Yu Ra Jung, Myo Hyeon Park, Eun Bi Choi, Bu-Mahn Park, Jeonghwan Timothy Hwang, Miyoung Park
{"title":"Anti-Inflammatory and skin barrier-improving effects of lipimoide in relation to epidermal TRPM8 upregulation.","authors":"Yu Ra Jung, Myo Hyeon Park, Eun Bi Choi, Bu-Mahn Park, Jeonghwan Timothy Hwang, Miyoung Park","doi":"10.1159/000548409","DOIUrl":"https://doi.org/10.1159/000548409","url":null,"abstract":"<p><strong>Introduction: </strong>The skin serves as a barrier, preventing internal moisture loss and protecting against the invasion of external harmful factors while also playing a role in immune responses. Barrier disruption is a hallmark of inflammatory skin diseases characterized by dryness and itching, notably in conditions like atopic dermatitis (AD). Recent research has focused on exploring novel compounds that can enhance skin barrier function and modulate inflammatory responses. Therefore, this study aimed to investigate the barrier-protective role and underlying mechanisms of lipimoide in an AD-like skin barrier impairment model using normal human keratinocytes (NHKs) and human skin equivalent models.</p><p><strong>Method: </strong>An in vitro AD-like condition was induced in NHEKs and a human skin equivalent models by treating with a stimulus cocktail containing Th2 cytokines (IL-4 and IL-13), leading to impaired keratinocyte differentiation, increased inflammation, and epidermal thickening. Functional studies on skin barrier function, anti-inflammatory effects, and the molecular mechanisms involving TRPM8 expression were conducted using RT-qPCR, Western blotting, immunofluorescence analysis, immunohistochemistry, and transepithelial electrical resistance (TEER) measurements to assess skin barrier integrity.</p><p><strong>Results: </strong>Treatment with lipimoide, a novel synthetic compound, increased the gene and protein expression of TRPM8, which had been downregulated in NHEKs and skin equivalents induced by the stimulus cocktail. Additionally, lipimoide was found to restore the expression of epidermal differentiation markers, reduce inflammation, and enhance skin barrier function in AD-like skin conditions.</p><p><strong>Conclusion: </strong>This study indicates that TRPM8 plays a crucial role in maintaining skin barrier integrity and may serve as a therapeutic target for treating dermatitis in AD. Furthermore, as a TRPM8 modulator, lipimoide promotes epidermal barrier homeostasis and function, providing a potential therapeutic strategy for managing dry and inflammatory skin conditions.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-22"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristian Reich, Natalie Trettel, Jeremias L K Reich, Christina Sorbe, Thomas Bickert, Jan Hartmann, Inken Harder, Sascha Gerdes, Stephan Weidinger
{"title":"Effects of a gel containing the defined microalgae extract Spiralin® on the skin microbiome and clinical activity in atopic dermatitis - a double-blind, intraindividual vehicle-controlled proof-of-concept study.","authors":"Kristian Reich, Natalie Trettel, Jeremias L K Reich, Christina Sorbe, Thomas Bickert, Jan Hartmann, Inken Harder, Sascha Gerdes, Stephan Weidinger","doi":"10.1159/000547835","DOIUrl":"https://doi.org/10.1159/000547835","url":null,"abstract":"<p><strong>Introduction: </strong>Changes in the skin microbiome in atopic dermatitis include a reduced bacterial diversity and increased abundance of Staphylococcus aureus. Topical antibiotics and antiseptics may decrease bacterial pathogens, but lack positive effects on microbiome diversity.</p><p><strong>Methods: </strong>In this double-blind, intraindividual vehicle-controlled pilot study, n = 20 patients received a gel containing a defined extract (Spiralin®) of the microalgae Spirulina platensis, previously shown to exert anti-microbial effects, or vehicle on target lesions of similar size and clinical activity. The Shannon index reflecting -diversity and the abundance of S. aureus were calculated from the analysis of 16s rRNA gene libraries with untreated non-lesional skin serving as control. Clinical activity was determined by the Target Lesion Severity Score (TLSS) and lesion size.</p><p><strong>Results: </strong>Positive effects of the active gel on the microbiome after 4 weeks of treatment were indicated by a significant increase of the Shannon index in areas treated with verum (mean increase 16.7%; p<0.01 vs. baseline), but not in areas treated with vehicle. This increase in verum-treated lesions was more pronounced in lesions with an at least 50% (26.3%) or an at least 75% reduction of the TLSS (33.3%). There was also a stronger decrease of the abundance of S. aureus in lesions treated with active gel compared to those treated with vehicle (25.5% vs. 9.4%), but significance was not met. There were several trends indicating clinical effects of the active gel. For example, vehicle-treated areas showed no reduction in area size (77.8 cm2 at week 4 compared to 77.0 cm2 at baseline), while verum-treated lesion area decreased on average by 6.9 cm2. Active and vehicle gel were well tolerated and very few local side effects were noted.</p><p><strong>Conclusion: </strong>These preliminary results indicate a positive effect of a gel containing Spiralin® on the skin microbiome in patients with active atopic dermatitis (AD) lesions combined with reductions in clinical disease activity supporting further investigations of the active gel alone or in combination with anti-inflammatory treatments in larger AD studies.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peptides as Master Keys to Skin Aging.","authors":"Qianqian Zhang, Zijian Liu, Peng Shu, Ligang Jiang, Wenfeng Ding","doi":"10.1159/000547734","DOIUrl":"10.1159/000547734","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key messages: </strong>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.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epidermal Homeostasis in Space from the Stand Point of Keratinocyte Physiology.","authors":"Mitsuhiro Denda","doi":"10.1159/000547984","DOIUrl":"https://doi.org/10.1159/000547984","url":null,"abstract":"<p><p>The human epidermis is the interface between the human body and the environment. It is mainly comprised of keratinocytes. Since the beginning of this century, functional expression of a series of receptors for various environmental factors has been reported. Moreover, neurotransmitters and hormones originally found in the central nervous system are generated and released from keratinocytes. Thus, the pathophysiology of the epidermis is important not only for skin health but also for whole-body conditions. In outer space, humans must confront environmental factors different from those on Earth, such as electromagnetic fields, drastic changes in atmospheric pressure or humidity, and microgravity. In this review, the author discusses the potential effects of these factors on epidermal homeostasis and whole-body conditions.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxidative Stress-Mediated Modulation of Fibrosis and Inflammation in Keloid Fibroblasts by Cold Atmospheric Plasma.","authors":"Razaul Haque, Sung Eun Chang, Ik Jun Moon","doi":"10.1159/000547259","DOIUrl":"10.1159/000547259","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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 H<sub>2</sub>O<sub>2</sub> treatment.</p><p><strong>Results: </strong>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 H<sub>2</sub>O<sub>2</sub> treatment on PKF cells demonstrated that CAP-mediated alterations in gene expression are primarily linked to enhanced ROS production in PKF cells.</p><p><strong>Conclusion: </strong>These findings suggest that CAP may mitigate keloid formation by modifying fibrotic and inflammatory profiles through ROS production and inhibition of cell proliferation.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruno D Martimiano, Maria C V Belli, Mariana de R Lai, Mariana M Morita, Fernando H Minagawa, Ana C C Espósito, Vitor C de Oliveira, Mariana P S Coelho, Hélio A Miot
{"title":"Influence of Physical, Chemical, and Sympathetic Stimuli on Water-Immersion Finger Wrinkling.","authors":"Bruno D Martimiano, Maria C V Belli, Mariana de R Lai, Mariana M Morita, Fernando H Minagawa, Ana C C Espósito, Vitor C de Oliveira, Mariana P S Coelho, Hélio A Miot","doi":"10.1159/000546695","DOIUrl":"10.1159/000546695","url":null,"abstract":"<p><strong>Introduction: </strong>Stimulated skin wrinkling (SSW) reflects the integrity of the autonomic nervous system, eccrine sweat glands, and microcirculation. Specific stimuli, as water immersion or mechanical pressure usually elicit it. This study explored the influence of some physical, chemical, sympathetic stimuli, and circadian cycle on SSW.</p><p><strong>Methods: </strong>Time required to achieve grade III finger wrinkling was assessed in 24 healthy adults. SSW induced by room-temperature filtered water (RTFW) for comparison across temperature variations: warm water (40°C) and iced water; tonicity: Distilled water and hypertonic saline (36% NaCl); pH variations: acidic and alkaline solution; oily medium: soybean oil; or pressure: immersion under hydrostatic pressure (30 cm water column). To evaluate the influence of sympathetic activity, SSW was assessed under caffeine stimulation: 30 min after ingestion of 60 mg caffeine (Ristretto espresso); diurnal variation: testing at 10 a.m. versus 10 p.m.; or ischemic influence: under sub-systolic ischemia induced by an arm cuff. Additionally, 12 participants underwent 10 min fingertip exposures to EMLA and room-temperature vinegar for comparison.</p><p><strong>Results: </strong>The time to reach grade III SSW under RTFW varied widely across the sample (from 2.1 to 37.0 min). The acidic solution reduced the time to SSW compared to RTFW (mean: 6.4 vs. 13.9 min; p < 0.01), with a more pronounced effect observed with a warm (40°C) acidic solution (4.0 vs. 15.5 min; p < 0.01). Hot water, distilled water, and 30 cm hydrostatic pressure stimulation shortened the time to SSW compared to RTFW (p < 0.01). No SSW was observed after 30 min of immersion in the oily medium, iced water, alkaline solution, hypertonic solution, or following ischemia. A circadian influence on SSW was also observed, with morning measurements resulting in a faster response than at night (10.4 vs. 14.6 min; p < 0.01). SSW was also accelerated after coffee consumption (6.1 vs. 10.5 min; p < 0.01). After 10 min of stimulation with either EMLA or vinegar, 75% of participants reached grade III SSW (p = 1.00).</p><p><strong>Conclusion: </strong>SSW is influenced by multiple factors, including solution temperature, pH, osmolarity, hydrostatic pressure, caffeine ingestion, and circadian timing. Warm vinegar elicited a faster and more consistent SSW response compared to other tested conditions, highlighting its use in experimental settings. No difference in SSW was observed between room-temperature vinegar and EMLA after 10 min, supporting its potential for clinical application.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"121-126"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Da-Been Lee, Seung-Lim Yoo, June Seok Heo, Ja-Yun Lim, Sang Shin Pyo, Ji Sun Moon, Mi-Ran Lee, Jinkwan Kim, Suhng-Wook Kim, Dae-Wui Yoon
{"title":"Skin Transcriptomic Analysis Reveals Altered Fatty Acid Metabolism Pathways in Mice Subjected to Sleep Fragmentation.","authors":"Da-Been Lee, Seung-Lim Yoo, June Seok Heo, Ja-Yun Lim, Sang Shin Pyo, Ji Sun Moon, Mi-Ran Lee, Jinkwan Kim, Suhng-Wook Kim, Dae-Wui Yoon","doi":"10.1159/000544736","DOIUrl":"10.1159/000544736","url":null,"abstract":"<p><strong>Introduction: </strong>Sleep fragmentation (SF) is a hallmark of sleep disorders and has been associated with systemic health issues, but its specific impact on skin health remains unclear. This study aimed to investigate whether SF impairs skin barrier function and identify the biological pathways involved in SF-induced skin damage.</p><p><strong>Methods: </strong>Twenty-four 6-week-old male BALB/c mice were divided into home cage control (HC) and SF groups. SF was induced using a commercially available SF chamber. Skin barrier function was assessed by measuring transepidermal water loss (TEWL) at 4 and 8 weeks. Epidermal thickness and dermal collagen density were also measured. Total RNA sequencing (RNA-Seq) and bioinformatics analysis were conducted to identify the affected pathways.</p><p><strong>Results: </strong>TEWL was significantly higher in the SF group than in the HC group at 8 weeks. Epidermal thickness and dermal collagen density were significantly lower in the SF group than in the HC group. In the SF group, 133 differentially expressed genes were identified, of which 14 were upregulated and 119 were downregulated. RNA-Seq and bioinformatics analysis revealed an altered fatty acid metabolism pathway in the skin of mice subjected to chronic SF. This was validated through quantitative real-time polymerase chain reaction.</p><p><strong>Conclusion: </strong>SF caused physiological and histological changes in the skin, altering the fatty acid metabolism pathway. The role of this pathway in SF-induced skin damage requires further exploration.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"21-34"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kinetic Monitoring of in vitro Release Testing Using UV-Vis Spectrophotometry with Hydrocortisone Creams.","authors":"Kelsey Leach, Lola Sibaud, Bradley Towey","doi":"10.1159/000546534","DOIUrl":"10.1159/000546534","url":null,"abstract":"<p><strong>Introduction: </strong>A new method for conducting in vitro release testing (IVRT) was developed by adapting Higuchi's square root approximation for use with UV-Vis spectrophotometry, and over the counter hydrocortisone formulations at 0.5% and 1.0% concentrations. This IVRT method was investigated for the required validation elements as specified by abbreviated new drug applications (ANDAs) and USP General Chapter <1724> for linearity and range, precision and reproducibility, and discrimination sensitivity, specificity, and selectivity.</p><p><strong>Methods: </strong>IVRT kinetic experiments were conducted using UV-Vis spectrophotometer, a quartz cuvette, with measurements collected every 15 s for 5 min, and methanol as the receptor solution. Six measurements of the 1% hydrocortisone formulation were conducted over 3 different days, for a total of 18 measurements. The 0.5% formulation was measured 6 times over 1 day. Release rates were obtained by plotting the slope of Abs<sub>242</sub> vs. √t. HPLC was used to demonstrate specificity via an alternate analytical technique and to show membrane inertness.</p><p><strong>Results: </strong>The hydrocortisone cream formulations demonstrated specificity via HPLC compared to a USP traceable hydrocortisone reference standard. IVRT sensitivity and selectivity were demonstrated by the statistically different release rates (slopes) of the 0.5% vs. the 1% hydrocortisone formulations at 90% confidence interval (75-133.33%). Linearity throughout the duration of the assay was demonstrated through a r2 value of ≥0.97 for each experiment and for each formulation. All intra-run and inter-run precision calculations relating to the IVRT experiments had %CV values of ≤15%.</p><p><strong>Conclusion: </strong>IVRT experiments were conducted using UV-Vis spectrophotometry kinetic monitoring of 0.5% and 1% hydrocortisone formulations. This IVRT method was validated for specificity, selectivity, sensitivity, linearity and range, precision and reproducibility following the guidance for ANDAs and USP General Chapter <1724>, thus demonstrating the capability of UV-Vis spectrophotometry as a reliable way of discerning release rates of semisolid formulations. This novel approach can be conducted in a matter of minutes as opposed to hours, a vast improvement over conventional IVRT studies.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"165-171"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leonhard Zastrow, Jürgen Lademann, Martina C Meinke, Silke B Lohan
{"title":"A Rigorously Simple Quantitative Model for Free Radical Behavior in Aerobic Biological Systems.","authors":"Leonhard Zastrow, Jürgen Lademann, Martina C Meinke, Silke B Lohan","doi":"10.1159/000542600","DOIUrl":"10.1159/000542600","url":null,"abstract":"<p><strong>Background: </strong>Human life is based on oxygen respiration and an enzymatic, free radical-dependent water chemistry, whose billions of parallel reactions take place at pH ∼7.4 and a temperature of 37°C, in accordance with the laws of chemistry. The cellular metabolic processes occur over time periods covered by the half-lives of reactive oxygen species (ROS) for °OH to over 10 s for lipid oxygen species (LOS), indicating that mixtures of free radicals form the basic components for these processes.</p><p><strong>Summary: </strong>The main source of radicals is the mitochondrial conversion of 1-5% oxygen into \"primary\" ROS and \"secondary\" LOS. Every endogenous and exogenous radical generation, triggered by \"natural background radiation,\" \"natural environment,\" or \"solar radiation\" leads to qualitatively similar mixtures of \"primary\" ROS and \"secondary\" LOS or RNS (reactive nitrogen species). A Multilevel Antioxidant Regulation, Repair and Protection System (MARRPS) keeps these radical mixtures in a steady state. Depending on the total number of free radicals, different areas of radical action are defined. The Free Radical Ground State (FRGS) with \"homeostasis\" and \"adaptive homeostasis,\" the Free Radical Threshold Value (FRTV), and Free Radical Pathological Conditions (FRPC). The quantitative ratio ROS > LOS comprehensively characterizes the \"'homeostasis\" and \"adaptive homeostasis\" area of the FRGS. The total number of free radicals cannot be measured directly in the \"homeostasis\" area. \"Adaptive homeostasis\" is achieved when excess radicals are stable produced beyond \"homeostasis\" of the FRGS. The quantity that remains controllable in this range is a maximum of ∼3.58 × 1012 radicals/mg, the value of the body constant FRTV. The sensitized MARRPS provides \"semi-stable homeostatic\" states characterized by dual stability with ROS > LOS and a stable total ROS/LOS and RNS count beyond the basal FRGS \"homeostasis.\" If the total number of all radicals exceeds the FRTV, where LOS > ROS, this initiates uncontrolled radical chain reactions. The partial failure of the MARRPS in the FRPC area leads to pathological processes which are the starting point for a hundred different diseases.</p><p><strong>Key messages: </strong>The universal body constant FRTV is the basis for all regular life processes. The design principle described by this simple model applies universally to all aerobic life.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"45-58"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Moritz Reuter, Hans Schoenfelder, Annette Gaiser, Sebastian Volc, Dominique Lunter
{"title":"Emulsifier-Induced Changes to the Human Skin Barrier: Connection to Ceramide Profiles and Assessment as a Skin Lesion Model.","authors":"Moritz Reuter, Hans Schoenfelder, Annette Gaiser, Sebastian Volc, Dominique Lunter","doi":"10.1159/000545234","DOIUrl":"10.1159/000545234","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"79-91"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}