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Lv L, Yan X, Zhou M, He H, Jia Y. Circadian Rhythms of Skin Surface Lipids and Physiological Parameters in Healthy Chinese Women Reveals Circadian Changes in Skin Barrier Function. BIOLOGY 2024; 13:1031. [PMID: 39765698 PMCID: PMC11673904 DOI: 10.3390/biology13121031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Circadian rhythms are driven by the biological clock, an endogenous oscillator that generates approximately 24 h cycles in mammals. The circadian regulation of the lipid metabolism plays a crucial role in overall metabolic health. An analysis of the correlation between the skin's physiological parameters and skin lipids can provide a better insight into the rhythmic changes in skin condition. OBJECTIVES The aim was to reveal how skin surface lipids (SSLs) participate in the regulation of circadian rhythms in the skin and the importance of the circadian oscillation of facial lipid molecules in maintaining epidermal homeostasis. METHODS Changes in SSLs were assessed using UPLC-QTOF-MS. The skin's physiological parameters were quantified using non-invasive instruments. Multivariate data analysis was employed to evaluate the differences. RESULTS Both skin surface lipids and physiological parameters exhibited certain circadian variation patterns. Four major lipid classes (fatty acids, glycerophospholipids, prenol lipids, saccharolipids) exhibited circadian rhythmic trends, with seven lipid subclasses contributing most significantly to the overall patterns observed. Among the physiological parameters assessed, sebum secretion, transepidermal water loss, moisture measurement value, and skin surface temperature exhibited sinusoidal circadian rhythms. Further analysis revealed significant correlations between fatty acids and saccharolipids with moisture measurement values, and between glycerolipids and pH value. In addition, lipids closely associated with the barrier such as unsaturated fatty acids and ceramide chain lengths correlated significantly with moisture measurement values. CONCLUSIONS Through correlation analysis, the study elucidates the influence of diurnal fluctuations in skin surface lipids on skin barrier function. These findings hold significant implications for understanding skin barrier impairment associated with circadian rhythm disruptions.
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Affiliation(s)
- Lanxing Lv
- Beijing Key Laboratory of Plant Resources Research and Development, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China; (L.L.); (X.Y.); (M.Z.)
- Key Laboratory of Cosmetic of China National Light Industry, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
- International School of Cosmetics, Beijing Technology and Business University, Beijing 100048, China
| | - Xiaoxi Yan
- Beijing Key Laboratory of Plant Resources Research and Development, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China; (L.L.); (X.Y.); (M.Z.)
- Key Laboratory of Cosmetic of China National Light Industry, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
- International School of Cosmetics, Beijing Technology and Business University, Beijing 100048, China
| | - Mingyue Zhou
- Beijing Key Laboratory of Plant Resources Research and Development, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China; (L.L.); (X.Y.); (M.Z.)
- Key Laboratory of Cosmetic of China National Light Industry, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
- International School of Cosmetics, Beijing Technology and Business University, Beijing 100048, China
| | - Huaming He
- Beijing Key Laboratory of Plant Resources Research and Development, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China; (L.L.); (X.Y.); (M.Z.)
- Key Laboratory of Cosmetic of China National Light Industry, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
- International School of Cosmetics, Beijing Technology and Business University, Beijing 100048, China
| | - Yan Jia
- Beijing Key Laboratory of Plant Resources Research and Development, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China; (L.L.); (X.Y.); (M.Z.)
- Key Laboratory of Cosmetic of China National Light Industry, School of Light industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China
- International School of Cosmetics, Beijing Technology and Business University, Beijing 100048, China
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Sroczyk EA, Tarasiuk A, Talar M, Rutledge GC, Makaro A, Misztal Z, Wołyniak M, Berniak K, Sałaga M, Fichna J, Stachewicz U. Cholesterol Nanofiber Patches with Sustainable Oil Delivery Eliminate Inflammation in Atopic Skin. ACS APPLIED MATERIALS & INTERFACES 2024; 16:37783-37794. [PMID: 38994590 DOI: 10.1021/acsami.4c09400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
Atopic skin is dry and itchy and lacks integrity. Impaired skin barrier results from altered lipid composition of the skin. A crucial skin lipid, cholesterol, provides flexibility and homeostasis of the cell membranes' lipid bilayer. Cholesterol-based creams and natural oils, especially blackcurrant seed oil, are beneficial for skin care as they hydrate the skin and improve its integrity. The major atopic symptom, skin dryness, can be overcome by the application of porous patches enhanced with cholesterol and natural oil. The base of the patches is constructed of polyimide (PI) nanofibers with cholesterol coatings and externally added blackcurrant seed oil. The presence of cholesterol in PI mats hinders the passage of oil through the patches to the skin, resulting in sustained and prolonged skin hydration. The theoretical and numerical investigations of oil dynamics in porous mats confirmed the experimental results, showing a prolonged skin hydration effect up to 6 h. Additionally, as demonstrated by in vivo tests on atopic mice, cholesterol patches lower serum immunoglobulin E levels and expression of proinflammatory cytokines in the skin, thereby accelerating skin healing. Our results hold great promise for the long-term application of the patches in atopic dermatitis treatment.
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Affiliation(s)
- Ewa A Sroczyk
- Faculty of Metals Engineering and Industrial Computer Science, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Krakow, Poland
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, Massachusetts, United States
| | - Aleksandra Tarasiuk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Marcin Talar
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Gregory C Rutledge
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, Massachusetts, United States
| | - Adam Makaro
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Zofia Misztal
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Maria Wołyniak
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Krzysztof Berniak
- Faculty of Metals Engineering and Industrial Computer Science, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Krakow, Poland
| | - Maciej Sałaga
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Urszula Stachewicz
- Faculty of Metals Engineering and Industrial Computer Science, AGH University of Krakow, Al. Mickiewicza 30, 30-059 Krakow, Poland
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Upadhyay PR, Seminario-Vidal L, Abe B, Ghobadi C, Sims JT. Cytokines and Epidermal Lipid Abnormalities in Atopic Dermatitis: A Systematic Review. Cells 2023; 12:2793. [PMID: 38132113 PMCID: PMC10741881 DOI: 10.3390/cells12242793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/28/2023] [Accepted: 12/05/2023] [Indexed: 12/23/2023] Open
Abstract
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant TH2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with TH1 and TH17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.
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Affiliation(s)
- Parth R. Upadhyay
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA (C.G.); (J.T.S.)
| | - Lucia Seminario-Vidal
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA (C.G.); (J.T.S.)
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Bouwstra JA, Nădăban A, Bras W, McCabe C, Bunge A, Gooris GS. The skin barrier: An extraordinary interface with an exceptional lipid organization. Prog Lipid Res 2023; 92:101252. [PMID: 37666282 PMCID: PMC10841493 DOI: 10.1016/j.plipres.2023.101252] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 08/29/2023] [Accepted: 08/30/2023] [Indexed: 09/06/2023]
Abstract
The barrier function of the skin is primarily located in the stratum corneum (SC), the outermost layer of the skin. The SC is composed of dead cells with highly organized lipid lamellae in the intercellular space. As the lipid matrix forms the only continuous pathway, the lipids play an important role in the permeation of compounds through the SC. The main lipid classes are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). Analysis of the SC lipid matrix is of crucial importance in understanding the skin barrier function, not only in healthy skin, but also in inflammatory skin diseases with an impaired skin barrier. In this review we provide i) a historical overview of the steps undertaken to obtain information on the lipid composition and organization in SC of healthy skin and inflammatory skin diseases, ii) information on the role CERs, CHOL and FFAs play in the lipid phase behavior of very complex lipid model systems and how this knowledge can be used to understand the deviation in lipid phase behavior in inflammatory skin diseases, iii) knowledge on the role of both, CER subclasses and chain length distribution, on lipid organization and lipid membrane permeability in complex and simple model systems with synthetic CERs, CHOL and FFAs, iv) similarity in lipid phase behavior in SC of different species and complex model systems, and vi) future directions in modulating lipid composition that is expected to improve the skin barrier in inflammatory skin diseases.
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Affiliation(s)
- Joke A Bouwstra
- Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
| | - Andreea Nădăban
- Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
| | - Wim Bras
- Chemical Sciences Division, Oak Ridge National Laboratory, One Bethel Valley Road, Oak Ridge, TN 37831, United States of America
| | - Clare McCabe
- School of Engineering & Physical Science, Heriot-Watt University, Edinburgh, Scotland, UK
| | - Annette Bunge
- Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO 80401, United States of America
| | - Gerrit S Gooris
- Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Todorov A, Torah R, Wagih M, Ardern-Jones MR, Beeby SP. Electromagnetic Sensing Techniques for Monitoring Atopic Dermatitis-Current Practices and Possible Advancements: A Review. SENSORS (BASEL, SWITZERLAND) 2023; 23:3935. [PMID: 37112275 PMCID: PMC10144024 DOI: 10.3390/s23083935] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/29/2023] [Accepted: 04/04/2023] [Indexed: 06/19/2023]
Abstract
Atopic dermatitis (AD) is one of the most common skin disorders, affecting nearly one-fifth of children and adolescents worldwide, and currently, the only method of monitoring the condition is through an in-person visual examination by a clinician. This method of assessment poses an inherent risk of subjectivity and can be restrictive to patients who do not have access to or cannot visit hospitals. Advances in digital sensing technologies can serve as a foundation for the development of a new generation of e-health devices that provide accurate and empirical evaluation of the condition to patients worldwide. The goal of this review is to study the past, present, and future of AD monitoring. First, current medical practices such as biopsy, tape stripping and blood serum are discussed with their merits and demerits. Then, alternative digital methods of medical evaluation are highlighted with the focus on non-invasive monitoring using biomarkers of AD-TEWL, skin permittivity, elasticity, and pruritus. Finally, possible future technologies are showcased such as radio frequency reflectometry and optical spectroscopy along with a short discussion to provoke research into improving the current techniques and employing the new ones to develop an AD monitoring device, which could eventually facilitate medical diagnosis.
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Affiliation(s)
- Alexandar Todorov
- Centre of Flexible Electronics and E-Textiles, School of Electronics and Computer Science, University of Southampton, Southampton SO17 1BJ, UK;
| | - Russel Torah
- Centre of Flexible Electronics and E-Textiles, School of Electronics and Computer Science, University of Southampton, Southampton SO17 1BJ, UK;
| | - Mahmoud Wagih
- James Watt School of Engineering, University of Glasgow, Glasgow G12 8QQ, UK;
| | - Michael R. Ardern-Jones
- Clinical Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 1DU, UK;
| | - Steve P. Beeby
- Centre of Flexible Electronics and E-Textiles, School of Electronics and Computer Science, University of Southampton, Southampton SO17 1BJ, UK;
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Genetic polymorphism (rs6587666) in FLG protects from eczema in admixed Brazilian children population with high African ancestry. Heliyon 2023; 9:e13659. [PMID: 36865480 PMCID: PMC9970909 DOI: 10.1016/j.heliyon.2023.e13659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 02/02/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
Genetic variants in filaggrin (FLG) are key in eczema and are less common in Africans than in Europeans and Asians. Here we examined the association between FLG Single Nucleotide Polymorphisms (SNPs) and eczema in a population of admixed Brazilian children and whether African ancestry modifies this association. We included 1010 controls and 137 cases and ran logistic regressions between SNPs in FLG and eczema in the studied population and also stratified the analyses according to the degree of African ancestry. In addition, we tested the replication of the findings on an independent set of individuals, as well as, we verified the impact on FLG expression according to each SNP genotype. The T allele of SNP rs6587666 was negatively associated with eczema in additive model (OR: 0.66, 95% CI: 0.47-0.93, P: 0.017). Moreover, African ancestry modifies the association between rs6587666 and eczema. The effect of the T allele was higher among individuals with higher African ancestry and the association with eczema was lost in individuals with lower African ancestry. In our analyses the expression of FLG in skin was slightly downregulated by the presence of the T allele of rs6587666. In our population, the T allele of rs6587666 in FLG was associated with protection to eczema and the degree of African ancestry was able to modify the observed association.
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Patel N, Clarke JF, Salem F, Abdulla T, Martins F, Arora S, Tsakalozou E, Hodgkinson A, Arjmandi-Tash O, Cristea S, Ghosh P, Alam K, Raney SG, Jamei M, Polak S. Multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) model to predict local and systemic exposure of drug products applied on skin. CPT Pharmacometrics Syst Pharmacol 2022; 11:1060-1084. [PMID: 35670226 PMCID: PMC9381913 DOI: 10.1002/psp4.12814] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 03/15/2022] [Accepted: 04/26/2022] [Indexed: 01/31/2023] Open
Abstract
Physiologically-based pharmacokinetic models combine knowledge about physiology, drug product properties, such as physicochemical parameters, absorption, distribution, metabolism, excretion characteristics, formulation attributes, and trial design or dosing regimen to mechanistically simulate drug pharmacokinetics (PK). The current work describes the development of a multiphase, multilayer mechanistic dermal absorption (MPML MechDermA) model within the Simcyp Simulator capable of simulating uptake and permeation of drugs through human skin following application of drug products to the skin. The model was designed to account for formulation characteristics as well as body site- and sex- population variability to predict local and systemic bioavailability. The present report outlines the structure and assumptions of the MPML MechDermA model and includes results from simulations comparing absorption at multiple body sites for two compounds, caffeine and benzoic acid, formulated as solutions. Finally, a model of the Feldene (piroxicam) topical gel, 0.5% was developed and assessed for its ability to predict both plasma and local skin concentrations when compared to in vivo PK data.
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Affiliation(s)
| | | | | | | | | | | | - Eleftheria Tsakalozou
- Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, Maryland, USA
| | | | | | | | - Priyanka Ghosh
- Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, Maryland, USA
| | - Khondoker Alam
- Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, Maryland, USA
| | - Sam G Raney
- Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, Maryland, USA
| | | | - Sebastian Polak
- Simcyp Division, Certara UK, Sheffield, UK.,Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
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Efficacy of Pseudo-Ceramide-Containing Steroid Lamellar Cream in Patients with Mild to Moderate Atopic Dermatitis: A Randomized, Double-Blind Study. Dermatol Ther (Heidelb) 2022; 12:1823-1834. [PMID: 35852694 PMCID: PMC9357596 DOI: 10.1007/s13555-022-00766-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 06/23/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving decreased barrier function of the stratum corneum. This decrease, caused by a reduction in ceramide, the primary component of intercellular lipids in the stratum corneum, leads to a disturbance in the lamellar structure. Methods We developed a formulation (test cream) containing a steroid and synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethyl hexadecanamide) that forms a lamellar structure on the skin after its application and drying. The formulation or control cream (a formulation containing a steroid but not pseudo-ceramide that does not form a lamellar structure) was applied twice daily for 2 weeks to the lesional area of 34 participants with mild to moderate AD symptoms. Results The test cream showed a periodic structure with an interface space of approximately 8.2 nm in transmission electron microscopy and small- and wide-angle X-ray scattering, similar to the lamellar structure in the human stratum corneum. In the double-blind test, the anti-inflammatory effects of the test cream (n = 17) were comparable to those of the control cream (n = 17). In the test cream group, a significant increase in the stratum corneum moisture content (p < 0.01) and significant decrease in transepidermal water loss (p < 0.05) were observed at weeks 1 and 2 after application compared with those before application. No such change was observed in the control group. Conclusion The results indicate that, even with a relatively short application period of 2 weeks, the test cream not only suppressed inflammation of the lesional area, but also improved the inherent barrier function of the stratum corneum, suggesting its potential as a treatment option for patients with AD.
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Yoshida T, Beck LA, De Benedetto A. Skin barrier defects in atopic dermatitis: From old idea to new opportunity. Allergol Int 2022; 71:3-13. [PMID: 34916117 PMCID: PMC8934597 DOI: 10.1016/j.alit.2021.11.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 11/22/2021] [Indexed: 01/31/2023] Open
Abstract
Atopic dermatitis (AD) is the most common chronic skin inflammatory disease, with a profound impact on patients’ quality of life. AD varies considerably in clinical course, age of onset and degree to which it is accompanied by allergic and non-allergic comorbidities. Skin barrier impairment in both lesional and nonlesional skin is now recognized as a critical and often early feature of AD. This may be explained by a number of abnormalities identified within both the stratum corneum and stratum granulosum layers of the epidermis. The goal of this review is to provide an overview of key barrier defects in AD, starting with a historical perspective. We will also highlight some of the commonly used methods to characterize and quantify skin barrier function. There is ample opportunity for further investigative work which we call out throughout this review. These include: quantifying the relative impact of individual epidermal abnormalities and putting this in a more holistic view with physiological measures of barrier function, as well as determining whether these barrier-specific endotypes predict clinical phenotypes (e.g. age of onset, natural history, comorbidities, response to therapies, etc). Mechanistic studies with new (and in development) AD therapies that specifically target immune pathways, Staphylococcus aureus abundance and/or skin barrier will help us understand the dynamic crosstalk between these compartments and their relative importance in AD.
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Abstract
Ceramides are a class of sphingolipid that is the backbone structure for all sphingolipids, such as glycosphingolipids and phosphosphingolipids. While being a minor constituent of cellular membranes, ceramides are the major lipid component (along with cholesterol, free fatty acid, and other minor components) of the intercellular spaces of stratum corneum that forms the epidermal permeability barrier. These stratum corneum ceramides consist of unique heterogenous molecular species that have only been identified in terrestrial mammals. Alterations of ceramide molecular profiles are characterized in skin diseases associated with compromised permeability barrier functions, such as atopic dermatitis, psoriasis and xerosis. In addition, hereditary abnormalities of some ichthyoses are associated with an epidermal unique ceramide species, omega-O-acylceramide. Ceramides also serve as lipid modulators to regulate cellular functions, including cell cycle arrest, differentiation, and apoptosis, and it has been demonstrated that changes in ceramide metabolism also cause certain diseases. In addition, ceramide metabolites, sphingoid bases, sphingoid base-1-phosphate and ceramide-1-phosphate are also lipid mediators that regulate cellular functions. In this review article, we describe diverse physiological and pathological roles of ceramides and their metabolites in epidermal permeability barrier function, epidermal cell proliferation and differentiation, immunity, and cutaneous diseases. Finally, we summarize the utilization of ceramides as therapy to treat cutaneous disease.
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Fujii M. The Pathogenic and Therapeutic Implications of Ceramide Abnormalities in Atopic Dermatitis. Cells 2021; 10:2386. [PMID: 34572035 PMCID: PMC8468445 DOI: 10.3390/cells10092386] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/05/2021] [Accepted: 09/07/2021] [Indexed: 11/16/2022] Open
Abstract
Ceramides play an essential role in forming a permeability barrier in the skin. Atopic dermatitis (AD) is a common chronic skin disease associated with skin barrier dysfunction and immunological abnormalities. In patients with AD, the amount and composition of ceramides in the stratum corneum are altered. This suggests that ceramide abnormalities are involved in the pathogenesis of AD. The mechanism underlying lipid abnormalities in AD has not yet been fully elucidated, but the involvement of Th2 and Th1 cytokines is implicated. Ceramide-dominant emollients have beneficial effects on skin barrier function; thus, they have been approved as an adjunctive barrier repair agent for AD. This review summarizes the current understanding of the mechanisms of ceramide abnormalities in AD. Furthermore, the potential therapeutic approaches for correcting ceramide abnormalities in AD are discussed.
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Affiliation(s)
- Masanori Fujii
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
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12
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Jung I, Choi J, Nam J, No KT. Modeling lipid layers of atopic skin and observation of changes in lipid layer properties with changes in ceramide content. J Cosmet Dermatol 2021; 20:2924-2931. [PMID: 33238053 PMCID: PMC8451888 DOI: 10.1111/jocd.13861] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 07/09/2020] [Accepted: 11/18/2020] [Indexed: 01/11/2023]
Abstract
BACKGROUND Studies have shown that there is a high correlation between atopic dermatitis and decrease in ceramide content in the lipid bilayer of skin. Moreover, it has been shown that the reduction in ceramide content in the stratum corneum is unique to atopic dermatitis, indicating that there are particular structural differences between the lipid bilayers of normal and atopic skin. AIM This study aimed to compare the lipid bilayer of the atopic skin with that of the healthy skin and to establish a structural model of the lipid bilayer for atopy. METHODS Molecular dynamics simulations were performed using NAMD 2.8. Models of lipid bilayers of normal skin and atopic skin, and a model of lipid bilayer containing only ceramide were built with CHARMM-GUI. The thickness, area occupied per lipid, and alignment of lipids were compared among the three models. Potential mean force (PMF) of the sodium laureth sulfate (SLES) on lipid bilayers was calculated to predict the affinity between SLES and lipid bilayers. RESULTS Potential mean force calculations showed that the lipid bilayer of atopic skin was able to absorb the surfactant more easily than that of normal skin. CONCLUSIONS When the ceramide ratio is low, the thickness of lipid bilayer is reduced and its structure is weakened. Other structural differences between the lipid layers of normal and atopic skin included increased area per lipid and poor alignment of lipids. Further, the atopy lipid bilayer model was found to absorb more SLES than the normal skin lipid bilayer model.
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Affiliation(s)
- In‐Keun Jung
- Amore‐Pacific Research and Development CenterYonginKorea
- Yonsei UniversitySeoulKorea
| | - Joonho Choi
- Amore‐Pacific Research and Development CenterYonginKorea
| | - Jin Nam
- Amore‐Pacific Research and Development CenterYonginKorea
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Wertz PW. Roles of Lipids in the Permeability Barriers of Skin and Oral Mucosa. Int J Mol Sci 2021; 22:ijms22105229. [PMID: 34063352 PMCID: PMC8155912 DOI: 10.3390/ijms22105229] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/05/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
PubMed searches reveal much literature regarding lipids in barrier function of skin and less literature on lipids in barrier function of the oral mucosa. In terrestrial mammals, birds, and reptiles, the skin’s permeability barrier is provided by ceramides, fatty acids, and cholesterol in the outermost layers of the epidermis, the stratum corneum. This layer consists of about 10–20 layers of cornified cells embedded in a lipid matrix. It effectively prevents loss of water and electrolytes from the underlying tissue, and it limits the penetration of potentially harmful substances from the environment. In the oral cavity, the regions of the gingiva and hard palate are covered by keratinized epithelia that much resemble the epidermis. The oral stratum corneum contains a lipid mixture similar to that in the epidermal stratum corneum but in lower amounts and is accordingly more permeable. The superficial regions of the nonkeratinized oral epithelia also provide a permeability barrier. These epithelial regions do contain ceramides, cholesterol, and free fatty acids, which may underlie barrier function. The oral epithelial permeability barriers primarily protect the underlying tissue by preventing the penetration of potentially toxic substances, including microbial products. Transdermal drug delivery, buccal absorption, and lipid-related disease are discussed.
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14
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Chung BY, Kim HO, Kang SY, Jung MJ, Kim SW, Yoo KS, Shin KO, Jeong SK, Park CW. Increased 1-Deoxysphingolipids and Skin Barrier Dysfunction in the Skin of X-ray or Ultraviolet B Irradiation and Atopic Dermatitis Lesion Could Be Prevented by Moisturizer with Physiological Lipid Mixture. Ann Dermatol 2021; 32:306-318. [PMID: 33911758 PMCID: PMC7992660 DOI: 10.5021/ad.2020.32.4.306] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 03/31/2020] [Accepted: 04/07/2020] [Indexed: 12/31/2022] Open
Abstract
Background Skin diseases characterized by epithelial barrier dysfunction show altered sphingolipid metabolism, which results in changes in the stratum corneum intercellular lipid components and structure. Under pathological conditions, 1-deoxysphingolipids form as atypical sphingolipids from de novo sphingolipid biosynthesis. Objective This study investigated the potential role of 1-deoxysphingolipids in skin barrier dysfunction secondary to X-ray and ultraviolet B (UVB) irradiation in vitro and in vivo. It was also evaluated changes in the expression of 1-deoxysphingolipids in lesional human skin of atopic dermatitis. Methods In this study, the changes in these 1-deoxysphingolipids levels of skin and serum samples were investigated in skin barrier dysfunction associated with X-ray and UVB irradiation in vitro and in vivo. Results Increased 1-deoxysphingolipids were observed in cultured normal human epidermal keratinocytes after X-ray irradiation. X-ray or UVB irradiation increased the production of 1-deoxysphingosine in a reconstituted 3-dimensional (3D) skin model. Interestingly, treatment with a physiological lipid mixture (multi-lamellar emulsion contained pseudoceramide), which can strengthen the epidermal permeability barrier function, resulted in decreased 1-deoxysphingosine formation in a reconstituted 3D skin model. Further investigation using a hairless mouse model showed similar preventive effects of physiological lipid mixture against 1-deoxysphingosine formation after X-ray irradiation. An increased level of 1-dexoysphingosine in the stratum corneum was also observed in lesional skin of atopic dermatitis. Conclusion 1-deoxysphingosine might be a novel biomarker of skin barrier dysfunction and a physiological lipid mixture treatment could prevent 1-deoxysphingosine production and consequent skin barrier dysfunction.
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Affiliation(s)
- Bo Young Chung
- Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Hye One Kim
- Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Seok Young Kang
- Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Min Je Jung
- Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | | | | | - Kyong Oh Shin
- Department of Food Science and Nutrition, College of Natural Sciences, Hallym University, Chuncheon, Korea
| | - Se Kyoo Jeong
- Department of Cosmetic Science, Seowon University, Cheongju, Korea
| | - Chun Wook Park
- Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
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15
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Knox S, O'Boyle NM. Skin lipids in health and disease: A review. Chem Phys Lipids 2021; 236:105055. [PMID: 33561467 DOI: 10.1016/j.chemphyslip.2021.105055] [Citation(s) in RCA: 95] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 01/20/2021] [Accepted: 01/21/2021] [Indexed: 12/20/2022]
Abstract
Our skin is the interface between us and our environment - a flexible barrier that has evolved for protection, immunity, regulation and sensation. Once regarded as inert, we now know that it is a dynamic environment. Skin lipids are crucial to the structure and function of skin. From deep in the hypodermis, through the ceramide-rich epidermis, to the lipids of the skin surface, there are a vast array of different lipids with important roles to play. This review firstly discusses the lipid composition of human skin and secondly, changes that have been found in skin lipid composition in different skin diseases. Further research into skin lipids facilitated by ever-improving methodologies will no doubt generate new knowledge, paving the way for diagnosis, prevention and treatment of skin disorders and diseases.
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Affiliation(s)
- Sophie Knox
- School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, D02 PN40, Ireland
| | - Niamh M O'Boyle
- School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, D02 PN40, Ireland.
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16
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Kamimoto-Kuroki J, Yamashita M, Tanaka K, Kadomatsu Y, Tsukamoto D, Aramaki K, Adachi K, Konno Y. Formulation of bicelles with cholesterol using a semi-spontaneous method. Colloids Surf A Physicochem Eng Asp 2020. [DOI: 10.1016/j.colsurfa.2020.125418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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17
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Han C, Jang M, Kim MJ, Han MH, Lee KR, Hahn JS, Ahn J. Engineering Yarrowia lipolytica for de novo production of tetraacetyl phytosphingosine. J Appl Microbiol 2020; 130:1981-1992. [PMID: 33190388 DOI: 10.1111/jam.14931] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/15/2020] [Accepted: 11/04/2020] [Indexed: 11/26/2022]
Abstract
AIMS To genetically engineer the oleaginous yeast Yarrowia lipolytica for de novo production of tetraacetylphytosphingosine (TAPS), a precursor of phytosphingosine, and optimization of fermentation conditions for high yield. METHODS AND RESULTS We successfully constructed a TAPS-producing Y. lipolytica CE3 strain by co-expression of Wickerhamomyces ciferrii-derived acetyl transferases, Sli1p and Atf2p. Next, we optimized several environmental factors including temperature, initial pH and C/N ratio for TAPS production in a shake culture. Deletion of LCB4 in CE3 strain increased the volumetric TAPS titre and cell-specific yield to 142·1 ± 10·7 mgTAPS l-1 and 3·08 ± 0·11 mgTAPS gDCW -1 , respectively, in a shake flask culture incubated for 120 h at 28°C with glycerol as the carbon source. Finally, we developed a 5-l fed-batch process with NaOH-mediated pH control and olive oil as a carbon source, exhibiting 650 ± 24 mgTAPS l-1 of TAPS production within 56 h of the fermentation. CONCLUSIONS The introduction of codon-optimized Sli1p and Atf2p, deletion of LCB4 gene and sexual hybridization, accompanied by specific fermentation conditions, enhanced TAPS yield in Y. lipolytica. SIGNIFICANCE AND IMPACT OF THE STUDY Our results highlight Y. lipolytica as a promising candidate for the industrial production of TAPS, an important component of cosmetic formulations.
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Affiliation(s)
- Changpyo Han
- Biotechnology Process Engineering Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si, Republic of Korea.,Interdisciplinary Program for Bioengineering, Institute of Chemical Processes, Seoul National University, Seoul, Republic of Korea
| | - Minjeong Jang
- Biotechnology Process Engineering Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si, Republic of Korea
| | - Min Ju Kim
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si, Republic of Korea
| | - Man-Ho Han
- Biotechnology Process Engineering Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si, Republic of Korea.,KRIBB School of Biotechnology, UST, Daejeon, Republic of Korea
| | - Kyeong-Ryoon Lee
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si, Republic of Korea
| | - Ji-Sook Hahn
- Interdisciplinary Program for Bioengineering, Institute of Chemical Processes, Seoul National University, Seoul, Republic of Korea.,School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea
| | - Jungoh Ahn
- Biotechnology Process Engineering Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si, Republic of Korea.,KRIBB School of Biotechnology, UST, Daejeon, Republic of Korea
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18
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Franco J, Rajwa B, Ferreira CR, Sundberg JP, HogenEsch H. Lipidomic Profiling of the Epidermis in a Mouse Model of Dermatitis Reveals Sexual Dimorphism and Changes in Lipid Composition before the Onset of Clinical Disease. Metabolites 2020; 10:metabo10070299. [PMID: 32708296 PMCID: PMC7408197 DOI: 10.3390/metabo10070299] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/17/2020] [Accepted: 07/18/2020] [Indexed: 02/07/2023] Open
Abstract
Atopic dermatitis (AD) is a multifactorial disease associated with alterations in lipid composition and organization in the epidermis. Multiple variants of AD exist with different outcomes in response to therapies. The evaluation of disease progression and response to treatment are observational assessments with poor inter-observer agreement highlighting the need for molecular markers. SHARPIN-deficient mice (Sharpincpdm) spontaneously develop chronic proliferative dermatitis with features similar to AD in humans. To study the changes in the epidermal lipid-content during disease progression, we tested 72 epidermis samples from three groups (5-, 7-, and 10-weeks old) of cpdm mice and their WT littermates. An agnostic mass-spectrometry strategy for biomarker discovery termed multiple-reaction monitoring (MRM)-profiling was used to detect and monitor 1,030 lipid ions present in the epidermis samples. In order to select the most relevant ions, we utilized a two-tiered filter/wrapper feature-selection strategy. Lipid categories were compressed, and an elastic-net classifier was used to rank and identify the most predictive lipid categories for sex, phenotype, and disease stages of cpdm mice. The model accurately classified the samples based on phospholipids, cholesteryl esters, acylcarnitines, and sphingolipids, demonstrating that disease progression cannot be defined by one single lipid or lipid category.
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Affiliation(s)
- Jackeline Franco
- Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA;
| | - Bartek Rajwa
- Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA
- Correspondence: (B.R.); (H.H.)
| | - Christina R. Ferreira
- Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA;
| | | | - Harm HogenEsch
- Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA;
- Purdue Institute of Inflammation, Immunology and Infectious Diseases, Purdue University, West Lafayette, IN 47907, USA
- Correspondence: (B.R.); (H.H.)
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19
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Eberlin S, Silva MSD, Facchini G, Silva GHD, Pinheiro ALTA, Eberlin S, Pinheiro ADS. The Ex Vivo Skin Model as an Alternative Tool for the Efficacy and Safety Evaluation of Topical Products. Altern Lab Anim 2020; 48:10-22. [DOI: 10.1177/0261192920914193] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The development of alternative approaches for safety and efficacy testing that avoid the use of animals is a worldwide trend, which relies on the improvement of current models and tools so that they better reproduce human biology. Human skin from elective plastic surgery is a promising experimental model to test the effects of topically applied products. As the structure of native skin is maintained, including cell population (keratinocytes, melanocytes, Langerhans cells and fibroblasts) and dermal matrix (containing collagen, elastin, glycosaminoglycans, etc.), it most closely matches the effects of substances on in vivo human skin. In this review, we present a collection of results that our group has generated over the last years, involving the use of human skin and scalp explants, demonstrating the feasibility of this model. The development of a test system with ex vivo skin explants, of standard size and thickness, and cultured at the air–liquid interface, can provide an important tool for understanding the mechanisms involved in several cutaneous disorders.
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20
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Lipsky ZW, Marques CNH, German GK. Lipid depletion enables permeation of Staphylococcus aureus bacteria through human stratum corneum. Tissue Barriers 2020; 8:1754706. [PMID: 32338129 PMCID: PMC7549745 DOI: 10.1080/21688370.2020.1754706] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 04/01/2020] [Accepted: 04/06/2020] [Indexed: 02/01/2023] Open
Abstract
Atopic dermatitis (AD) is a chronic inflammatory disease that affects approximately 2-5% of adults worldwide. The pathogenesis of AD continues to be a well-debated point of conjecture, with numerous hypotheses having been proposed. AD conditions are associated with increased populations of Staphylococcus aureus and reduced skin lipids. In this study, we evaluate the ability of S. aureus to permeate across human stratum corneum (SC) exhibiting both normal and depleted lipid conditions consistent with AD. This permeation would enable bacteria to interact with underlying viable epidermal cells, which could serve as a trigger for inflammation and disease onset. Our results indicate that permeation of S. aureus through SC exhibiting normal lipid conditions is not statistically significant. However, bacteria can readily permeate through lipid depleted tissue over a 9-d period. These findings suggest that S. aureus may potentially act as the mechanistic cause, rather than merely the result of AD. ABBREVIATIONS AD: Atopic dermatitis; SC: Stratum Corneum; AMP: Antimicrobial peptide; DIW: Deionized water; PDMS: Polydimethylsiloxane; GFP: Green fluorescent protein; BHI: Brain heart infusion medium.
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Affiliation(s)
- Zachary W. Lipsky
- Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA
- Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, USA
| | - Cláudia N. H. Marques
- Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, USA
- Department of Biological Sciences, Binghamton University, Binghamton, NY, USA
| | - Guy K. German
- Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA
- Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, USA
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21
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Glucocerebrosidase: Functions in and Beyond the Lysosome. J Clin Med 2020; 9:jcm9030736. [PMID: 32182893 PMCID: PMC7141376 DOI: 10.3390/jcm9030736] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/03/2020] [Accepted: 03/04/2020] [Indexed: 02/07/2023] Open
Abstract
Glucocerebrosidase (GCase) is a retaining β-glucosidase with acid pH optimum metabolizing the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose. Inherited deficiency of GCase causes the lysosomal storage disorder named Gaucher disease (GD). In GCase-deficient GD patients the accumulation of GlcCer in lysosomes of tissue macrophages is prominent. Based on the above, the key function of GCase as lysosomal hydrolase is well recognized, however it has become apparent that GCase fulfills in the human body at least one other key function beyond lysosomes. Crucially, GCase generates ceramides from GlcCer molecules in the outer part of the skin, a process essential for optimal skin barrier property and survival. This review covers the functions of GCase in and beyond lysosomes and also pays attention to the increasing insight in hitherto unexpected catalytic versatility of the enzyme.
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22
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Fujii M. Current Understanding of Pathophysiological Mechanisms of Atopic Dermatitis: Interactions among Skin Barrier Dysfunction, Immune Abnormalities and Pruritus. Biol Pharm Bull 2020; 43:12-19. [DOI: 10.1248/bpb.b19-00088] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Masanori Fujii
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University
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23
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Opálka L, Kováčik A, Pullmannová P, Maixner J, Vávrová K. Effects of omega- O-acylceramide structures and concentrations in healthy and diseased skin barrier lipid membrane models. J Lipid Res 2019; 61:219-228. [PMID: 31857390 DOI: 10.1194/jlr.ra119000420] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 12/10/2019] [Indexed: 11/20/2022] Open
Abstract
Ceramides (Cers) with ultralong (∼32-carbon) chains and ω-esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ∼10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content-namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.
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Affiliation(s)
- Lukáš Opálka
- Charles University, Faculty of Pharmacy in Hradec Králové, Prague, Czech Republic
| | - Andrej Kováčik
- Charles University, Faculty of Pharmacy in Hradec Králové, Prague, Czech Republic
| | - Petra Pullmannová
- Charles University, Faculty of Pharmacy in Hradec Králové, Prague, Czech Republic
| | - Jaroslav Maixner
- Hradec Králové, Czech Republic. University of Chemistry and Technology Prague, Prague, Czech Republic
| | - Kateřina Vávrová
- Charles University, Faculty of Pharmacy in Hradec Králové, Prague, Czech Republic
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24
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Muresan XM, Narzt MS, Woodby B, Ferrara F, Gruber F, Valacchi G. Involvement of cutaneous SR-B1 in skin lipid homeostasis. Arch Biochem Biophys 2019; 666:1-7. [DOI: 10.1016/j.abb.2019.03.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/06/2019] [Accepted: 03/09/2019] [Indexed: 12/16/2022]
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Abstract
BACKGROUND Atopic dermatitis (AD) is a common disease, which involves a disruption of the skin barrier function. Skin ceramide (CER) composition, which plays crucial roles in maintaining the barrier function of the stratum corneum, is changed in patients with AD. OBJECTIVE The aim of this study was to identify and quantify skin CER subclasses in association with disease severity in pediatric patients with AD. METHODS Two hundred thirteen patients were entered into the observational study. We compared their CER profiles using normal-phase high-performance liquid chromatography coupled with dynamic multiple reaction monitoring mass spectrometry. RESULTS In total, 12 subclasses of CERs were identified. We found that 2 subclasses, that is, CER[AS] and CER[NS], were elevated (P = 0.007 and 0.012, respectively) and correlated with Severity Scoring of Atopic Dermatitis (P = 0.004 and 0.004, respectively). CONCLUSIONS Skin CER abundances are changed in children with AD compared with control subjects.
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26
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27
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Mori K, Seki T, Kaizu K, Takagi Y, Miyaki M, Ishizaki C, Katayama I. Efficacy of a moisturizer containing a pseudo-ceramide and a eucalyptus extract for Japanese patients with mild atopic dermatitis in the summer. J Cosmet Dermatol 2018; 18:850-856. [PMID: 30084152 DOI: 10.1111/jocd.12735] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 03/08/2018] [Accepted: 06/27/2018] [Indexed: 12/01/2022]
Abstract
BACKGROUND Skin moisturizing is advocated to take care of the skin of patients with atopic dermatitis (AD). However, many patients stop using moisturizers in the summer because of excessive sweating and high humidity. OBJECTIVES To examine the efficacy of a moisturizing gel containing a pseudo-ceramide and a eucalyptus extract, which enhances epidermal ceramide synthesis of patients with mild AD in the summer. METHODS We performed a single-blinded 4-week clinical trial of body care on 44 Japanese subjects who had mild AD. They had not applied any moisturizer on their body in the summer. Twenty-seven subjects used the moisturizing gel containing a pseudo-ceramide and a eucalyptus extract twice a day and the 17 other subjects did not use any moisturizer. Prior to and at the end of weeks 2 and 4, the skin conditions of each subject were evaluated. RESULTS During the test period, the atmospheric temperature increased and skin dryness and scaling significantly improved with or without application of the moisturizing gel. However, the improvement in dryness of the treated group was significantly higher than that of the nontreated group. Erythema and itchiness were significantly improved only in the treated group. The skin hydration on the forearm increased significantly only in the treated group. Accompanying those improvements, the quality of life of the subjects, evaluated by Skindex-16® , was significantly improved. CONCLUSION The usage of a moisturizer containing a pseudo-ceramide and a eucalyptus extract is effective for care of the skin of AD subjects even in the summer.
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Affiliation(s)
- Katsura Mori
- Skin Care Product Research, Kao Corporation, Tokyo, Japan
| | - Tsuyoshi Seki
- Skin Care Product Research, Kao Corporation, Tokyo, Japan
| | - Kazuhiro Kaizu
- Skin Care Product Research, Kao Corporation, Tokyo, Japan
| | - Yutaka Takagi
- Skin Care Product Research, Kao Corporation, Tokyo, Japan
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28
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Agrawal K, Hassoun LA, Foolad N, Borkowski K, Pedersen TL, Sivamani RK, Newman JW. Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles. Prostaglandins Leukot Essent Fatty Acids 2018; 134:7-16. [PMID: 29886894 PMCID: PMC6800162 DOI: 10.1016/j.plefa.2018.05.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 04/30/2018] [Accepted: 05/10/2018] [Indexed: 01/10/2023]
Abstract
Skin disease alters cutaneous lipid mediator metabolism, and if skin secretions contain evidence of these changes, they may constitute useful clinical matrices with low associated subject burden. The influences of skin diseases on sebum lipid mediators are understudied. Here, sebum oxylipins, endocannabinoids, sphingolipids, and fatty acids were quantified from the non-lesional bilateral cheeks of subjects with and without quiescent atopic dermatitis (AD) using LC-MS/MS and GC-MS. AD decreased C36 [NS] and [NdS] ceramide concentrations. Compared to males, females demonstrated increased concentrations of oxylipin alcohols and ketones, and saturated and monounsaturated non-esterified fatty acids, as well as decreased concentrations of C42 [NS] and [NdS] ceramides. Additionally, contemporaneously collected sweat lipid mediator profiles were distinct, with sebum showing higher concentrations of most targets, but fewer highly polar lipids. Therefore, AD and gender appear to alter sebum lipid metabolism even in non-lesional skin of quiescent subjects.
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Affiliation(s)
- Karan Agrawal
- Department of Nutrition, University of California-Davis, Davis, CA 95616, USA; West Coast Metabolomics Center, University of California-Davis Genome Center, Davis, CA 95616, USA
| | - Lauren A Hassoun
- Department of Dermatology, University of California-Davis Medical Center, Sacramento, CA 95816, USA
| | - Negar Foolad
- Department of Dermatology, University of California-Davis Medical Center, Sacramento, CA 95816, USA
| | - Kamil Borkowski
- West Coast Metabolomics Center, University of California-Davis Genome Center, Davis, CA 95616, USA
| | | | - Raja K Sivamani
- Department of Dermatology, University of California-Davis Medical Center, Sacramento, CA 95816, USA; Department of Biological Sciences, California State University, Sacramento, CA 95819, USA.
| | - John W Newman
- Department of Nutrition, University of California-Davis, Davis, CA 95616, USA; West Coast Metabolomics Center, University of California-Davis Genome Center, Davis, CA 95616, USA; Obesity and Metabolism Research Unit, Western Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Davis, CA 95616, USA.
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Abstract
Atopic dermatitis (AD) is the most common itchy dermatosis that affects millions of children and adults worldwide. Chronic itch in this condition has significant impact on measures of quality of life, such as sleep. Treating itch in AD has been challenging for decades, but new drugs have emerged in the last year with significant anti-pruritic effect. The optimal treatment regimen for atopic itch addresses barrier dysfunction, inflammation, neural hypersensitivity, and the itch-scratch cycle. Topical moisturizers remain the foundation of treatment and should be used by all patients with AD-associated pruritus. Step-wise therapy, from topical anti-inflammatory creams to systemic monoclonal antibodies and immunosuppressants, is recommended. There are multiple adjuvant therapies that can be used, especially to target itch in the setting of minimal skin inflammation. Finally, patient education, sleep management, and stress relief are important components to optimize outcomes. This review assesses the latest advances and treatment recommendations for pruritus in AD. Finally, suggested therapeutic ladders and emerging treatments are discussed.
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30
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Franco J, Ferreira C, Paschoal Sobreira TJ, Sundberg JP, HogenEsch H. Profiling of epidermal lipids in a mouse model of dermatitis: Identification of potential biomarkers. PLoS One 2018; 13:e0196595. [PMID: 29698466 PMCID: PMC5919619 DOI: 10.1371/journal.pone.0196595] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 04/16/2018] [Indexed: 12/22/2022] Open
Abstract
Lipids are important structural and functional components of the skin. Alterations in the lipid composition of the epidermis are associated with inflammation and can affect the barrier function of the skin. SHARPIN-deficient cpdm mice develop a chronic dermatitis with similarities to atopic dermatitis in humans. Here, we used a recently-developed approach named multiple reaction monitoring (MRM)-profiling and single ion monitoring to rapidly identify discriminative lipid ions. Shorter fatty acyl residues and increased relative amounts of sphingosine ceramides were observed in cpdm epidermis compared to wild type mice. These changes were accompanied by downregulation of the Fasn gene which encodes fatty acid synthase. A profile of diverse lipids was generated by fast screening of over 300 transitions (ion pairs). Tentative attribution of the most significant transitions was confirmed by product ion scan (MS/MS), and the MRM-profiling linear intensity response was validated with a C17-ceramide lipid standard. Relative quantification of sphingosine ceramides CerAS(d18:1/24:0)2OH, CerAS(d18:1/16:0)2OH and CerNS(d18:1/16:0) discriminated between the two groups with 100% accuracy, while the free fatty acids cerotic acid, 16-hydroxy palmitic acid, and docosahexaenoic acid (DHA) had 96.4% of accuracy. Validation by liquid chromatography tandem mass spectrometry (LC-MS/MS) of the above-mentioned ceramides was in agreement with MRM-profiling results. Identification and rapid monitoring of these lipids represent a tool to assess therapeutic outcomes in SHARPIN-deficient mice and other mouse models of dermatitis and may have diagnostic utility in atopic dermatitis.
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Affiliation(s)
- Jackeline Franco
- Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States of America
| | - Christina Ferreira
- Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, United States of America
| | - Tiago J. Paschoal Sobreira
- Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, United States of America
| | - John P. Sundberg
- The Jackson Laboratory, Bar Harbor, Maine, United States of America
| | - Harm HogenEsch
- Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States of America
- The Jackson Laboratory, Bar Harbor, Maine, United States of America
- Purdue Institute of Inflammation, Immunology and Infectious Diseases, Purdue University, West Lafayette, Indiana, United States of America
- * E-mail:
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Fujii M, Ohyanagi C, Kawaguchi N, Matsuda H, Miyamoto Y, Ohya S, Nabe T. Eicosapentaenoic acid ethyl ester ameliorates atopic dermatitis-like symptoms in special diet-fed hairless mice, partly by restoring covalently bound ceramides in the stratum corneum. Exp Dermatol 2018; 27:837-840. [PMID: 29392772 DOI: 10.1111/exd.13507] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2018] [Indexed: 01/15/2023]
Abstract
Skin barrier dysfunction has a key role in the development of atopic dermatitis (AD). Covalently bound ceramides (Cer), which are essential lipids for permeability barrier homoeostasis, are reportedly decreased in the stratum corneum (SC) of AD patients. Hairless mice fed a special diet develop pruritic dermatitis resembling human AD. Our previous study found that oral administration of the n-3 polyunsaturated fatty acid α-linolenic acid ameliorated skin barrier dysfunction in AD mice with concomitant increase in serum eicosapentaenoic acid (EPA). In this study, we examined the effects of EPA ethyl ester (EPA-E) on diet-induced AD in hairless mice. Oral administration of EPA-E ameliorated skin barrier dysfunction and pruritus in AD mice. In the SC of AD mice, covalently bound Cer were markedly diminished. EPA-E administration restored the lack of bound Cer. Our findings imply the possible therapeutic clinical application of EPA-E in the treatment of human AD.
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Affiliation(s)
- Masanori Fujii
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Chie Ohyanagi
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Naomi Kawaguchi
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Hiroyuki Matsuda
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Yoshitaka Miyamoto
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Susumu Ohya
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.,Pharmacology, Graduate School of Medical Sciences and Medical School, Nagoya City University, Nagoya, Japan
| | - Takeshi Nabe
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.,Faculty of Pharmaceutical Sciences, Laboratory of Immunopharmacology, Setsunan University, Osaka, Japan
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Røpke MA, Alonso C, Jung S, Norsgaard H, Richter C, Darvin ME, Litman T, Vogt A, Lademann J, Blume-Peytavi U, Kottner J. Effects of glucocorticoids on stratum corneum lipids and function in human skin—A detailed lipidomic analysis. J Dermatol Sci 2017; 88:330-338. [DOI: 10.1016/j.jdermsci.2017.08.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 06/29/2017] [Accepted: 08/17/2017] [Indexed: 12/11/2022]
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Tokudome Y, Masutani N, Uchino S, Fukai H. Recovery Effects of Oral Administration of Glucosylceramide and Beet Extract on Skin Barrier Destruction by UVB in Hairless Mice. Nutrients 2017; 9:E1178. [PMID: 29077010 PMCID: PMC5707650 DOI: 10.3390/nu9111178] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 10/20/2017] [Accepted: 10/24/2017] [Indexed: 12/01/2022] Open
Abstract
Purified glucosylceramide from beet extract (beet GlcCer) and beet extract containing an equal amount of GlcCer were administered orally to ultra violet B (UVB)-irradiated mice, and differences in the protective effects against skin barrier dysfunction caused by UVB irradiation were compared. In the beet GlcCer group, epidermal thickening and the decrease in stratum corneum (SC) ceramide content caused by UVB irradiation were reduced. In the group that was orally administered beet extract containing glucosylceramide, effects similar to those in the beet GlcCer group were observed. Oral administration of beet GlcCer had no obvious effects against an increase in TEWL or decrease in SC water content after UVB irradiation, but there was improvement in the beet extract group. Oral administration of beet GlcCer is effective in improving skin barrier function in UVB-irradiated mice. Beet extract contains constituents other than GlcCer that are also effective in improving skin barrier function.
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Affiliation(s)
- Yoshihiro Tokudome
- Laboratory of Dermatological Physiology, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
| | - Noriomi Masutani
- Laboratory of Dermatological Physiology, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
| | - Shohei Uchino
- Laboratory of Dermatological Physiology, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
| | - Hisano Fukai
- Laboratory of Dermatological Physiology, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
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Wakeman MP. An open-label forearm-controlled pilot study to assess the effect of a proprietary emollient formulation on objective parameters of skin function of eczema-prone individuals over 14 days. Clin Cosmet Investig Dermatol 2017; 10:275-283. [PMID: 28794649 PMCID: PMC5538541 DOI: 10.2147/ccid.s135841] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background This study examines the efficacy of a new plant-based emollient and assesses product acceptability. Methods Primary efficacy endpoints were improvement in transepidermal water loss, hydration, skin elasticity and firmness, erythema, and skin roughness and smoothness as measured using the versions of Tewameter, Corneometer, Cutometer, Mexameter, and Visioscan VC98, respectively. The cream was applied twice daily by 32 participants to an area of one forearm unaffected by eczema, while the same area of the other forearm was used as a control. Measurements were taken at day 0 and day 14. Secondary endpoints assessed the acceptability of the product. Results At the end of 2 weeks, transepidermal water loss, hydration, skin elasticity and firmness, erythema, and skin roughness and smoothness improved. All changes were statistically significant (p<0.01). The rate of satisfaction with the emollient properties was 82%, and the rate of absorption into the skin was 88%. Results show that the emollient hydrates and repairs eczema-prone skin with high levels of acceptability.
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Affiliation(s)
- Michael Paul Wakeman
- Department of Cancer Sciences, School of Medicine, University of Birmingham, Edgbaston, Birmingham, UK
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35
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Abstract
Itch, or pruritus, is a hallmark feature of atopic dermatitis (AD). The impact of AD-related pruritus can range from mildly distressing or distracting to completely disabling. Traditionally, management of itch in AD patients has focused on restoring the altered skin barrier with topical emollients and/or reducing inflammation. A growing emphasis has been placed on directly targeting the neural transmission pathways that mediate itch signaling. Off-label use of neuromodulatory agents has helped reduce this aggravating symptom in atopic patients. This article reviews the current literature on the use of neuromodulatory agents and nonpharmacologic alternative therapies used to treat AD-related pruritus.
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Affiliation(s)
- Sarina B Elmariah
- Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
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Wijesinghe DS, Warncke UO, Diegelmann RF. Human as the Ultimate Wound Healing Model: Strategies for Studies Investigating the Dermal Lipidome. CURRENT DERMATOLOGY REPORTS 2016; 5:244-251. [PMID: 28503364 PMCID: PMC5423676 DOI: 10.1007/s13671-016-0156-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
PURPOSE OF REVIEW Educate the reader of the multiple roles undertaken by the human epidermal lipidome and the experimental techniques of measuring them. RECENT FINDINGS Damage to skin elicits a wound healing process that is capped by the recreation of the lipid barrier. In addition to barrier function, lipids also undertake an active signaling role during wound healing. Achievement of these multiple functions necessitates a significant complexity and diversity in the lipidome resulting in a composition that is unique to the human skin. As such, any attempts to delineate the function of the lipidome during the wound healing process in humans need to be addressed via studies undertaken in humans. SUMMARY The human cutaneous lipidome is unique and play a functionally significant role in maintaining barrier and regulating wound healing. Modern mass spectrometry and Raman spectroscopy based methods enable the investigation epidermal lipidome with respect to those functions.
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Affiliation(s)
- Dayanjan S Wijesinghe
- Department of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia 23298
| | - Urszula Osinska Warncke
- C. Kenneth and Dianne Wright Center for Clinical and Translational Research (CCTR), Virginia Commonwealth University Richmond, Virginia 23298
| | - Robert F Diegelmann
- Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298
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Barba C, Alonso C, Martí M, Manich A, Coderch L. Skin barrier modification with organic solvents. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2016; 1858:1935-43. [PMID: 27184268 DOI: 10.1016/j.bbamem.2016.05.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 04/29/2016] [Accepted: 05/09/2016] [Indexed: 12/30/2022]
Abstract
The primary barrier to body water loss and influx of exogenous substances resides in the stratum corneum (SC). The barrier function of the SC is provided by patterned lipid lamellae localized to the extracellular spaces between corneocytes. SC lipids are intimately involved in maintaining the barrier function. It is generally accepted that solvents induce cutaneous barrier disruption. The main aim of this work is the evaluation of the different capability of two solvent systems on inducing changes in the SC barrier function. SC lipid modifications will be evaluated by lipid analysis, water sorption/desorption experiments, confocal-Raman visualization and FSTEM images. The amount of SC lipids extracted by chloroform/methanol was significantly higher than those extracted by acetone. DSC results indicate that acetone extract has lower temperature phase transitions than chloroform/methanol extract. The evaluation of the kinetics of the moisture uptake and loss demonstrated that when SC is treated with chloroform/methanol the resultant sample reach equilibrium in shorter times indicating a deterioration of the SC tissue with higher permeability. Instead, acetone treatment led to a SC sample with a decreased permeability thus with an improved SC barrier function. Confocal-Raman and FSTEM images demonstrated the absence of the lipids on SC previously treated with chloroform/methanol. However, they were still present when the SC was treated with acetone. Results obtained with all the different techniques used were consistent. The results obtained increases the knowledge of the interaction lipid-solvent, being this useful for understanding the mechanism of reparation of damaged skin.
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Affiliation(s)
- Clara Barba
- Department of Chemicals and Surfactants Technology, Institute of Advanced Chemistry of Catalonia, Spain.
| | - Cristina Alonso
- Department of Chemicals and Surfactants Technology, Institute of Advanced Chemistry of Catalonia, Spain
| | - Meritxell Martí
- Department of Chemicals and Surfactants Technology, Institute of Advanced Chemistry of Catalonia, Spain
| | - Albert Manich
- Department of Chemicals and Surfactants Technology, Institute of Advanced Chemistry of Catalonia, Spain
| | - Luisa Coderch
- Department of Chemicals and Surfactants Technology, Institute of Advanced Chemistry of Catalonia, Spain
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Li S, Ganguli-Indra G, Indra AK. Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans. Expert Rev Proteomics 2016; 13:451-6. [PMID: 27121756 PMCID: PMC4939172 DOI: 10.1080/14789450.2016.1177462] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
INTRODUCTION Lipidomics is the large-scale profiling and characterization of lipid species in a biological system using mass spectrometry. The skin barrier is mainly comprised of corneocytes and a lipid-enriched extracellular matrix. The major skin lipids are ceramides, cholesterol and free fatty acids (FFA). Lipid compositions are altered in inflammatory skin disorders with disrupted skin barrier such as atopic dermatitis (AD). AREAS COVERED Here we discuss some of the recent applications of lipidomics in human skin biology and in inflammatory skin diseases such as AD, psoriasis and Netherton syndrome. We also review applications of lipidomics in human skin equivalent and in pre-clinical animal models of skin diseases to gain insight into the pathogenesis of the skin disease. Expert commentary: Skin lipidomics analysis could be a fast, reliable and noninvasive tool to characterize the skin lipid profile and to monitor the progression of inflammatory skin diseases such as AD.
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Affiliation(s)
- Shan Li
- Department of Pharmaceutical Sciences, College of Pharmacy, OSU-OHSU
| | - Gitali Ganguli-Indra
- Department of Pharmaceutical Sciences, College of Pharmacy, OSU-OHSU
- Molecular Cell Biology Program
| | - Arup K. Indra
- Department of Pharmaceutical Sciences, College of Pharmacy, OSU-OHSU
- Molecular Cell Biology Program
- Linus Pauling Science Institute, OSU, Corvallis, OR
- Department of Dermatology, Oregon Health & Science University, OR
- Knight Cancer Institute, OHSU, OR
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de Farias Pires T, Azambuja AP, Horimoto ARVR, Nakamura MS, de Oliveira Alvim R, Krieger JE, Pereira AC. A population-based study of the stratum corneum moisture. Clin Cosmet Investig Dermatol 2016; 9:79-87. [PMID: 27143945 PMCID: PMC4845893 DOI: 10.2147/ccid.s88485] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND The stratum corneum (SC) has important functions as a bound-water modulator and a primary barrier of the human skin from the external environment. However, no large epidemiological study has quantified the relative importance of different exposures with regard to these functional properties. In this study, we have studied a large sample of individuals from the Brazilian population in order to understand the different relationships between the properties of SC and a number of demographic and self-perceived variables. METHODS One thousand three hundred and thirty-nine individuals from a rural Brazilian population, who were participants of a family-based study, were submitted to a cross-sectional examination of the SC moisture by capacitance using the Corneometer® CM820 and investigated regarding environmental exposures, cosmetic use, and other physiological and epidemiological measurements. Self-perception-scaled questions about skin conditions were also applied. RESULTS We found significant associations between SC moisture and sex, age, high sun exposure, and sunscreen use frequency (P<0.025). In specific studied sites, self-reported race and obesity were also found to show significant effects. Dry skin self-perception was also found to be highly correlated with the objective measurement of the skin. Other environmental effects on SC moisture are also reported.
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Affiliation(s)
- Thiago de Farias Pires
- Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Cajamar, SP, Brazil
| | | | | | | | - Rafael de Oliveira Alvim
- Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Cajamar, SP, Brazil
| | - José Eduardo Krieger
- Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Cajamar, SP, Brazil
| | - Alexandre Costa Pereira
- Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Cajamar, SP, Brazil
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40
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The Relationship of Proper Skin Cleansing to Pathophysiology, Clinical Benefits, and the Concomitant Use of Prescription Topical Therapies in Patients with Acne Vulgaris. Dermatol Clin 2016; 34:133-45. [DOI: 10.1016/j.det.2015.11.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Janssens M, van Smeden J, Puppels GJ, Lavrijsen APM, Caspers PJ, Bouwstra JA. Lipid to protein ratio plays an important role in the skin barrier function in patients with atopic eczema. Br J Dermatol 2016; 170:1248-55. [PMID: 24641443 DOI: 10.1111/bjd.12908] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2014] [Indexed: 01/09/2023]
Abstract
BACKGROUND The barrier function of the skin is primarily provided by the stratum corneum (SC), the outermost layer of the skin. Skin barrier impairment is thought to be a primary factor in the pathogenesis of atopic eczema (AE). Filaggrin is an epidermal barrier protein and common mutations in the filaggrin gene strongly predispose for AE. However, the role of filaggrin mutations in the decreased skin barrier in AE is not fully understood. It was recently shown that changes in SC lipid composition and organization play a role in the reduced skin barrier in AE. OBJECTIVES To determine whether the lipid/protein ratio and the total dry SC mass per surface area are related to the skin barrier function of controls and patients with AE. METHODS A case-control study was performed to compare nonlesional and lesional skin of AE with skin of controls. The dry SC mass was determined by tape-stripping and Squamescan(™) . The ratio between lipid and protein bands in the Raman spectrum was used to determine the lipid/protein ratio. Skin barrier function was assessed by transepidermal water loss. RESULTS The results show that the dry SC mass per skin area is altered only in lesional SC of patients with AE compared with control subjects. The observed reduction in the lipid/protein ratio in SC of patients with AE was more pronounced, both in lesional and nonlesional SC and correlated strongly with the skin barrier function and disease severity. CONCLUSIONS The lipid/protein ratio plays a role in the reduced skin barrier function in AE.
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Affiliation(s)
- M Janssens
- Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands
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The role of epidermal sphingolipids in dermatologic diseases. Lipids Health Dis 2016; 15:13. [PMID: 26786937 PMCID: PMC4717587 DOI: 10.1186/s12944-016-0178-7] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 01/04/2016] [Indexed: 12/15/2022] Open
Abstract
Sphingolipids, a group of lipids containing the sphingoid base, have both structural and biological functions in human epidermis. Ceramides, as a part of extracellular lipids in the stratum corneum, are important elements of the skin barrier and are involved in the prevention of transepidermal water loss. In addition, ceramides regulate such processes as proliferation, differentiation and apoptosis of keratinocytes. Another important sphingolipid, sphingosine-1-phosphate (S1P), inhibits proliferation and induces differentiation of keratinocytes. A recent clinical study of the efficacy and safety of ponesimod (a selective modulator of the S1P receptor 1) suggested that sphingolipid metabolism may become a new target for the pharmacological treatment of psoriasis. The role of sphingolipids in some dermatologic diseases, including psoriasis, atopic dermatitis and ichthyoses was summarized in this article.
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Abstract
Over two decades ago, it was discovered that the human T-cell repertoire contains T cells that do not recognize peptide antigens in the context of MHC molecules but instead respond to lipid antigens presented by CD1 antigen-presenting molecules. The ability of T cells to 'see' lipid antigens bound to CD1 enables these lymphocytes to sense changes in the lipid composition of cells and tissues as a result of infections, inflammation, or malignancies. Although foreign lipid antigens have been shown to function as antigens for CD1-restricted T cells, many CD1-restricted T cells do not require foreign antigens for activation but instead can be activated by self-lipids presented by CD1. This review highlights recent developments in the field, including the identification of common mammalian lipids that function as autoantigens for αβ and γδ T cells, a novel mode of T-cell activation whereby CD1a itself rather than lipids serves as the autoantigen, and various mechanisms by which the activation of CD1-autoreactive T cells is regulated. As CD1 can induce T-cell effector functions in the absence of foreign antigens, multiple mechanisms are in place to regulate this self-reactivity, and stimulatory CD1-lipid complexes appear to be tightly controlled in space and time.
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44
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Uchida Y, Kim YI, Park K. Signaling roles of ceramide and its metabolites in cutaneous antimicrobial defense. DERMATOL SIN 2015. [DOI: 10.1016/j.dsi.2015.04.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Park K. Role of micronutrients in skin health and function. Biomol Ther (Seoul) 2015; 23:207-17. [PMID: 25995818 PMCID: PMC4428712 DOI: 10.4062/biomolther.2015.003] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Revised: 02/04/2015] [Accepted: 02/05/2015] [Indexed: 12/12/2022] Open
Abstract
Skin is the first line of defense for protecting our bodies against external perturbations, including ultraviolet (UV) irradiation, mechanical/chemical stress, and bacterial infection. Nutrition is one of many factors required for the maintenance of overall skin health. An impaired nutritional status alters the structural integrity and biological function of skin, resulting in an abnormal skin barrier. In particular, the importance of micronutrients (such as certain vitamins and minerals) for skin health has been highlighted in cell culture, animal, and clinical studies. These micronutrients are employed not only as active compounds in therapeutic agents for treating certain skin diseases, but also as ingredients in cosmetic products. Here, the author describes the barrier function of the skin and the general nutritional requirements for skin health. The goal of this review is to discuss the potential roles and current knowledge of selected micronutrients in skin health and function.
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Affiliation(s)
- Kyungho Park
- Department of Dermatology, Northern California Institute for Research and Education (NCIRE)-VA Medical Center, University of California, San Francisco, San Francisco, California 94158, USA
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46
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Popa I, Portoukalian J, Haftek M. Specificity in the alteration of lesional and non-lesional skin lipids in atopic dogs. World J Dermatol 2015; 4:1-7. [DOI: 10.5314/wjd.v4.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2014] [Revised: 11/29/2014] [Accepted: 12/17/2014] [Indexed: 02/07/2023] Open
Abstract
The present paper is in the same time an overview of the literature concerning the alterations of lipids in the stratum corneum (SC) of atopic dogs and a review of data based on our publications. Knowing the importance of the SC barrier function for against pathogens in atopic dermatitis, we show for the first time a detailed biochemical analysis of lipids corresponding to the same amount of proteins in the successive layers of canine SC taken using tape stripping and their specificity as compared to humans. Also we show new results concerning the changes in the composition for protein-bound ceramides, and for the other lipids in involved and non-involved skin areas in atopic dogs. We show how a topical or oral treatment can restore the SC lipid composition and reconstruct the barrier integrity by up-regulating the biosynthesis of protein-bound ceramides.
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47
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Singh B, Haftek M, Harding CR. Retention of corneodesmosomes and increased expression of protease inhibitors in dandruff. Br J Dermatol 2014; 171:760-70. [PMID: 24815089 DOI: 10.1111/bjd.13111] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2014] [Indexed: 12/22/2022]
Abstract
BACKGROUND Dandruff is a common, relapsing and uncomfortable scalp condition affecting a large proportion of the global population. The appearance of flakes on the scalp and in the hair line, and associated itch are thought to be consequences of a damaged skin barrier, altered corneocyte cohesion and abnormal desquamation in dandruff. The balance between skin proteases and protease inhibitors is essential for driving the key events, including corneodesmosome degradation, in the desquamation process and to maintain stratum corneum (SC) barrier integrity. OBJECTIVES To investigate the distribution of corneodesmosomes, the key component of the SC cohesivity and barrier function, and the protease inhibitors lympho-epithelial Kazal-type-related inhibitor (LEKTI-1) and squamous cell carcinoma antigen (SCCA1) in the scalp of dandruff-affected participants. METHODS The methods utilized were immunohistochemistry, scanning immunoelectron microscopy, phase-contrast microscopy, Western blotting and serine protease activity assay on tape-stripped SC or scalp skin biopsies. RESULTS In SC samples from healthy subjects, corneodesmosomes were peripherally located in the corneocytes. In samples of dandruff lesions, corneodesmosomes were located both peripherally and on the entire surface area of the corneocytes. LEKTI-1 and SCCA1 protein levels and parakeratosis were found to be highly elevated in the lesional samples. CONCLUSIONS The persistence of nonperipheral corneodesmosomes is a characteristic feature of the perturbed desquamation seen in dandruff. The increased expression levels of LEKTI-1 and SCCA1 are consistent with the view that the dandruff condition is characterized by an imbalance in protease-protease inhibitor interaction in the SC.
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Affiliation(s)
- B Singh
- Unilever Research & Development, Port Sunlight, Bebington, U.K
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48
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Angelbeck-Schulze M, Mischke R, Rohn K, Hewicker-Trautwein M, Naim HY, Bäumer W. Canine epidermal lipid sampling by skin scrub revealed variations between different body sites and normal and atopic dogs. BMC Vet Res 2014; 10:152. [PMID: 25012966 PMCID: PMC4107596 DOI: 10.1186/1746-6148-10-152] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Accepted: 06/30/2014] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Previously, we evaluated a minimally invasive epidermal lipid sampling method called skin scrub, which achieved reproducible and comparable results to skin scraping. The present study aimed at investigating regional variations in canine epidermal lipid composition using the skin scrub technique and its suitability for collecting skin lipids in dogs suffering from certain skin diseases. Eight different body sites (5 highly and 3 lowly predisposed for atopic lesions) were sampled by skin scrub in 8 control dogs with normal skin. Additionally, lesional and non-lesional skin was sampled from 12 atopic dogs and 4 dogs with other skin diseases by skin scrub. Lipid fractions were separated by high performance thin layer chromatography and analysed densitometrically. RESULTS No significant differences in total lipid content were found among the body sites tested in the control dogs. However, the pinna, lip and caudal back contained significantly lower concentrations of ceramides, whereas the palmar metacarpus and the axillary region contained significantly higher amounts of ceramides and cholesterol than most other body sites. The amount of total lipids and ceramides including all ceramide classes were significantly lower in both lesional and non-lesional skin of atopic dogs compared to normal skin, with the reduction being more pronounced in lesional skin. The sampling by skin scrub was relatively painless and caused only slight erythema at the sampled areas but no oedema. Histological examinations of skin biopsies at 2 skin scrubbed areas revealed a potential lipid extraction from the transition zone between stratum corneum and granulosum. CONCLUSIONS The present study revealed regional variations in the epidermal lipid and ceramide composition in dogs without skin abnormalities but no connection between lipid composition and predilection sites for canine atopic dermatitis lesions. The skin scrub technique proved to be a practicable sampling method for canine epidermal lipids, revealed satisfying results regarding alterations of skin lipid composition in canine atopic dermatitis and might be suitable for epidermal lipid investigations of further canine skin diseases. Although the ceramide composition should be unaffected by the deeper lipid sampling of skin scrub compared to other sampling methods, further studies are required to determine methodological differences.
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Affiliation(s)
| | - Reinhard Mischke
- Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Buenteweg 9, Hanover 30559, Germany.
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Kim J, Kim YS, Cho Y. WITHDRAWN: Lithospermum erythrorhizon extract improves the hydration, sebum, and ceramide content of healthy skin: results from a randomized, placebo-controlled, double-blind study. Nutr Res 2014. [DOI: 10.1016/j.nutres.2014.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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50
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Wu Z, Shon JC, Liu KH. Mass Spectrometry-based Lipidomics and Its Application to Biomedical Research. J Lifestyle Med 2014; 4:17-33. [PMID: 26064851 PMCID: PMC4390758 DOI: 10.15280/jlm.2014.4.1.17] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 03/14/2014] [Indexed: 11/22/2022] Open
Abstract
Lipidomics, a branch of metabolomics, is the large-scale study of pathways and networks of all cellular lipids in biological systems such as cells, tissues or organisms. The recent advance in mass spectrometry technologies have enabled more comprehensive lipid profiling in the biological samples. In this review, we compared four representative lipid profiling technoligies including GC-MS, LC-MS, direct infusion-MS and imaging-MS. We also summarized representative lipid database, and further discussed the applications of lipidomics to the diagnostics of various diseases such as diabetes, obesity, hypertension, and Alzheimer diseases.
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Affiliation(s)
- Zhexue Wu
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea
| | - Jong Cheol Shon
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea
| | - Kwang-Hyeon Liu
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea
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