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Suzuki T, Komaki Y, Amano M, Ando S, Shobu K, Ibuki Y. Faulty Gap Filling in Nucleotide Excision Repair Leads to Double-Strand Break Formation in Senescent Cells. J Invest Dermatol 2025; 145:32-41.e11. [PMID: 38871024 DOI: 10.1016/j.jid.2024.04.033] [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: 08/08/2023] [Revised: 04/19/2024] [Accepted: 04/25/2024] [Indexed: 06/15/2024]
Abstract
The change of repair efficiency of UV-induced pyrimidine dimers due to aging was examined in replicatively senesced fibroblasts. The fibroblasts with repeated passages showed the characteristics of cellular senescence, including irreversible cell cycle arrest, elevated β-galactosidase activity, and senescence-associated secretory phenotype. The incision efficiency of oligonucleotide containing UV lesions was similar regardless of cell doubling levels, but the gap filling process was impaired in replicatively senescent cells. The releases of xeroderma pigmentosum group G, proliferating cell nuclear antigen, and replication protein A from damaged sites were delayed, which might have disturbed the DNA polymerase progression. The persistent single-stranded DNA was likely converted to double-strand breaks, leading to ataxia telangiectasia-mutated phosphorylation and 53BP1 foci formation. Phosphorylated histone H2AX (γ-H2AX) induction mainly occurred in G1 phase in senescent cells, not in S phase such as in normal cells, indicating that replication stress-independent double-strand breaks might be formed. MRE11 having nuclease activity accumulated to damaged sites at early time point after UV irradiation but not released in senescent cells. The pharmacological studies using specific inhibitors for the nuclease activity suggested that MRE11 contributed to the enlargement of single-stranded DNA gap, facilitating the double-strand break formation.
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Affiliation(s)
- Takashi Suzuki
- Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan
| | - Yukako Komaki
- Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan
| | - Momoka Amano
- Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan
| | - Satoko Ando
- Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan
| | - Kosuke Shobu
- Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan
| | - Yuko Ibuki
- Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
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2
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Zhang M, Lin Y, Han Z, Huang X, Zhou S, Wang S, Zhou Y, Han X, Chen H. Exploring mechanisms of skin aging: insights for clinical treatment. Front Immunol 2024; 15:1421858. [PMID: 39582871 PMCID: PMC11581952 DOI: 10.3389/fimmu.2024.1421858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 10/23/2024] [Indexed: 11/26/2024] Open
Abstract
The skin is the largest organ in the human body and is made up of various cells and structures. Over time, the skin will age, which is not only influenced by internal factors, but also by external environmental factors, especially ultraviolet radiation. Aging causes immune system weakening in the elderly, which makes them more susceptible to dermatosis, such as type 2 inflammatory mediated pruritus. The immune response in this condition is marked by senescent cells consistently releasing low amounts of pro-inflammatory cytokines through a senescence-associated secretory phenotype (SASP). This continuous inflammation may accelerate immune system aging and establish a connection between immune aging and type 2 inflammatory skin diseases. In addition, two chronic pigmentation disorders, vitiligo and chloasma, are also associated with skin aging. Aged cells escape the immune system and accumulate in tissues, forming a microenvironment that promotes cancer. At the same time, "photoaging" caused by excessive exposure to ultraviolet radiation is also an important cause of skin cancer. This manuscript describes the possible links between skin aging and type 2 inflammation, chronic pigmentation disorders, and skin cancer and suggests some treatment options.
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Affiliation(s)
- Meiqi Zhang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yumeng Lin
- Health Management Center, Nanjing Tongren Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zhongyu Han
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xuewen Huang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Science and Education Department, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, China
| | - Shuwei Zhou
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Siyu Wang
- Science and Education Department, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, China
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yan Zhou
- Science and Education Department, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, China
- Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, China
| | - Xuan Han
- Science and Education Department, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, China
- First Clinical College of Changzhi Medical College, Changzhi, China
| | - Haoran Chen
- Science and Education Department, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, China
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3
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Shu X, Dong X, Ma Y, Huo W, Li Z, Zou L, Tang Y, Li L, Wang X. The whitening efficacy of a compound formula examined using an ultraviolet-induced skin melanization model. J Cosmet Dermatol 2024; 23:2750-2756. [PMID: 38664985 DOI: 10.1111/jocd.16332] [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: 10/03/2023] [Revised: 03/25/2024] [Accepted: 04/04/2024] [Indexed: 07/26/2024]
Abstract
BACKGROUND In Eastern culture, a fair complexion is the standard of beauty, leading to appearance-related distress among women with darker skin or facial pigmentation. Women seek whitening cosmetics to enhance their skin tone or correct their pigmentation, but their safety and effectiveness are paramount factors to consider. In this study, we evaluated the safety and whitening effects of a compound formula denoted as TEST comprising astaxanthin, nicotinamide, arbutin, and tranexamic acid. METHODS Primary skin irritation and skin-whitening efficacy were examined. Three qualified melanization areas were treated with TEST, 7% ascorbic acid, or a blank. Skin color, the individual type angle (ITA°), and the melanin index (MI) were compared among treatment areas. RESULTS TEST did not induce a skin response and exhibited a significantly higher ITA° than the blank, while no significant difference was observed with that of 7% ascorbic acid. Furthermore, the MI of TEST was significantly reduced posttreatment. CONCLUSIONS TEST could be integrated into spot-fading and skin-whitening cosmeceuticals or functional cosmetics.
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Affiliation(s)
- Xiaohong Shu
- Center of Cosmetic Evaluation, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Dong
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuhong Ma
- Xi'an Runyu Medical Technology Co., Ltd, Xi'an, Shaanxi, China
| | - Wei Huo
- Center of Cosmetic Evaluation, West China Hospital, Sichuan University, Chengdu, China
| | - Zhaoxia Li
- Center of Cosmetic Evaluation, West China Hospital, Sichuan University, Chengdu, China
| | - Lin Zou
- Center of Cosmetic Evaluation, West China Hospital, Sichuan University, Chengdu, China
| | - Ying Tang
- Center of Cosmetic Evaluation, West China Hospital, Sichuan University, Chengdu, China
| | - Li Li
- Center of Cosmetic Evaluation, West China Hospital, Sichuan University, Chengdu, China
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
| | - Xi Wang
- Center of Cosmetic Evaluation, West China Hospital, Sichuan University, Chengdu, China
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
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Geeta Sai G, Jacob SM, D SK, S A, Wahab AJ, R VC. Clinical, Dermoscopic and Histopathological Features of Non-melanoma Skin Cancers in People With Skin of Colour: A Series of Five Cases. Cureus 2024; 16:e61192. [PMID: 38939265 PMCID: PMC11210335 DOI: 10.7759/cureus.61192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 05/27/2024] [Indexed: 06/29/2024] Open
Abstract
Non-melanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) as well as squamous cell carcinoma (SCC) are the two most common skin malignancies globally. They are observed more frequently among Caucasians than Asians, and their incidence is inversely proportional to the pigmentation levels. Even though the occurrence of skin cancers in India is lower, the absolute quantity of cases may be considerable due to the vast population. Here, we report five cases of NMSC in people having skin of colour.
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Affiliation(s)
- Guntamukkala Geeta Sai
- Department of Dermatology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
| | - Sheba Mariam Jacob
- Department of Dermatology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
| | - Sai Kavya D
- Department of Dermatology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
| | - Anannya S
- Department of Dermatology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
| | - Afthab Jameela Wahab
- Department of Dermatology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
| | - Vimal Chander R
- Department of Pathology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Saveetha University, Chennai, IND
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Ramaraj JA, Narayan S. Anti-aging Strategies and Topical Delivery of Biopolymer-based Nanocarriers for Skin Cancer Treatment. Curr Aging Sci 2024; 17:31-48. [PMID: 36941817 DOI: 10.2174/1874609816666230320122018] [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: 08/03/2022] [Revised: 01/07/2023] [Accepted: 01/23/2023] [Indexed: 03/23/2023]
Abstract
Environmental factors like UV radiation and epigenetic changes are significant factors for skin cancer that trigger early aging. This review provides essential information on cancer development concerning aging, the receptors involved, and the therapeutic targets. Biopolymers like polysaccharide, polyphenols, proteins, and nucleic acid plays a vital role in the regulation of normal cell homeostasis. Therefore, it is pertinent to explore the role of biopolymers as antiaging formulations and the possibility of these formulations being used against cancer via topical administrations. As UV radiation is one of the predominant factors in causing skin cancer, the association of receptors between aging and cancer indicated that insulin receptor, melatonin receptor, toll-like receptor, SIRT 1 receptor, tumor-specific T cell receptor and mitochondria-based targeting could be used to direct therapeutics for suppression of cancer and prevent aging. Biopolymer-based nanoformulations have tremendously progressed by entrapment of drugs like curcumin and resveratrol which can prevent cancer and aging simultaneously. Certain protein signaling or calcium and ROS signaling pathways are different for cancer and aging. The involvement of mitochondrial DNA mutation along with telomere shortening with a change in cellular energetics leading to genomic instability in the aging process can also induce mitochondrial dysfunction and epigenetic alterations leading to skin cancer. Therefore, the use of biopolymers as a topical supplement during the aging process can result in the prevention of cancer.
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Affiliation(s)
- Jino Affrald Ramaraj
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, 603103, India
| | - Shoba Narayan
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, 603103, India
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Yim W, Zhou J, Sasi L, Zhao J, Yeung J, Cheng Y, Jin Z, Johnson W, Xu M, Palma-Chavez J, Fu L, Qi B, Retout M, Shah NJ, Bae J, Jokerst JV. 3D-Bioprinted Phantom with Human Skin Phototypes for Biomedical Optics. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2206385. [PMID: 36305604 PMCID: PMC9868107 DOI: 10.1002/adma.202206385] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/21/2022] [Indexed: 06/16/2023]
Abstract
3D-bioprinted skin-mimicking phantoms with skin colors ranging across the Fitzpatrick scale are reported. These tools can help understand the impact of skin phototypes on biomedical optics. Synthetic melanin nanoparticles of different sizes (70-500 nm) and clusters are fabricated to mimic the optical behavior of melanosome. The absorption coefficient and reduced scattering coefficient of the phantoms are comparable to real human skin. Further the melanin content and distribution in the phantoms versus real human skins are validated via photoacoustic (PA) imaging. The PA signal of the phantom can be improved by: 1) increasing melanin size (3-450-fold), 2) increasing clustering (2-10.5-fold), and 3) increasing concentration (1.3-8-fold). Then, multiple biomedical optics tools (e.g., PA, fluorescence imaging, and photothermal therapy) are used to understand the impact of skin tone on these modalities. These well-defined 3D-bioprinted phantoms may have value in translating biomedical optics and reducing racial bias.
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Affiliation(s)
- Wonjun Yim
- Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, USA
| | - Jiajing Zhou
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Lekshmi Sasi
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Jiayu Zhao
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Justin Yeung
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
| | - Yong Cheng
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Zhicheng Jin
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Wade Johnson
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Ming Xu
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Jorge Palma-Chavez
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Lei Fu
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Baiyan Qi
- Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, USA
| | - Maurice Retout
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
| | - Nisarg J. Shah
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
- Chemical Engineering Program, University of California San Diego, La Jolla, CA, USA
| | - Jinhye Bae
- Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, USA
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
- Chemical Engineering Program, University of California San Diego, La Jolla, CA, USA
| | - Jesse V. Jokerst
- Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, USA
- Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA
- Chemical Engineering Program, University of California San Diego, La Jolla, CA, USA
- Department of Radiology, University of California San Diego, La Jolla, CA, USA
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7
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Abdelwahab R, Huang R, Potla S, Bhalla S, AlQabandi Y, Nandula SA, Boddepalli CS, Gutlapalli SD, Lavu VK, Mohammed L. The Relationship between Vitamin D and Basal Cell Carcinoma: A Systematic Review. Cureus 2022; 14:e29496. [PMID: 36312675 PMCID: PMC9595244 DOI: 10.7759/cureus.29496] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/23/2022] [Indexed: 11/14/2022] Open
Abstract
This systematic review studies the relationship between vitamin D serum levels and basal cell carcinoma (BCC). The primary source of vitamin D is sunlight exposure. Recently, an increase in the intake of vitamin D supplements has been noticed. The protective value of vitamin D is well established and has been studied several times for the health of the bones, cartilage, growth, various dermatological diseases, and also as a chemoprotective agent against several cancers. On the scientific front, it has yet to be established that increasing serum vitamin D levels increase the incidence of BCC. We included reports that investigated this relationship in this review. We applied keywords in published papers in PubMed, ScienceDirect, Cochrane, and Google Scholar to find relevant studies. After applying the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and the quality appraisal for 68 records, we included only ten studies. In these studies, serum levels of vitamin D were measured. Five of them supported the link between BCC incidence and development and high serum vitamin D levels (e.g., Mahamat-Saleh Y, et al.), while the other five did not (e.g., Tang JY, et al.). We included only two studies that investigated the vitamin D receptor (VDR) polymorphism. Experts debate adding a high dose of vitamin D supplements to our daily routine. After studying most of the reports, it was ascertained that the literature supports keeping vitamin D serum levels below 30-60 nmol/L. However, further studies should be done to help find a healthy balance of vitamin D serum levels, especially when it comes to increasing the risk of cancer like BCC.
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Affiliation(s)
- Rana Abdelwahab
- Dermatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Dermatology, Mansoura University, Mansoura, EGY
| | - Ruimin Huang
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Shanthi Potla
- Psychiatry and Behavioral Sciences, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Medical College, Avalon University School of Medicine, Cleveland, USA
| | - Sushen Bhalla
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Yousif AlQabandi
- Ministry of Health, Al Bahar Ophthalmology Center, Sabah Area, KWT
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Chinmayi Sree Boddepalli
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sai Dheeraj Gutlapalli
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Vamsi Krishna Lavu
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lubna Mohammed
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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8
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Chang Villacreses MM, Karnchanasorn R, Panjawatanan P, Ou HY, Chiu KC. Conundrum of vitamin D on glucose and fuel homeostasis. World J Diabetes 2021; 12:1363-1385. [PMID: 34630895 PMCID: PMC8472505 DOI: 10.4239/wjd.v12.i9.1363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/10/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
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Affiliation(s)
- Maria Mercedes Chang Villacreses
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
| | - Panadeekarn Panjawatanan
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 700, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
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Majoros H, Borsos BN, Ujfaludi Z, Páhi ZG, Mórocz M, Haracska L, Boros IM, Pankotai T. SerpinB10, a Serine Protease Inhibitor, Is Implicated in UV-Induced Cellular Response. Int J Mol Sci 2021; 22:ijms22168500. [PMID: 34445206 PMCID: PMC8395218 DOI: 10.3390/ijms22168500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 12/31/2022] Open
Abstract
UV-induced DNA damage response and repair are extensively studied processes, as any malfunction in these pathways contributes to the activation of tumorigenesis. Although several proteins involved in these cellular mechanisms have been described, the entire repair cascade has remained unexplored. To identify new players in UV-induced repair, we performed a microarray screen, in which we found SerpinB10 (SPB10, Bomapin) as one of the most dramatically upregulated genes following UV irradiation. Here, we demonstrated that an increased mRNA level of SPB10 is a general cellular response following UV irradiation regardless of the cell type. We showed that although SPB10 is implicated in the UV-induced cellular response, it has no indispensable function in cell survival upon UV irradiation. Nonetheless, we revealed that SPB10 might be involved in delaying the duration of DNA repair in interphase and also in S-phase cells. Additionally, we also highlighted the interaction between SPB10 and H3. Based on our results, it seems that SPB10 protein is implicated in UV-induced stress as a “quality control protein”, presumably by slowing down the repair process.
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Affiliation(s)
- Hajnalka Majoros
- Institute of Pathology, Faculty of Medicine, University of Szeged, 1 Állomás utca, H-6725 Szeged, Hungary; (H.M.); (B.N.B.); (Z.U.); (Z.G.P.)
| | - Barbara N. Borsos
- Institute of Pathology, Faculty of Medicine, University of Szeged, 1 Állomás utca, H-6725 Szeged, Hungary; (H.M.); (B.N.B.); (Z.U.); (Z.G.P.)
| | - Zsuzsanna Ujfaludi
- Institute of Pathology, Faculty of Medicine, University of Szeged, 1 Állomás utca, H-6725 Szeged, Hungary; (H.M.); (B.N.B.); (Z.U.); (Z.G.P.)
| | - Zoltán G. Páhi
- Institute of Pathology, Faculty of Medicine, University of Szeged, 1 Állomás utca, H-6725 Szeged, Hungary; (H.M.); (B.N.B.); (Z.U.); (Z.G.P.)
| | - Mónika Mórocz
- HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, H-6726 Szeged, Hungary; (M.M.); (L.H.)
| | - Lajos Haracska
- HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre, H-6726 Szeged, Hungary; (M.M.); (L.H.)
| | - Imre Miklós Boros
- Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary;
- Institute of Biochemistry, Biological Research Centre, H-6726 Szeged, Hungary
| | - Tibor Pankotai
- Institute of Pathology, Faculty of Medicine, University of Szeged, 1 Állomás utca, H-6725 Szeged, Hungary; (H.M.); (B.N.B.); (Z.U.); (Z.G.P.)
- Correspondence: ; Tel.: +36-62-546-164
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Lee EJ, Kim J, Jeong MK, Lee YM, Chung YJ, Kim EM. Whitening effect of novel peptide mixture by regulating melanosome biogenesis, transfer and degradation. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2021; 25:15-26. [PMID: 33361534 PMCID: PMC7756534 DOI: 10.4196/kjpp.2021.25.1.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 10/23/2020] [Accepted: 10/23/2020] [Indexed: 12/22/2022]
Abstract
Peptides are short chain of amino acids linked by peptide bonds. They are widely used as effective and biocompatible active ingredients in cosmetic industry. In this study, we developed novel peptide mixture and identified its anti-pigmentation effect on melanocytes and keratinocytes. Our results revealed that peptide mixture inhibited melanosome biogenesis through the regulation of microphthalmia-associated transcription factor, a key factor of melanogenesis in melanocytes. And we observed that peptide mixture inhibited melanosome uptake through the reduction of protease-activated receptor 2, a phagocytosis-related receptor in keratinocytes. Furthermore, peptide mixture activated autophagy system resulting in degradation of transferred melanosomes in keratinocytes. The anti-pigmentation effect of multi-targeting peptide mixture was assessed in a human skin equivalent model (MelanoDerm). Melanin contents in epidermal layer were significantly decreased by topical treatment of peptide mixture, suggesting that it can be applied as a novel cosmetics material having a whitening function.
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Affiliation(s)
| | - Jandi Kim
- Caregen R&D Center, Anyang 14119, Korea
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Boo YC. Up- or Downregulation of Melanin Synthesis Using Amino Acids, Peptides, and Their Analogs. Biomedicines 2020; 8:biomedicines8090322. [PMID: 32882959 PMCID: PMC7555855 DOI: 10.3390/biomedicines8090322] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 08/30/2020] [Accepted: 08/31/2020] [Indexed: 02/07/2023] Open
Abstract
Harmonious synthesis and distribution of melanin in the skin contribute to the expression of beauty and the maintenance of health. When skin pigmentary disorders occur because of internal or external factors or, when there is a need to artificially increase or reduce the pigmentation level of the skin for aesthetic or therapeutic purposes, various pharmacological therapies are applied but the results are not always satisfactory. Studies have been conducted to improve the efficacy and safety of these treatment strategies. In this review, we present the latest studies regarding peptides and related compounds that may be useful in artificially increasing or reducing skin melanin levels. Certain analogs of α-melanocyte stimulating hormone (MSH) and oligopeptides with the sequences derived from the hormone were shown to promote melanin synthesis in cells and in vivo models. Various amino acids, peptides, their analogs, and their hybrid compounds with other chemical moieties were shown to inhibit tyrosinase (TYR) catalytic activity or downregulate TYR gene expression. Certain peptides were shown to inhibit melanosome biogenesis or induce autophagy, leading to decreased pigmentation. In vivo and clinical evidence are available for some compounds, including [Nle4-D-Phe7]-α-MSH, glutathione disulfide, and glycinamide hydrochloride. For many other compounds, additional studies are required to verify their efficacy and safety in vivo and in clinical trials. The accumulating information regarding pro- and antimelanogenic activity of peptides and related compounds will lead to the development of novel drugs for the treatment of skin pigmentary disorders.
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Affiliation(s)
- Yong Chool Boo
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea; ; Tel.: +82-53-420-4946
- BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 41944, Korea
- Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Korea
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12
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The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride. Biomedicines 2020; 8:biomedicines8080257. [PMID: 32751779 PMCID: PMC7460399 DOI: 10.3390/biomedicines8080257] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/13/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022] Open
Abstract
A previous study identified certain low molecular anti-melanogenic peptides that share a common sequence with α-melanocyte stimulating hormone (MSH) and end with a glycinamide moiety. Glycinamide itself also showed anti-melanogenic activity in cell-based assays, but neither glycine nor acetyl glycinamide were active, which indicated a special structure and activity relationship. The aim of this study was to examine the skin depigmentation efficacy of glycinamide hydrochloride in human subjects. The primary skin irritation potential of glycinamide hydrochloride was evaluated by patch testing in 30 human subjects. The skin depigmentation efficacy of glycinamide hydrochloride was evaluated in a double-blinded clinical test in 21 human subjects. The test product and a control product were applied to designated sites on the right or left side of the face twice daily for eight weeks. Skin color parameters, i.e., the melanin index, the L* value (representing skin lightness), a* value (redness), and b* value (yellowness) were measured using instruments. The individual topology angle (ITAo, representing skin color) was calculated from L* and b values. The degree of skin pigmentation was visually assessed by two testers. The primary skin irritation test showed that a solution containing glycinamide hydrochloride up to 10% did not induce any adverse skin responses. In the efficacy test, the test product significantly reduced the melanin index, and increased L* value and ITAo after two weeks of application relative to the baseline value at the start of the test. It also significantly lowered the degree of pigmentation after 6 weeks of application, relative to the baseline value. Differences in the melanin index, L* value, ITAo and the degree of pigmentation between the test and control groups became statistically significant after six weeks or eight weeks of application. No signs of skin irritation were observed during the efficacy test. The present study suggests that glycinamide hydrochloride has great potential to be used in the control of skin hyperpigmentation.
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13
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Boo YC. Emerging Strategies to Protect the Skin from Ultraviolet Rays Using Plant-Derived Materials. Antioxidants (Basel) 2020; 9:E637. [PMID: 32708455 PMCID: PMC7402153 DOI: 10.3390/antiox9070637] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/14/2020] [Accepted: 07/17/2020] [Indexed: 12/15/2022] Open
Abstract
Sunlight contains a significant amount of ultraviolet (UV) ray, which leads to various effects on homeostasis in the body. Defense strategies to protect from UV rays have been extensively studied, as sunburn, photoaging, and photocarcinogenesis are caused by excessive UV exposure. The primary lines of defense against UV damage are melanin and trans-urocanic acid, which are distributed in the stratum corneum. UV rays that pass beyond these lines of defense can lead to oxidative damage. However, cells detect changes due to UV rays as early as possible and initiate cell signaling processes to prevent the occurrence of damage and repair the already occurred damage. Cosmetic and dermatology experts recommend using a sunscreen product to prevent UV-induced damage. A variety of strategies using antioxidants and anti-inflammatory agents have also been developed to complement the skin's defenses against UV rays. Researchers have examined the use of plant-derived materials to alleviate the occurrence of skin aging, diseases, and cancer caused by UV rays. Furthermore, studies are also underway to determine how to promote melanin production to protect from UV-induced skin damage. This review provides discussion of the damage that occurs in the skin due to UV light and describes potential defense strategies using plant-derived materials. This review aims to assist researchers in understanding the current research in this area and to potentially plan future studies.
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Affiliation(s)
- Yong Chool Boo
- Department of Molecular Medicine, School of Medicine, BK21 Plus KNU Biomedical Convergence Program, Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Korea
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14
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Song H, Hwang YJ, Ha JW, Boo YC. Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)- N-(2-hydroxyethyl)- N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms. Int J Mol Sci 2020; 21:ijms21134589. [PMID: 32605171 PMCID: PMC7370187 DOI: 10.3390/ijms21134589] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/17/2020] [Accepted: 06/27/2020] [Indexed: 12/16/2022] Open
Abstract
The aim of this study was to identify novel antimelanogenic drugs from an epigenetic screening library containing various modulators targeting DNA methyltransferases, histone deacetylases, and other related enzymes/proteins. Of 141 drugs tested, K8 (4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit the α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently inhibited the catalytic activity TYR in vitro (IC50, 1.1-1.5 µM) as compared to β-arbutin (IC50, 500-700 µM) or kojic acid (IC50, 63 µM). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8 inhibits cellular melanin synthesis not by downregulation of TYR protein expression through an epigenetic mechanism, but by direct inhibition of TYR catalytic activity through copper chelation. Metal chelating activity of K8 is not surprising because it is known to inhibit histone deacetylase (HDAC) 6 through zinc chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis, which may be useful for the treatment of hyperpigmentation disorders.
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Affiliation(s)
- Hyerim Song
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea; (H.S.); (Y.J.H.); (J.W.H.)
- Brain Korea (BK) 21 Plus Kyungpook National University (KNU) Biomedical Convergence Program, Kyungpook National University, Daegu 41944, Korea
| | - Yun Jeong Hwang
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea; (H.S.); (Y.J.H.); (J.W.H.)
- Brain Korea (BK) 21 Plus Kyungpook National University (KNU) Biomedical Convergence Program, Kyungpook National University, Daegu 41944, Korea
| | - Jae Won Ha
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea; (H.S.); (Y.J.H.); (J.W.H.)
- Brain Korea (BK) 21 Plus Kyungpook National University (KNU) Biomedical Convergence Program, Kyungpook National University, Daegu 41944, Korea
| | - Yong Chool Boo
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea; (H.S.); (Y.J.H.); (J.W.H.)
- Brain Korea (BK) 21 Plus Kyungpook National University (KNU) Biomedical Convergence Program, Kyungpook National University, Daegu 41944, Korea
- Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Korea
- Correspondence: ; Tel.: +82-53-420-4946
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Park KY, Kim J. Synthesis and Biological Evaluation of the Anti-Melanogenesis Effect of Coumaric and Caffeic Acid-Conjugated Peptides in Human Melanocytes. Front Pharmacol 2020; 11:922. [PMID: 32625101 PMCID: PMC7311773 DOI: 10.3389/fphar.2020.00922] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 06/05/2020] [Indexed: 12/20/2022] Open
Abstract
Excessive pigmentation and reduced elasticity are the major skin problems that dermatologists and cosmetologists address. Compounds that inhibit melanin production might contribute to improving skin problems. In this study, we investigated whether coumaric acid- and caffeic acid-conjugated peptides might affect alpha-melanocyte stimulating hormone-induced melanin production, tyrosinase activity, and melanin synthesis-related gene expression in SK-MEL-2 human melanoma cells. Coumaric acid and caffeic acid showed no significant cytotoxicity, and they inhibited melanin production. In addition, coumaric acid- and caffeic acid-conjugated peptides suppressed tyrosinase activity more than arbutin, a known tyrosinase inhibitor. Quantitative real-time PCR (qRT-PCR) results also showed that both peptides inhibited the expression of melanin synthesis-related genes, TYR, TYRP1, TYRP2, and MITF. In particular, among the nine conjugated peptides tested, caffeic acid linked to a Gly-Gly-Gly linker and conjugated to the tripeptide, ARP, showed the greatest inhibition of gene expression in the qRT-PCR analysis. These results suggested that the inhibition of melanin exerted by coumaric acid- and caffeic acid-conjugated peptides might provide important information for the development of pigmentation-related skin diseases and cosmetic products.
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Affiliation(s)
- Kyeong-Yong Park
- Department of Integrated Material's Development, CHA Meditech Co., Ltd, Daejeon, South Korea
| | - Jiyeon Kim
- Department of Medical Laboratory Science, College of Health Science, Dankook University, Cheonan, South Korea
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16
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Shim SY, Lee YE, Song HY, Lee M. p-Hydroxybenzoic Acid β-d-Glucosyl Ester and Cimidahurinine with Antimelanogenesis and Antioxidant Effects from Pyracantha angustifolia via Bioactivity-Guided Fractionation. Antioxidants (Basel) 2020; 9:antiox9030258. [PMID: 32245245 PMCID: PMC7139487 DOI: 10.3390/antiox9030258] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/09/2020] [Accepted: 03/18/2020] [Indexed: 11/28/2022] Open
Abstract
This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from Pyracantha angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, and ABTS and DPPH radical-scavenging activities, which have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid β-d-glucosylester (HG), and cimidahurinine (CH) had strong inhibitory effects on melanin production and TYR activity, as well as ABTS and DPPH radical-scavenging activities. Western blot analysis showed that HG and CH suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. Moreover, HG and CH inhibited reactive oxygen species (ROS) generation in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.
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Affiliation(s)
- Sun-Yup Shim
- Fish Health Center, Chonnam National University, 50 Daehak-Ro, Yeosu-si, Jeonnam 59626, Korea;
| | - Ye Eun Lee
- College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon-si, Jeonnam 57922, Korea; (Y.E.L.); (H.Y.S.)
| | - Hwa Young Song
- College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon-si, Jeonnam 57922, Korea; (Y.E.L.); (H.Y.S.)
| | - Mina Lee
- College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon-si, Jeonnam 57922, Korea; (Y.E.L.); (H.Y.S.)
- Correspondence:
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17
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Wang HH, Wang YH, Liang CW, Li YC. Assessment of Deep Learning Using Nonimaging Information and Sequential Medical Records to Develop a Prediction Model for Nonmelanoma Skin Cancer. JAMA Dermatol 2019; 155:1277-1283. [PMID: 31483437 DOI: 10.1001/jamadermatol.2019.2335] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Importance A prediction model for new-onset nonmelanoma skin cancer could enhance prevention measures, but few patient data-driven tools exist for more accurate prediction. Objective To use machine learning to develop a prediction model for incident nonmelanoma skin cancer based on large-scale, multidimensional, nonimaging medical information. Design, Setting, and Participants This study used a database comprising 2 million randomly sampled patients from the Taiwan National Health Insurance Research Database from January 1, 1999, to December 31, 2013. A total of 1829 patients with nonmelanoma skin cancer as their first diagnosed cancer and 7665 random controls without cancer were included in the analysis. A convolutional neural network, a deep learning approach, was used to develop a risk prediction model. This risk prediction model used 3-year clinical diagnostic information, medical records, and temporal-sequential information to predict the skin cancer risk of a given patient within the next year. Stepwise feature selection was also performed to investigate important and determining factors of the model. Statistical analysis was performed from November 1, 2016, to October 31, 2018. Main Outcomes and Measures Sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were used to evaluate the performance of the models. Results A total of 1829 patients (923 women [50.5%] and 906 men [49.5%]; mean [SD] age, 65.3 [15.7] years) with nonmelanoma skin cancer and 7665 random controls without cancer (3951 women [51.5%] and 3714 men [48.4%]; mean [SD] age, 47.5 [17.3] years) were included in the analysis. The 1-year incident nonmelanoma skin cancer risk prediction model using sequential diagnostic information and drug prescription information as a time-incorporated feature matrix could attain an AUROC of 0.89 (95% CI, 0.87-0.91), with a mean (SD) sensitivity of 83.1% (3.5%) and mean (SD) specificity of 82.3% (4.1%). Carcinoma in situ of skin (AUROC, 0.867; -2.80% loss) and other chronic comorbidities (eg, degenerative osteopathy [AUROC, 0.872; -2.32% loss], hypertension [AUROC, 0.879; -1.53% loss], and chronic kidney insufficiency [AUROC, 0.879; -1.52% loss]) served as more discriminative factors for the prediction. Medications such as trazodone, acarbose, systemic antifungal agents, statins, nonsteroidal anti-inflammatory drugs, and thiazide diuretics were the top-ranking discriminative features in the model; each led to more than a 1% decrease of the AUROC when eliminated individually (eg, trazodone AUROC, 0.868; -2.67% reduction; acarbose AUROC, 0.870; -2.50 reduction; and systemic antifungal agents AUROC, 0.875; -1.99 reduction). Conclusions and Relevance The findings of this study suggest that a risk prediction model may have potential predictive factors for nonmelanoma skin cancer. This model may help health care professionals target high-risk populations for more intensive skin cancer preventive methods.
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Affiliation(s)
- Hsiao-Han Wang
- Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan.,Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yu-Hsiang Wang
- International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan.,School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chia-Wei Liang
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan
| | - Yu-Chuan Li
- Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan.,TMU Research Center of Cancer Translational Medicine, Taipei, Taiwan
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18
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van der Poort EKJ, Gunn DA, Beekman M, Griffiths CEM, Slagboom PE, van Heemst D, Noordam R. Basal cell carcinoma genetic susceptibility increases the rate of skin ageing: a Mendelian randomization study. J Eur Acad Dermatol Venereol 2019; 34:97-100. [PMID: 31419349 DOI: 10.1111/jdv.15880] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 08/07/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Onset of basal cell carcinoma (BCC) is connected to skin ageing, but it is unclear whether higher BCC genetic susceptibility drives skin ageing. OBJECTIVES To investigate whether loci increasing genetic susceptibility to BCC also drive multiple features of skin ageing, independently of confounding factors, using Mendelian randomization. METHODS A Mendelian randomization study was conducted in older adults from the Leiden Longevity Study (N = 604). A total of 25 BCC loci, selected based on a published genome-wide association study on BCC (P-value < 5 × 10-8 ), were used as genetic instruments for the calculation of a standardized (mean = 0, SD = 1) weighted BCC genetic risk score. Based on facial photographs, we determined perceived age, and skin wrinkling and pigmented spot grading. RESULTS A higher BCC genetic risk score was associated with a higher perceived age (adjusted for chronological age and sex) of 0.88 years (95% CI: 0.44, 1.31; P-value = 7.1e-5 ), greater wrinkling by 0.14 grades (95% CI: 0.05, 0.23; P-value = 2.3e-3 ), and greater pigmented spots by 0.17 grades (95% CI: 0.08, 0.25; P-value = 1.1e-4 ). These findings were weakened but still present after exclusion of gene variants in MC1R and IRF4 which have potential pleiotropic effects. CONCLUSIONS Mechanisms influenced by genetic loci increasing susceptibility to BCC also drive skin ageing suggesting shared biology and shared targets for interventions.
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Affiliation(s)
- E K J van der Poort
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - D A Gunn
- Colworth Science Park, Unilever Research and Development, Sharnbrook, Bedfordshire, UK
| | - M Beekman
- Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - C E M Griffiths
- Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - P E Slagboom
- Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - D van Heemst
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - R Noordam
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
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19
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Boo YC. p-Coumaric Acid as An Active Ingredient in Cosmetics: A Review Focusing on its Antimelanogenic Effects. Antioxidants (Basel) 2019; 8:E275. [PMID: 31382682 PMCID: PMC6720745 DOI: 10.3390/antiox8080275] [Citation(s) in RCA: 126] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 08/01/2019] [Accepted: 08/02/2019] [Indexed: 12/16/2022] Open
Abstract
Controlling unwanted hyperpigmentation is a major challenge in dermatology and cosmetology, and safe and efficacious antimelanogenic agents are deemed useful for this purpose. p-Coumaric acid is a natural metabolite contained in many edible plants, and its antioxidant activities in reducing oxidative stress and inflammatory reactions have been demonstrated in various experimental models. p-Coumaric acid has the optimal structure to be a competitive inhibitor of tyrosinase that catalyzes key reactions in the melanin biosynthetic pathway. Experimental evidence supports this notion as it was found to be a more potent inhibitor of tyrosinase, especially toward human enzymes, than other well-known tyrosinase inhibitors such as arbutin and kojic acid. p-Coumaric acid inhibited melanin synthesis in murine melanoma cells, human epidermal melanocytes, and reconstituted three-dimensional human skin models. Ex-vivo skin permeation experiments and in-vivo efficacy tests for p-coumaric acid confirmed its efficient transdermal delivery and functional efficacy in reducing erythema development and skin pigmentation due to ultraviolet radiation exposure. Human studies further supported its effectiveness in hypopigmentation and depigmentation. These findings suggest that p-coumaric acid has good potential to be used as a skin-lightening active ingredient in cosmetics. Future studies are needed to extensively examine its safety and efficacy and to develop an optimized cosmetic formulation for the best performance in skin lightening.
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Affiliation(s)
- Yong Chool Boo
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
- BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 41944, Korea.
- Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Korea.
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20
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SerpinB2 is involved in cellular response upon UV irradiation. Sci Rep 2019; 9:2753. [PMID: 30808882 PMCID: PMC6391458 DOI: 10.1038/s41598-019-39073-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 12/10/2018] [Indexed: 01/01/2023] Open
Abstract
Ultraviolet light induced pyrimidine dimer is a helix distortion DNA damage type, which recruits repair complexes. However, proteins of these complexes that take part in both DNA damage recognition and repair have been well-described, the regulation of the downstream steps of nucleotide excision repair (NER) have not been clearly clarified yet. In a high-throughput screen, we identified SerpinB2 (SPB2) as one of the most dramatically upregulated gene in keratinocytes following UV irradiation. We found that both the mRNA and the protein levels of SPB2 were increased upon UV irradiation in various cell lines. Additionally, UV damage induced translocation of SPB2 from the cytoplasm to the nucleus as well as the damage induced foci formation of it. Here we show that SPB2 co-localizes with XPB involved in the NER pathway at UV-induced repair foci. Finally, we demonstrated that UV irradiation promoted the association of SPB2 with ubiquitylated proteins. In basal cell carcinoma tumour cells, we identified changes in the subcellular localization of SPB2. Based on our results, we conclude that SPB2 protein has a novel role in UV-induced NER pathway, since it regulates the removal of the repair complex from the damaged site leading to cancerous malformation.
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21
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Swope VB, Abdel-Malek ZA. MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair. Int J Mol Sci 2018; 19:E2667. [PMID: 30205559 PMCID: PMC6163888 DOI: 10.3390/ijms19092667] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 08/31/2018] [Accepted: 09/03/2018] [Indexed: 12/17/2022] Open
Abstract
Melanin, the pigment produced by specialized cells, melanocytes, is responsible for skin and hair color. Skin pigmentation is an important protective mechanism against the DNA damaging and mutagenic effects of solar ultraviolet radiation (UV). It is acknowledged that exposure to UV is the main etiological environmental factor for all forms of skin cancer, including melanoma. DNA repair capacity is another major factor that determines the risk for skin cancer. Human melanocytes synthesize eumelanin, the dark brown form of melanin, as well as pheomelanin, which is reddish-yellow in color. The relative rates of eumelanin and pheomelanin synthesis by melanocytes determine skin color and the sensitivity of skin to the drastic effects of solar UV. Understanding the complex regulation of melanocyte function and how it responds to solar UV has a huge impact on developing novel photoprotective strategies to prevent skin cancer, particularly melanoma, the most fatal form, which originates from melanocytes. This review provides an overview of the known differences in the photoprotective effects of eumelanin versus pheomelanin, how these two forms of melanin are regulated genetically and biochemically, and their impact on the DNA damaging effects of UV exposure. Additionally, this review briefly discusses the role of paracrine factors, focusing on α-melanocortin (α-melanocyte stimulating hormone; α-MSH), in regulating melanogenesis and the response of melanocytes to UV, and describes a chemoprevention strategy based on targeting the melanocortin 1 receptor (MC1R) by analogs of its physiological agonist α-MSH.
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Affiliation(s)
- Viki B Swope
- Department of Dermatology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
| | - Zalfa A Abdel-Malek
- Department of Dermatology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
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22
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Ujfaludi Z, Tuzesi A, Majoros H, Rothler B, Pankotai T, Boros IM. Coordinated activation of a cluster of MMP genes in response to UVB radiation. Sci Rep 2018; 8:2660. [PMID: 29422610 PMCID: PMC5805780 DOI: 10.1038/s41598-018-20999-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 01/19/2018] [Indexed: 12/19/2022] Open
Abstract
Ultraviolet (UV) B radiation is a dangerous environmental stressor, which can lead to photoaging, inflammation, immune suppression and tumour formation. A recent report has shown the transcriptional activation of several skin-specific genes including matrix metalloproteases (MMPs) in response to UV irradiation. Here, we use a novel human keratinocyte model, HKerE6SFM, to demonstrate that UVB activates the transcription of most members of the 11q22.3 MMP gene cluster including MMP13, MMP12, MMP3, MMP1 and MMP10. Curiously, the expression of the well-characterized UVB-inducible MMP9, which is located outside of the cluster, remains unchanged. In accordance with the increased expression of the MMP gene cluster upon UVB irradiation, RNA polymerase II showed increased occupancy at their promoters following UVB irradiation. The results also demonstrate increased acetylated histone H3K9 levels at the promoters of the MMP13, MMP12, MMP3, MMP1 and MMP10 genes. These findings suggest a coordinated transcriptional activation of genes in the MMP cluster at 11q22.3 and that acetylation of histone H3 at lysine 9 has an important role in the UVB-dependent enhancement of transcription of MMP genes in this region.
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Affiliation(s)
- Zsuzsanna Ujfaludi
- Department of Biochemistry and Molecular Biology, FSI, USZ, Közép fasor 52, Szeged, H6726, Hungary
| | - Agota Tuzesi
- Institute of Biochemistry, BRC, HAS, Temesvári körút 62, H6726, Szeged, Hungary
| | - Hajnalka Majoros
- Department of Biochemistry and Molecular Biology, FSI, USZ, Közép fasor 52, Szeged, H6726, Hungary
| | - Balint Rothler
- Department of Biochemistry and Molecular Biology, FSI, USZ, Közép fasor 52, Szeged, H6726, Hungary
| | - Tibor Pankotai
- Department of Biochemistry and Molecular Biology, FSI, USZ, Közép fasor 52, Szeged, H6726, Hungary.
| | - Imre M Boros
- Department of Biochemistry and Molecular Biology, FSI, USZ, Közép fasor 52, Szeged, H6726, Hungary. .,Institute of Biochemistry, BRC, HAS, Temesvári körút 62, H6726, Szeged, Hungary.
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23
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Yanik EL. Skin cancer in the end-stage renal disease population: unique risk factors for patients on dialysis. Br J Dermatol 2016; 175:1136-1137. [PMID: 27996124 DOI: 10.1111/bjd.15032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- E L Yanik
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, U.S.A
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24
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Kwak JY, Seok JK, Suh HJ, Choi YH, Hong SS, Kim DS, Boo YC. Antimelanogenic effects of luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino. Br J Dermatol 2016; 175:501-11. [PMID: 26914711 DOI: 10.1111/bjd.14496] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2016] [Indexed: 01/10/2023]
Abstract
BACKGROUND Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research. OBJECTIVES To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects. METHODS The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM). RESULTS Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7-sulfate and luteolin 7-sulfate. Luteolin 7-sulfate inhibited human TYR more strongly than hispidulin 7-sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7-sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7-sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α-melanocyte-stimulating hormone and l-tyrosine than arbutin. CONCLUSIONS This study demonstrates that luteolin 7-sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation.
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Affiliation(s)
- J Y Kwak
- Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu, 41944, Korea
| | - J K Seok
- Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu, 41944, Korea
| | - H-J Suh
- Gyeongbuk Natural Color Industry Institute, 181, Cheonmun-ro, Yeongcheon-si, Gyeongsangbuk-do, 38896, Korea
| | - Y-H Choi
- Bio-Center, Gyeonggi Institute of Science and Technology Promotion, 147, Gwanggyo-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Korea
| | - S S Hong
- Bio-Center, Gyeonggi Institute of Science and Technology Promotion, 147, Gwanggyo-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Korea
| | - D S Kim
- Korea Marine Ecology Institute, 60, Centum jungang-ro, Haeundae-gu, Busan, 48059, Korea
| | - Y C Boo
- Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu, 41944, Korea. .,Ruby Crown Co., Ltd, Kyungpook National University Business Incubation Center, 80, Daehak-ro, Buk-gu, Daegu, 41566, Korea.
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25
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Dobos G, Trojahn C, D'Alessandro B, Patwardhan S, Canfield D, Blume-Peytavi U, Kottner J. Effects of intrinsic aging and photodamage on skin dyspigmentation: an explorative study. JOURNAL OF BIOMEDICAL OPTICS 2016; 21:66016. [PMID: 27330007 DOI: 10.1117/1.jbo.21.6.066016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 05/25/2016] [Indexed: 06/06/2023]
Abstract
Photoaging is associated with increasing pigmentary heterogeneity and darkening of skin color. However, little is known about age-related changes in skin pigmentation on sun-protected areas. The aim of this explorative study was to measure skin color and dyspigmentation using image processing and to evaluate the reliability of these parameters. Twenty-four volunteers of three age-groups were included in this explorative study. Measurements were conducted at sun-exposed and sun-protected areas. Overall skin-color estimates were similar among age groups. The hyper- and hypopigmentation indices differed significantly by age groups and their correlations with age ranged between 0.61 and 0.74. Dorsal forearm skin differed from the other investigational areas (p<0.001). We observed an increase in dyspigmentation at all skin areas, including sun-protected skin areas, already in young adulthood. Associations between age and dyspigmentation estimates were higher compared to color parameters. All color and dyspigmentation estimates showed high reliability. Dyspigmentation parameters seem to be better biomarkers for UV damage than the overall color measurements.
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Affiliation(s)
- Gabor Dobos
- Charité-Universitätsmedizin Berlin, Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charitéplatz 1, 10117 Berlin, Germany
| | - Carina Trojahn
- Charité-Universitätsmedizin Berlin, Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charitéplatz 1, 10117 Berlin, Germany
| | - Brian D'Alessandro
- Canfield Scientific Inc., 4 Wood Hollow Road, Parsippany, New Jersey 07054, United States
| | - Sachin Patwardhan
- Canfield Scientific Inc., 4 Wood Hollow Road, Parsippany, New Jersey 07054, United States
| | - Douglas Canfield
- Canfield Scientific Inc., 4 Wood Hollow Road, Parsippany, New Jersey 07054, United States
| | - Ulrike Blume-Peytavi
- Charité-Universitätsmedizin Berlin, Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charitéplatz 1, 10117 Berlin, Germany
| | - Jan Kottner
- Charité-Universitätsmedizin Berlin, Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charitéplatz 1, 10117 Berlin, Germany
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26
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Park S, Seok JK, Kwak JY, Choi YH, Hong SS, Suh HJ, Park W, Boo YC. Anti-melanogenic effects of resveratryl triglycolate, a novel hybrid compound derived by esterification of resveratrol with glycolic acid. Arch Dermatol Res 2016; 308:325-34. [PMID: 27059716 DOI: 10.1007/s00403-016-1644-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 03/13/2016] [Accepted: 03/30/2016] [Indexed: 11/26/2022]
Abstract
Resveratrol is known to inhibit cellular melanin synthesis by multiple mechanisms. Glycolic acid (GA) is used in skin care products for its excellent skin penetration. The purpose of this study was to examine the anti-melanogenic effects of resveratryl triglycolate (RTG), a novel hybrid compound of resveratrol and GA, in comparison with resveratrol, GA, resveratryl triacetate (RTA) and arbutin. Resveratrol, RTG, and RTA inhibited the catalytic activity human tyrosinase (TYR) more potently than arbutin or GA did. Their cytotoxic and anti-melanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEMs). The cytotoxicity of RTG was similar to that of resveratrol and RTA. RTG at 3-10 μM decreased melanin levels and cellular TYR activities in α-melanocyte-stimulating hormone-stimulated B16/F10 cells, and L-tyrosine-stimulated HEMs. RTG also suppressed mRNA and protein expression of TYR, tyrosinase-related protein 1, L-3,4-dihydroxyphenylalanine chrome tautomerase, and microphthalmia-associated transcription factor (MITF) in HEMs stimulated with L-tyrosine. This study suggests that, like resveratrol and RTA, RTG can attenuate cellular melanin synthesis effectively through the suppression of MITF-dependent expression of melanogenic enzymes and the inhibition of catalytic activity of TYR enzyme. RTG therefore has potential for use as a cosmeceutical ingredient for skin whitening.
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Affiliation(s)
- Soojin Park
- Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 101 Dongin-dong 2-ga, Jung-gu, Daegu, 41944, Republic of Korea
| | - Jin Kyung Seok
- Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 101 Dongin-dong 2-ga, Jung-gu, Daegu, 41944, Republic of Korea
| | - Jun Yup Kwak
- Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 101 Dongin-dong 2-ga, Jung-gu, Daegu, 41944, Republic of Korea
| | - Yun-Hyeok Choi
- Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Republic of Korea
| | - Seong Su Hong
- Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Republic of Korea
| | - Hwa-Jin Suh
- Gyeongbuk Natural Color Industry Institute, Gyeongbuk, Republic of Korea
| | | | - Yong Chool Boo
- Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 101 Dongin-dong 2-ga, Jung-gu, Daegu, 41944, Republic of Korea.
- Ruby Crown Co. Ltd., Daegu, Republic of Korea.
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27
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Couteau C, Diarra H, Coiffard L. Effect of the product type, of the amount of applied sunscreen product and the level of protection in the UVB range on the level of protection achieved in the UVA range. Int J Pharm 2016; 500:210-6. [DOI: 10.1016/j.ijpharm.2016.01.041] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 01/15/2016] [Accepted: 01/16/2016] [Indexed: 11/26/2022]
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28
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Lewis JM, Bürgler CD, Freudzon M, Golubets K, Gibson JF, Filler RB, Girardi M. Langerhans Cells Facilitate UVB-Induced Epidermal Carcinogenesis. J Invest Dermatol 2015; 135:2824-2833. [PMID: 26053049 PMCID: PMC4640962 DOI: 10.1038/jid.2015.207] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 05/21/2015] [Accepted: 05/25/2015] [Indexed: 12/29/2022]
Abstract
UVB light is considered the major environmental inducer of human keratinocyte (KC) DNA mutations, including within the tumor-suppressor gene p53, and chronic exposure is associated with cutaneous squamous cell carcinoma formation. Langerhans cells (LCs) comprise a dendritic network within the suprabasilar epidermis, yet the role of LCs in UVB-induced carcinogenesis is largely unknown. Herein we show that LC-intact epidermis develops UVB-induced tumors more readily than LC-deficient epidermis. Although levels of epidermal cyclopyrimidine dimers following acute UVB exposure are equivalent in the presence or absence of LCs, chronic UVB-induced p53 mutant clonal islands expand more readily in association with LCs, which remain largely intact and are preferentially found in proximity to the expanding mutant KC populations. The observed LC facilitation of mutant p53 clonal expansion is completely αβ and γδ T-cell independent and is associated with increased intraepidermal expression of IL-22 and the presence of group 3 innate lymphoid cells. These data demonstrate that LCs have a key role in UVB-induced cutaneous carcinogenesis and suggest that LCs locally stimulate KC proliferation and innate immune cells that provoke tumor outgrowth.
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Affiliation(s)
- Julia M Lewis
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Christina D Bürgler
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Marianna Freudzon
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Kseniya Golubets
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Juliet F Gibson
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Renata B Filler
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Michael Girardi
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
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29
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Kwak JY, Park S, Seok JK, Liu KH, Boo YC. Ascorbyl coumarates as multifunctional cosmeceutical agents that inhibit melanogenesis and enhance collagen synthesis. Arch Dermatol Res 2015; 307:635-43. [DOI: 10.1007/s00403-015-1583-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 05/21/2015] [Accepted: 06/05/2015] [Indexed: 11/30/2022]
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30
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Kim W, Kim E, Yang HJ, Kwon T, Han S, Lee S, Youn H, Jung Y, Kang C, Youn B. Inhibition of hedgehog signalling attenuates UVB-induced skin photoageing. Exp Dermatol 2015; 24:611-7. [DOI: 10.1111/exd.12735] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2015] [Indexed: 02/06/2023]
Affiliation(s)
- Wanyeon Kim
- Department of Biological Sciences; Pusan National University; Busan South Korea
- Nuclear Science Research Institute; Pusan National University; Busan South Korea
| | - EunGi Kim
- Department of Integrated Biological Science; Pusan National University; Busan South Korea
| | - Hee Jung Yang
- Department of Biological Sciences; Pusan National University; Busan South Korea
| | - TaeWoo Kwon
- Department of Integrated Biological Science; Pusan National University; Busan South Korea
| | - SeoYoung Han
- Department of Integrated Biological Science; Pusan National University; Busan South Korea
| | - Sungmin Lee
- Department of Integrated Biological Science; Pusan National University; Busan South Korea
| | - HyeSook Youn
- Department of Biological Sciences; Pusan National University; Busan South Korea
- Nuclear Science Research Institute; Pusan National University; Busan South Korea
| | - Youngmi Jung
- Department of Biological Sciences; Pusan National University; Busan South Korea
- Department of Integrated Biological Science; Pusan National University; Busan South Korea
| | - ChulHee Kang
- Department of Chemistry; Washington State University; Pullman Washington USA
| | - BuHyun Youn
- Department of Biological Sciences; Pusan National University; Busan South Korea
- Nuclear Science Research Institute; Pusan National University; Busan South Korea
- Department of Integrated Biological Science; Pusan National University; Busan South Korea
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31
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Rinnerthaler M, Bischof J, Streubel MK, Trost A, Richter K. Oxidative stress in aging human skin. Biomolecules 2015; 5:545-89. [PMID: 25906193 PMCID: PMC4496685 DOI: 10.3390/biom5020545] [Citation(s) in RCA: 555] [Impact Index Per Article: 55.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 03/18/2015] [Accepted: 04/09/2015] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis.
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Affiliation(s)
- Mark Rinnerthaler
- Department of Cell Biology, Division of Genetics, University of Salzburg, Salzburg 5020, Austria.
| | - Johannes Bischof
- Department of Cell Biology, Division of Genetics, University of Salzburg, Salzburg 5020, Austria.
| | - Maria Karolin Streubel
- Department of Cell Biology, Division of Genetics, University of Salzburg, Salzburg 5020, Austria.
| | - Andrea Trost
- Department of Ophthalmology and Optometry, Paracelsus Medical University, Muellner Hauptstrasse 48, 5020 Salzburg, Austria.
| | - Klaus Richter
- Department of Cell Biology, Division of Genetics, University of Salzburg, Salzburg 5020, Austria.
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32
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Ryu JH, Seok JK, An SM, Baek JH, Koh JS, Boo YC. A study of the human skin-whitening effects of resveratryl triacetate. Arch Dermatol Res 2015; 307:239-47. [PMID: 25750159 DOI: 10.1007/s00403-015-1556-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 02/06/2015] [Accepted: 02/28/2015] [Indexed: 12/22/2022]
Abstract
Resveratrol has a variety of bioactivities that include its anti-melanogenic effects, but its use in cosmetics has been challenging partly because of its chemical instability. Resveratryl triacetate (RTA) is a prodrug that can enhance stability. The purpose of this study was to examine the skin safety and whitening effects of RTA in human subjects. The primary skin irritation potentials of RTA and resveratrol were tested at 0.1 and 0.5 % on human subjects. Resveratrol at a concentration of 0.5 % induced weak skin irritation, whereas RTA did not induce any skin responses. The skin-whitening efficacy of a cosmetic formulation containing 0.4 % RTA was evaluated in two different test models. In the artificial tanning model, the test product and the control product were applied twice daily to the skin of the forearms of 22 human subjects after pigmentation induction by ultraviolet irradiation. Applying the test and the control products to the artificial tanning model for 8 weeks increased the individual topology angles (ITA°) by 17.06 and 13.81 %, respectively, a difference that was statistically significant (p < 0.05). In the hyperpigmentation model, the test product and the control product were applied twice daily to the faces of 21 human subjects. The averaged intensity of the hyperpigmented spots decreased by 2.67 % in the test group and 1.46 % in the control group, a difference that was statistically significant (p < 0.05). Therefore, RTA incorporated into cosmetic formulations can whiten human skin without inducing skin irritation.
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Affiliation(s)
- Ja Hyun Ryu
- Dermapro Skin Research Center, Dermapro Ltd., Seoul, Republic of Korea
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33
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Huang YC, Huang CT, Hu C, Wong TW. Portable ultraviolet light A1 light source to treat hypertrophic scar. DERMATOL SIN 2015. [DOI: 10.1016/j.dsi.2014.10.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Blue-violet light irradiation dose dependently decreases carotenoids in human skin, which indicates the generation of free radicals. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:579675. [PMID: 25741404 PMCID: PMC4337113 DOI: 10.1155/2015/579675] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Accepted: 01/27/2015] [Indexed: 02/07/2023]
Abstract
In contrast to ultraviolet and infrared irradiation, which are known to facilitate cutaneous photoaging, immunosuppression, or tumour emergence due to formation of free radicals and reactive oxygen species, potentially similar effects of visible light on the human skin are still poorly characterized. Using a blue-violet light irradiation source and aiming to characterize its potential influence on the antioxidant status of the human skin, the cutaneous carotenoid concentration was measured noninvasively in nine healthy volunteers using resonance Raman spectroscopy following irradiation. The dose-dependent significant degradation of carotenoids was measured to be 13.5% and 21.2% directly after irradiation at 50 J/cm² and 100 J/cm² (P < 0.05). The irradiation intensity was 100 mW/cm². This is above natural conditions; the achieved doses, though, are acquirable under natural conditions. The corresponding restoration lasted 2 and 24 hours, respectively. The degradation of cutaneous carotenoids indirectly shows the amount of generated free radicals and especially reactive oxygen species in human skin. In all volunteers the cutaneous carotenoid concentration dropped down in a manner similar to that caused by the infrared or ultraviolet irradiations, leading to the conclusion that also blue-violet light at high doses could represent a comparably adverse factor for human skin.
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35
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Greenwald MBY, Anzi S, Ben Sasson S, Bianco-Peled H, Kohen R. Can nitroxides evoke the Keap1-Nrf2-ARE pathway in skin? Free Radic Biol Med 2014; 77:258-69. [PMID: 25236737 DOI: 10.1016/j.freeradbiomed.2014.08.021] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Revised: 07/29/2014] [Accepted: 08/20/2014] [Indexed: 01/14/2023]
Abstract
Nitroxides are stable cyclic radicals of diverse size, charge, and lipophilicity. They are cell-permeative, which effectively protects cells, tissues, isolated organs, and laboratory animals from radical-induced damage. The mechanisms of activity through which nitroxides operate are diverse, including superoxide dismutase-mimetic activity, oxidation of semiquinone radicals, oxidation of reduced metal ions, procatalase-mimetic activity, interruption of radical chain reactions, and indirect modulation of NO levels. Nitroxides possess both a nucleophilic (reducing properties) and an electrophilic (oxidizing properties) nature and, therefore, they may affect different cellular pathways. In the current study, a novel mechanism of action by which nitroxides provide skin protection based on their electrophilic nature is suggested. This study shows that nitroxides may act as electrophiles, directly or indirectly, capable of activating the Keap1-Nrf2-ARE pathway in human keratinocytes (HaCaT) and in human skin (human organ culture model). The high potency of oxoammonium cations versus hydroxylamines in activating the system is demonstrated. The mechanism of action by which nitroxides activate the Keap1-Nrf2-ARE pathway is discussed. Understanding the mechanism of activity may expand the usage of nitroxides as a skin protection strategy against oxidative stress-related conditions.
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Affiliation(s)
- Maya Ben Yehuda Greenwald
- The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel; Department of Chemical Engineering and Technion-Israel Institute of Technology, Haifa 32000, Israel; The Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000, Israel; Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Ein-Karem Campus, Jerusalem 91120, Israel
| | - Shira Anzi
- Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Ein-Karem Campus, Jerusalem 91120, Israel
| | - Shmuel Ben Sasson
- Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Ein-Karem Campus, Jerusalem 91120, Israel
| | - Havazelet Bianco-Peled
- Department of Chemical Engineering and Technion-Israel Institute of Technology, Haifa 32000, Israel; The Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Ron Kohen
- The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
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Gardenia jasminoides Extract Attenuates the UVB-Induced Expressions of Cytokines in Keratinocytes and Indirectly Inhibits Matrix Metalloproteinase-1 Expression in Human Dermal Fibroblasts. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:429246. [PMID: 24711853 PMCID: PMC3966326 DOI: 10.1155/2014/429246] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 01/28/2014] [Accepted: 02/03/2014] [Indexed: 12/02/2022]
Abstract
Ultraviolet radiation (UV) is a major cause of photoaging, which also involves inflammatory cytokines and matrix metalloproteinases (MMP). The present study was undertaken to examine the UVB-protecting effects of yellow-colored plant extracts in cell-based assays. HaCaT keratinocytes were exposed to UVB in the absence or presence of plant extracts, and resulting changes in cell viability and inflammatory cytokine expression were measured. Of the plant extracts tested, Gardenia jasminoides extract showed the lowest cytotoxicity and dose-dependently enhanced the viabilities of UVB-exposed cells. Gardenia jasminoides extract also attenuated the mRNA expressions of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in HaCaT cells stimulated by UVB. Conditioned medium from UVB-exposed HaCaT cells was observed to stimulate MMP-1 protein expression in human dermal fibroblasts, and this effect was much smaller for the conditioned medium of HaCaT cells exposed to UVB in the presence of Gardenia jasminoides extract. Gardenia jasminoides extract also exhibited antioxidative and antiapoptotic effects in HaCaT cells exposed to UVB. These results indicated that UVB-induced injury and inflammatory responses of skin cells can be attenuated by yellow-colored plant extracts, such as Gardenia jasminoides extract.
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Effects of resveratrol, oxyresveratrol, and their acetylated derivatives on cellular melanogenesis. Arch Dermatol Res 2014; 306:475-87. [PMID: 24414332 DOI: 10.1007/s00403-014-1440-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Revised: 12/07/2013] [Accepted: 01/02/2014] [Indexed: 10/25/2022]
Abstract
Resveratrol and oxyresveratrol are naturally occurring phenolic compounds with various bioactivities, but their uses in cosmetics have been partly limited by their chemical instabilities. This study was performed to examine the anti-melanogenic effects of the acetylated derivatives from resveratrol and oxyresveratrol. Resveratrol and oxyresveratrol were chemically modified to triacetyl resveratrol and tetraacetyl oxyresveratrol, respectively. The acetylated compounds were less susceptible than the parent compounds to oxidative discoloration. The acetylated compounds inhibited the activities of tyrosinases less than parent compounds in vitro, but they were as effective at cellular melanogenesis inhibition, indicating bioconversion to parent compounds inside cells. Supporting this notion, the parent compounds were regenerated when the acetylated compounds were digested with cell lysates. Although resveratrol and triacetyl resveratrol inhibited tyrosinase activity less effectively than oxyresveratrol and tetraacetyl oxyresveratrol in vitro, they inhibited cellular melanogenesis more effectively. This discrepancy was explained by strong inhibition of tyrosinase expression by resveratrol and triacetyl resveratrol. Experiments using a reconstituted skin model indicated that resveratrol derivatives can affect melanin synthesis and cell viability to different extents. Collectively, this study suggests that acetylated derivatives of resveratrol have great potential as anti-melanogenic agents for cosmetic use in terms of efficacy, safety, and stability.
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Gamba CS, Stefanick ML, Shikany JM, Larson J, Linos E, Sims ST, Marshall J, Van Horn L, Zeitouni N, Tang JY. Low-fat diet and skin cancer risk: the women's health initiative randomized controlled dietary modification trial. Cancer Epidemiol Biomarkers Prev 2013; 22:1509-19. [PMID: 23697610 DOI: 10.1158/1055-9965.epi-13-0341] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Large cohort studies have reported no relationship between dietary fat and nonmelanoma skin cancer (NMSC), although a low-fat diet intervention reduced NMSC risk in a small clinical trial. In animal studies, skin tumor development has been reduced by low-fat diet. We evaluated the effect of a low-fat dietary pattern on NMSC and melanoma in the Women's Health Initiative Dietary Modification trial. METHODS Postmenopausal women aged 50 to 79 years (n = 48,835) were randomly assigned to the low-fat dietary pattern intervention (n = 19,541) or comparison group (n = 29,294). The intervention goals included decreasing fat intake to 20% or less of calories, increasing vegetable and fruit intake, and increasing grain intake. Self-reported incident NMSC (n = 4,907) and physician-adjudicated incident melanoma (n = 279) were ascertained every 6 months. RESULTS Over 8.1 years of follow-up, the low-fat diet intervention did not affect overall incidence of NMSC [HR 0.98; 95% confidence interval (CI), 0.92-1.04] or melanoma (HR, 1.04; 95% CI, 0.82-1.32). In subgroup analyses of melanoma risk, baseline fat intake interacted significantly with group assignment (Pinteraction = 0.006). Among women with higher baseline fat intake, the dietary intervention significantly increased risk (HR, 1.48; 95% CI, 1.06-2.07), whereas, among women with lower baseline fat intake, the intervention tended to reduce melanoma risk (HR, 0.72; 95% CI, 0.50-1.02). CONCLUSIONS In this large randomized trial, a low-fat dietary pattern did not affect overall incidence of NMSC or melanoma. IMPACT A low-fat diet does not reduce incidence of NMSC, but an interaction between baseline fat intake and dietary intervention on melanoma risk warrants further investigation.
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Plasma lipoproteins as mediators of the oxidative stress induced by UV light in human skin: a review of biochemical and biophysical studies on mechanisms of apolipoprotein alteration, lipid peroxidation, and associated skin cell responses. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:285825. [PMID: 23738035 PMCID: PMC3655670 DOI: 10.1155/2013/285825] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 03/21/2013] [Indexed: 12/15/2022]
Abstract
There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.
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Isolation of resveratrol from vitis viniferae caulis and its potent inhibition of human tyrosinase. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:645257. [PMID: 23476698 PMCID: PMC3583093 DOI: 10.1155/2013/645257] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 12/27/2012] [Accepted: 01/05/2013] [Indexed: 12/22/2022]
Abstract
Tyrosinase (TYR) catalyzes rate-limiting reactions of cellular melanin synthesis, and its inhibitors are of commercial interest as potential skin whitening agents. However, the limited availability of human TYR makes the screening of TYR inhibitors difficult. To overcome this hurdle, we transformed nonmelanocytic human embryonic kidney (HEK) 293 cells to express human TYR constitutively. Using these cells as a source of human TYR, the ethanolic extracts of 52 medicinal plants grown in Korea were tested for human TYR activity, and the extract of Vitis Viniferae Caulis (dried stems of the grape tree, Vitis vinifera L.) was found to inhibit human TYR activity potently. An active compound was isolated from this extract by solvent fractionation followed by liquid column chromatography and identified as resveratrol by spectroscopic and chromatographic analyses. Resveratrol was determined to be a highly potent inhibitor of human TYR (IC50 = 0.39 μg mL−1) as compared with p-coumaric acid (IC50 = 0.66 μg mL−1) and arbutin (IC50 > 100 μg mL−1) and inhibited melanin synthesis by human epidermal melanocytes at subtoxic concentrations. This study suggests that resveratrol and resveratrol-containing extracts of Vitis Viniferae Caulis have a potential use as skin whitening agents.
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Khan SR, Kuzminov A. Replication forks stalled at ultraviolet lesions are rescued via RecA and RuvABC protein-catalyzed disintegration in Escherichia coli. J Biol Chem 2012; 287:6250-65. [PMID: 22194615 PMCID: PMC3307332 DOI: 10.1074/jbc.m111.322990] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2011] [Revised: 12/09/2011] [Indexed: 11/06/2022] Open
Abstract
Ultraviolet (UV) irradiation is not known to induce chromosomal fragmentation in sublethal doses, and yet UV irradiation causes genetic instability and cancer, suggesting that chromosomes are fragmented. Here we show that UV irradiation induces fragmentation in sublethal doses, but the broken chromosomes are repaired or degraded by RecBCD; therefore, to observe full fragmentation, RecBCD enzyme needs to be inactivated. Using quantitative pulsed field gel electrophoresis and sensitive DNA synthesis measurements, we investigated the mechanisms of UV radiation-induced chromosomal fragmentation in recBC mutants, comparing five existing models of DNA damage-induced fragmentation. We found that fragmentation depends on active DNA synthesis before, but not after, UV irradiation. At low UV irradiation doses, fragmentation does not need excision repair or daughter strand gap repair. Fragmentation absolutely depends on both RecA-catalyzed homologous strand exchange and RuvABC-catalyzed Holliday junction resolution. Thus, chromosomes fragment when replication forks stall at UV lesions and regress, generating Holliday junctions. Remarkably, cells specifically utilize fork breakage to rescue stalled replication and avoid lethality.
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Affiliation(s)
- Sharik R. Khan
- From the Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801
| | - Andrei Kuzminov
- From the Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801
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Anti-oxidative and anti-aging activities of 2-O-α-glucopyranosyl-L-ascorbic acid on human dermal fibroblasts. Eur J Pharmacol 2012; 674:126-31. [DOI: 10.1016/j.ejphar.2011.11.013] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Revised: 11/01/2011] [Accepted: 11/04/2011] [Indexed: 11/30/2022]
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López-Camarillo C, Ocampo EA, Casamichana ML, Pérez-Plasencia C, Álvarez-Sánchez E, Marchat LA. Protein kinases and transcription factors activation in response to UV-radiation of skin: implications for carcinogenesis. Int J Mol Sci 2011; 13:142-172. [PMID: 22312244 PMCID: PMC3269678 DOI: 10.3390/ijms13010142] [Citation(s) in RCA: 104] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Revised: 12/14/2011] [Accepted: 12/16/2011] [Indexed: 12/18/2022] Open
Abstract
Solar ultraviolet (UV) radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF-κB, AP-1, and NRF2 transcription factors in the control of gene expression after UV-irradiation. In addition, we discussed the promising chemotherapeutic intervention of transcription factors signaling by natural compounds. Finally, we focused on the review of data emerging from the use of DNA microarray technology to determine changes in global gene expression in keratinocytes and melanocytes in response to UV treatment. Efforts to obtain a comprehensive portrait of the transcriptional events regulating photodamage of intact human epidermis after UV exposure reveals the existence of novel factors participating in UV-induced cell death. Progress in understanding the multitude of mechanisms induced by UV-irradiation could lead to the potential use of protein kinases and novel proteins as specific targets for the prevention and control of skin cancer.
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Affiliation(s)
- César López-Camarillo
- Genomics Sciences Program, Oncogenomics and Cancer Proteomics Laboratory, University Autonomous of Mexico City, Av. San Lorenzo 290, 03100, Mexico; E-Mails: (M.L.-C.); (E.Á.-S.)
| | - Elena Aréchaga Ocampo
- Carcinogenesis Laboratory, National Institute of Cancerology, Av. Saint Fernando 22, 14080, México; E-Mail:
| | - Mavil López Casamichana
- Genomics Sciences Program, Oncogenomics and Cancer Proteomics Laboratory, University Autonomous of Mexico City, Av. San Lorenzo 290, 03100, Mexico; E-Mails: (M.L.-C.); (E.Á.-S.)
| | - Carlos Pérez-Plasencia
- Massive Sequencing Unit, National Institute of Cancerology, Av. Saint Fernando 22, 14080, México; E-Mail:
- Genomics Laboratory, FES-I, UBIMED, National Autonomous University of Mexico, Av. De los Barrios 1, 54090, México
| | - Elizbeth Álvarez-Sánchez
- Genomics Sciences Program, Oncogenomics and Cancer Proteomics Laboratory, University Autonomous of Mexico City, Av. San Lorenzo 290, 03100, Mexico; E-Mails: (M.L.-C.); (E.Á.-S.)
| | - Laurence A. Marchat
- Biotechnology Program, Institutional Program of Molecular Biomedicine, National School of Medicine and Homeopathy of the National Polytechnic Institute, Guillermo Massieu Helguera 239, 07320, Mexico; E-Mail:
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Khlebnikova AN, Khlebnikova AN. Current approaches to the external therapy of photodermatoses. VESTNIK DERMATOLOGII I VENEROLOGII 2011. [DOI: 10.25208/vdv1053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Remedial measures for photodamages of skin are mainly aimed at elimination of inflammation and subjective sensations
such as burning and itching. Topical corticosteroids remain leading drugs in the external therapy of phototrauma,
phototoxic and photoallergic reactions. Mometasone furoate (Elocom) has high anti-inflammatory and antiallergic
activity. Moreover, the composition of the Elocom cream is based on titanium dioxide, a classical mineral screen,
which makes it possible to use the Elocom cream in case of steroid-sensitive pathology under conditions of high solar
exposure. The Elocom cream has been used in the monotherapy and complex treatment of solar dermatitis, actinic
cheilitis, polymorphous light eruption, discoid lupus erythematosus and actinic prurigo. Regression of manifestations of
solar dermatitis was recorded on Day 1-3 of treatment, and regression of manifestations of actinic cheilitis - during
Week 2 of treatment. The process in case of photoallergic reactions and discoid lupus erythematosus was over during
Week 3-4 of treatment. Substances making a part of the composition of the Elocom cream and having photoprotective
properties make this cream a drug of choice for its use on skin areas subject to solar exposure in case of steroidsensitive
pathology including phototrauma, phototoxic and photoallergic reactions. Besides, photoprotective properties
of the Elocom cream explain why it should be selected for treatment of steroid-sensitive dermatoses becoming more
severe or appearing after solar exposure, in case of localization of eruptions on open skin areas (face, neck, decollete
area, hands, etc.)
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Tang JY, Fu T, Leblanc E, Manson JE, Feldman D, Linos E, Vitolins MZ, Zeitouni NC, Larson J, Stefanick ML. Calcium plus vitamin D supplementation and the risk of nonmelanoma and melanoma skin cancer: post hoc analyses of the women's health initiative randomized controlled trial. J Clin Oncol 2011; 29:3078-84. [PMID: 21709199 PMCID: PMC3157967 DOI: 10.1200/jco.2011.34.5967] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Accepted: 05/04/2011] [Indexed: 11/20/2022] Open
Abstract
PURPOSE In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial. METHODS Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Women's Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication. RESULTS Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; P(interaction) = .038), which was not observed in women without history of NMSC. CONCLUSION Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation.
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Affiliation(s)
- Jean Y Tang
- Department of Dermatology, Stanford University School of Medicine, 450 Broadway, Pavilion C, MC 5334, Redwood City, CA, USA.
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Abstract
Incidence of skin cancers has been increasing since the last few decades worldwide. Nonmelanoma skin cancer (NMSC) is the commonest variety of cutaneous malignancy. Conventional wisdom has it that the incidence of all varieties of skin cancers is lower among Indians due to the protective effects of melanin. Though national surveys and cross-country data in India are unavailable, there are indirect indications from several smaller reports that NMSCs may be on the rise in India. Reports of quite a few atypical cases lead us to hypothesize that factors other than ultraviolet radiation may be important in the occurrences of these cancers, particularly in the skin types prevalent in India. The descriptive epidemiology and clinical characteristics of squamous and basal cell carcinoma in India, including their variants, are discussed here along with hypotheses on their etiopathogenesis. Novel management techniques currently available in India are also highlighted.
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Affiliation(s)
- Saumya Panda
- From the Department of Dermatology, KPC Medical College, Kolkata, India
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Marks R. The pathology of chronic solar damage and the effects of topical tretinoin. J DERMATOL TREAT 2009. [DOI: 10.3109/09546639609080604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
Throughout history, humankind has won the battle against deadly diseases, including small pox and polio, by defeating them through prevention. Cancer prevention is a global priority, but studying history suggests that the journey towards achieving this goal is difficult and full of detours and roadblocks. Epidemiology and clinical evidence clearly indicate that specific genetic, environmental and behavioural factors are associated with an increased risk for cancer development. What can we learn from the past that is applicable to the reality of successful cancer prevention?
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Affiliation(s)
- Ann M Bode
- The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, Minnesota 55912, USA
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Abdel-Malek ZA, Ruwe A, Kavanagh-Starner R, Kadekaro AL, Swope V, Haskell-Luevano C, Koikov L, Knittel JJ. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. Pigment Cell Melanoma Res 2009; 22:635-44. [PMID: 19558415 DOI: 10.1111/j.1755-148x.2009.00598.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
One skin cancer prevention strategy that we are developing is based on synthesizing and testing melanocortin analogs that reduce and repair DNA damage resulting from exposure to solar ultraviolet (UV) radiation, in addition to stimulating pigmentation. Previously, we reported the effects of tetrapeptide analogs of alpha-melanocortin (alpha-MSH) that were more potent and stable than the physiological alpha-MSH, and mimicked its photoprotective effects against UV-induced DNA damage in human melanocytes. Here, we report on a panel of tripeptide analogs consisting of a modified alpha-MSH core His(6)-d-Phe(7)-Arg(8), which contained different N-capping groups, C-terminal modifications, or arginine mimics. The most potent tripeptides in activating cAMP formation and tyrosinase of human melanocytes were three analogs with C-terminal modifications. The most effective C-terminal tripeptide mimicked alpha-MSH in reducing hydrogen peroxide generation and enhancing nucleotide excision repair following UV irradiation. The effects of these three analogs required functional MC1R, as they were absent in human melanocytes that expressed non-functional receptor. These results demonstrate activation of the MC1R by tripeptide melanocortin analogs. Designing small analogs for topical delivery should prove practical and efficacious for skin cancer prevention.
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Ultraviolet light output of compact fluorescent lamps: comparison to conventional incandescent and halogen residential lighting sources. Lupus 2009; 18:556-60. [DOI: 10.1177/0961203309103052] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Patients with photosensitive dermatologic and systemic diseases often question the ultraviolet light (UVL) output of household lighting sources. Such individuals have increasing concern about potential UVL exposure from energy-efficient compact fluorescent lamps (CFL), as little data have been presented concerning their UVL output. The objective was to compare, via pilot study, the levels of ultraviolet A (UVA) and ultraviolet B (UVB) leak between residential lighting sources. Equivalent wattage CFL, incandescent and halogen bulbs were purchased from local retailers in Oklahoma City, Oklahoma, USA. The UVA and UVB outputs of these sources were measured under controlled conditions at 10, 25, 50, 100 and 150 cm away from the light source using an IL-1700 research radiometer equipped with UVA and UVB detectors. Negligible UVB and UVA was detected at 100 and 150 cm. Therefore, data were analysed from measurements at 10, 25 and 50 cm only. The results demonstrated UVA leak highest from incandescent and halogen bulbs, and UVB leak highest from CFL. The overall UVA/UVB leak was lowest from CFL shielded during the manufacturing process. In conclusion, patients with photosensitivity have choices depending on their relative risk from different UVL wavelength spectra. UVB exposure risk may be reduced the greatest by utilising CFL with manufacturer-provided shields.
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