Skin Barrier Research Articles

Preparation and immunological study of Ichthyophthirius multifiliis β-tubulin DNA vaccine in grass carp (Ctenopharyngodon idella)

Grass carp, a common aquatic species in China, suffer significant annual losses due to infection by the parasitic ciliate Ichthyophthirius multifiliis (Ich), thus necessitating effective prevention and control measures. In the present study, the Ich β-tubulin gene was cloned and inserted into the eukaryotic expression vector pVAX1 plasmid to construct the Ich β-tubulin DNA vaccine (pVAX1-Bt). After two doses of the pVAX1-Bt vaccine, the relative percentage survival (RPS) reached 70.0 %, whereas the RPS after 2 doses of pVAX1 reached 10.0 %. The β-tubulin antibody, specific antibody IgM, and immune enzymes (MDA, SOD, CAT, ACP, AKP, and cortisol) were tested over13 weeks. The findings revealed a significant enhancement in the vaccinated fish compared to their unvaccinated counterparts, indicating that the vaccine can activate the humoral immune pathway and non-specific immunity in fish, thereby promoting the production of specific antibodies and memory B cells. Collectively, these results indicate that the Ich β-tubulin DNA vaccine has potential in treatment of Ich infection (ichthyophthiriasis).

The Design Features, Quality by Design Approach, Characterization, Therapeutic Applications, and Clinical Considerations of Transdermal Drug Delivery Systems—A Comprehensive Review

Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient’s skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs.

Deficient functional wound closure as measured by elevated trans-epidermal water loss predicts chronic wound recurrence: An exploratory observational study

A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m–2.h–1 (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.

Single-cell transcriptomics reveals aberrant skin-resident cell populations and identifies fibroblasts as a determinant in rosacea

Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

CGF therapy: bridging androgenetic alopecia observations to psoriasis treatment via IL-17 pathway.

Concentrated Growth Factor (CGF), rich in CD34 + stem cells, is widely used in treatments for androgenetic alopecia and skin rejuvenation due to its immune-modulating properties. Psoriasis, a chronic inflammatory skin condition, presents significant treatment challenges, particularly for patients who cannot use biologics due to conditions such as cancer and lesions resistant to treatments. The potential of CGF in treating psoriasis is promising, given its broad immunoregulatory effects which confirmed in our previous androgenetic alopecia work. We evaluated the impact of CGF on IL-17 levels in two contexts: patients treated for androgenetic alopecia and a psoriasis mouse model. Twelve patients received three monthly injections of CGF, with serum IL-17 levels measured before and after treatment. In the psoriasis mouse model, groups were treated with CGF, and outcomes were assessed using the Psoriasis Area and Severity Index (PASI), skin barrier scores, histological analysis, and RNA sequencing. Additionally, in vitro experiments applied CD34 + cells from CGF to keratinocytes to measure levels of TNF-α, IFN-γ, IL-23, and IL-17. In patients with androgenetic alopecia, three monthly CGF injections resulted in significantly reduced serum IL-17 levels. In the psoriatic mouse model, CGF-treated groups exhibited lower PASI scores and improved skin barrier scores compared to controls. Histological analysis revealed enhanced skin characteristics, while RNA sequencing demonstrated downregulated IL-17 and upregulated CD34 expression, as well as improved expression of barrier-related genes. In vitro, the application of CD34 + cells from CGF to keratinocytes led to a significant reduction in TNF-α, IFN-γ, IL-23, and IL-17 levels, indicating strong anti-inflammatory effects. A clinical case of a psoriasis patient unresponsive to IL-23 therapy (Guselkumab) showed significant improvement following CGF treatment. These findings indicate that CGF could serve as an effective and versatile treatment for psoriasis, especially for patients who have already undergone biologic therapies but continue to experience resistant lesions.

Anti-inflammatory effects of phytosphingosine-regulated cytokines and NF-kB and MAPK mechanism.

Phytosphingosine (PHS) is a major component of the skin barrier and a multifunctional physiologically active substance. This study aimed to investigate the types of cytokines regulated by PHS, their anti-skin inflammatory effects, and their anti-inflammatory mechanisms. RAW264.7 cells stimulated with Lipopolysaccharides (LPS) were treated with PHS to measure inflammatory factors such as nitric oxide (NO) and prostaglandin E2 (PGE2), and gene expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX2) were confirmed by q-PCR. Cytokines regulated by PHS against LPS-induced inflammation were found through cytokine array, and each factor was reconfirmed through ELISA. Western blot was performed to confirm anti-inflammatory mechanism of Iκbα and MAPK. To confirm anti-skin inflammatory efficacy, HaCaT cells stimulated with TNF-α/IFN-γ were treated with PHS, and TARC, IL-6, and IL-8 were detected by ELISA. PHS suppressed the gene expression of iNOS and COX2, which were increased by LPS, and suppressed NO and PGE2 production. Through cytokine array, it was confirmed that IL-6, IL-10, IL-27 p28/IL-30, IP-10, I-TAC, MCP-5, and TIMP-1 increased by LPS were decreased by PHS. PHS inhibited NF-κB signaling by inhibiting LPS-induced NF-κB nuclear migration and p-Iκbα-mediated Iκbα degradation, and inhibited p38, ERK, and JNK signaling pathways. PHS reduced the production of TARC, IL-6, and IL-8 increased by TNF-α/IFN-γ. These results indicate PHS has anti-inflammatory effects via the suppression of inflammatory factors and pro-inflammatory cytokines through the NF-κB and MAPK pathways. Moreover, these results may explain beneficial effects of PHS in the treatment of skin inflammatory conditions induced by TNF-α/IFN-γ.

Skin infections in atopic dermatitis: clinic, treatment. A review

Infection is the most common complication of atopic dermatitis (AtD). In particular, some patients with AtD exhibit increased susceptibility to skin infections of bacterial, viral, and fungal etiologies. In some cases, infections can even be systemic. Bacterial skin infections are more common than viral and fungal ones. An especially severe infection caused by the herpes virus is herpetic eczema, which can cause life-threatening complications. Infections of fungal etiology are represented mainly by the Malassezia species, especially in patients with dermatitis of the head and neck. The review focuses on the pathophysiological mechanisms identified to date that are thought to predispose to skin infections. The main ones are impaired skin barrier function, complex immunological changes, as well as poorly understood factors such as environmental exposure and skin dysbiosis. The review also includes the clinical characteristics of patients with various skin infections, as well as appropriate treatment for complications of AtD.

Acne and rosacea: similarities and differences. A review

Acne and rosacea are frequently encountered in the clinical practice of a dermatologist. These diseases can develop simultaneously in the same patient. Most often, the erythematous form of rosacea is combined with acne. Because of the similarity of clinical manifestations with acne, the diagnosis of rosacea can be easily missed. Common pathogenetic factors in the 2 diseases are thought to be genetics, alterations in the microbiome, immune disorders, and skin barrier dysfunction. There are few works addressing the relationship between acne and rosacea. A recent study identified a number of common differentially expressed genes, including interleukin-1B and matrix metalloproteinase 9, and showed that gamma delta T cells may play an important role in the development of both diseases. Despite the common pathogenesis and the similarity of some clinical manifestations (papules and pustules), acne and rosacea must be distinguished. In rosacea, there is persistent facial erythema induced by vasoregulatory neutropeptides, whereas in acne, the inflammatory process is due to excess sebum and changes in the skin microbiome. Isotretinoin is used for systemic therapy of both diseases. The drug affects the level of some cytokines, including inhibiting the expression of matrix metalloproteinase 9. In addition, it reduces sebum production in acne, and due to its ability to alter the skin microenvironment, it can reduce Propionibacterium acnes in acne and Demodex folliculorum in rosacea. Daily and cumulative doses for rosacea and acne will differ, as will topical therapy for these conditions. For acne, the combination of clindamycin and benzoyl peroxide is well established for the treatment of acne, allowing rapid meaningful clinical effect. In rosacea, metronidazole in cream form, which has better tolerability, is recommended as a topical agent. In patients suffering from both diseases simultaneously, a combination of clindamycin and benzoyl peroxide should be used to relieve acute inflammation, after which it is possible to switch to metronidazole.

Umbelliferone alleviates impaired wound healing and skin barrier dysfunction in high glucose-exposed dermal fibroblasts and diabetic skins.

Skin wound healing is a complex process involving various cellular and molecular events. However, chronic wounds, particularly in individuals with diabetes, often experience delayed wound healing, potentially leading to diabetic skin complications. In this study, we examined the effects of umbelliferone on skin wound healing using dermal fibroblasts and skin tissues from a type 2 diabetic mouse model. Our results demonstrate that umbelliferone enhances several crucial aspects of wound healing. It increases the synthesis of key extracellular matrix components such as collagen I and fibronectin, as well as proteins involved in cell migration like EVL and Fascin-1. Additionally, umbelliferone boosts the secretion of angiogenesis factors VEGF and HIF-1α, enhances the expression of cell adhesion proteins including E-cadherin, ZO-1, and Occludin, and elevates levels of skin hydration-related proteins like HAS2 and AQP3. Notably, umbelliferone reduces the expression of HYAL, thereby potentially decreasing tissue permeability. As a result, it promotes extracellular matrix deposition, activates cell migration and proliferation, and stimulates pro-angiogenic factors while maintaining skin barrier functions. In summary, these findings underscore the therapeutic potential of umbelliferone in diabetic wound care, suggesting its promise as a treatment for diabetic skin complications. KEY MESSAGES: Umbelliferone suppressed the breakdown of extracellular matrix components in the skin dermis while promoting their synthesis. Umbelliferone augmented the migratory and proliferative capacities of fibroblasts. Umbelliferone activated the release of angiogenic factors in diabetic wounds, leading to accelerated wound healing. Umbelliferone bolstered intercellular adhesion and reinforced the skin barrier by preventing moisture loss and preserving skin hydration.

Development and Characterization of Film-Forming Solution Loaded with Syzygium cumini (L.) Skeels for Topical Application in Post-Surgical Therapies.

Considering the antioxidant and antimicrobial properties attributed to compounds in Syzygium cumini extract, this research aimed to advance postoperative therapeutic innovations. Specifically, the study assessed the physicochemical properties of a film-forming solution (FFS) incorporated with S. cumini, evaluating its therapeutic potential for postoperative applications. The S. cumini extract was meticulously characterized to determine its chemical composition, with particular emphasis on the concentration of phenolic compounds. Antioxidant and antimicrobial assays were conducted to assess the extract's efficacy in these domains. Following this, an FFS containing S. cumini was formulated and evaluated comprehensively for skin adhesion, mechanical and barrier properties, and thermal behavior. The antioxidant and antimicrobial activities of the S. cumini extract demonstrated promising results, indicating its potential utility as an adjunct in postoperative care. The developed FFS exhibited favorable physicochemical properties for topical application, including adequate skin adhesion and appropriate pH levels. Moreover, chemical and thermal analyses confirmed the formulation's stability and the retention of the extract's beneficial properties. Overall, the findings suggest that the S. cumini-loaded FFS holds significant potential as a valuable therapeutic tool for post-surgical management.

Epidermal RORα Maintains Barrier Integrity and Prevents Allergic Inflammation by Regulating Late Differentiation and Lipid Metabolism.

The skin epidermis provides a barrier that is imperative for preventing transepidermal water loss (TEWL) and protecting against environmental stimuli. The underlying molecular mechanisms for regulating barrier functions and sustaining its integrity remain unclear. RORα is a nuclear receptor highly expressed in the epidermis of normal skin. Clinical studies showed that the epidermal RORα expression is significantly reduced in the lesions of multiple inflammatory skin diseases. In this study, we investigate the central roles of RORα in stabilizing skin barrier function using mice with an epidermis-specific Rora gene deletion (RoraEKO). While lacking spontaneous skin lesions or dermatitis, RoraEKO mice exhibited an elevated TEWL rate and skin characteristics of barrier dysfunction. Immunostaining and Western blot analysis revealed low levels of cornified envelope proteins in the RoraEKO epidermis, suggesting disturbed late epidermal differentiation. In addition, an RNA-seq analysis showed the altered expression of genes related to "keratinization" and "lipid metabolism" in RORα deficient epidermis. A lipidomic analysis further uncovered an aberrant ceramide composition in the RoraEKO epidermis. Importantly, epidermal Rora ablation greatly exaggerated percutaneous allergic inflammatory responses to oxazolone in an allergic contact dermatitis (ACD) mouse model. Our results substantiate the essence of epidermal RORα in maintaining late keratinocyte differentiation and normal barrier function while suppressing cutaneous inflammation.

Emerging Biologic Therapies for the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease having a significant impact on patients' quality of life. Conventional treatments, including topical therapies and systemic immunosuppressants, often have limited efficacy and long-term safety concerns. Emerging biologic therapies target specific immune pathways implicated in AD pathogenesis, offering new therapeutic options in a disease known for its complex immune pathomechanisms. This review focuses on novel biologics under investigation, particularly those targeting specific immune pathways such as interleukin-4 (IL-4), IL-13, IL-22, IL-31, thymic stromal lymphopoietin (TSLP), and OX40-OX40L axis. Interleukin-4 and IL-13 inhibitors aim to reduce Th2-driven inflammation, while IL-22 inhibitors focus on restoring skin barrier function. Interleukin-31 inhibitors help alleviate pruritus, a major symptom in AD. OX40-OX40L pathway inhibitors can selectively suppress the activity of pathogenic T cells, without inducing significant immunosuppression. Bispecific antibodies targeting both IL-4 and IL-31 pathways are emerging as potential dual-action treatment for AD. Thymic stromal lymphopoietin inhibitors offer a novel strategy to control inflammation. While many of these therapies offer promising safety and efficacy profiles, long-term studies and real-world data are essential to confirm their lasting impact. This review highlights the potential of these emerging systemic therapies to continue transforming AD management and improve patient outcomes.

Global Trends and Scientific Impact of Topical Probiotics in Dermatological Treatment and Skincare.

The skin plays a crucial role in maintaining homeostasis and protecting against external aggressors. Recent research has highlighted the potential of probiotics and postbiotics in dermatological treatments and skincare. These beneficial microorganisms interact with the skin microbiota, modulate the immune response, and enhance the skin barrier, offering a promising therapeutic avenue for various skin conditions, such as acne, dermatitis, eczema, and psoriasis. This bibliometric study aims to analyze the global trends and scientific impact of topical probiotics in dermatology. By reviewing 106 articles published between 2013 and 2023, the study categorizes the applications of probiotics in wound healing, inflammatory skin diseases, and general skincare. The findings indicate a significant increase in publications from 2021 onwards, attributed to the heightened focus on medical research during the COVID-19 pandemic. This study also identifies the most productive countries, institutions, and authors in this field, highlighting the importance of international collaborations. The results underscore the efficacy of probiotic-based topical formulations in improving skin health, reducing inflammation, and enhancing wound healing. This comprehensive analysis supports the development of new therapeutic strategies based on topical probiotics and encourages high-quality research in this promising area.

Natural Skin Care Regimen Improves Clinical Parameters and Quality of Life in Children with Atopic Dermatitis

Background: Atopic dermatitis (AD) is a prevalent, chronic inflammatory skin disorder, characterized by xerosis, itching and recurrent eczematous lesions. The condition also has major psychosocial implications for patients and their families. A daily skincare regimen of gentle cleansing and moisturization is an important part of atopic dermatitis therapy. Objective: This study evaluated the tolerability and efficacy of a nature-based shampoo/wash and moisturizer in children with mild to moderate atopic dermatitis Methods: This open-label study involved 23 children (6 months – 13 years) with atopic dermatitis. A daily skin care regimen of nature-based shampoo/wash and moisturizer was used for 4 weeks. The primary endpoint was tolerability assessed through clinical grading of erythema, dryness and roughness. The study pediatrician graded the eczema condition using the Eczema Area and Severity Index (EASI), and assessments of stratum corneum hydration and transepidermal water loss were performed before and after treatment. Parent/guardian completed two validated quality of life questionnaires. Results: Twenty children completed the study. Clinical evaluations showed significant improvement in subjects’ atopic disease with daily use of nature-based regimen. Significant reduction in dryness and roughness was observed, indicating that both products were well-tolerated. Moisture content and transepidermal water loss measurements showed directional improvements in skin barrier function. Parent/guardian reported significant improvements in quality-of-life assessments. Conclusions: The study demonstrated that nature-based skin care regimen was well tolerated and improved quality of life and skin condition in children with atopic dermatitis and can be used either alone or in adjunction with traditional treatment for disease control.

Trehalose Prevents IL-4/IL-13–Induced Skin Barrier Impairment by Suppressing IL-33 Expression and Increasing NRF2 Activation in Human Keratinocytes In Vitro

Skin barrier dysfunction initiates or deteriorates various cutaneous problems, such as atopic dermatitis (AD). At high concentrations, the nonreducing disaccharide α-d-glucopyranosyl α-d-glucopyranoside (trehalose) induces a transient senescence-like state in fibroblasts and promotes wound repair. Here, we investigated the effect of trehalose on normal human keratinocytes (KCs) and demonstrated its specific role in the skin barrier. RNA-seq analysis revealed that trehalose regulates the expression of many skin-barrier-associated genes. T helper 2 (Th2) cytokines interleukin (IL)-4/IL-13 were observed to downregulate several differentiation markers (FLG, LOR, K1, and K10) and epidermal antimicrobial proteins in monolayer-cultured KCs and living skin equivalents (LSE), and impaired skin barrier function in LSE, all of which were significantly upregulated or restored by trehalose. Trehalose inhibited IL-33 expression and reduced nuclear IL-33 levels by activating MEK5-extracellular signal-regulated kinase 5 (ERK5) and suppressing MEK1/2-ERK pathway. It also increased nuclear factor erythroid 2-related factor 2 (Nrf2) activation to trigger antioxidant enzyme production via c-Jun N-terminal kinase (JNK), thus, neutralizing IL-4/IL-13-mediated oxidative stress. Trehalose prevented IL-4/IL-13-mediated signal transducer and activator of transcription (STAT)3/STAT6 activation and restored IL-4/IL-13-suppressed skin barrier molecules via IL-33 downregulation and Nrf2 activation. This study demonstrated that trehalose may play a role in skin barrier repair in AD.

Skin Barrier Function and Microtopography in Patients with Atopic Dermatitis.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease whose incidence is increasing. Skin barrier dysfunction plays an important role in this disease. It has been observed that AD patients have higher transepidermal water loss (TEWL) and lower stratum corneum hydration (SCH); however, there is little information about skin microtopography in this pathology. The objective of this study is to evaluate skin barrier dysfunction and structural changes in patients with AD. Methods: A cross-sectional study was conducted including patients with AD. Parameters of skin barrier function were measured (TEWL, temperature, erythema, pH, skin hydration, elasticity) and also other topographical parameters (scaliness, wrinkles, smoothness, surface, contrast, variance) in both healthy skin and flexural eczematous lesions. Results: A total of 32 patients with AD were included in the study. Flexural eczematous lesions had higher erythema (369.12 arbitrary unit (AU) vs. 223.89 AU, p < 0.001), higher TEWL (27.24 g/h/m2 vs. 13.51 g/h/m2, p < 0.001), lower SCH (20.3 AU vs. 31.88 AU, p < 0.001) and lower elasticity (0.56% vs. 0.65%, p = 0.05). Regarding topographic parameters, flexural eczematous lesions presented greater scaliness (5.57 SEsc vs. 0.29 SEsc, p = 0.02), greater smoothness (316.98 SEsm vs. 220.95 SEsm p < 0.001), more wrinkles (73.33 SEw vs. 62.15 SEw p = 0.03), greater surface area (836.14% vs. 696.31%. p < 0.001), greater contrast (2.02 AU vs. 1.31 AU p = 0.01), greater variance (6.22 AU vs. 4.96 AU p < 0.001) and a lower number of cells (105.5 vs. 132.5 p < 0.001) compared to unaffected healthy skin, reflecting a decrease in skin quality in AD patients. Conclusions: Both skin barrier function and skin topography are damaged in patients with AD, with differences between healthy skin and flexural eczema.

Assessment of the Vehicle for Roflumilast Cream Compared to a Ceramide-Containing Moisturizing Cream in Mild Eczema.

Inflammatory dermatologic conditions suitable for topical treatments benefit from a hydrating vehicle that improves the skin barrier without irritation. This research was designed to assess skin barrier effects and aesthetic attributes of the vehicle for topical roflumilast cream (vehicle) vs a currently marketed ceramide-containing moisturizing cream (moisturizer). This was a single-site, randomized, intraindividual, double-blind, controlled study conducted over 17 days. Patients (aged 18 years or older) with mild, symmetric asteatotic eczema of the lower extremities were enrolled to receive lower leg applications of the vehicle on one leg and moisturizer on the other. The primary efficacy endpoint was a change in transepidermal water loss (TEWL) from baseline to day 15. Secondary efficacy endpoints included change from baseline in TEWL at other study visits, change from baseline in hydration as assessed via corneometry, and patient- and investigator-rated assessments of the products. Safety and tolerability were also assessed. A total of 40 patients enrolled in the study. The primary efficacy endpoint was met for both treatments. A statistically significant difference in TEWL on day 1 favored the moisturizer, but no difference was seen between vehicle and moisturizer at any other timepoint. Both vehicle and moisturizer also met the secondary efficacy endpoint of change from baseline in hydration. The sample size was small. The vehicle for roflumilast cream performed similarly to a leading, currently marketed, dermatologist-recommended, ceramide-containing moisturizer across all patient- and investigator-rated assessments of efficacy, tolerability, and aesthetic properties in patients with mild asteatotic eczema. J Drugs Dermatol. 2024;23(10):834-840. doi:10.36849/JDD.7958 &nbsp.

Polymeric Advancements in Transdermal Drug Delivery: A Comprehensive Review on Stability, Safety, and Biocompatibility

AbstractTransdermal drug delivery systems have received a lot of attention due to their noninvasive nature and possible advantages over standard drug administration methods. Because transdermal administration systems skip the gastrointestinal tract and hence avoid hepatic first pass metabolism, also the chance of adverse effects such as liver malfunction and gastrointestinal tract discomfort is low. This comprehensive review explores the various aspects of polymeric advancements in transdermal drug delivery, encompassing their roles as matrix and microreservoir formers, microneedles, pressure sensitive adhesives, rate controlling membranes, and many other components. The article emphasizes the importance of biocompatibility, chemical compatibility, and stability of polymers within the transdermal delivery system. Furthermore, it delves into the recent advancements in synthetic and natural polymer‐based transdermal drug delivery systems. Thus, a comprehensive search strategy is conducted in electronic databases such as PubMed, Scopus, and Web of Science to write this review paper. The scope of this investigation involves an in‐depth study of the various polymeric materials used, their formulations, and the mechanisms that support their efficacy in delivering medications over the skin barrier. Additionally, it explores the challenges associated with stability and safety concerns, while highlighting novel approaches to overcome these problems. Furthermore, the review discusses the biocompatibility of polymeric materials, crucial for ensuring minimal adverse effects and maximum therapeutic efficacy.

Cellular Senescence and Anti-Aging Strategies in Aesthetic Medicine: A Bibliometric Analysis and Brief Review.

Skin aging is the most obvious feature of human aging, and delaying aging has become a hot and difficult research topic in aesthetic medicine. The accumulation of dysfunctional senescent cells is one of the important mechanisms of skin aging, based on which a series of anti-aging strategies have been generated. In this paper, from the perspective of cellular senescence, we utilize bibliometrics and research review to explore the research hotspots and trends in this field, with a view to providing references for skin health and aesthetic medicine. We obtained literature related to this field from the Web of Science Core Collection database from 1994 to 2024. Bibliometrix packages in R, CiteSpace, VOSviewer, Origin, and Scimago Graphica were utilized for data mining and visualization. A total of 2,796 documents were included in the analysis. The overall trend of publications showed a continuous and rapid increase from 2016-2023, but the total citations improved poorly over time. In this field, Journal of Cosmetic Dermatology, Journal of Investigative Dermatology, Experimental Gerontology are core journals. Kim J, Lee JH, Lee S, Rattan SIS, Chung JH and Kim JH are the core authors in this field. Seoul National University is the first in terms of publications. Korea is the country with the most publications, but USA has the most total citations. Top 10 keywords include: gene-expression, skin, cellular senescence, cell, oxidative stress, antioxidants, in vitro, fibroblasts, mechanism, cancer. Current research trends are focused on neurodegeneration, skin rejuvenation, molecular docking, fibrosis, wound healing, SASP, skin barrier, and antioxidants. The core literature and references reflect topics such as the major molecular pathways in the aging process, and the relationship with tumors. This field of research has been rapidly rising in recent years. Relevant research hotspots focus on oxidative stress, fibroblasts, and senescence-associated secretory phenotype. Anti-aging strategies targeting cellular senescence hold great promise, including removal of senescent cells or attenuation of SASP factors, corresponding to senolytics and senomorphics therapies, respectively.

P2X7R-primed keratinocytes are susceptible to apoptosis via GPCR-Gβγ-pERK signal pathways

BackgroundCell death constitutes a pivotal biological phenomenon essential for the preservation of homeostasis within living organisms. In the context of maintaining a functional skin barrier, keratinocytes exert positively and negatively control cell death signals. However, in patients with severe drug eruptions, anomalous overexpression of the formyl peptide receptor 1 (FPR1) in keratinocytes elicits a distinctive mode of cell death known as necroptosis, thereby suffering a loss of the skin barrier. The precise molecular mechanisms connecting FPR1 activation to this cell death remain unclear. ObjectiveWe have investigated the intracellular signal transduction cascade governing FPR1-mediated cell death in cultured keratinocytes. MethodsWe used HaCaT cells as a model keratinocyte. The expression of FPR1 was detected with qPCR. The presence of cell death events was monitored through live-cell fluorescent staining and LDH release assays. Furthermore, the phosphorylation of ERK was assessed via Western blot analysis. Intracellular signal pathways were investigated using specific inhibitors. ResultsLigand stimulation of an endogenous ion channel, purinergic receptor P2X7 (P2X7R), increased the FPR1 expression level. This upregulated FPR1 demonstrated functional competence in the phosphorylation of downstream MAP kinase and the initiation of cell death. Notably, this cell death was ameliorated upon the administration of inhibitors targeting Gβγ, ERK, and caspases. ConclusionThe induction and stimulation of FPR1 initiated apoptosis in keratinocytes via the Gβγ-pERK signaling pathway. Our findings postulate that the downstream components of FPR1 represent an alternative therapeutic target for preventing unintended keratinocyte cell death.