penetration/permeation of active pharmaceutical ingredients through this structure, searching for effective topical pharmaceutical forms is needed. Foams have been widely studied over the years due to their high capacity to favor the active to overcome the cutaneous barrier and because this form of presentation has ease of application and high acceptability by users. The objective of this review was to analyze the potential of foam as a topical pharmaceutical form for treating skin disorders, upon clinical cases reported in the literature. Foam presents technical advantages when compared to other conventional topical pharmaceutical forms due to its fast action, high tolerance, and safety, with reduction or total remission of adverse events. Regarding the patient, foam increased the rate of adherence to the treatment. Therefore, it is concluded that foam is an effective, secure, and stable topical presentation form for carrying active pharmaceutical ingredients and widely accepted by patients.

T-cell subsets in the skin and their role in inflammatory skin disorders.

T lymphocytes (T cells) are major players of the adaptive immune response. Naive T cells are primed in the presence of cytokines, leading to polarization into distinct T-cell subsets with specific functions. These subsets are classified based on their T-cell receptor profile, expression of transcription factors, surface cytokine and chemokine receptors, and their cytokine production, which together determine their specific function. This review provides an overview of the various T-cell subsets and their function in several inflammatory skin disorders ranging from allergic inflammation to skin tumors. Moreover, we highlight similarities of T-cell responses across different skin disorders, demonstrating the presence of similar and opposing functions for the different T-cell subsets. Finally, we discuss the effects of currently available and promising therapeutic approaches to harness T cells in inflammatory skin diseases for which efficacy next to unwanted side effects provide new insights into the pathophysiology of skin disorders.

Efficacy and safety of picosecond 755-nm alexandrite laser for treatment of nevus of Ota in Taiwanese children: A retrospective study.

OBJECTIVES: To evaluate the efficacy and safety of picosecond 755-nm alexandrite laser in the treatment of nevus of Ota in children. MATERIALS AND METHODS: A retrospective study was conducted by reviewing medical charts and photographs of 86 Taiwanese children with various types of nevus of Ota between January 2017 and September 2020. Picosecond 755-nm alexandrite laser therapy was used to treat pigmentary lesions. Percent clearance of lesions during treatment and the treatment time required to achieve 95%-100% clearance were determined. RESULTS: According to Tanino's classification or Peking University Medical College Hospital (PUMCH) classification of nevus of Ota, most patients belonged to Tanino's Type II (32%) and Type III (38%) or PUMCH Type IIb (33%) and Type IIIb (26%), which indicated that the nevus was mainly distributed in the forehead, upper and lower eyelid, zygomatic, cheek, and temple regions. After treatment with picosecond 755-nm alexandrite laser, 96.5% of the patients achieved 95%-100% clearance with an average of 4.3 treatment sessions. The earlier onset of lesions (before 5 months of age) and the darker Fitzpatrick skin types (type IV vs. type III) significantly increased the number of treatments required to achieve clear response, while sex, age at first treatment, Tanino's classification of nevus, and color of nevus had no significant effect. Posttreatment hypopigmentation or hyperpigmentation was transient and resolved within 6 months. No serious response of the skin was evident. CONCLUSION: Picosecond 755-nm alexandrite laser treatment of nevus of Ota in children was safe and effective. The treatment was well-tolerated, and only a few transient, minor side effects occurred.

Dermatology consultation requests from a university hospital's pediatric and adult emergency departments: A 5-year retrospective analysis.

BACKGROUND: Unnecessary dermatology consultation requests from emergency departments (EDs) are a common occurrence worldwide. AIM: This study aimed to analyze the demographic and clinical characteristics of patients consulted to the dermatology department for dermatologic disorders by a university hospital's pediatric ED (PED) and adult ED (AED). MATERIALS AND METHODS: The electronic medical records of 2316 dermatology consultation requests from the PED and AED during a 5-year period were retrospectively reviewed. Patient demographic and clinical characteristics, dermatological diagnoses, and time of day of dermatology consultation requests from the PED and AED were retrospectively analyzed. RESULTS: The electronic medical records of 1845 consultation requests with complete data were included in the study. There were 969 (52.5%) consultation requests from the PED and 876 (47.5%) from the AED. Mean time from onset of dermatological symptoms to ED presentation was 31.6 d. Herpes zoster infections (18.5%), adverse cutaneous drug reactions (8.1%), and urticaria with angioedema (7.9%) were the most common skin disorders resulting in consultation requests from the AED, versus non-specific viral infections (9.2%), insect bites (8.3%), and atopic dermatitis (8.2%) from the PED. In all, 11.5% of ED patients that received dermatology department consultation required hospitalization due to dermatologic disorders. CONCLUSION: As patients commonly present to EDs with non-urgent dermatological diseases, ED physicians should receive training on common dermatological diseases so as to decrease the number of unnecessary dermatology consultation requests.

Cannabinoids: Therapeutic Use in Clinical Practice.

Medical case reports suggest that cannabinoids extracted from Cannabis sativa have therapeutic effects; however, the therapeutic employment is limited due to the psychotropic effect of its major component, Δ9-tetrahydrocannabinol (THC). The new scientific discoveries related to the endocannabinoid system, including new receptors, ligands, and mediators, allowed the development of new therapeutic targets for the treatment of several pathological disorders minimizing the undesirable psychotropic effects of some constituents of this plant. Today, FDA-approved drugs, such as nabiximols (a mixture of THC and non-psychoactive cannabidiol (CBD)), are employed in alleviating pain and spasticity in multiple sclerosis. Dronabinol and nabilone are used for the treatment of chemotherapy-induced nausea and vomiting in cancer patients. Dronabinol was approved for the treatment of anorexia in patients with AIDS (acquired immune deficiency syndrome). In this review, we highlighted the potential therapeutic efficacy of natural and synthetic cannabinoids and their clinical relevance in cancer, neurodegenerative and dermatological diseases, and viral infections.

Nanoparticles for Topical Application in the Treatment of Skin Dysfunctions-An Overview of Dermo-Cosmetic and Dermatological Products.

Nanomaterials (NM) arouse interest in various fields of science and industry due to their composition-tunable properties and the ease of modification. They appear currently as components of many consumer products such as sunscreen, dressings, sports clothes, surface-cleaning agents, computer devices, paints, as well as pharmaceutical and cosmetics formulations. The use of NPs in products for topical applications improves the permeation/penetration of the bioactive compounds into deeper layers of the skin, providing a depot effect with sustained drug release and specific cellular and subcellular targeting. Nanocarriers provide advances in dermatology and systemic treatments. Examples are a non-invasive method of vaccination, advanced diagnostic techniques, and transdermal drug delivery. The mechanism of action of NPs, efficiency of skin penetration, and potential threat to human health are still open and not fully explained. This review gives a brief outline of the latest nanotechnology achievements in products used in topical applications to prevent and treat skin diseases. We highlighted aspects such as the penetration of NPs through the skin (influence of physical-chemical properties of NPs, the experimental models for skin penetration, methods applied to improve the penetration of NPs through the skin, and methods applied to investigate the skin penetration by NPs). The review summarizes various therapies using NPs to diagnose and treat skin diseases (melanoma, acne, alopecia, vitiligo, psoriasis) and anti-aging and UV-protectant nano-cosmetics.

Zinc and Zinc Transporters in Dermatology.

Zinc is an important trace mineral in the human body and a daily intake of zinc is required to maintain a healthy status. Over the past decades, zinc has been used in formulating topical and systemic therapies for various skin disorders owing to its wound healing and antimicrobial properties. Zinc transporters play a major role in maintaining the integrity of the integumentary system by controlling zinc homeostasis within dermal layers. Mutations and abnormal function of zinc-transporting proteins can lead to disease development, such as spondylocheirodysplastic Ehlers-Danlos syndrome (SCD-EDS) and acrodermatitis enteropathica (AE) which can be fatal if left untreated. This review discusses the layers of the skin, the importance of zinc and zinc transporters in each layer, and the various skin disorders caused by zinc deficiency, in addition to zinc-containing compounds used for treating different skin disorders and skin protection.

Ceramide Acyl Chain Length and Its Relevance to Intracellular Lipid Regulation.

Ceramides are a class of sphingolipids which are implicated in skin disorders, obesity, and other metabolic diseases. As a class with pleiotropic effects, recent efforts have centred on discerning specific ceramide species and their effects on atopic dermatitis, obesity, type 2 diabetes, and cardiovascular diseases. This delineation has allowed the identification of disease biomarkers, with long acyl chain ceramides such as C16- and C18-ceramides linked to metabolic dysfunction and cardiac function decline, while ultra-long acyl chain ceramides (>25 carbon acyl chain) were reported to be essential for maintaining a functional skin barrier. Given the intricate link between free fatty acids with ceramides, especially the de novo synthetic pathway, intracellular lipid droplet formation is increasingly viewed as an important mechanism for preventing accumulation of toxic ceramide species. Here, we review recent reports of various ceramide species involved in skin abnormalities and metabolic diseases, and we propose that promotion of lipid droplet biogenesis can be seen as a potential protective mechanism against deleterious ceramides.

Phytochemistry and Biological Activity of Medicinal Plants in Wound Healing: An Overview of Current Research.

Wound healing is a complicated process, and the effective management of wounds is a major challenge. Natural herbal remedies have now become fundamental for the management of skin disorders and the treatment of skin infections due to the side effects of modern medicine and lower price for herbal products. The aim of the present study is to summarize the most recent in vitro, in vivo, and clinical studies on major herbal preparations, their phytochemical constituents, and new formulations for wound management. Research reveals that several herbal medicaments have marked activity in the management of wounds and that this activity is ascribed to flavonoids, alkaloids, saponins, and phenolic compounds. These phytochemicals can act at different stages of the process by means of various mechanisms, including anti-inflammatory, antimicrobial, antioxidant, collagen synthesis stimulating, cell proliferation, and angiogenic effects. The application of natural compounds using nanotechnology systems may provide significant improvement in the efficacy of wound treatments. Increasing the clinical use of these therapies would require safety assessment in clinical trials.

Ischemia-Modified Albumin-A Potential New Marker of Oxidative Stress in Dermatological Diseases.

There is growing evidence that oxidative stress is involved in the pathogenesis of numerous conditions, including dermatological diseases. Various markers are available to assess oxidative stress, but none of these can be considered the ideal marker. Recent studies have shown that ischemia-modified albumin (IMA) is not only an indicator of ischemia, but also a marker of oxidative stress. We have conducted a narrative review to evaluate the role of IMA in dermatological diseases. We have identified 24 original articles that evaluated IMA in skin disorders (psoriasis, acne vulgaris, hidradenitis suppurativa, urticaria, vitiligo and Behcet's disease) and hair disorders (alopecia areata, androgenetic alopecia and telogen effluvium). The results of the studies analyzed reveal that IMA may be considered a new marker of oxidative stress in dermatological diseases and offer new insights into the pathogenesis of these disorders and the theoretical basis for the development of new, effective, targeted therapies. To the best of our knowledge, this is the first review that gathers up data on the role of IMA in dermatological diseases.

The skin and associated disorders.

This article aims to increase knowledge of the skin and associated disorders. Anatomy and physiology of the skin are briefly reviewed, and reference is made to common skin disorders. The main characteristics of a holistic skin assessment are discussed, and the signs to look for when undertaking an examination. The article concludes with a case study for context and reflection.