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      A Clinical and Biochemical Evaluation of a Temperature-Controlled Continuous Non-Invasive Radiofrequency Device for the Treatment of Melasma

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          Abstract

          Background

          Melasma shows characteristic histological features of photoaged skin.

          Objective

          We evaluated the effect of dermal rejuvenation using a temperature-controlled continuous non-invasive radiofrequency (RF) device on melasma.

          Methods

          Continuous skin heating at the temperature of 43°C for 20 minutes was performed in ten subjects with melasma who underwent 3 tri-weekly RF sessions. Pigmentation was evaluated with Mexameter® and investigator’s global assessment (IGA). Immunohistochemical staining and image analysis was performed to evaluate biopsies from melasma skin before and after the treatment.

          Results

          The lesional melanin index was decreased by 13.7% at week 9. IGA score was improved from 3.50 at baseline to 2.95 at week 9. No significant adverse event was reported. Histologic analysis revealed reduced melanin and increased collagen density and thickness. The expression of procollagen-1 and type IV collagen was increased after the treatment. The number of p16 INK4A-positive senescent fibroblasts was reduced after the treatment, while the expression of heat shock protein 70 and 90 was increased. Stromal derived factor-1, a senescence-associated anti-melanogenic factor secreted from the fibroblasts, was up-regulated after the treatment, while the level of c-kit was not changed.

          Conclusion

          Thermal skin stimulation by the temperature-controlled continuous RF device improved melasma through dermal rejuvenation.

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          Most cited references40

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          Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders.

          Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a)-positive senescent cells upon drug treatment. In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
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            Quantitative analysis of histological staining and fluorescence using ImageJ.

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              Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone.

              Hsp47, a collagen-specific molecular chaperone that localizes in the endoplasmic reticulum (ER), is indispensable for molecular maturation of collagen. Hsp47, which is encoded by the SERPINH1 gene, belongs to the serpin family and has the serpin fold; however, it has no serine protease inhibitory activity. Hsp47 transiently binds to procollagen in the ER, dissociates in the cis-Golgi or ER-Golgi intermediate compartment (ERGIC) in a pH-dependent manner, and is then transported back to the ER via its RDEL retention sequence. Hsp47 recognizes collagenous (Gly-Xaa-Arg) repeats on triple-helical procollagen and can prevent local unfolding and/or aggregate formation of procollagen. Gene disruption of Hsp47 in mice causes embryonic lethality due to impairments in basement membrane and collagen fibril formation. In Hsp47-knockout cells, the type I collagen triple helix forms abnormally, resulting in thin and frequently branched fibrils. Secretion of type I collagens is slow and plausible in making aggregates of procollagens in the ER of hsp47-knocked out fibroblasts, which are ultimately degraded by autophagy. Mutations in Hsp47 are causally associated with osteogenesis imperfecta. Expression of Hsp47 is strongly correlated with expression of collagens in multiple types of cells and tissues. Therefore, Hsp47 represents a promising target for treatment of collagen-related disorders, including fibrosis of the liver, lung, and other organs.
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                Author and article information

                Journal
                Ann Dermatol
                Ann Dermatol
                AD
                Annals of Dermatology
                The Korean Dermatological Association; The Korean Society for Investigative Dermatology
                1013-9087
                2005-3894
                December 2021
                04 November 2021
                : 33
                : 6
                : 522-530
                Affiliations
                Department of Dermatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
                [1 ]Department of Dermatology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
                Author notes
                Corresponding Author: Kyoung-Chan Park. Department of Dermatology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea. Tel: +82-31-787-7311, Fax: +82-31-787-4058, gcpark@ 123456snu.ac.kr
                Author information
                https://orcid.org/0000-0002-7295-5725
                https://orcid.org/0000-0002-5717-2490
                https://orcid.org/0000-0003-3944-7777
                https://orcid.org/0000-0002-1588-3307
                Article
                10.5021/ad.2021.33.6.522
                8577901
                34858003
                6c3037c4-df83-4f6c-aef0-1662c99e9b9e
                Copyright © 2021 The Korean Dermatological Association and The Korean Society for Investigative Dermatology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 February 2021
                : 01 April 2021
                : 02 April 2021
                Categories
                Original Article

                Dermatology
                fibroblasts,melanosis,radiofrequency therapy,skin aging
                Dermatology
                fibroblasts, melanosis, radiofrequency therapy, skin aging

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