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Hartung F, Krutmann J, Haarmann-Stemmann T. Evidence that the aryl hydrocarbon receptor orchestrates oxinflammatory responses and contributes to airborne particulate matter-induced skin aging. Free Radic Biol Med 2025; 233:264-278. [PMID: 40157462 DOI: 10.1016/j.freeradbiomed.2025.03.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 03/14/2025] [Accepted: 03/27/2025] [Indexed: 04/01/2025]
Abstract
Exposure to airborne particulate matter (PM) is a substantial threat to public health, contributing to respiratory, cardiovascular, and skin-related diseases. Population-based studies strongly indicate that chronic exposure to airborne PM, especially combustion-derived PM2.5, accelerates skin aging and thus reduces the quality of life of those affected. There is increasing evidence that especially PM-bound polycyclic aromatic hydrocarbons (PAHs) critically contribute to the clinical manifestation of skin aging, i.e. the development of lentigines/pigment spots and coarse wrinkles. PAHs harm human skin primarily by activating the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor amongst others involved in orchestrating xenobiotic metabolism and immune responses. In this review, we summarize the available population-based data linking particulate air pollution exposure to skin aging. We explain in detail how PAH-rich PM induces the formation of oxidative stress, the release of pro-inflammatory mediators, the expression extracellular matrix degrading metalloproteases, and melanin synthesis, in an AHR-dependent manner, and how these events may culminate in the development of pigment spots and wrinkles, respectively. We also review the current data on the interaction of airborne PM with another factor of the skin aging exposome that exerts its deleterious effects in part through AHR-dependent signaling pathways, namely solar ultraviolet radiation.
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Affiliation(s)
- Frederick Hartung
- IUF - Leibniz-Research Institute for Environmental Medicine, 40225, Düsseldorf, Germany
| | - Jean Krutmann
- IUF - Leibniz-Research Institute for Environmental Medicine, 40225, Düsseldorf, Germany; Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany
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Han HS, Seok J, Park KY. Air Pollution and Skin Diseases. Ann Dermatol 2025; 37:53-67. [PMID: 40165563 PMCID: PMC11965873 DOI: 10.5021/ad.24.159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/11/2025] [Accepted: 02/10/2025] [Indexed: 04/02/2025] Open
Abstract
Air pollution is a widespread environmental issue, with substantial global implications for human health. Recent epidemiological studies have shown that exposure to air pollution exacerbates various inflammatory skin conditions, including atopic dermatitis, psoriasis, or acne. Furthermore, air pollutants are associated with accelerated skin aging, hair loss, and skin cancer. The aim of this review is to elucidate the current understanding of the impact of air pollution on skin health, emphasizing the underlying mechanisms involved and existing therapeutic and cosmetic interventions available to prevent or mitigate these effects. A pivotal factor in the harmful effects of air pollution is the formation of reactive oxygen species and the resulting oxidative stress. The aryl hydrocarbon receptor signaling pathway also substantially contributes to mediating the effects of air pollutants on various skin conditions. Moreover, air pollutants can disrupt the skin barrier function and trigger inflammation. Consequently, antioxidant and anti-inflammatory therapies, along with treatments designed to restore the skin barrier function, have the potential to mitigate the adverse effects of air pollutants on skin health.
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Affiliation(s)
- Hye Sung Han
- Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea
- Institute of Clinical Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - Joon Seok
- Department of Dermatology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Kui Young Park
- Department of Dermatology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
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Zhu C, Hong T, Li H, Chen Y, Zheng M, Li Z, Jiang Z, Ni H, Zhu Y. κ-Carrageenan tetrasaccharide ameliorates particulate matter-induced defects in skin hydration of human keratinocytes cells and skin barrier disorders. Int J Biol Macromol 2025; 301:140395. [PMID: 39880261 DOI: 10.1016/j.ijbiomac.2025.140395] [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: 10/23/2024] [Revised: 01/11/2025] [Accepted: 01/26/2025] [Indexed: 01/31/2025]
Abstract
Urban air pollutants, mainly represented by PM containing organic and inorganic substances, can penetrate the human skin and trigger oxidative stress, potentially causing skin barrier damage and aging. κ-Carrageenan oligosaccharides as degradation products of natural sulfated polysaccharide have a great potential for skin moisturization as well as improving oxidative stress and inflammation. In this study, κ-carrageenan tetrasaccharide was obtained by enzymatic digestion of κ-carrageenan, and its role in alleviating particulate matter-induced inflammatory response in HaCaT keratinocyte cell line and skin barrier dysfunction was evaluated. The results showed that particulate matter significantly increased the cellular levels of the pollutant metal ions, stimulated ROS production and cellular inflammatory response, and inhibited enzyme precursors for ceramide synthesis and interfered with lipid synthesis. In contrast, κ-carrageenan tetrasaccharide treatment can downregulate pro-inflammatory factors by chelating metal ions to reduce ROS levels and revert the action of PM on STAT3 and PI3K/AKT pathways and PPAR-γ expression. The beneficial roles of κ-carrageenan tetrasaccharide in protection of dehydration and inflammation suggest that it can be used as a cosmetic ingredient for skincare.
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Affiliation(s)
- Chunhua Zhu
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China
| | - Tao Hong
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China
| | - Hebin Li
- Department of Pharmacy, Xiamen Medical College, Xiamen 361008, China
| | - Yanhong Chen
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China
| | - Mingjing Zheng
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China
| | - Zhipeng Li
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China
| | - Zedong Jiang
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China
| | - Hui Ni
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China
| | - Yanbing Zhu
- College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China.
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Singh N, Wigmann C, Vijay P, Phuleria HC, Kress S, Majmudar G, Kong R, Krutmann J, Schikowski T. Combined Effect of Ambient Temperature and Relative Humidity on Skin Aging Phenotypes in the Era of Climate Change: Results From an Indian Cohort Study. Dermatitis 2025; 36:72-79. [PMID: 39539237 PMCID: PMC11840058 DOI: 10.1089/derm.2024.0301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Background: There is no doubt that global warming, with its extreme heat events, is having an increasing impact on human health. Heat is not independent of ambient temperature but acts synergistically with relative humidity (RH) to increase the risk of several diseases, such as cardiovascular and pulmonary diseases. Although the skin is the organ in direct contact with the environment, it is currently unknown whether skin health is similarly affected. Objective: While mechanistic studies have demonstrated the mechanism of thermal aging, this is the first epidemiological study to investigate the effect of long-term exposure to heat index (HI) as a combined function of elevated ambient temperature and RH on skin aging phenotypes in Indian women. Methods: The skin aging phenotypes of 1510 Indian women were assessed using the Score of Intrinsic and Extrinsic Skin Aging (SCINEXA™) scoring tool. We used data on ambient temperature and RH, combined into an HI with solar ultraviolet radiation (UVR), and air pollution (particulate matter <2.5 µm [PM2.5]; nitrogen dioxide [NO2]) from secondary data sources with a 5-year mean residential exposure window. An adjusted ordinal multivariate logistic regression model was used to assess the effects of HI on skin aging phenotypes. Results: HI increased pigmentation such as hyperpigmented macula on the forehead (odds ratios [OR]: 1.31, 95% confidence interval [CI]: 1.12, 1.54) and coarse wrinkles such as crow's feet (OR: 1.17, 95% CI: 1.05, 1.30) and under-eye wrinkles (OR: 1.3, 95% CI: 1.15, 1.47). These associations were robust to the confounding effects of solar UVR and age. Prolonged exposure to extreme heat, as indicated by high HI, contributes to skin aging phenotypes. Conclusion: Thus, ambient temperature and RH are important factors in assessing the skin aging exposome.
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Affiliation(s)
- Nidhi Singh
- From the IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | - Claudia Wigmann
- From the IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | - Prince Vijay
- Environmental Science and Engineering Department, IIT Bombay, Mumbai, India
| | - Harish C. Phuleria
- Environmental Science and Engineering Department, IIT Bombay, Mumbai, India
| | - Sara Kress
- From the IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | | | - Rong Kong
- Amway Corporation, Ada, Michigan, USA
| | - Jean Krutmann
- From the IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
| | - Tamara Schikowski
- From the IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
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5
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Seong SH, Kim JY, Kim SH, Lee J, Lee EJ, Bae YJ, Park S, Kwon IJ, Yoon SM, Lee J, Kim TG, Oh SH. Interleukin-24: A molecular mediator of particulate matter's impact on skin aging. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 282:116738. [PMID: 39029221 DOI: 10.1016/j.ecoenv.2024.116738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 07/11/2024] [Accepted: 07/13/2024] [Indexed: 07/21/2024]
Abstract
Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging.
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Affiliation(s)
- Seol Hwa Seong
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Ji Young Kim
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sung Hee Kim
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Joohee Lee
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun Jung Lee
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Yu Jeong Bae
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sujin Park
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Il Joo Kwon
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sei-Mee Yoon
- College of Pharmacy, Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahakro, Yeonsu-gu, Incheon, South Korea
| | - Jinu Lee
- College of Pharmacy, Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahakro, Yeonsu-gu, Incheon, South Korea.
| | - Tae-Gyun Kim
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
| | - Sang Ho Oh
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
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Konstantinou E, Longange E, Kaya G. Mechanisms of Senescence and Anti-Senescence Strategies in the Skin. BIOLOGY 2024; 13:647. [PMID: 39336075 PMCID: PMC11428750 DOI: 10.3390/biology13090647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/13/2024] [Accepted: 08/20/2024] [Indexed: 09/30/2024]
Abstract
The skin is the layer of tissue that covers the largest part of the body in vertebrates, and its main function is to act as a protective barrier against external environmental factors, such as microorganisms, ultraviolet light and mechanical damage. Due to its important function, investigating the factors that lead to skin aging and age-related diseases, as well as understanding the biology of this process, is of high importance. Indeed, it has been reported that several external and internal stressors contribute to skin aging, similar to the aging of other tissues. Moreover, during aging, senescent cells accumulate in the skin and express senescence-associated factors, which act in a paracrine manner on neighboring healthy cells and tissues. In this review, we will present the factors that lead to skin aging and cellular senescence, as well as ways to study senescence in vitro and in vivo. We will further discuss the adverse effects of the accumulation of chronic senescent cells and therapeutic agents and tools to selectively target and eliminate them.
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Affiliation(s)
- Evangelia Konstantinou
- Department of Medicine, University of Geneva, Rue Michel-Servet 1, CH-1206 Geneva, Switzerland; (E.K.); (E.L.)
| | - Eliane Longange
- Department of Medicine, University of Geneva, Rue Michel-Servet 1, CH-1206 Geneva, Switzerland; (E.K.); (E.L.)
| | - Gürkan Kaya
- Department of Medicine, University of Geneva, Rue Michel-Servet 1, CH-1206 Geneva, Switzerland; (E.K.); (E.L.)
- Departments of Dermatology and Clinical Pathology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, CH-1205 Geneva, Switzerland
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Gu X, Li Z, Su J. Air pollution and skin diseases: A comprehensive evaluation of the associated mechanism. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 278:116429. [PMID: 38718731 DOI: 10.1016/j.ecoenv.2024.116429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/28/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024]
Abstract
Air pollutants deteriorate the survival environment and endanger human health around the world. A large number of studies have confirmed that air pollution jeopardizes multiple organs, such as the cardiovascular, respiratory, and central nervous systems. Skin is the largest organ and the first barrier that protects us from the outside world. Air pollutants such as particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) will affect the structure and function of the skin and bring about the development of inflammatory skin diseases (atopic dermatitis (AD), psoriasis), skin accessory diseases (acne, alopecia), auto-immune skin diseases (cutaneous lupus erythematosus(CLE) scleroderma), and even skin tumors (melanoma, basal cell carcinoma (BCC), squamous-cell carcinoma (SCC)). Oxidative stress, skin barrier damage, microbiome dysbiosis, and skin inflammation are the pathogenesis of air pollution stimulation. In this review, we summarize the current evidence on the effects of air pollution on skin diseases and possible mechanisms to provide strategies for future research.
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Affiliation(s)
- Xiaoyu Gu
- Department of Dermatology | Hunan Engineering Research Center of Skin Health and Disease | Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha 410008, China; Furong Laboratory, Changsha, Hunan 410008, China
| | - Zhengrui Li
- XiangYa School of Medicine, Central South University, Changsha 410008, China
| | - Juan Su
- Department of Dermatology | Hunan Engineering Research Center of Skin Health and Disease | Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha 410008, China; Furong Laboratory, Changsha, Hunan 410008, China.
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8
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Gu X, Li Z, Su J. Air pollution and skin diseases: A comprehensive evaluation of the associated mechanism. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 278:116429. [DOI: pmid: 38718731 doi: 10.1016/j.ecoenv.2024.116429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2025]
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Orasche J, Luschkova D, Traidl-Hoffmann C. [Allergies in the light of global environmental changes]. DERMATOLOGIE (HEIDELBERG, GERMANY) 2024; 75:93-103. [PMID: 38194098 DOI: 10.1007/s00105-023-05287-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/12/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND The increase in allergies began worldwide with the onset of the Great Acceleration. Environmental pollution and climate change now threaten to cancel out decades of success in health research. OBJECTIVE A summary of environmental influences is provided, which not only shows the significant increase in the prevalence of allergies worldwide but also that of noncommunicable diseases. The effects of the climate crisis on allergies and the multifactorial and interfunctional relationships with other environmental changes are described in detail. MATERIAL AND METHODS In order to obtain an overview of the possible effects of global environmental changes on allergies, a wide range of literature was evaluated and the study results were prepared and summarized. RESULTS A large number of allergens are influencing the human exposome on a daily basis. These allergens are triggered by environmental changes, such as air pollution in the ambient air and indoors, chemicals in everyday objects or residues in food. People are sensitized by the interaction of allergens and pollutants. CONCLUSION The prevalence of allergies is stagnating in industrialized countries. This is probably just the calm before the storm. The accelerating effects of global warming could make pollen and air pollutants even more aggressive in the future. Urgent action is therefore needed to minimize environmental pollution and mitigate climate change.
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Affiliation(s)
- Jürgen Orasche
- Medizinische Fakultät, Lehrstuhl für Umweltmedizin, Universität Augsburg, Neusässer Str. 47, 86156, Augsburg, Deutschland
| | - Daria Luschkova
- Medizinische Fakultät, Lehrstuhl für Umweltmedizin, Universität Augsburg, Neusässer Str. 47, 86156, Augsburg, Deutschland
| | - Claudia Traidl-Hoffmann
- Medizinische Fakultät, Lehrstuhl für Umweltmedizin, Universität Augsburg, Neusässer Str. 47, 86156, Augsburg, Deutschland.
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Ferrara F, Bondi A, Pula W, Contado C, Baldisserotto A, Manfredini S, Boldrini P, Sguizzato M, Montesi L, Benedusi M, Valacchi G, Esposito E. Ethosomes for Curcumin and Piperine Cutaneous Delivery to Prevent Environmental-Stressor-Induced Skin Damage. Antioxidants (Basel) 2024; 13:91. [PMID: 38247515 PMCID: PMC10812558 DOI: 10.3390/antiox13010091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/04/2024] [Accepted: 01/10/2024] [Indexed: 01/23/2024] Open
Abstract
Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure.
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Affiliation(s)
- Francesca Ferrara
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (F.F.); (A.B.); (W.P.); (C.C.); (M.S.)
| | - Agnese Bondi
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (F.F.); (A.B.); (W.P.); (C.C.); (M.S.)
| | - Walter Pula
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (F.F.); (A.B.); (W.P.); (C.C.); (M.S.)
| | - Catia Contado
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (F.F.); (A.B.); (W.P.); (C.C.); (M.S.)
| | - Anna Baldisserotto
- Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy; (A.B.); (S.M.)
| | - Stefano Manfredini
- Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy; (A.B.); (S.M.)
| | - Paola Boldrini
- Center of Electron Microscopy, University of Ferrara, 44121 Ferrara, Italy;
| | - Maddalena Sguizzato
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (F.F.); (A.B.); (W.P.); (C.C.); (M.S.)
| | - Leda Montesi
- Cosmetology Center, University of Ferrara, 44121 Ferrara, Italy;
| | - Mascia Benedusi
- Department of Neurosciences and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy;
| | - Giuseppe Valacchi
- Department of Neurosciences and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy;
- Animal Science Department, NC Research Campus, Plants for Human Health Institute, NC State University, Kannapolis, NC 28081, USA
- Department of Food and Nutrition, Kyung Hee University, Seoul 26723, Republic of Korea
| | - Elisabetta Esposito
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (F.F.); (A.B.); (W.P.); (C.C.); (M.S.)
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11
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Park S, Lim J, Kim S, Jeon M, Baek H, Park W, Park J, Kim SN, Kang NG, Park CG, Kim JW. Anti-Inflammatory Artificial Extracellular Vesicles with Notable Inhibition of Particulate Matter-Induced Skin Inflammation and Barrier Function Impairment. ACS APPLIED MATERIALS & INTERFACES 2023; 15:59199-59208. [PMID: 37983083 DOI: 10.1021/acsami.3c14377] [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: 11/21/2023]
Abstract
Particulate matter (PM) exposure disrupts the skin barrier, causing cutaneous inflammation that may eventually contribute to the development of various skin diseases. Herein, we introduce anti-inflammatory artificial extracellular vesicles (AEVs) fabricated through cell extrusion using the biosurfactant PEGylated mannosylerythritol lipid (P-MEL), hereafter named AEVP-MEL. The P-MEL has anti-inflammatory abilities with demonstrated efficacy in inhibiting the secretion of pro-inflammatory mediators. Mechanistically, AEVP-MEL enhanced anti-inflammatory response by inhibiting the mitogen-activated protein kinase (MAPK) pathway and decreasing the release of inflammatory mediators such as reactive oxygen species (ROS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines in human keratinocytes. Moreover, AEVP-MEL promoted increased expression levels of skin barrier proteins (e.g., involucrin, IVL) and water-proteins (e.g., aquaporin 3, AQP3). In vivo studies revealed that repeated PM exposure to intact skin resulted in cutaneous inflammatory responses, including increased skin thickness (hyperkeratosis) and mast cell infiltration. Importantly, our data showed that the AEVP-MEL treatment significantly restored immune homeostasis in the skin affected by PM-induced inflammation and enhanced the intrinsic skin barrier function. This study highlights the potential of the AEVP-MEL in promoting skin health against PM exposure and its promising implications for the prevention and treatment of PM-related skin disorders.
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Affiliation(s)
- Simon Park
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jaesung Lim
- Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
- Department of Intelligent Precision Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Seulgi Kim
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Minha Jeon
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Hwira Baek
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Wooram Park
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Juwon Park
- Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai'i at Manoa, Honolulu 96813, United States
| | - Se Na Kim
- Research and Development Center, MediArk Inc.,Cheongju 28644, Republic of Korea
- Department of Industrial Cosmetic Science, College of Bio-Health University System, Chungbuk National University, Cheongju 28644, Republic of Korea
| | - Nae-Gyu Kang
- R&D Campus, LG Household & Health Care, Seoul 07795, Republic of Korea
| | - Chun Gwon Park
- Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
- Department of Intelligent Precision Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jin Woong Kim
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
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Almendarez-Reyna CI, de la Trinidad Chacón CG, Ochoa-Martínez ÁC, Rico-Guerrero LA, Pérez-Maldonado IN. The aryl hydrocarbon receptor (AhR) activation mediates benzo(a)pyrene-induced overexpression of AQP3 and Notch1 in HaCaT cells. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2023; 64:466-472. [PMID: 37984337 DOI: 10.1002/em.22580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 11/15/2023] [Accepted: 11/17/2023] [Indexed: 11/22/2023]
Abstract
The aim of this study was twofold: (1) evaluate the effect of benzo[a]pyrene (BaP) on expression levels of AQP3 and Notch1 genes in HaCaT cells exposed "in vitro" and (2) investigate the possible biological role of assessed genes by bioinformatics methods. Cells were exposed to increasing concentrations of BaP (0.0-4.0 μM) for 1-4 days. After treatments, cell viability and expression levels of AhR, CYP1A1, AQP3, and Notch1 genes were evaluated. The possible biological role of assessed genes was evaluated using bioinformatics tools. Low cytotoxicity in HaCaT cells dosed with BaP was detected. A significant overexpression (p < .05) of CYP1A1, AQP3, and Notch1 was found in exposed HaCaT cells. The gene expression upregulation was dependent on AhR activation. The bioinformatics analysis showed that these genes were enriched in related cancer signaling pathways. The findings suggest that AQP3 and Notch1 are upregulated by AhR activation in HaCaT cells exposed to BaP.
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Affiliation(s)
- Claudia I Almendarez-Reyna
- Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
| | - Carlos Gabriel de la Trinidad Chacón
- Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
| | - Ángeles C Ochoa-Martínez
- Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
| | - Luis A Rico-Guerrero
- Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
- Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
| | - Iván N Pérez-Maldonado
- Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
- Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
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13
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Bocheva G, Slominski RM, Slominski AT. Environmental Air Pollutants Affecting Skin Functions with Systemic Implications. Int J Mol Sci 2023; 24:10502. [PMID: 37445680 PMCID: PMC10341863 DOI: 10.3390/ijms241310502] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/09/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The increase in air pollution worldwide represents an environmental risk factor that has global implications for the health of humans worldwide. The skin of billions of people is exposed to a mixture of harmful air pollutants, which can affect its physiology and are responsible for cutaneous damage. Some polycyclic aromatic hydrocarbons are photoreactive and could be activated by ultraviolet radiation (UVR). Therefore, such UVR exposure would enhance their deleterious effects on the skin. Air pollution also affects vitamin D synthesis by reducing UVB radiation, which is essential for the production of vitamin D3, tachysterol, and lumisterol derivatives. Ambient air pollutants, photopollution, blue-light pollution, and cigarette smoke compromise cutaneous structural integrity, can interact with human skin microbiota, and trigger or exacerbate a range of skin diseases through various mechanisms. Generally, air pollution elicits an oxidative stress response on the skin that can activate the inflammatory responses. The aryl hydrocarbon receptor (AhR) can act as a sensor for small molecules such as air pollutants and plays a crucial role in responses to (photo)pollution. On the other hand, targeting AhR/Nrf2 is emerging as a novel treatment option for air pollutants that induce or exacerbate inflammatory skin diseases. Therefore, AhR with downstream regulatory pathways would represent a crucial signaling system regulating the skin phenotype in a Yin and Yang fashion defined by the chemical nature of the activating factor and the cellular and tissue context.
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Affiliation(s)
- Georgeta Bocheva
- Department of Pharmacology and Toxicology, Medical University of Sofia, 1431 Sofia, Bulgaria;
| | - Radomir M. Slominski
- Department of Genetics, Informatics Institute in the School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Andrzej T. Slominski
- Department of Dermatology, Cancer Chemoprevention Program, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Veteran Administration Medical Center, Birmingham, AL 35294, USA
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14
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Yang CY, Pan CC, Tseng CH, Yen FL. Antioxidant, Anti-Inflammation and Antiaging Activities of Artocarpus altilis Methanolic Extract on Urban Particulate Matter-Induced HaCaT Keratinocytes Damage. Antioxidants (Basel) 2022; 11:2304. [PMID: 36421490 PMCID: PMC9687219 DOI: 10.3390/antiox11112304] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/16/2022] [Accepted: 11/17/2022] [Indexed: 07/29/2023] Open
Abstract
Particulate matter (PM) is one of the reasons that exacerbate skin diseases. Impaired barrier function is a common symptom in skin diseases, including atopic dermatitis, eczema and psoriasis. Herbal extracts rich in antioxidants are thought to provide excellent pharmacological activities; however, the anti-pollution activity of Artocarpus altilis extract (AAM) has not been investigated yet. The present study demonstrated that 5 μg/mL of AAM was considered to be a safe dose for further experiments without cytotoxicity. Next, we evaluated the anti-pollution activity of AAM through the PM-induced keratinocytes damage cell model. The results showed that AAM could reduce PM-induced overproduction of intracellular ROS and the final product of lipid peroxidation, 4-hydroxynonenal (4HNE). In addition, AAM not only reduced the inflammatory protein expressions, including tumor necrosis factor α (TNFα), TNF receptor 1 (TNFR1) and cyclooxygenase-2 (COX-2), but also balanced the aging protein ratio of matrix metalloproteinase (MMPs) and tissue inhibitors of metalloproteases (TIMPs) through downregulating the phosphorylation of mitogen-activated protein kinase (MAPK) signaling. For skin barrier protection, AAM could repair PM-induced barrier function proteins damage, including filaggrin, loricrin and aquaporin 3 for providing anti-aging bioactivity. In conclusion, AAM has the potential to be developed as an anti-pollution active ingredient for topical skin products to prevent skin oxidation, inflammation and aging, and restore the skin barrier function.
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Affiliation(s)
- Chun-Yin Yang
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | | | - Chih-Hua Tseng
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Department of Pharmacy, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan
| | - Feng-Lin Yen
- Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan
- College of Professional Studies, National Pingtung University of Science and Technology, Pingtung County 900, Taiwan
- Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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15
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Toolabi A, Bonyadi Z, Ramavandi B. Health impacts quantification attributed to ambient particulate matter in the nearest Iranian city to the main dust source. ENVIRONMENTAL MONITORING AND ASSESSMENT 2022; 194:666. [PMID: 35962291 DOI: 10.1007/s10661-022-10329-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 07/25/2022] [Indexed: 06/15/2023]
Abstract
Urban air contamination is one of the ten most dangerous parameters for human health, which causes cardiovascular disease, respiratory, metabolic diseases, and decreased lung function. Air Q is a reliable software for studying the impacts of atmospheric contaminants on human health, and today, it is widely used in the environment. The purpose of this research was to quantify the mortality and morbidity rates that corresponded to ambient particulate matter (PM) in Rigan City. To perform this, the Air Q software was used. The findings reflected that the yearly mean values of PM10 and PM2.5 are 264.83 and 50.45 μg/m3. The findings indicated that the PM10 and PM2.5 content in Rigan was above standard levels described by WHO. The total number of deaths, cardiovascular deaths, and respiratory deaths due to PM in Rigan were estimated as 70.3, 45.8, and 10.7 persons, respectively. Hospital admissions for cardiovascular and respiratory diseases correlated to PM10 were estimated at 154.2 and 59 persons, respectively. Acute myocardial infarction associated with PM2.5 was 2.7 persons. Overall, the data in this study may be helpful to national and regional policymakers who are responsible for managing and preventing atmospheric contamination and assessing the costs of health risks.
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Affiliation(s)
- Ali Toolabi
- Department of Environmental Health Engineering, School of Public Health, Bam University of Medical Sciences, Bam, Iran
| | - Ziaeddin Bonyadi
- Department of Environmental Health Engineering, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Bahman Ramavandi
- Department of Environmental Health Engineering, Faculty of Health, Bushehr University of Medical Sciences, Bushehr, Iran.
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16
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Fitoussi R, Faure MO, Beauchef G, Achard S. Human skin responses to environmental pollutants: A review of current scientific models. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 306:119316. [PMID: 35469928 DOI: 10.1016/j.envpol.2022.119316] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 04/11/2022] [Accepted: 04/14/2022] [Indexed: 06/14/2023]
Abstract
Whatever the exposure route, chemical, physical and biological pollutants modify the whole organism response, leading to nerve, cardiac, respiratory, reproductive, and skin system pathologies. Skin acts as a barrier for preventing pollutant modifications. This review aims to present the available scientific models, which help investigate the impact of pollution on the skin. The research question was "Which experimental models illustrate the impact of pollution on the skin in humans?" The review covered a period of 10 years following a PECO statement on in vitro, ex vivo, in vivo and in silico models. Of 582 retrieved articles, 118 articles were eligible. In oral and inhalation routes, dermal exposure had an important impact at both local and systemic levels. Healthy skin models included primary cells, cell lines, co-cultures, reconstructed human epidermis, and skin explants. In silico models estimated skin exposure and permeability. All pollutants affected the skin by altering elasticity, thickness, the structure of epidermal barrier strength, and dermal extracellular integrity. Some specific models concerned wound healing or the skin aging process. Underlying mechanisms were an exacerbated inflammatory skin reaction with the modulation of several cytokines and oxidative stress responses, ending with apoptosis. Pathological skin models revealed the consequences of environmental pollutants on psoriasis, atopic dermatitis, and tumour development. Finally, scientific models were used for evaluating the safety and efficacy of potential skin formulations in preventing the skin aging process or skin irritation after repeated contact. The review gives an overview of scientific skin models used to assess the effects of pollutants. Chemical and physical pollutants were mainly represented while biological contaminants were little studied. In future developments, cell hypoxia and microbiota models may be considered as more representative of clinical situations. Models considering humidity and temperature variations may reflect the impact of these changes.
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Affiliation(s)
| | - Marie-Odile Faure
- Scientific Consulting For You, 266 avenue Daumesnil, 75012, PARIS, France
| | | | - Sophie Achard
- HERA Team (Health Environmental Risk Assessment), INSERM UMR1153, CRESS-INRAE, Université Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75270 CEDEX 06, PARIS, France.
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17
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Farris PK, Valacchi G. Ultraviolet Light Protection: Is It Really Enough? Antioxidants (Basel) 2022; 11:1484. [PMID: 36009203 PMCID: PMC9405175 DOI: 10.3390/antiox11081484] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 11/17/2022] Open
Abstract
Our current understanding of the pathogenesis of skin aging includes the role of ultraviolet light, visible light, infrared, pollution, cigarette smoke and other environmental exposures. The mechanism of action common to these exposures is the disruption of the cellular redox balance by the directly or indirectly increased formation of reactive oxygen species that overwhelm the intrinsic antioxidant defense system, resulting in an oxidative stress condition. Altered redox homeostasis triggers downstream pathways that contribute to tissue oxinflammation (cross-talk between inflammation and altered redox status) and accelerate skin aging. In addition, both ultraviolet light and pollution increase intracellular free iron that catalyzes reactive oxygen species generation via the Fenton reaction. This disruption of iron homeostasis within the cell further promotes oxidative stress and contributes to extrinsic skin aging. More recent studies have demonstrated that iron chelators can be used topically and can enhance the benefits of topically applied antioxidants. Thus, an updated, more comprehensive approach to environmental or atmospheric aging protection should include sun protective measures, broad spectrum sunscreens, antioxidants, chelating agents, and DNA repair enzymes.
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Affiliation(s)
- Patricia K. Farris
- Department of Dermatology, Tulane University School of Medicine, New Orleans, LA 70112, USA;
| | - Giuseppe Valacchi
- Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, I-44121 Ferrara, Italy
- Animal Science Department, Plants for Human Health Institute, NC Research Campus, NC State University, Kannapolis, NC 28081, USA
- Department of Food and Nutrition, Kyung Hee University, Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Korea
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18
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Effects of Air Pollution on Cellular Senescence and Skin Aging. Cells 2022; 11:cells11142220. [PMID: 35883663 PMCID: PMC9320051 DOI: 10.3390/cells11142220] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 07/02/2022] [Accepted: 07/11/2022] [Indexed: 12/13/2022] Open
Abstract
The human skin is exposed daily to different environmental factors such as air pollutants and ultraviolet (UV) light. Air pollution is considered a harmful environmental risk to human skin and is known to promote aging and inflammation of this tissue, leading to the onset of skin disorders and to the appearance of wrinkles and pigmentation issues. Besides this, components of air pollution can interact synergistically with ultraviolet light and increase the impact of damage to the skin. However, little is known about the modulation of air pollution on cellular senescence in skin cells and how this can contribute to skin aging. In this review, we are summarizing the current state of knowledge about air pollution components, their involvement in the processes of cellular senescence and skin aging, as well as the current therapeutic and cosmetic interventions proposed to prevent or mitigate the effects of air pollution in the skin.
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19
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Prieux R, Ferrara F, Cervellati F, Guiotto A, Benedusi M, Valacchi G. Inflammasome involvement in CS-induced damage in HaCaT keratinocytes. In Vitro Cell Dev Biol Anim 2022; 58:335-348. [PMID: 35428946 PMCID: PMC9076721 DOI: 10.1007/s11626-022-00658-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/20/2022] [Indexed: 12/14/2022]
Abstract
Cigarette smoke (CS) alters cutaneous biological processes such as redox homeostasis and inflammation response that might be involved in promoting skin inflammatory conditions. Exposure to CS has also been linked to a destabilization of the NLRP3 inflammasome in pollution target tissues such as the lung epithelium, resulting in a more vulnerable immunological response to several exogenous and endogenous stimuli related to oxidative stress. Thus, CS has an adverse effect on host defense, increasing the susceptibility to develop lung infections and pathologies. In the skin, another direct target of pollution, inflammasome disorders have been linked to an increasing number of diseases such as melanoma, psoriasis, vitiligo, atopic dermatitis, and acne, all conditions that have been connected directly or indirectly to pollution exposure. The inflammasome machinery is an important innate immune sensor in human keratinocytes. However, the role of CS in the NLRP1 and NLRP3 inflammasome in the cutaneous barrier has still not been investigated. In the present study, we were able to determine in keratinocytes exposed to CS an increased oxidative damage evaluated by 4-HNE protein adduct and carbonyl formation. Of note is that, while CS inhibited NLRP3 activation, it was able to activate NLRP1, leading to an increased secretion of the proinflammatory cytokines IL-1β and IL-18. This study highlights the importance of the inflammasome machinery in CS that more in general, in pollution, affects cutaneous tissues and the important cross-talk between different members of the NLRP inflammasome family.
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Affiliation(s)
- Roxane Prieux
- Department of Neurosciences and Rehabilitation, University of Ferrara, Ferrara, Italy
| | - Francesca Ferrara
- Department of Neurosciences and Rehabilitation, University of Ferrara, Ferrara, Italy
| | - Franco Cervellati
- Department of Neurosciences and Rehabilitation, University of Ferrara, Ferrara, Italy
| | - Anna Guiotto
- Department of Neurosciences and Rehabilitation, University of Ferrara, Ferrara, Italy
| | - Mascia Benedusi
- Department of Neurosciences and Rehabilitation, University of Ferrara, Ferrara, Italy.
| | - Giuseppe Valacchi
- Department of Environment and Prevention, University of Ferrara, Ferrara, Italy.
- Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, USA.
- Department of Food and Nutrition, Kyung Hee University, Seoul, 02447, South Korea.
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20
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Diesel Particulate Extract Accelerates Premature Skin Aging in Human Fibroblasts via Ceramide-1-Phosphate-Mediated Signaling Pathway. Int J Mol Sci 2022; 23:ijms23052691. [PMID: 35269833 PMCID: PMC8910364 DOI: 10.3390/ijms23052691] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 02/24/2022] [Accepted: 02/24/2022] [Indexed: 02/06/2023] Open
Abstract
Both intrinsic (i.e., an individual’s body clock) and extrinsic factors (i.e., air pollutants and ultraviolet irradiation) accelerate premature aging. Epidemiological studies have shown a correlation between pollutant levels and aging skin symptoms. Diesel particle matter in particular leads to some diseases, including in the skin. Our recent study demonstrates that diesel particulate extract (DPE) increases apoptosis via increases in an anti-mitogenic/pro-apoptotic lipid mediator, ceramide in epidermal keratinocytes. Here, we investigated whether and how DPE accelerates premature skin aging using cultured normal human dermal fibroblasts (HDF). We first demonstrated that DPE increases cell senescence marker β-galactosidase activity in HDF. We then found increases in mRNA and protein levels, along with activity of matrix metalloprotease (MMP)-1 and MMP-3, which are associated with skin aging following DPE exposure. We confirmed increases in collagen degradation in HDF treated with DPE. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is activated by DPE and results in increased ceramide production by sphingomyelinase activation in HDF. We identified that ceramide-1-phosphate (C1P) (produced from ceramide by ceramide kinase activation) activates MMP-1 and MMP-3 through activation of arachidonate cascade, followed by STAT 1- and STAT 3-dependent transcriptional activation.
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21
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Jara CP, de Andrade Berti B, Mendes NF, Engel DF, Zanesco AM, Pereira de Souza GF, de Medeiros Bezerra R, de Toledo Bagatin J, Maria-Engler SS, Morari J, Velander WH, Velloso LA, Araújo EP. Glutamic acid promotes hair growth in mice. Sci Rep 2021; 11:15453. [PMID: 34326383 PMCID: PMC8322389 DOI: 10.1038/s41598-021-94816-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 07/14/2021] [Indexed: 02/07/2023] Open
Abstract
Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases.
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Affiliation(s)
- Carlos Poblete Jara
- Faculty of Nursing, University of Campinas, UNICAMP, Tessalia Vieira de Camargo St., 126, Campinas, SP, 13083-887, Brazil.
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil.
- University of Campinas, Campinas, Brazil.
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE, USA.
| | - Beatriz de Andrade Berti
- Faculty of Nursing, University of Campinas, UNICAMP, Tessalia Vieira de Camargo St., 126, Campinas, SP, 13083-887, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - Natália Ferreira Mendes
- Faculty of Nursing, University of Campinas, UNICAMP, Tessalia Vieira de Camargo St., 126, Campinas, SP, 13083-887, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - Daiane Fátima Engel
- Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - Ariane Maria Zanesco
- Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - Gabriela Freitas Pereira de Souza
- Department of Organic Chemistry, Institute of Chemistry, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - Renan de Medeiros Bezerra
- Faculty of Nursing, University of Campinas, UNICAMP, Tessalia Vieira de Camargo St., 126, Campinas, SP, 13083-887, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - Julia de Toledo Bagatin
- School of Pharmaceutical Sciences, Clinical Chemistry and Toxicology Department, University of São Paulo, São Paulo, Brazil
| | - Silvya Stuchi Maria-Engler
- School of Pharmaceutical Sciences, Clinical Chemistry and Toxicology Department, University of São Paulo, São Paulo, Brazil
| | - Joseane Morari
- Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - William H Velander
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE, USA
| | - Lício A Velloso
- Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
| | - Eliana Pereira Araújo
- Faculty of Nursing, University of Campinas, UNICAMP, Tessalia Vieira de Camargo St., 126, Campinas, SP, 13083-887, Brazil
- Laboratory of Cell Signalling, Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas, Brazil
- University of Campinas, Campinas, Brazil
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22
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Natural compounds protect the skin from airborne particulate matter by attenuating oxidative stress. Biomed Pharmacother 2021; 138:111534. [PMID: 34311532 DOI: 10.1016/j.biopha.2021.111534] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 02/18/2021] [Accepted: 03/21/2021] [Indexed: 02/05/2023] Open
Abstract
Particulate matter (PM) is a common indirect indicator of air pollution and threatens public health upon prolonged exposure, leading to oxidative stress, increasing the risk of develop respiratory and cardiovascular, as well as several autoimmune diseases and cancer. Nowadays, as a first line defense against PM, skin health attracted much attention. Our review summarized the skin damage mechanism induced by PM, including damage skin barrier directly, reactive oxygen species (ROS) accumulation, autophagy, and two canonical signaling pathways. Furthermore, ROS and oxidative stress have been considered pathogenesis centers, with essential skin damage roles. Extracts from plants and natural compounds which present high antioxidant capacity could be used to treat or protect against air pollution-related skin damage. We conclude the extracts reported in recent studies with protective effects on PM-mediated skin damage. Besides, the mechanism of extracts' positive effects has been revealed partially.
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23
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Park S, Ha KH, Kim TG, Kim HC, Kim C, Oh SH. Air pollution and risk of hospital outpatient visits for eczematous skin disorders in metropolitan cities of South Korea. Br J Dermatol 2021; 185:641-644. [PMID: 33760223 DOI: 10.1111/bjd.20079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 02/19/2021] [Accepted: 03/22/2021] [Indexed: 11/28/2022]
Affiliation(s)
- S Park
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - K H Ha
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
| | - T-G Kim
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - H C Kim
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - C Kim
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - S H Oh
- Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Kim BE, Kim J, Goleva E, Berdyshev E, Lee J, Vang KA, Lee UH, Han S, Leung S, Hall CF, Kim NR, Bronova I, Lee EJ, Yang HR, Leung DY, Ahn K. Particulate matter causes skin barrier dysfunction. JCI Insight 2021; 6:145185. [PMID: 33497363 PMCID: PMC8021104 DOI: 10.1172/jci.insight.145185] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 01/21/2021] [Indexed: 11/17/2022] Open
Abstract
The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, the effects of PM2.5 on filaggrin (FLG) and skin barrier function were investigated in vitro and in vivo. The levels of FLG degradation products, including pyrrolidone carboxylic acid, urocanic acid (UCA), and cis/trans-UCA, were significantly decreased in skin tape stripping samples of study subjects when they moved from Denver, an area with low PM2.5, to Seoul, an area with high PM2.5 count. Experimentally, PM2.5 collected in Seoul inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin but did not modulate involucrin or claudin-1 in keratinocyte cultures. Moreover, FLG protein expression was inhibited in human skin equivalents and murine skin treated with PM2.5. We demonstrate that this process was mediated by PM2.5-induced TNF-α and was aryl hydrocarbon receptor dependent. PM2.5 exposure compromised skin barrier function, resulting in increased transepidermal water loss, and enhanced the penetration of FITC-dextran in organotypic and mouse skin. PM2.5-induced TNF-α caused FLG deficiency in the skin and subsequently induced skin barrier dysfunction. Compromised skin barrier due to PM2.5 exposure may contribute to the development and the exacerbation of allergic diseases such as atopic dermatitis.
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Affiliation(s)
- Byung Eui Kim
- Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.,Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jihyun Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, South Korea
| | - Elena Goleva
- Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
| | - Evgeny Berdyshev
- Department of Medicine, National Jewish Health, Denver, Colorado, USA
| | - Jinyoung Lee
- Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, South Korea
| | - Kathryn A Vang
- Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
| | - Un Ha Lee
- Department of Dermatology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea
| | - SongYi Han
- Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, South Korea
| | - Susan Leung
- Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
| | - Clifton F Hall
- Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
| | - Na-Rae Kim
- Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, South Korea
| | - Irina Bronova
- Department of Medicine, National Jewish Health, Denver, Colorado, USA
| | - Eu Jin Lee
- Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, South Korea
| | - Hye-Ran Yang
- Seoul Metropolitan Government Research Institute of Public Health and Environment, Seoul, South Korea
| | - Donald Ym Leung
- Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
| | - Kangmo Ahn
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, South Korea
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Development of Epidermal Equivalent from Electrospun Synthetic Polymers for In Vitro Irritation/Corrosion Testing. NANOMATERIALS 2020; 10:nano10122528. [PMID: 33339410 PMCID: PMC7766501 DOI: 10.3390/nano10122528] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/10/2020] [Accepted: 12/10/2020] [Indexed: 12/14/2022]
Abstract
The development of products for topical applications requires analyses of their skin effects before they are destined for the market. At present, the ban on animal use in several tests makes the search for in vitro models (such as artificial skin) necessary to characterize the risks involved. In this work, tissue engineering concepts were used to manufacture collagen-free three-dimensional scaffolds for cell growth and proliferation. Two different human skin models-reconstructed human epidermis and full-thickness skin-were developed from electrospun scaffolds using synthetic polymers such as polyethylene terephthalate, polybutylene terephthalate, and nylon 6/6. After the construction of these models, their histology was analyzed by H&E staining and immunohistochemistry. The results revealed a reconstructed epidermal tissue, duly stratified, obtained from the nylon scaffold. In this model, the presence of proteins involved in the epidermis stratification process (cytokeratin 14, cytokeratin 10, involucrin, and loricrin) was confirmed by immunohistochemistry and Western blot analysis. The nylon reconstructed human epidermis model's applicability was evaluated as a platform to perform irritation and corrosion tests. Our results demonstrated that this model is a promising platform to assess the potential of dermal irritation/corrosion of chemical products.
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26
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Ferrara F, Pambianchi E, Woodby B, Messano N, Therrien JP, Pecorelli A, Canella R, Valacchi G. Evaluating the effect of ozone in UV induced skin damage. Toxicol Lett 2020; 338:40-50. [PMID: 33279629 DOI: 10.1016/j.toxlet.2020.11.023] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 11/24/2020] [Accepted: 11/29/2020] [Indexed: 12/12/2022]
Abstract
Air pollution represents one of the main risks for both environment and human health. The rapid urbanization has been leading to a continuous release of harmful manmade substances into the atmosphere which are associated to the exacerbation of several pathologies. The skin is the main barrier of our body against the external environment and it is the main target for the outdoor stressors. Among the pollutants, Ozone (O3) is one of the most toxic, able to initiate oxidative reactions and activate inflammatory response, leading to the onset of several skin conditions. Moreover, skin is daily subjected to the activity of Ultraviolet Radiation which are well known to induce harmful cutaneous effects including skin aging and sunburn. Even though both UV and O3 are able to affect the skin homeostasis, very few studies have investigated their possible additive effect. Therefore, in this study we evaluated the effect of the combined exposure of O3 and UV in inducing skin damage, by exposing human skin explants to UV alone or in combination with O3 for 4-days. Markers related to inflammation, redox homeostasis and tissue structure were analyzed. Our results demonstrated that O3 is able to amplify the UV induced skin oxinflammation markers.
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Affiliation(s)
- Francesca Ferrara
- Plants for Human Health Institute Animal Science Dept., NC Research Campus Kannapolis, NC, 28081, United States; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
| | - Erika Pambianchi
- Plants for Human Health Institute Animal Science Dept., NC Research Campus Kannapolis, NC, 28081, United States
| | - Brittany Woodby
- Plants for Human Health Institute Animal Science Dept., NC Research Campus Kannapolis, NC, 28081, United States
| | - Nicolo' Messano
- Plants for Human Health Institute Animal Science Dept., NC Research Campus Kannapolis, NC, 28081, United States
| | | | - Alessandra Pecorelli
- Plants for Human Health Institute Animal Science Dept., NC Research Campus Kannapolis, NC, 28081, United States
| | - Rita Canella
- Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
| | - Giuseppe Valacchi
- Plants for Human Health Institute Animal Science Dept., NC Research Campus Kannapolis, NC, 28081, United States; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy; Kyung Hee University, Department of Food and Nutrition, South Korea.
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27
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Dijkhoff IM, Drasler B, Karakocak BB, Petri-Fink A, Valacchi G, Eeman M, Rothen-Rutishauser B. Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies. Part Fibre Toxicol 2020; 17:35. [PMID: 32711561 PMCID: PMC7382801 DOI: 10.1186/s12989-020-00366-y] [Citation(s) in RCA: 103] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 07/14/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles. MAIN TEXT To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health. CONCLUSION Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.
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Affiliation(s)
- Irini M Dijkhoff
- Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland
| | - Barbara Drasler
- Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland
| | - Bedia Begum Karakocak
- Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland
| | - Alke Petri-Fink
- Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland
| | - Giuseppe Valacchi
- Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy
- Department of Animal Sciences, PHHI NCRC, North Carolina State University, Kannapolis, NC, USA
| | | | - Barbara Rothen-Rutishauser
- Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland.
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