INDIVIDUAL ARTICLE: Atopic Dermatitis Skincare and Impact on Quality of Life for Patients with Skin of Color.

Atopic Dermatitis (AD) epidemiologic studies report a higher incidence and prevalence among populations with skin of color (SOC). Additionally, differences in AD underlying gene mutations and skin morphology are observed to lead to frequent and prominent xerosis, pruritus, and pigmentary sequelae in patients of color. However, populations with SOC are underrepresented in dermatology clinical trials, including AD. This article reviews the nuances in AD epidemiology, clinical presentation, and impact on quality-of-life among populations with SOC, plus highlight the role of skincare in AD management. J Drugs Dermatol. 2024;23:3(Suppl 2):s6-11.

INDIVIDUAL ARTICLE: Efficacy of a Prebiotic Skincare Regimen on Improving Mild Atopic Dermatitis and Severe Xerosis in Diverse Ethnically Patients.

Atopic Dermatitis (AD) is a chronic relapsing inflammatory skin disease associated with a significant patient burden on quality-of-life. Given skin barrier including skin microbiome changes are linked to AD pathogenesis, prebiotic emollients are shown to improve disease symptoms and maintain skin barrier integrity, normalizing skin microbiota. In this study, we evaluated the efficacy and safety of a prebiotic skincare routine in improving AD and xerosis, and ultimately quality-of-life in ethnically diverse patients. A total of 140 subjects from different racial/ethnic backgrounds, aged 3-80 years old with skin phototypes I-VI, and presenting with mild-AD or severe xerosis completed study. Expert grading, instrumentation, self-assessment questionnaires, plus clinical imaging demonstrated that a prebiotic cleanser and moisturizer routine significantly reduced skin conditions severity, strengthened skin barrier properties in both lesional and normal skin, and improved patients' quality-of-life while providing itch relief as soon as 4 weeks. The results of this research indicate that a prebiotic cleanser and moisturizer regimen offers benefits for diverse patient’s daily skincare routine by effectively managing AD and xerosis severity and symptoms, normalizing skin microbiota, plus preserving skin barrier integrity to prevent long-term sequelae. J Drugs Dermatol. 2024;23:3(Suppl 2):s12-22.

Alteration to the Skin Ceramide Profile Following Broad-Spectrum UV Exposure.

The epidermal stratum corneum (SC) lipid matrix, principally consisting of an equimolar ratio of ceramides, free fatty acids, and cholesterol, plays a crucial role in maintaining proper skin barrier function. Conditions which impair barrier integrity, such as in atopic dermatitis, correlate with the alternation of key ceramide subclasses and reduced chain length of acyl moieties. However, there is limited knowledge about the impact of unprotected repeat sun exposure on the skin lipid composition, especially ceramide profiles.This study investigated the effects of ultraviolet (UV) radiation on the ceramide profile using both an ex vivo skin and a clinical model. Lipidomic analysis of UV-exposed skin showed shifts to the composition of ceramide subclasses essential in repairing and strengthening the SC barrier (including CER1[EOS], CER3[NP], and CER6[AP]) and reduced very long-chain acyl moieties. Gene expression analysis and immunohistochemical staining of key enzymes (aSMase, DES1, CerS5, CerS3) suggested that lipid alterations can be attributed to changes within the ceramide biosynthesis process. Topical application of ceramide-containing suncare products help maintain SC-essential ceramide subclasses and proper ceramide chain length, demonstrating the importance of proper photoprotection to maintain healthy skin barrier and ceramide quality during daily sun exposure. J Drugs Dermatol. 2022;21(1):77-85. doi:10.36849/JDD.6331.

ARTICLE: Models to Study Skin Lipids in Relation to the Barrier Function: A Modern Update on Models and Methodologies Evaluating Skin Barrier Function.

The skin barrier is a multifaceted microenvironment, comprised not only of structural and molecular components that maintain its integrity, but also a lipid matrix comprising an equimolar ratio of cholesterol, free fatty acids, and ceramides. Lipid abnormalities induced by environmental or pathological stimuli are often associated with impaired skin barrier function and integrity. Incorporation of skin lipids in skincare formulations to help fortify barrier function has become widespread. While there are resources available to study the barrier, a comprehensive evaluation of skin models, from in situ to in vivo, that focus on alterations of the lipid content, seems to be lacking. This article reviews current methods to evaluate the skin lipid barrier and touches upon the significance of using such models within the cosmetic field to study formulations that incorporate barrier lipids. J Drugs Dermatol. 20(4 Suppl):s10-16. doi:10.36849/JDD.S589B.

ARTICLE: Efficacy of Ceramide-Containing Formulations on UV-Induced Skin Surface Barrier Alterations.

The human skin, particularly the stratum corneum, serves as a protective barrier against exogenous factors, including ultraviolet radiation (UVR) and pathogen invasions. The impact of UVR on skin cancer and photoaging has been extensively studied. However, the direct impact of UVR on skin barrier integrity under clinical settings remains poorly explored. Due to their benefits in reducing inflammation and promoting skin barrier repair, ceramide-containing formulations can provide added photoprotection benefits. In this study, the efficacy of a ceramide-containing sunscreen and moisturizer were evaluated in preventing UV-induced skin surface barrier changes. Expert grading, instrumental, and tape-stripping assessments demonstrated that UVR induced erythema and hyperpigmentation and caused changes in skin cells surface morphological organization and maturation. Treatment with a ceramide-containing sunscreen and moisturizing cream routine reduced erythema and hyperpigmentation, improved skin hydration, and maintained normal superficial skin cells morphology and turnover after UVR. Our results indicate that barrier-enforcing lipids formulations can provide additional benefits in patient’s daily routine by strengthening the barrier and improving skin health overall against chronic sun exposure. J Drugs Dermatol. 20(4 Suppl):s29-35. doi:10.36849/JDD.S589E.

Cross talk between calcium and ROS regulate the UVA-induced melanin response in human melanocytes.

Exposure to high doses of solar long wavelength ultraviolet radiation (UVA) damages human skin via reactive oxygen species (ROS). Whether physiological UVA doses also generate ROS that has an effect on the skin remains unknown. We previously showed that in human epidermal melanocytes UVA activates a G-protein coupled signaling pathway that leads to calcium mobilization and increased melanin. Here, we report that ROS generated by the UVA phototransduction pathway are critical cellular messengers required to augment melanin. Using simultaneous UVA exposure and live-cell imaging of primary human melanocytes, we found that physiological doses of UVA generate two spatiotemporally distinct sources of ROS: one upstream of the G-protein activation that potentiates calcium responses, and another source downstream of calcium, in the mitochondria (ROSmito ). UVA-evoked signaling led to mitochondrial calcium uptake via mitochondrial calcium uniporter to promote ROSmito production leading to melanin synthesis. Our findings reveal a novel mechanism in which ROS function as signaling messengers necessary for melanin production, thus having a protective role in the UVA-induced skin response.

Impact of Iron-Oxide Containing Formulations Against Visible Light-Induced Skin Pigmentation in Skin of Color Individuals.

Visible light (400-700nm), which contributes to 45% of solar radiation, contributes to skin darkening and worsening of dyschromias, particularly in individuals with Fitzpatrick skin phototypes III and higher. Currently, sunscreens provide limited protection against that spectrum. Due to their capabilities in absorbing, scattering, and reflecting visible light, topical products containing pigments and/or metal oxides can provide additional photoprotection. In this study, the efficacy of two formulations containing iron oxide was evaluated in preventing visible light-induced pigmentation compared with a non-tinted mineral SPF 50+ sunscreen. Expert grading and colorimetry demonstrated that the iron-oxide containing formulations significantly protected against visible light-induced pigmentation compared to untreated skin or mineral SPF 50+ sunscreen in Fitzpatrick IV individuals. These results highlight that iron-oxide containing formulas in a foundation format have dual functions and can provide additional benefits in patients' daily routine by masking existing pigmentation and preventing the development of pigmentation triggered by sunlight exposure, extending protection beyond UV spectrum. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.5032 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Targeting cancer cells with the natural compound obtusaquinone.

BACKGROUND: Tumor cells present high levels of oxidative stress. Cancer therapeutics exploiting such biochemical changes by increasing reactive oxygen species (ROS) production or decreasing intracellular ROS scavengers could provide a powerful treatment strategy. METHODS: To test the effect of our compound, obtusaquinone (OBT), we used several cell viability assays on seven different glioblastoma (GBM) cell lines and primary cells and on 12 different cell lines representing various cancer types in culture as well as on subcutaneous (n = 7 mice per group) and two intracranial GBM (n = 6-8 mice per group) and breast cancer (n = 6 mice per group) tumor models in vivo. Immunoblotting, immunostaining, flow cytometry, and biochemical assays were used to investigate the OBT mechanism of action. Histopathological analysis (n = 2 mice per group) and blood chemistry (n = 2 mice per group) were used to test for any compound-related toxicity. Statistical tests were two-sided. RESULTS: OBT induced rapid increase in intracellular ROS levels, downregulation of cellular glutathione levels and increase in its oxidized form, and activation of cellular stress pathways and DNA damage, subsequently leading to apoptosis. Oxidative stress is believed to be the main mechanism through which this compounds targets cancer cells. OBT was well tolerated in mice, slowed tumor growth, and statistically prolonged survival in GBM tumor models. The ratio of median survival in U251 intracranial model in OBT vs control was 1.367 (95% confidence interval [CI] of ratio = 1.031 to 1.367, P = .008). Tumor growth inhibition was also observed in a mouse breast cancer model (average tumor volume per mouse, OBT vs control: 36.3 vs 200.4mm(3), difference = 164.1mm(3), 95% CI =72.6 to 255.6mm(3), P = .005). CONCLUSIONS: Given its properties and efficacy in cancer killing, our results suggest that OBT is a promising cancer therapeutic.