1.Targeting senescent dermal fibroblasts responsible for hyperactive melanocytes in melasma.
Jing WAN ; Zhikai LIAO ; Bingqi DONG ; Shan JIANG ; Tiechi LEI
Chinese Medical Journal 2023;136(13):1563-1565
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			Melanosis
		                        			;
		                        		
		                        			Fibroblasts
		                        			;
		                        		
		                        			Skin
		                        			
		                        		
		                        	
2.Exosomes released by melanocytes modulate fibroblasts to promote keloid formation: a pilot study.
Zeren SHEN ; Jinjin SHAO ; Jiaqi SUN ; Jinghong XU
Journal of Zhejiang University. Science. B 2022;23(8):699-704
		                        		
		                        			
		                        			Keloids are a common type of pathological scar as a result of skin healing, which are extremely difficult to prevent and treat without recurrence. The pathological mechanism of keloids is the excessive proliferation of fibroblasts, which synthesize more extracellular matrices (ECMs), including type I/III collagen (COL-1/3), mucopolysaccharides, connective tissue growth factor (CTGF, also known as cellular communication network factor 2 (CCN2)), and fibronectin (FN) in scar tissue, mostly through the abnormal activation of transforming growth factor-β (TGF-β)/Smads pathway (Finnson et al., 2013; Song et al., 2018). Genetic factors, including race and skin tone, are considered to contribute to keloid formation. The reported incidence of keloids in black people is as high as 16%, whereas white people are less affected. The prevalence ratio of colored people to white people is 5:1-15:1 (Rockwell et al., 1989; LaRanger et al., 2019). In addition, keloids have not been reported in albinism patients of any race, and those with darker skin in the same race are more likely to develop this disease (LaRanger et al., 2019). Skin melanocyte activity is significantly different among people with different skin tones. The more active the melanocyte function, the more melanin is produced and the darker the skin. Similarly, in the same individual, the incidence of keloids increases during periods when melanocytes are active, such as adolescence and pregnancy. Keloids rarely appear in areas where melanocytes synthesize less melanin, such as in the palms and soles. Thus, the formation of keloids seems to be closely related to melanocyte activity.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Cells, Cultured
		                        			;
		                        		
		                        			Exosomes/metabolism*
		                        			;
		                        		
		                        			Fibroblasts/metabolism*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Keloid/pathology*
		                        			;
		                        		
		                        			Melanins/metabolism*
		                        			;
		                        		
		                        			Melanocytes/pathology*
		                        			;
		                        		
		                        			Pilot Projects
		                        			;
		                        		
		                        			Skin/metabolism*
		                        			;
		                        		
		                        			Transforming Growth Factor beta/metabolism*
		                        			
		                        		
		                        	
3.Chronic stress induces fur color change from dark to brown by decreasing follicle melanocytes and tyrosinase activity in female C57BL/6 mice.
Xiao-Liang SHEN ; Yun-Zi LIU ; Hong GONG ; Yi ZHANG ; Teng-Yun WU ; Min XIA ; Chun-Lei JIANG
Acta Physiologica Sinica 2020;72(2):139-147
		                        		
		                        			
		                        			Increasing evidence suggests that stress may induce changes in hair color, with the underlying mechanism incompletely understood. In this study, female C57BL/6 mice subjected to electric foot shock combined with restraint stress were used to build chronic stress mouse model. The melanin contents and tyrosinase activity were measured in mouse skin and B16F10 melanoma cells. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor α (TNF-α), interleukin- 1β (IL-1β) and interleukin-6 (IL-6) in the mouse skin. The content of nuclear factor κB (NFκB)/p65 subunit in mouse skins was valued by immunofluorescence staining. The results demonstrated that under chronic stress, the fur color turned from dark to brown in C57BL/6 mice due to the decrease of follicle melanocytes and tyrosinase activity in C57BL/6 mouse skin. Simultaneously, inflammatory responses in skins were detected as shown by increased NFκB activity and TNF-α expression in stressed mouse skin. In cultured B16F10 melanoma cells, TNF-α reduced the melanogenesis and tyrosinase activity in a dose-dependent manner. These findings indicate that chronic stress induces fur color change by decreasing follicle melanocytes and tyrosinase activity in female C57BL/6 mice, and TNF-α may play an important role in stress-induced hair color change.
		                        		
		                        		
		                        		
		                        			Animal Fur
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Color
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Melanins
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			enzymology
		                        			;
		                        		
		                        			Melanoma, Experimental
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Mice, Inbred C57BL
		                        			;
		                        		
		                        			Monophenol Monooxygenase
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Pigmentation
		                        			;
		                        		
		                        			Skin
		                        			;
		                        		
		                        			physiopathology
		                        			;
		                        		
		                        			Stress, Physiological
		                        			
		                        		
		                        	
4.Efficacy and local irritation evaluation of Eriobotrya japonica leaf ethanol extract
Nak Won SEONG ; Won Jun OH ; Il Soo KIM ; Su Jin KIM ; Ji Eun SEO ; Chang Eon PARK ; Da Young KIM ; Je Won KO ; Jong Choon KIM
Laboratory Animal Research 2019;35(1):13-22
		                        		
		                        			
		                        			BACKGROUND: Although Eriobotrya japonica leaves have been studied as a raw material for various cosmetic products, little is known about the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of Eriobotrya japonica leaf ethanol extract (EJEE). METHODS: This study was conducted to evaluate the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of EJEE using different in vitro models. In addition, we investigated the potential irritation of EJEE to skin and eye using animal alternative tests. RESULTS: The total content of polyphenols, one of the active constituents of EJEE, was analyzed by high-performance liquid chromatography and found to contain 88.68 mg tannic acid equivalent/g. EJEE showed a concentration-dependent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity, and a superoxide dismutase-like activity. The anti-inflammatory effect of 0.5% (w/v) EJEE was demonstrated by a reduction in lipopolysaccharide-induced nitric oxide and tumor necrosis factor-alpha levels in RAW 264.7 cells. EJEE also significantly inhibited melanogenesis in melanocyte stimulating hormone-induced B16F1 cells. EJEE did not show any irritation in skin and eye in animal alternative test. CONCLUSIONS: These results indicate that the EJEE possesses anti-oxidant, anti-inflammatory, and anti-melanogenic activities, while it did not induce toxicity or irritation in neither skin nor eye. Therefore, EJEE can be used as a cosmetic ingredient for skin improvement.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Chromatography, Liquid
		                        			;
		                        		
		                        			Eriobotrya
		                        			;
		                        		
		                        			Ethanol
		                        			;
		                        		
		                        			In Vitro Techniques
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			Nitric Oxide
		                        			;
		                        		
		                        			Polyphenols
		                        			;
		                        		
		                        			RAW 264.7 Cells
		                        			;
		                        		
		                        			Skin
		                        			;
		                        		
		                        			Superoxides
		                        			;
		                        		
		                        			Tannins
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha
		                        			
		                        		
		                        	
5.Adipose-Derived Stem Cell Coculturing Stimulates Integrin-Mediated Extracellular Matrix Adhesion of Melanocytes by Upregulating Growth Factors
Hyangmi KIM ; Nayoung YI ; Byung Rok DO ; Ai Young LEE
Biomolecules & Therapeutics 2019;27(2):185-192
		                        		
		                        			
		                        			Coculture with adipose-derived stem cells (ADSCs) can stimulate proliferation and migration of melanocytes. To enhance outcomes of skin disorders caused by melanocyte loss or death, mixed transplantation with ADSCs has been suggested. However, role of cocultured ADSCs in proliferation and migration of melanocytes remains unclear. This study determined the effect of ADSCs on production of growth factors and expression levels of intergrins in primary culture of adult human melanocytes with or without ADSCs and in nude mice grafted with such melanocytes. Higher amounts of growth factors for melanocytes, such as bFGF and SCF were produced and released from ADSCs by coculturing with melanocytes. Relative levels of integrins β1, α5, and α6 as well as adhesion to fibronectin and laminin were increased in melanocytes cocultured with ADSCs. Such increases were inhibited by neutralization of bFGF or SCF. Relative levels of bFGF, SCF and integrins were increased in nude mice skin after grafting with melanocyte+ADSC cocultures. Collectively, these results indicate that ADSCs can stimulate proliferation and migration of melanocytes by increasing expression of integrins in melanocytes through upregulation of production/release of melanocyte growth factors such as bFGF and SCF.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Coculture Techniques
		                        			;
		                        		
		                        			Extracellular Matrix
		                        			;
		                        		
		                        			Fibronectins
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Integrins
		                        			;
		                        		
		                        			Intercellular Signaling Peptides and Proteins
		                        			;
		                        		
		                        			Laminin
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Mice, Nude
		                        			;
		                        		
		                        			Skin
		                        			;
		                        		
		                        			Stem Cells
		                        			;
		                        		
		                        			Transplants
		                        			;
		                        		
		                        			Up-Regulation
		                        			
		                        		
		                        	
6.Research progress in melanogenesis signaling pathway.
Meijuan ZHAO ; Jingjing HU ; Hui NI ; Zedong JIANG ; Li WANG
Chinese Journal of Biotechnology 2019;35(9):1633-1642
		                        		
		                        			
		                        			Melanogenesis is a biosynthetic pathway to produce melanin pigment in melanocyte, involving a series of intricate enzymatic and chemical catalyzed reactions. Melanogenesis involves five signaling pathways that converge on microphthalmia-associated transcription factor. In addition, many cytokines, involved in the regulation of melanogenesis, play an important role in the development, proliferation, differentiation and migration of melanocytes. Polyoxometalate can be used as a potential inhibitor of melanin production. Hence, this paper reviews the signaling pathways of melanogenesis and their regulatory mechanism, to apply polyoxometalates in the melanin production pathway, and briefly introduces the regulatory factors of related pathways.
		                        		
		                        		
		                        		
		                        			Cell Differentiation
		                        			;
		                        		
		                        			Melanins
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			Microphthalmia-Associated Transcription Factor
		                        			;
		                        		
		                        			Signal Transduction
		                        			
		                        		
		                        	
7.A preliminary study of markers for human hair follicle melanin stem cell.
Xing-Yu MEI ; Zhou-Wei WU ; Cheng-Zhong ZHANG ; Yue SUN ; Wei-Min SHI
Chinese Medical Journal 2019;132(9):1117-1119
		                        		
		                        		
		                        		
		                        			Antigens, CD34
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Biomarkers
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Cell Differentiation
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Hair Follicle
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Intramolecular Oxidoreductases
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Keratinocytes
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Melanins
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			PAX3 Transcription Factor
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Stem Cells
		                        			;
		                        		
		                        			metabolism
		                        			
		                        		
		                        	
8.Increased Circulating CXCL10 in Non-Segmental Vitiligo Concomitant with Autoimmune Thyroid Disease and Alopecia Areata
Li ZHANG ; Xinya XU ; Shujun CHEN ; Yuli KANG ; Xiuxiu WANG ; Chengfeng ZHANG ; Leihong XIANG
Annals of Dermatology 2019;31(4):393-402
		                        		
		                        			
		                        			BACKGROUND: Vitiligo is a common acquired pigmentary disease caused by destruction of epidermal melanocytes in underlying autoimmune response. Few studies have been focused on the role of chemokines in non-segmental vitiligo (NSV) concomitant with autoimmune thyroid disease (AITD) and alopecia areata (AA). OBJECTIVE: The aim of this study was to determine the best serum biomarker for predictive role in the progression of vitiligo and to evaluate the influence of AA and/or AITD on vitiligo by using the biomarker. METHODS: This prospective cohort study recruited 45 NSV patients: 14 without either AITD or AA, 12 with AITD, 11 with AA, and 8 with both AITD and AA. Serum levels of CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL16 were analyzed by ELISA. CXCR3 mRNA expression was detected on PBMCs by RT-PCR. Improvement was evaluated using repigmentation scales. RESULTS: Serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with AITD or AA alone than in those without AITD or AA. Moreover, serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with both AITD and AA than in those with AITD or AA alone. Poorer repigmentation was observed in NSV patients with both AA and AITD than in those with AA or AITD alone. CONCLUSION: CXCL10 could be a biomarker to predict the progression of NSV. Dermatologists should pay much attention to those NSV patients concomitant with AITD and/or AA, for comorbidity might lead to more active autoimmune reaction.
		                        		
		                        		
		                        		
		                        			Alopecia Areata
		                        			;
		                        		
		                        			Alopecia
		                        			;
		                        		
		                        			Autoimmunity
		                        			;
		                        		
		                        			Chemokine CXCL10
		                        			;
		                        		
		                        			Chemokines
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Comorbidity
		                        			;
		                        		
		                        			Enzyme-Linked Immunosorbent Assay
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			RNA, Messenger
		                        			;
		                        		
		                        			Thyroid Diseases
		                        			;
		                        		
		                        			Thyroid Gland
		                        			;
		                        		
		                        			Vitiligo
		                        			;
		                        		
		                        			Weights and Measures
		                        			
		                        		
		                        	
9.Anti-melanogenic effects of Hordeum vulgare L. barely sprout extract in murine B16F10 melanoma cells
Jeong Hwa CHOI ; Jong Gi JUNG ; Jung Eun KIM ; Mi Ae BANG
Journal of Nutrition and Health 2019;52(2):168-175
		                        		
		                        			
		                        			PURPOSE: Barely sprout is a well-known oriental herbal medicine with a wide range of health benefits. Recent studies have provided scientific evidence of its therapeutic effects with expanded application. This study investigated anti-melanogenic effect of barley sprout water extract (BSE) in murine melanocyte B16F10. METHODS: Various concentrations (0, 50, 125, and 250 µg/mL) of BSE and arbutin (150 ppm) were applied to B16F10 stimulated with or without alpha-melanocyte stimulating hormone (100 nM) for 72 hours. The whitening potency of BSE was determined altered cellular melanin contents. Activity and expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were also assayed. RESULTS: Experimental results revealed that treatment with BSE reduced cellular melanin production by approximately 40% compared to the control. Molecular findings supported that suppressed activity and expression of tyrosinase and MITF proteins by BSE were associated with declined cellular melanogenesis. Furthermore, anti-melanogenic effect of BSE (250 µg/mL) was similar to that of arbutin, a commonly used whitening agent. Lastly, polyphenols including p-coumaric, ferulic, and vanillic acids were identified in BSE using HPLC analyses. They might be potential active ingredients showing such melanogenesis-reducing effect. CONCLUSION: BSE was evident to possess favorable anti-melanogenic potency in an in vitro model. As a natural food sourced material, BSE could be an effective depigmentation agent with potential application in pharmaceutical and cosmetic industries.
		                        		
		                        		
		                        		
		                        			Arbutin
		                        			;
		                        		
		                        			Chromatography, High Pressure Liquid
		                        			;
		                        		
		                        			Herbal Medicine
		                        			;
		                        		
		                        			Hordeum
		                        			;
		                        		
		                        			In Vitro Techniques
		                        			;
		                        		
		                        			Insurance Benefits
		                        			;
		                        		
		                        			Melanins
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			Melanoma
		                        			;
		                        		
		                        			Microphthalmia-Associated Transcription Factor
		                        			;
		                        		
		                        			Monophenol Monooxygenase
		                        			;
		                        		
		                        			Polyphenols
		                        			;
		                        		
		                        			Therapeutic Uses
		                        			;
		                        		
		                        			Vanillic Acid
		                        			;
		                        		
		                        			Water
		                        			
		                        		
		                        	
10.Increased Expression of Dickkopf-1 in Acral Lentiginous Melanoma.
Yoon Hyuk CHOI ; Seok Min KIM ; Jun Young KIM ; Man Hoon HAN ; Seok Jong LEE
Korean Journal of Dermatology 2018;56(4):259-264
		                        		
		                        			
		                        			BACKGROUND: Dickkopf-1 (DKK-1), an inhibitor of the Wnt signaling pathway, is known as an inhibitor of melanocyte proliferation. In recent studies, the expression of DKK-1 gene is reduced in melanoma and they lose their preventive role during development or progression of melanoma. There are no available data regarding the changes in DKK-1 gene expression in acral lentiginous melanoma (ALM), which is common in Asians. OBJECTIVE: To analyze changes in DKK-1 expression in the development or progression of ALM in Koreans. METHODS: Immunohistochemical staining using DKK-1 antibody of 13 invasive ALM, six ALM in situ, nine acral nevi, and four benign non-related palmoplantar specimens as controls were evaluated by the semi-quantitative grading scale, which is divided into three distinctive grades according to the degree of cytoplasmic staining of DKK-1. RESULTS: Among the invasive ALM specimens, seven of 13 (53.8%) were graded as strongly positive (2+), and only one case (7.7%) was negative. In cases of ALM in situ, two specimens (33.3%) stained positive (1+) and the remaining four specimens (66.6%) were not stained. All specimens from both acral nevus and benign palmoplantar lesions, which were used as the control group, were also negative. CONCLUSION: In contrast with recent reports, DKK-1 expression showed a positive correlation with ALM progression or invasiveness. The role of DKK-1 as a potential predictor of ALM progression warrants further study.
		                        		
		                        		
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Cytoplasm
		                        			;
		                        		
		                        			Gene Expression
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Melanocytes
		                        			;
		                        		
		                        			Melanoma*
		                        			;
		                        		
		                        			Nevus
		                        			;
		                        		
		                        			Wnt Signaling Pathway
		                        			
		                        		
		                        	
            
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