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https://www.readbyqxmd.com/read/29914002/pain-sensitivity-and-experimentally-induced-sensitisation-in-red-haired-females
#1
Trine Andresen, Dagmar Lunden, Asbjørn M Drewes, Lars Arendt-Nielsen
Introduction and aim Pain sensitivity has been linked to the melanocortin-1 receptor (MC1R) gene. A mutation in MC1R can result in pale skin and red hair in humans and may modulate pain responses in general. Human studies have shown that women with non-functional MC1R's were sensitive to experimental induced cold and heat pain. A study demonstrated that females with red hair required higher dose of anesthesia than females with dark hair to experience analgesia to electrical stimulation. Moreover, women expressing non-functional MC1Rs display greater analgesia from opioid analgesia...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29898205/contributions-by-mc1r-variants-to-melanoma-risk-in-males-and-females
#2
Judith Wendt, Christoph Mueller, Sabine Rauscher, Ingrid Fae, Gottfried Fischer, Ichiro Okamoto
Importance: Recently, the red hair variants of MC1R were found to contribute differently to pigmentation phenotype in males and females. Objective: To investigate the role of these variants in melanoma risk in males and females separately because carriers of the red hair variants of MC1R are at increased risk of melanoma. Design, Setting, and Participants: In this hospital-based, case-control study, we evaluated the effect of MC1R and melanoma risk for males and females separately by performing multivariate logistic regression analyses...
June 13, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29893870/polymorphisms-in-mc1r-and-asip-genes-are-associated-with-coat-colour-variation-in-the-arabian-camel
#3
Faisal Almathen, Haitham Elbir, Hussain Bahbahani, Joram Mwacharo, Olivier Hanotte
Pigmentation in mammals is primarily determined by the distribution of eumelanin and pheomelanin, the ratio of which is mostly controlled by the activity of melanocortin 1 receptor (MC1R) and agouti signalling protein (ASIP) genes. Using 91 animals from ten Arabian camel populations, that included the four predominant coat color phenotypes observed in the dromedary (light brown, dark brown, black and white), we investigated the effects of the MC1R and ASIP sequence variants and identified candidate polymorphisms associated with coat color variation...
June 9, 2018: Journal of Heredity
https://www.readbyqxmd.com/read/29890168/assessing-the-incremental-contribution-of-common-genomic-variants-to-melanoma-risk-prediction-in-two-population-based-studies
#4
Anne E Cust, Martin Drummond, Peter A Kanetsky, Alisa M Goldstein, Jennifer H Barrett, Stuart MacGregor, Matthew H Law, Mark M Iles, Minh Bui, John L Hopper, Myriam Brossard, Florence Demenais, John C Taylor, Clive Hoggart, Kevin M Brown, Maria Teresa Landi, Julia A Newton-Bishop, Graham J Mann, D Timothy Bishop
It is unclear to what degree genomic and traditional (phenotypic and environmental) risk factors overlap in their prediction of melanoma risk. We evaluated the incremental contribution of common genomic variants (in pigmentation, nevus and other pathways) and their overlap with traditional risk factors, using data from two population-based case-control studies from Australia (n=1,035) and the UK (n=1,460) that used the same questionnaires. Polygenic risk scores were derived from 21 gene regions associated with melanoma and odds ratios from published meta-analyses...
June 8, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29873290/melanocortin-1-receptor-targeted-imaging-of-melanoma-with-gold-nanocages-and-positron-emission-tomography
#5
Yongfeng Zhao, Bo Pang, Lisa Detering, Hannah Luehmann, Miaoxin Yang, Kvar Black, Deborah Sultan, Younan Xia, Yongjian Liu
PURPOSE: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. METHOD: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64 Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model...
January 2018: Molecular Imaging
https://www.readbyqxmd.com/read/29846953/exploring-pathways-for-sustained-melanogenesis-in-facial-melasma-an-immunofluorescence-study
#6
Ana C C Esposito Lemos, Gabrielli Brianezi, Nathalia P de Sousa, Luciane D B Miot, Mariângela E A Marques, Hélio A Miot
BACKGROUND: The physiopathology of epidermal hypermelanization in melasma is not completely understood. Several cytokines and growth factors are increased in skin with melasma, nevertheless, nor the pathways involved in the increased αMSH expression have been adequately evaluated, nor a model for sustained focal melanogenesis is available. OBJECTIVE: To explore stimulatory pathways for epidermal pigmentation in facial melasma related to αMSH: those linked to ultraviolet radiation, oxidative stress, inflammation, neural crest pigmentation cell differentiation and antagonism of αMSH...
May 30, 2018: International Journal of Cosmetic Science
https://www.readbyqxmd.com/read/29843606/landscape-of-copy-number-variations-in-bos-taurus-individual-and-inter-breed-variability
#7
M Mielczarek, M Frąszczak, E Nicolazzi, J L Williams, J Szyda
BACKGROUND: The number of studies of Copy Number Variation in cattle has increased in recent years. This has been prompted by the increased availability of data on polymorphisms and their relationship with phenotypes. In addition, livestock species are good models for some human phenotypes. In the present study, we described the landscape of CNV driven genetic variation in a large population of 146 individuals representing 13 cattle breeds, using whole genome DNA sequence. RESULTS: A highly significant variation among all individuals and within each breed was observed in the number of duplications (P < 10-15 ) and in the number of deletions (P < 10-15 )...
May 29, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29801061/interest-and-uptake-of-mc1r-testing-for-melanoma-risk-in-a-diverse-primary-care-population-a-randomized-clinical-trial
#8
Jennifer L Hay, Kate Zielaskowski, Kirsten Meyer White, Kimberly Kaphingst, Erika Robers, Dolores Guest, Andrew Sussman, Yvonne Talamantes, Matthew Schwartz, Vivian M Rodríguez, Yuelin Li, Elizabeth Schofield, Jessica Bigney, Keith Hunley, David Buller, Marianne Berwick
Importance: Germline variants in the MC1R gene are common and confer moderate melanoma risk in those with varied skin types. Approaches to precision skin cancer prevention that include genetic information may promote risk awareness and risk reduction in the general population, including Hispanics. Objective: To examine prevalence of interest in and uptake of MC1R testing in the general population and examine patterns across demographic and skin cancer risk factors...
May 9, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29795986/-mc1r-variants-as-melanoma-risk-factors-independent-of-at-risk-phenotypic-characteristics-a-pooled-analysis-from-the-m-skip-project
#9
Elena Tagliabue, Sara Gandini, Rino Bellocco, Patrick Maisonneuve, Julia Newton-Bishop, David Polsky, DeAnn Lazovich, Peter A Kanetsky, Paola Ghiorzo, Nelleke A Gruis, Maria Teresa Landi, Chiara Menin, Maria Concetta Fargnoli, Jose Carlos García-Borrón, Jiali Han, Julian Little, Francesco Sera, Sara Raimondi
Purpose: Melanoma represents an important public health problem, due to its high case-fatality rate. Identification of individuals at high risk would be of major interest to improve early diagnosis and ultimately survival. The aim of this study was to evaluate whether MC1R variants predicted melanoma risk independently of at-risk phenotypic characteristics. Materials and methods: Data were collected within an international collaboration - the M-SKIP project. The present pooled analysis included data on 3,830 single, primary, sporadic, cutaneous melanoma cases and 2,619 controls from seven previously published case-control studies...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29790964/evidence-of-evolutionary-history-and-selective-sweeps-in-the-genome-of-meishan-pig-reveals-its-genetic-and-phenotypic-characterization
#10
Pengju Zhao, Ying Yu, Wen Feng, Heng Du, Jian Yu, Huimin Kang, Xianrui Zheng, Zhiquan Wang, George E Liu, Catherine W Ernst, Xueqin Ran, Jiafu Wang, Jian-Feng Liu
Background: Meishan is a pig breed indigenous to China and famous for its high fecundity. The traits of Meishan are strongly associated with its distinct evolutionary history and domestication. However, the genomic evidence linking the domestication of Meishan pigs with the unique features are still poorly understood. The goal of this study is to investigate the genomic signatures and evolutionary evidence related to phenotypic traits of Meishan by large-scale sequencing. Results: We found the unique domestication of Meishan pigs happened at the Taihu Basin area between the Majiabang and the Liangzhu culture, during which 300 protein-coding genes have undergone positive selection...
May 22, 2018: GigaScience
https://www.readbyqxmd.com/read/29774366/cdkn2a-cdk4-status-in-greek-patients-with-familial-melanoma-and-association-with-clinico-epidemiological-parameters
#11
Fani Karagianni, Ching-Ni Njauw, Katerina P Kypreou, Aravela Stergiopoulou, Michaela Plaka, Dorothea Polydorou, Vasiliki Chasapi, Leon Pappas, Ioannis Stratigos, Gregory Champsas, Peter Panagiotou, Helen Gogas, Evangelos Evangelou, Hensin Tsao, Alexander Stratigos, Irene Stefanaki
Approximately 5-10% of melanoma cases occur in a familial context. CDKN2A/CDK4 were the first high-penetrance melanoma genes identified. The aims of this study were to evaluate CDKN2A/CDK4 variants in Greek familial melanoma patients and to correlate the mutational status with specific clinico-epidemiological characteristics. A cross-sectional study was conducted by genotyping CDKN2A/CDK4 variants and selected MC1R polymorphisms in 52 melanoma-prone families. Descriptive statistics were calculated and comparisons were made using the χ2 test, Fisher's exact test and Student's t-test for statistical analysis, as appropriate...
May 18, 2018: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29771307/assessment-of-rosacea-symptom-severity-by-genome-wide-association-study-and-expression-analysis-highlights-immuno-inflammatory-and-skin-pigmentation-genes
#12
Jennifer L Aponte, Mathias N Chiano, Laura M Yerges-Armstrong, David A Hinds, Chao Tian, Akansha Gupta, Cong Guo, Dana J Fraser, Johannes M Freudenberg, Deepak K Rajpal, Margaret G Ehm, Dawn M Waterworth
Rosacea is a common, chronic skin disease of variable severity with limited treatment options. The cause of rosacea is unknown, but it is believed to be due to a combination of hereditary and environmental factors. Little is known about the genetics of the disease. We performed a genome-wide association study (GWAS) of rosacea symptom severity with data from 73,265 research participants of European ancestry from the 23andMe customer base. Seven loci had variants associated with rosacea at the genome-wide significance level (p≤5 × 10-8)...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29714486/melanoma-imaging-using-18-f-labeled-%C3%AE-melanocyte-stimulating-hormone-derivatives-with-positron-emission-tomography
#13
Chengcheng Zhang, Zhengxing Zhang, Kuo-Shyan Lin, Joseph Lau, Jutta Zeisler, Nadine Colpo, David M Perrin, Francois Benard
Melanocortin 1 receptor (MC1R) is specifically expressed in the majority of melanomas, a leading cause of death related to skin cancers. Accurate staging and early detection is crucial in managing melanoma. Based on the α-melanocyte-stimulating hormone (αMSH) sequence, MC1R-targeted peptides have been studied for melanoma imaging, predominately for use with single-photon emission computed tomography (SPECT), with few attempts made for positron emission tomography (PET). 18 F is a commonly used PET isotope due to readily available cyclotron production, pure positron emission and a favorable half-life (109...
May 1, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29679901/replacement-of-arg-with-nle-and-modified-d-phe-in-the-core-sequence-of-mshs-ac-his-d-phe-arg-trp-nh-2-leads-to-hmc1r-selectivity-and-pigmentation
#14
Saghar Mowlazadeh Haghighi, Yang Zhou, Jixun Dai, Jonathon R Sawyer, Victor J Hruby, Minying Cai
Melanoma skin cancer is the fastest growing cancer in the US [1]. A great need exists for improved formulations and mechanisms to prevent and protect human skin from cancers and other skin damage caused by sunlight exposure. Current efforts to prevent UV damage to human skin, which in many cases leads to melanoma and other skin cancers. The primordial melanocortin-1 receptor (MC1R) is involved in regulating skin pigmentation and hair color, which is a natural prevention from UV damage. The endogenous melanocortin agonists induce pigmentation and share a core pharmacophore sequence "His-Phe-Arg-Trp", and it was found that substitution of the Phe by D-Phe results in increasing melanocortin receptor potency...
May 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29678289/pathophysiology-of-melanocortin-receptors-and-their-accessory-proteins
#15
REVIEW
T V Novoselova, L F Chan, A J L Clark
The melanocortin receptors (MCRs) and their accessory proteins (MRAPs) are involved in regulation of a diverse range of endocrine pathways. Genetic variants of these components result in phenotypic variation and disease. The MC1R is expressed in skin and variants in the MC1R gene are associated with ginger hair color. The MC2R mediates the action of ACTH in the adrenal gland to stimulate glucocorticoid production and MC2R mutations result in familial glucocorticoid deficiency (FGD). MC3R and MC4R are involved in metabolic regulation and their gene variants are associated with severe pediatric obesity, whereas the function of MC5R remains to be fully elucidated...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29659520/comparative-microrna-seq-analysis-depicts-candidate-mirnas-involved-in-skin-color-differentiation-in-red-tilapia
#16
Lanmei Wang, Wenbin Zhu, Zaijie Dong, Feibiao Song, Juanjuan Dong, Jianjun Fu
Differentiation and variation in body color has been a growing limitation to the commercial value of red tilapia. Limited microRNA (miRNA) information is available on skin color differentiation and variation in fish so far. In this study, a high-throughput Illumina sequencing of sRNAs was conducted on three color varieties of red tilapia and 81,394,491 raw reads were generated. A total of 158 differentially expressed miRNAs (|log₂(fold change)| &ge; 1 and q -value &le; 0.001) were identified. Target prediction and functional analysis of color-related miRNAs showed that a variety of putative target genes&mdash;including slc7a11 , mc1r and asip &mdash;played potential roles in pigmentation...
April 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29659163/synthesis-characterization-and-initial-biological-evaluation-of-99m-tc-tc-tricarbonyl-labeled-dpa-%C3%AE-msh-peptide-derivatives-for-potential-melanoma-imaging
#17
Feng Gao, Wiebke Sihver, Ralf Bergmann, Birgit Belter, Cristina Bolzati, Nicola Salvarese, Jörg Steinbach, Jens Pietzsch, Hans-Jürgen Pietzsch
α-Melanocyte stimulating hormone (α-MSH) derivatives target the melanocortin-1 receptor (MC1R) specifically and selectively. In this study, the α-MSH-derived peptide NAP-NS1 (Nle-Asp-His-d-Phe-Arg-Trp-Gly-NH2 ) with and without linkers was conjugated with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (DPA-COOH) and labeled with [99m Tc]Tc-tricarbonyl by two methods. With the one-pot method the labeling was faster than with the two-pot method, while obtaining similarly high yields. Negligible trans-chelation and high stability in physiological solutions was determined for the [99m Tc]Tc-tricarbonyl-peptide conjugates...
June 6, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29642438/sesamol-inhibited-melanogenesis-by-regulating-melanin-related-signal-transduction-in-b16f10-cells
#18
Po-Yuan Wu, Ya-Jhen You, Yi-Jung Liu, Chien-Wei Hou, Chin-Sheng Wu, Kuo-Ching Wen, Chien-Yih Lin, Hsiu-Mei Chiang
Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from melanogenesis has the protective effect of absorbing ultraviolet radiation. However, overproduction of melanin, in addition to altering the appearance of skin, may lead to skin disorders such as melasma, solar lentigo, and postinflammatory hyperpigmentation...
April 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29622793/camp-independent-non-pigmentary-actions-of-variant-melanocortin-1-receptor-akt-mediated-activation-of-protective-responses-to-oxidative-dna-damage
#19
María Castejón-Griñán, Cecilia Herraiz, Conchi Olivares, Celia Jiménez-Cervantes, Jose Carlos García-Borrón
The melanocortin 1 receptor gene (MC1R), a well-established melanoma susceptibility gene, regulates the amount and type of melanin pigments formed within epidermal melanocytes. MC1R variants associated with increased melanoma risk promote the production of photosensitizing pheomelanins as opposed to photoprotective eumelanins. Wild-type (WT) MC1R activates DNA repair and antioxidant defenses in a cAMP-dependent fashion. Since melanoma-associated MC1R variants are hypomorphic in cAMP signaling, these non-pigmentary actions are thought to be defective in MC1R-variant human melanoma cells and epidermal melanocytes, consistent with a higher mutation load in MC1R-variant melanomas...
April 6, 2018: Oncogene
https://www.readbyqxmd.com/read/29605997/development-of-novel-melanocortin-receptor-agonists-based-on-the-cyclic-peptide-framework-of-sunflower-trypsin-inhibitor-1
#20
Thomas Durek, Philipp M Cromm, Andrew M White, Christina I Schroeder, Quentin Kaas, Joachim Weidmann, Abdullah Ahmad Fuaad, Olivier Cheneval, Peta J Harvey, Norelle L Daly, Yang Zhou, Anita Dellsén, Torben Österlund, Niklas Larsson, Laurent Knerr, Udo Bauer, Horst Kessler, Minying Cai, Victor J Hruby, Alleyn T Plowright, David J Craik
Ultrastable cyclic peptide frameworks offer great potential for drug design due to their improved bioavailability compared to their linear analogues. Using the sunflower trypsin inhibitor-1 (SFTI-1) peptide scaffold in combination with systematic N-methylation of the grafted pharmacophore led to the identification of novel subtype selective melanocortin receptor (MCR) agonists. Multiple bicyclic peptides were synthesized and tested toward their activity at MC1R and MC3-5R. Double N-methylated compound 18 showed a p Ki of 8...
April 26, 2018: Journal of Medicinal Chemistry
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