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Vitiligo is a depigmentation disease commonly seen in clinical practice, mainly involving loss of functional epidermal pigment cells and hair follicle melanocytes. Narrow‑band ultraviolet B (NB‑UVB) has emerged as the first choice of treatment for vitiligo, but long‑term exposure may have serious consequences. Recently, it was reported that adipose‑derived stem cells (ADSCs) improve melanocyte growth and the efficacy of melanocyte transplantation. The present study aimed to examine the efficacy of NB‑UVB/ADSC‑transplantation combined therapy on a mouse vitiligo model and explore the underlying mechanisms by focusing on endoplasmic reticulum stress and cellular calcium (Ca 2+ ) homeostasis. Vitiligo mice models were established by applying 40% monobenzone (MBZ) cream twice daily and treated with NB‑UVB/ADSC combination therapy. Some treated mice were also given ML385, a nuclear factor erythroid 2 like 2 (Nr2) inhibitor. Histopathological changes were evaluated using a depigmentation evaluation score and observed with hematoxylin and eosin staining on skin tissues. ELISA was used to measure diagnostic markers in plasma. Flow cytometric assay was performed to quantify CD3 + , CD4 +  and CD8 + levels. Expression levels of associated proteins were detected with western blot and immunofluorescence. Treatment of mice with MBZ‑induced depigmentation patches on the skin was accompanied with loss of redox balance and disruption of cellular Ca 2+ homeostasis. Oxidative stress and Ca 2+ unbalancing were improved after the mice were treated by NB‑UVB/ADSCs transplantation combination therapy. ML385, strongly negated the protective effect of NB‑UVB/ADSC transplantation combination therapy, indicating the critical role of Nr2 signaling. The findings improved the understanding of the pathogenesis of vitiligo and will guide future development of therapeutic strategies against it.

Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and anti‑melanogenic effects were investigated against the background of skin photoprotective and anti‑melanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVA‑and UVB‑irradiated keratinocytes and α‑melanocyte stimulating hormone (α‑MSH)‑stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant anti‑apoptotic effects on UVA‑and UVB‑irradiated keratinocytes. After α‑MSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the α‑MSH‑induced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmia‑associated transcription factor (MITF), tyrosinase, tyrosinase‑related protein (TRP)‑1 and TRP‑2 in α‑MSH‑stimulated melanocytes. In addition, gomisin D markedly downregulated α‑MSH‑induced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP‑1 and TRP‑2 genes. Overall, gomisin D has photoprotective and anti‑melanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.

A suspected case of localized visceral hyperpigmentation was described for a breed of broiler in China. Using optical microscopy, the accumulation of pigments in the abdominal skin and visceral peritoneum was observed. Electron microscopy was used to further study the ultrastructure of the pigmented peritoneum, and pigment granules resembling melanosomes at different stages were found, and melanocytes were present in this tissue. Infrared spectroscopy was used to analyze the physical-chemical properties of pigments extracted from these broilers. Using synthetic melanin as a reference and the melanin from the peritoneum of Silkie fowls as a control, the pigments in the peritonea of these broilers were found to be melanin, and it had a chemical structure similar to that of melanin from the Silkie fowl peritoneum. In this way, the black abdomens of these broilers were found to have been caused by accumulation of melanin produced by melanocytes in visceral peritonea.

Vitiligo is an acquired depigmentation disorder, and reactive oxygen species play an important role in melanocyte damage. Base excision repair is the major pathway responsible for removing reactive oxygen species-induced DNA damage, in which APE1, ADPRT, and XRCC1 play key roles. To investigate the association between genetic variations of these genes and the risk of vitiligo in Chinese populations, we genotyped APE1-Asp148Glu, ADPRT-Val762Ala, and XRCC1-Arg399Gln polymorphisms and measured serum 8-OHdG levels in a hospital-based case-control study. We found that a significantly increased risk of vitiligo was associated with the APE1 Asp/Glu (adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.02-1.52) and Glu/Glu genotypes (adjusted OR 1.48; 95% CI 1.13-1.93), compared with the APE1 Asp/Asp genotype, whereas no vitiligo risk was associated with the genotypes ADPRT-Val762Ala and XRCC1-Arg399Gln. Furthermore, serum 8-OHdG levels were elevated in the APE1-148Glu allele carriers (Asp/Glu+Glu/Glu), in an allele dose-response manner, with the risk of vitiligo (Ptrend<0.05). In addition, we found that the APE1-148Glu variant increased the 8-OHdG levels of cultured human melanocytes treated with H2O2, without any impact on the endonuclease activity. These data suggest that the APE1-Asp148Glu polymorphism aggravates oxidative stress in human melanocytes and contributes to genetic predisposition to vitiligo in Chinese people., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Recent evidence indicates that oxidative stress and genetic factors play an important role in the pathogenesis of vitiligo. SNPs in miRNAs involved in oxidative stress could potentially influence the development of vitiligo. In this case-control study, we investigated the association of a functional SNP of rs11614913 in miR-196a-2 with risk of vitiligo. A significantly lower risk of vitiligo was associated with the rs11614913 miR-196a-2 CC genotype (adjusted OR, 0.77; CI, 0.60-0.98). In addition, TYRP1 gene expression was considerably down-regulated by the rs11614913 C allele in miR-196a-2, which lowered the levels of intracellular reactive oxygen species (ROS) and reduced the proportion of early apoptosis in human melanocytes in response to H2 O2 treatment. Our data suggest that the rs11614913 C allele in miR-196a-2 confers potential protection against oxidative effects on human melanocytes through the modulation of the target gene, TYRP1, which may account for the decreased risk of vitiligo in this study population., (© 2013 John Wiley & Sons A/S.)

The ventri-yellow pigmentation mouse (temporarily named VY(Slac)) arose spontaneously in the C57BL/6J inbred mouse strain, found and bred by Shanghai SLAC Laboratory Animal Co., Ltd. VY(Slac) presented a special phenotype marked by yellow coat on the ventral surface of neck and trunk that was without melanin deposition but maintained a normal structure. The number of melanocytes in epidermis and melanin in hair follicle of the abdominal skin of the mutant mouse were less than that of their background strain, while there was no significant difference between the dorsal skins of the two strains. This mutant phenotype was inherited as single-gene dominant inheritance, confirmed by genetic experiment, and there was no significant difference between VY(Slac) and B(6) for other biological parameters such as weight, anatomic and histological structures of major organs and blood physiology. When the linkage relationship between the genomic DNA samples of F(2) 48 mice (VY(Slac)D(2)F(1)×D(2)) and mutant phenotype were evaluated, the mutant gene was confirmed on chromosome 2 near D2Mit229. New microsatellite and SNP markers were selected to amplify genomic DNA samples of 196 F(2) mice and the mutant gene was narrowed down to 5.3 Mb region between rs13476833 and rs27310903 on chromosome 2. The preliminary results of our phenotype analysis and gene location provides a solid basis for further identification of this mutant gene.