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Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
Xuelei Lai, Harry J Wichers, Montserrat Soler-Lopez, Bauke W Dijkstra
Melanin is the main pigment responsible for the colour of human skin, hair and eye. Its biosynthesis requires three melanogenic enzymes, tyrosinase (TYR), and the tyrosinase-related proteins TYRP1 and TYRP2. The difficulty of isolating pure and homogeneous proteins from endogenous sources has hampered their study, and resulted in many contradictory findings regarding their physiological functions. In this review, we summarize recent advances on the structure and function of TYR and TYRPs by virtue of the crystal structure of human TYRP1, which is the first available structure of a mammalian melanogenic enzyme...
October 20, 2017: Chemistry: a European Journal
Liao Peiran, Liu Ying, Zhao Mingzhuo, Yang Ye, Cui Xiuming
Panax notoginseng medicinal liquor (PML) has a long history of use in the function of blood circulation. However, the processing of PML is currently dependent on experience, which results in low efficiency and unstable quality of PML. A variety of substances of P. notoginseng have a strong ability to scavenge free radicals and antioxidant activity, but the antioxidant activity of PML has not been formally researched. The aim of the present study was to optimize the processing technology of PML and to verify the anti-oxidation and anti-deposition of melanin functions of PML...
October 20, 2017: Food & Function
S Yu, J Liao, M Tang, Y Wang, X Wei, L Mao, C Zeng
The tyrosinase (TYR) gene is the major melanogenesis-related gene for skin (fur) or plumage color in mammals and birds. Genetic variation in the promoter region of a gene may affect gene expression and phenotypes. This study compared the TYR promoter region between pooled DNA (n = 8) of chickens (Gallus gallus) with black and white skin using direct sequencing. The single nucleotide polymorphism (SNP) c.-2228A>T was found to have the opposite allele distribution in the two groups. The results of genotyping in a larger population (n = 188) revealed that SNP c...
September 1, 2017: Poultry Science
Shuji Nakamura, Toshio Kunikata, Yohsuke Matsumoto, Toshiharu Hanaya, Akira Harashima, Tomoyuki Nishimoto, Shimpei Ushio
Cyclic nigerosyl nigerose (CNN) is a cyclic tetrasaccharide that exhibits properties distinct from other conventional cyclodextrins. Herein, we demonstrate that treatment of B16 melanoma with CNN results in a dose-dependent decrease in melanin synthesis, even under conditions that stimulate melanin synthesis, without significant cytotoxity. The effects of CNN were prolonged for more than 27 days, and were gradually reversed following removal of CNN. Undigested CNN was found to accumulate within B16 cells at relatively high levels...
2017: PloS One
Sue Kyung Kim, Seung-Jae Oh, Se-Yeon Park, Woo-Jung Kim, You-Sun Kim, You Chan Kim
Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles and whitening, on aged skin. In the present study, we investigated the mechanism underlying the whitening effects of PDT on melanocytes in vitro and in vivo. Exposure of melanocytes to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. Interestingly, melanogenesis was also inhibited by exposing melanocytes to conditioned media of PDT-treated keratinocytes or dermal fibroblasts...
October 17, 2017: Pigment Cell & Melanoma Research
Jovana B Veselinović, Aleksandar M Veselinović, Tatjana Ilic-Tomic, Reeta Davis, Kevin O'Connor, Aleksandar Pavic, Jasmina Nikodinovic-Runic
7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have been evaluated as potential anti-melanogenic agents in the zebrafish (Danio rerio) model in comparison to commercially utilized depigmenting agents hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5µg/mL, while did not affect the embryos development and survival at doses ≤50µg/mL and ≤25µg/mL. Unlike hydroquinone and kojic acid, 4-phenyl hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects, neither caused neutropenia in zebrafish embryos, suggesting these compounds may present novel skin-whitening agents with improved pharmacological properties...
September 18, 2017: Bioorganic & Medicinal Chemistry
Mayumi Ikeda, Yu Ishima, Ryo Kinoshita, Victor T G Chuang, Nanami Tasaka, Nana Matsuo, Hiroshi Watanabe, Taro Shimizu, Tatsuhiro Ishida, Masaki Otagiri, Toru Maruyama
Products of ultraviolet (UV) irradiation such as reactive oxygen species (ROS) and nitric oxide (NO) stimulate melanin synthesis. Reactive sulfur species (RSS) have been shown to have strong ROS and NO scavenging effects. However, the instability and low retention of RSS limit their use as inhibitors of melanin synthesis. The free thiol at Cys34 on human serum albumin (HSA) is highly stable, has a long retention and possess a high reactivity for RSS. We report herein on the development of an HSA based RSS delivery system...
October 11, 2017: Redox Biology
Fayaz Ali Larik, Aamer Saeed, Pervaiz Ali Channar, Urooj Muqadar, Qamar Abbas, Mubashir Hassan, Sung-Yum Seo, Michael Bolte
A series of novel 1-pentanoyl-3-arylthioureas was designed as new mushroom tyrosinase inhibitors and free radical scavengers. The title compounds were obtained in excellent yield and characterized by FTIR, (1)H NMR, (13)C NMR and X-ray crystallography in case of compound (4a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 1-Pentanoyl-3-(4-methoxyphenyl) thiourea (4f) showed tyrosinase inhibitory activity (IC50 1.568 ± 0.01 mM) comparable to Kojic acid (IC50 16...
September 29, 2017: European Journal of Medicinal Chemistry
Guillermo Cásedas, Francisco Les, María Pilar Gómez-Serranillos, Carine Smith, Víctor López
Cranberry (Vaccinium macrocarpon) and blueberry (Vaccinium myrtillus) juices are commonly consumed as a source of antioxidants. The aim of this study was to compare bioactivities as well as the differences in the polyphenol content and anthocyanin profile of both juices. Polyphenol and anthocyanin contents were quantified using spectrophotometric and chromatographic methods. Bioassays were carried out in terms of antioxidant properties in cell and cell free systems as well as inhibition of physiological enzymes that are targets involved in the prevention of chronic diseases (monoamine oxidase A, tyrosinase, acetylcholinesterase, α-glucosidase and dipeptidyl peptidase-4)...
October 17, 2017: Food & Function
Le-Le Shao, Xiao-Ling Wang, Kai Chen, Xiao-Wu Dong, Li-Min Kong, De-Yin Zhao, Robert C Hider, Tao Zhou
A range of hydroxypyridinone derivatives were synthesized starting from kojic acid. Among them, 10 and 11 were found to possess the strongest inhibitory effect on monophenolase activity of mushroom tyrosinase, having IC50 values of 2.04 and 1.60μM, respectively. The IC50 values of 10 and 11 for the inhibition of diphenolase activity of mushroom tyrosinase were determined as 13.89 and 7.99μM, respectively. Investigation of the inhibitory mechanism of these two compounds indicated that the inhibition was reversible and of a competitive-uncompetitive mixed type...
March 1, 2018: Food Chemistry
Mark P Heitz, Jason W Rupp
The inhibition effects of imidazolium ionic liquids (ILs) on the enzyme kinetics of mushroom tyrosinase is reported. A simple UV-VIS spectrophotometric assay was used to measure the reaction kinetics of the reaction between mushroom tyrosinase and L-dopa. Seven different imidazolium ILs, comprised of 1-alkyl-3-methylimidazolium ([Imn1(+)], n=2, 4, 6) cations paired with several anions that included Cl(-), [NO3(-)], methanesulfonate ([MeSO3(-)]), trifluoromethanesulfonate (or triflate, [TFMS(-)]), and bis(trifluoromethylsulfonyl)imide ([Tf2N(-)])...
October 12, 2017: International Journal of Biological Macromolecules
Chenjia Guo, Ping Wu, Jinghua Xue, Hanxiang Li, Xiaoyi Wei
Two new γ-pyrones, xylaropyrones B (1) and C (2), together with three known compounds, xylaropyrone (3), annularin A (4) and annularin C (5), were isolated from solid cultures of the endophytic fungus Xylaria sp. SC1440. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. The relative configurations of 1 and 2 were assigned on the basis of J-based configurational analysis, and the absolute configurations were established by experimental and TDDFT calculated ECD spectra...
October 12, 2017: Natural Product Research
Dae Young Lee, Jongsung Lee, Yong Tae Jeong, Geon Hee Byun, Jin Hee Kim
BACKGROUND: Panax ginseng is a traditional herb used for medicinal purposes in eastern Asia. P. ginseng contains various ginsenosides with pharmacological effects. In this study, floralginsenoside A (FGA), ginsenoside Rd (GRD), and ginsenoside Re (GRE) were purified from P. ginseng berry. METHODS: Chemical structures of FGA, GRD, and GRE were determined based on spectroscopic methods, including fast atom bombardment mass spectroscopy, ID-nuclear magnetic resonance, and infrared spectroscopy...
October 2017: Journal of Ginseng Research
Yu-Mi Kim, Sang-Eun Cho, Soo-Chan Kim, Hyun-Joon Jang, Young-Kwon Seo
This study evaluated frequency-dependent effects of extremely low frequency electromagnetic fields (ELF-EMFs) on melanogenesis by melanocytes in vitro. Melanocytes were exposed to 2 mT EMFs at 30-75 Hz for 3 days before melanogenesis was examined. Exposure to ELF-EMFs at 50 and 60 Hz induced melanogenic maturation without cell damage, without changing cell proliferation and mitochondrial activity. Melanin content and tyrosinase activity of cells exposed to 50 Hz were higher than in controls, and mRNA expression of tyrosinase-related protein-2 was elevated relative to controls at 50 Hz...
October 11, 2017: International Journal of Molecular Sciences
You Chul Chung, Seoyeon Kim, Jin Hwa Kim, Geun Soo Lee, Jung No Lee, Nam Ho Lee, Chang-Gu Hyun
Tyrosinase is the rate-limiting enzyme critical for melanin synthesis. It controls pigmentation in the skin. Activation of tyrosinase is currently the most common approach in the development of tanning and haircare products. Pratol is a 7-hydroxy-4-methoxyflavone found in Trifoliumpratense. In this study, we investigated the effects of pratol on melanogenesis. We also studied the mechanism of action of pratol in B16F10 mouse melanoma cells. The cells were treated with various concentrations (6.25, 12.5, 25, and 50 μM) of pratol to observe its effects...
October 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
A S Kubasch, M Meurer
Albinism can be divided into oculocutaneous albinism (OCA) and ocular albinism (OA). In the differential diagnostics these can be distinguished from rarer syndromes with partial albinism, which are frequently associated with susceptibility to infections and neurological symptoms. The OCA is an autosomal recessive inherited disease of melanin biosynthesis, which leads to complete or partial loss of melanin in the skin, hair follicles and eyes. Of the seven currently known subtypes (OCA 1-7), four are well-characterized (OCA 1-4)...
October 10, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Yoon Ju Jeong, Jae-Young Lee, Jino Park, Soo Nam Park
AIMS: To report the effects of a novel syringic-acid derivative, (R)-ethyl-2-acetamido-3-(4-hydroxy-3,5-dimethoxybenzoylthio)propanoate (EABTO), on melanin synthesis and to identify its mechanism of action in B16F1 melanoma cells. METHODS: The effects of EABTO on melanin synthesis in B16F1 cells and human epidermal melanocytes and the influence on cell-free tyrosinase activity were evaluated. EABTO-induced cellular signaling cascades were studied by western blotting...
October 6, 2017: Life Sciences
Matthew R Arkenberg, Chien-Chi Lin
Stiffening of the extracellular matrix is a hallmark in cancer progression, embryonic development, and wound healing. To mimic this dynamic process, our work explored orthogonal enzymatic reactions capable of modulating the properties of poly(ethylene glycol) (PEG)-peptide hydrogels. A hepta-mutant bacterial transpeptidase sortase A (SrtA7M) was used to ligate two PEG-peptide macromers (i.e., PEG-YLPRTG and NH2-GGGG-PEG) into a primary hydrogel network. The hydrogels were dynamically stiffened using mushroom tyrosinase (MT), which oxidized tyrosine residues into di-tyrosine and led to increased matrix stiffness...
October 9, 2017: Biomaterials Science
David Gilot, Mélodie Migault, Laura Bachelot, Fabrice Journé, Aljosja Rogiers, Emmanuelle Donnou-Fournet, Ariane Mogha, Nicolas Mouchet, Marie-Laure Pinel-Marie, Bernard Mari, Tristan Montier, Sébastien Corre, Arthur Gautron, Florian Rambow, Petra El Hajj, Rania Ben Jouira, Sophie Tartare-Deckert, Jean-Christophe Marine, Brice Felden, Ghanem Ghanem, Marie-Dominique Galibert
Competition among RNAs to bind miRNA is proposed to influence biological systems. However, the role of this competition in disease onset is unclear. Here, we report that TYRP1 mRNA, in addition to encoding tyrosinase-related protein 1 (TYRP1), indirectly promotes cell proliferation by sequestering miR-16 on non-canonical miRNA response elements. Consequently, the sequestered miR-16 is no longer able to repress its mRNA targets, such as RAB17, which is involved in melanoma cell proliferation and tumour growth...
October 9, 2017: Nature Cell Biology
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