Skin Pharmacology and Physiology最新文献

Introduction: Emulsifiers are common excipients in dermal products stabilizing formulations such as creams and emulsions. But due to their potential for skin irritation, emulsifiers for pharmaceutical use should be tested regarding their tolerability before introducing them to the skin of patients. In this study, a systematic investigation with six oil in water-emulsifiers was performed on the forearms of 12 healthy human volunteers, six female, and six male.

Methods: We analyzed the effects of pharmaceutical emulsifiers on the macroscopic skin health parameters measured as trans-epidermal water loss (TEWL) and skin hydration and measured the ceramide profile of the treated skin sites using liquid chromatography coupled to mass spectrometry in order to assess the skin tolerability of the investigated emulsifiers. In a second step, a Partial Least Squares Regression was employed to investigate relationships between changes in the ceramide profile to changes in the TEWL of skin treated with a nonionic as well as an anionic emulsifier.

Results: Skin health measurements showed that the applied emulsifiers inflicted no significant changes compared to the water-treated sample, demonstrating a remarkable skin tolerability. The employed regression model showed a good fit as well as adequate prediction and identified ceramide species associated with impaired skin barrier function. Furthermore, it was found that the relationship between the ceramide profile and the skin barrier function in emulsifier-induced skin damage shows distinct similarities to the interplay of ceramides and skin barrier function in lesional skin linked to atopic dermatitis, hinting toward a common underlying mechanism and opening up possibilities to simulate disease-related changes to the skin for the development of skin damage models.

Conclusion: In conclusion, these detailed investigations yield insight into possible mechanisms of emulsifier-induced skin damage and show its versatility in the investigation of pharmaceutical emulsifiers for formulation development as well as basic research.

Introduction: Regular use of leave-on skincare products has positive effects on the skin barrier and appears to influence the skin microbiome in atopic dermatitis (AD). However, product-related effects on the skin microbiome are unclear. The aim of this study was to investigate to which extent the application of an emollient plus product differs from a petrolatum-based basic skincare product in terms of skin physiology, skin barrier, and skin microbiome.

Methods: In an exploratory study regime, 50 subjects (children and adults) with mild AD were randomized to receive Bepanthen SensiDaily® (BSD) and Basiscreme DAC (DAC) for 3 months in a crossover design. Skin physiological measurements and skin microbiome swabs were taken on the forearm and lower leg before and after each 3-month application period of the respective product.

Results: Improvement of skin physiological parameters after 3 months was observed in both topical leave-on product groups. Statistically significant differences were observed in baseline microbiomes between children and adults (p < 0.001) but not between the product groups.

Conclusion: Regular application of leave-on products leads to better stratum corneum hydration after 3 months with better effects of BSD on the forearms of children and the lower legs of adults compared to DAC. The application of BSD and DAC did not lead to significant alterations in the overall composition of the skin microbiome. Although there were shifts in the frequency of certain microbial genera, these changes were not consistent between age groups and treatments.

Introduction: Several complex mathematical models have been developed using in vitro permeation test (IVPT) data to characterize percutaneous absorption. A less complicated approach, using basic pharmacokinetic parameters on IVPT data, is proposed here to predict skin barrier content and permeation kinetics following multiple-dose applications.

Methods: Published and archived data from the authors' files are used to define and test a proposed model using standard single-compartment pharmacokinetic parameters and to provide insight into percutaneous absorption profiles and skin barrier content.

Results: Pharmacokinetic parameters are derived and shown for a selection of diverse drugs from their IVPT data, which are then used to predict multiple-dose absorption kinetics. Flux profiles and skin barrier content are calculated and shown for periods of 7-30 days with 6-, 12-, and 24-h dosing intervals.

Conclusion: The model presented here allows one to predict the rate and extent of drug absorption over any number of dosing periods per day and across multiple days. This information may not only provide a new outlook on formulation selection or dosing regimens, but may also allow for estimation of skin or systemic levels of exposure to chemicals following multiple sequential topical dose applications.

Introduction: Soymilk okara, a rich source of protein and dietary fiber, is a byproduct of soymilk manufacturing. We investigated whether soymilk-okara intake improved skin conditions in Japanese women with self-reported constipation.

Methods: Thirty-seven Japanese women with self-reported constipation were included in this study. Two-thirds of the participants ingested 15 g of soymilk-okara powder daily for 8 weeks (okara group), whereas seasonal effects were evaluated in the remaining one-third (observation group). The participants' body composition and skin conditions (stratum corneum hydration, transepidermal water loss [TEWL], and gross elasticity [R2; epidermis and dermis]) of the malar and forehead were measured. Additionally, fecal concentrations of uremic toxins such as indole and p-cresol were analyzed.

Results: Eight participants withdrew consent during the study period owing to COVID-19, etc., and the final data analysis was performed using data from participants in the okara (n = 19) and observation (n = 10) groups. No significant interactions among stratum corneum hydration, TEWL, or epidermal gross elasticity of the malar and forehead in the okara and observation groups were observed. In contrast, interactions of the dermis gross elasticity of the malar and forehead in both groups (p = 0.065 and 0.043, respectively) were observed. In the okara group, negative correlations between the changes in uremic toxins and the difference in the dermis gross elasticity of the forehead were observed.

Conclusion: The intake of soymilk-okara powder improved skin elasticity, which may be a result of changes in the intestinal flora.

Introduction: Despite numerous therapeutic approaches, keloid treatment remains a challenge. Clinical studies have demonstrated the possible use of cold atmospheric plasma (CAP) to treat hypertrophic scars and keloids. This study investigated the effects and relative mechanisms of CAP treatment on primary keloid fibroblasts (PKF) in vitro.

Methods: PKF cells from 10 patients with keloid and human dermal fibroblast (HDFa) cell line were cultured to compare CAP treatment effects. Cell proliferation, migration via scratch assay, and reactive oxygen species (ROS) levels were measured using standard assays, while cell apoptosis was quantified by flow cytometry. A quantitative reverse transcription polymerase chain reaction was performed to analyze the effect of CAP on gene regulation in fibrosis and inflammation. Finally, the mode of action of CAP was compared to H₂O₂ treatment.

Results: CAP treatment in medium mode (CAP-mid), specifically for 30 and 60 s, significantly inhibited PKF proliferation and migration. No significant effects were seen in HDFa cells. Genetic analysis of pro-fibrotic components and inflammatory cytokines revealed that CAP-mid significantly reduced α-sma, periostin, h-col1, tgf-β, IL-6, and IL-31 expression in PKF cells, while it enhanced IL-10 expression. However, it had opposite effects on HDFa. Time-dependent analysis showed that CAP-mid at 60 and 30 s exerted the maximum effects on those molecules. Simultaneous analysis of CAP and H₂O₂ treatment on PKF cells demonstrated that CAP-mediated alterations in gene expression are primarily linked to enhanced ROS production in PKF cells.

Conclusion: These findings suggest that CAP may mitigate keloid formation by modifying fibrotic and inflammatory profiles through ROS production and inhibition of cell proliferation.

Introduction: Diabetic foot ulcers (DFUs) are a common complication in diabetes, leading to high amputation risk and significant healthcare costs. Given topical timolol's emergence as a potential wound-healing agent, our study explored its impact on epidermal integrity.

Methods: This study was a post hoc analysis conducted as part of a randomized controlled trial at the Veterans Affairs Northern California Health Care System. Twenty patients, who had DFUs healed in the original trial, 10 in the timolol arm, and 10 in the placebo arm, were enrolled in the study. The primary outcome was transepidermal water loss, measured monthly for 3 months of post-healing using a closed-chamber device. The secondary outcome was re-ulceration rates over 1 year.

Results: Transepidermal water loss at 1, 2, and 3 months of post-healing was significantly lower in the timolol group than in the placebo group (p < 0.01). Linear mixed models identified contralateral foot transepidermal water loss as a significant predictor of healed diabetic foot ulcer site transepidermal water loss (estimate = 0.76, p < 0.001). The interaction between timolol treatment and months since healing significantly reduced transepidermal water loss over time (estimate = -2.2, p = 0.002). The use of a wheelchair was also associated with a significant decrease in transepidermal water loss (estimate = -7.7, p = 0.01). Initial transepidermal water loss values were higher in patients who re-ulcerated, but the difference was not statistically significant (p = 0.42). There was no difference in re-ulceration rates in this small pilot study.

Conclusion: Topical timolol significantly improved skin barrier function in healed DFUs, reducing transepidermal water loss. Although re-ulceration rates were not significantly different, the trend suggests potential benefits. Further studies with larger sample sizes and longer follow-up are needed to confirm these findings and explore transepidermal water loss's predictive value for re-ulceration.

Introduction: Loss of skin integrity due to a wound or disease can lead to severe disability or even life threat. The highly expressed microRNAs in the skin are of great significance for skin development. The purpose of the investigation was to explore the effect and mechanism of miR-211 on inflammation, oxidative stress, and migration in keratinocytes.

Methods: The HaCaT keratinocytes were treated with hydrogen peroxide (H2O2) to establish a wound-healing model. The expression of miR-211 was examined by quantitative real-time PCR. The cell function was reflected in proliferative ability, migration, apoptosis, and inflammation, which were evaluated using the Cell Counting Kit-8 (CCK-8) assay, transwell test, flow cytometry technique, and enzyme-linked immunosorbent assay (ELISA). The target of miR-211 was verified by luciferase luminescence measurements.

Results: H2O2 inhibited HaCaT cell proliferation, migration, and promoted cell apoptosis, accompanied with the downregulation of miR-211. H2O2 led to inflammatory response and oxidative damage to HaCaT. miR-211 promoted proliferation and migration but improved cell apoptosis of HaCaT. The role of H2O2 on inflammatory response and oxidative stress was alleviated by miR-211. SRY-box transcription factor 11 (SOX11) was a targeted mediator of miR-211. SOX11 reversed the influence of miR-211 on cell proliferation, migration, apoptosis, inflammatory response, and oxidative stress.

Conclusion: miR-211 regulated the proliferation, migration, apoptosis, inflammation, and oxidative stress of keratinocytes by mediating SOX11, thus participating in cutaneous wound healing.

Background: Understanding skin aging and developing effective interventions represent fundamental challenges in dermatology. Key mechanisms driving this process include complex interactions among cellular senescence, extracellular matrix remodeling, oxidative stress, and inflammatory networks.

Summary: Recent advances have catalyzed the development of innovative peptide-based therapeutic strategies for skin aging. These include environment-responsive peptides, biomimetic peptides, and advanced nano-delivery systems. The integration of chronobiology and multi-omics analysis further supports the evolution of these approaches.

Key messages: We envision a new era of personalized solutions for skin aging, driven by the convergence of molecular understanding, delivery innovations, and precision medicine. This paradigm shift holds transformative potential not only for dermatology but also for broader aspects of human aging and health.

Background: Alopecia areata (AA) is a T-cell-mediated autoimmune disease that significantly impacts patient quality of life. The breakdown of hair follicle immune privilege underlies AA pathogenesis. However, the precise mechanism of this breakdown remains unclear. This study investigates the potential role of reactive oxygen species in AA pathogenesis.

Summary: A systematic review and meta-analysis were conducted on observational studies and randomized controlled trials from 2000 to 2024. Studies included AA patients and measured oxidative stress index (OSI), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), or paraoxonase-1 (PON1). Extracted data were analyzed using the Cochrane risk-of-bias tool and random-effects models. The review included 21 studies with 743 AA patients. OSI was elevated in AA patients (effect size = 1.58, 95% CI: 0.31-2.68, p = 0.00068). MDA levels were also elevated (effect size = 1.60, 95% CI: 0.43-2.6, p = 0.00023), while SOD (effect size = -0.97, 95% CI: -1.65 to -0.30, p = 0.00066) and GSH-Px (effect size = -1.41, 95% CI: -2.28 to -0.53, p = 0.00068) activities were reduced. PON1 levels showed no significant difference (effect size = -3.56, 95% CI: -8.63 to 1.51, p = 0.051).

Key messages: The elevated OSI and MDA, and decreased antioxidant activity in AA patients suggest a substantial role for reactive oxygen species and oxidative stress in AA pathogenesis, highlighting oxidative stress as a potential target for therapeutic intervention. These results underscore the importance of oxidative stress in AA and support further research into antioxidant-based therapies.