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Epigenetics skin

Mary Norval, Anna K Coussens, Robert J Wilkinson, Liza Bornman, Robyn M Lucas, Caradee Y Wright
In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor...
October 18, 2016: International Journal of Environmental Research and Public Health
Walter H Moos, Carl A Pinkert, Michael H Irwin, Douglas V Faller, Krishna Kodukula, Ioannis P Glavas, Kosta Steliou
Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population...
October 20, 2016: Drug Development Research
G L Uy, E J Duncavage, G S Chang, M A Jacoby, C A Miller, J Shao, S Heath, K Elliott, T Reinick, R S Fulton, C C Fronick, M O'Laughlin, L Ganel, C N Abboud, A F Cashen, J F DiPersio, R K Wilson, D C Link, J S Welch, T J Ley, T A Graubert, P Westervelt, M J Walter
Traditional response criteria in MDS and AML are based on bone marrow morphology and may not accurately reflect clonal tumor burden in patients treated with non-cytotoxic chemotherapy. We used next-generation sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced (exome or 285 gene panel). We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden (i...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Robert-Paul Juster, Jennifer J Russell, Daniel Almeida, Martin Picard
Stress-related pathophysiology drives comorbid trajectories that elude precise prediction. Allostatic load algorithms that quantify biological "wear and tear" represent a comprehensive approach to detect multisystemic disease processes of the mind and body. However, the multiple morbidities directly or indirectly related to stress physiology remain enigmatic. Our aim in this article is to propose that biological comorbidities represent discrete pathophysiological processes captured by measuring allostatic load...
November 2016: Development and Psychopathology
Anjit Sandhu, Sushil K Mohapatra, Himanshu Agrawal, Manoj K Singh, Prabhat Palta, Suresh K Singla, Manmohan S Chauhan, Radhey S Manik
Buffalo embryos were produced by hand-made cloning using skin fibroblasts from male and female buffaloes (n = 4 each) as donor cells for examining the effect of sex. Although the rate of blastocyst formation (43.8% ± 1.31% vs. 42.2% ± 1.22%) was similar, the total cell number (333 ± 10.4 vs. 270 ± 10.9) was higher (p < 0.05) whereas the apoptotic index (6.39 ± 0.25 vs. 8.52 ± 0.38) was lower (p < 0.05) for male than for female blastocysts. In the blastocysts, the global level of H3K18ac was found to be in the following order: male>female>IVF (in vitro fertilization) blastocysts (p < 0...
October 2016: Cellular Reprogramming
Gene H Brody, Tianyi Yu, Steven R H Beach
For the past quarter century, scientists at the Center for Family Research at the University of Georgia have conducted research designed to promote understanding of normative developmental trajectories among low socioeconomic status African American children, youths, and young adults. In this paper, we describe a recent expansion of this research program using longitudinal, epidemiological studies and randomized prevention trials to test hypotheses about the origins of disease among rural African American youths...
October 3, 2016: Development and Psychopathology
Aihua Zhang, Huiyao Li, Yun Xiao, Liping Chen, Xiaonian Zhu, Jun Li, Lu Ma, Xueli Pan, Wen Chen, Zhini He
OBJECTIVE: To define whether aberrant methylation of DNA repair genes is associated with chronic arsenic poisoning. METHODS: Hundred and two endemic arsenicosis patients and 36 healthy subjects were recruited. Methylight and bisulfite sequencing (BSP) assays were used to examine the methylation status of ERCC1, ERCC2 and XPC genes in peripheral blood lymphocytes (PBLs) and skin lesions of arsenicosis patients and NaAsO2-treated HaCaT cells. RESULTS: Hypermethylation of ERCC1 and ERCC2 and suppressed gene expression were found in PBLs and skin lesions of arsenicosis patients and was correlated with the level of arsenic exposure...
August 12, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Lien N Hoang, Amandeep Aneja, Niamh Conlon, Deborah F Delair, Sumit Middha, Ryma Benayed, Martee L Hensley, Kay J Park, Travis J Hollmann, Meera R Hameed, Cristina R Antonescu, Robert A Soslow, Sarah Chiang
Endometrial stromal sarcomas (ESS) are often underpinned by recurrent chromosomal translocations resulting in the fusion of genes involved in epigenetic regulation. To date, only YWHAE-NUTM2 rearrangements are associated with distinctive high-grade morphology and aggressive clinical behavior. We identified 3 ESS morphologically mimicking myxoid leiomyosarcoma of the uterus and sought to describe their unique histopathologic features and identify genetic alterations using next-generation sequencing. All cases displayed predominantly spindled cells associated with abundant myxoid stroma and brisk mitotic activity...
September 14, 2016: American Journal of Surgical Pathology
Wei-Ting Liao, Jian-He Lu, Chih-Hung Lee, Cheng-Che E Lan, Jan-Gowth Chang, Chee-Yin Chai, Hsin-Su Yu
Animal studies have shown that chemical carcinogenesis consists of a 3-stage process: initiation, promotion, and progression. However, due to the lack of a suitable tissue model, the molecular mechanisms of cell-cell interactions involved in those processes remain unclear. We have established a human intraepidermal carcinoma skin equivalent (SE) with organotypic culture - consisting of keratinocytes (KCs), fibroblasts, and peripheral blood mononuclear cells (PBMCs) - induced by arsenic treatment. This SE demonstrates the pathognomonic characteristics of arsenic-induced Bowen's disease (As-BD), including acanthosis, dysplasia, and dyskeratosis...
September 1, 2016: Journal of Investigative Dermatology
Aimee L Katen, Caitlin G Chambers, Brett Nixon, Shaun D Roman
Acute acrylamide exposure in male rodents results in reduced reproductive performance and dominant lethality. However, the reproductive effects of low dose chronic exposure, which better reflects the nature of human exposure, remain far less certain. Human dietary consumption of acrylamide has been estimated at an average of 1-4 µg/kg bw/day. In order to simulate this exposure, male mice were provided with acrylamide (1 µg/ml) via their drinking water continuously for six months, which was equivalent to a human dose of 10...
August 31, 2016: Biology of Reproduction
Fei Gao, Ningjie Ma, Hong Zhou, Qing Wang, Hao Zhang, Pu Wang, Haoli Hou, Huan Wen, Lijia Li
As an engineered nanomaterial, zinc oxide nanoparticles (ZnO NPs) are used frequently in biological applications and can make contact with human skin. Here, we systematically investigated the effects of ZnO NPs on non-tumorigenic human epidermal keratinocytes, which were used as a test model for this in vitro study, at the epigenetic and molecular levels. Our results showed that ZnO NPs induced cell cycle arrest at the G2/M checkpoint before the viability of human epidermal keratinocytes was reduced, which was associated with the chromatin changes at the epigenetic level, including increased methylation of histone H3K9 and decreased acetylation of histone H4K5 accompanied by chromatin condensation at 24 hours...
2016: International Journal of Nanomedicine
Zhixing Yao, Zaki A Sherif
The Li-Fraumeni Syndrome (LFS), a genetically rare heterogeneous cancer syndrome, is characterized primarily by a germline p53 (TP53) gene mutation. We recently discovered a balanced reciprocal chromosomal translocation t(11;15)(q23;q15) in the non-cancerous skin fibroblasts of a bilateral breast cancer patient in LFS family. This prompted us to investigate the breakpoint region of the translocation, which uncovered a gene that encodes a Notch ligand, DLL4, (locus at 15q15.1), a key target in tumor vasculature...
August 16, 2016: Oncotarget
Chengyue Zhang, Zheng-Yuan Su, Ling Wang, Limin Shu, Yuqing Yang, Yue Guo, Douglas Pung, Chas Bountra, Ah-Ng Kong
The neoplastic transformation of cells and inflammation are processes that contribute to tumor initiation. Recently, emerging evidence has suggested that epigenetic alterations are also implicated in the early stages of carcinogenesis. Therefore, potent small molecules targeting epigenetic regulators have been developed as novel cancer therapeutic and preventive strategies. Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that play key roles at the interface between chromatin modification and transcriptional regulation...
October 1, 2016: Biochemical Pharmacology
Justyna Podolak-Popinigis, Anna Ronowicz, Monika Dmochowska, Agnieszka Jakubiak, Paweł Sachadyn
AIM: Fetal skin is known to heal without scarring. In mice, the phenomenon is observed until the 16-17 day of gestation - the day of transition from scarless to normal healing. The study aims to identify key methylome and transcriptome changes following the transition. MATERIALS & METHODS: Methylome and transcriptome profiles were analyzed in murine dorsal skin using microarray approach. RESULTS & CONCLUSION: The genes associated with inflammatory response and hyaluronate degradation showed increased DNA methylation before the transition, while those involved in embryonic morphogenesis, neuron differentiation and synapse functions did so after...
October 2016: Epigenomics
Jun-Han Lee, Joo-Hyung Lee, Sang Hyuk Lee, Sung Im Do, Sung-Dae Cho, Ola Forslund, Kyung-Soo Inn, Jeong-Sang Lee, Fang-Ming Deng, Jonathan Melamed, Jae U Jung, Joseph H Jeong
Squamous cell carcinoma (SCC) and keratoacanthoma (KA) (SCC/KA) research has been hampered mainly by our lack of understanding the underlying genetic and epigenetic alterations associated with SCC/KA development, as well as the lack of animal models that faithfully recapitulate histopathological features of human SCC/KA. Here, we show that TPL2 overexpression induced both cell transformation in immortalized human keratinocytes and SCC and KA-like cutaneous SCC (cSCC) development in mice. Mechanistically, activation of TPL2 downstream signaling pathways such as MEK/ERK MAPK, mTOR, NF-κB and p38 MAPK leads to TPL2-mediated cell transformation in immortalized human keratinocytes and tumorigenesis in mice...
August 8, 2016: Cancer Research
Anastasia Petrova, Antonio Capalbo, Laureen Jacquet, Simon Hazelwood-Smith, Dimitra Dafou, Carl Hobbs, Matthew Arno, Alessio Farcomeni, Liani Devito, Heba Badraiq, Michael Simpson, John A McGrath, Wei-Li Di, Jeffrey B Cheng, Theodora M Mauro, Dusko Ilic
The epigenetic background of pluripotent stem cells can influence transcriptional and functional behavior. Most of these data have been obtained in standard monolayer cell culture systems. In this study, we used exome sequencing, array comparative genomic hybridization (CGH), miRNA array, DNA methylation array, three-dimensional (3D) tissue engineering, and immunostaining to conduct a comparative analysis of two induced pluripotent stem cell (iPSC) lines used in engineering of 3D human epidermal equivalent (HEE), which more closely approximates epidermis...
September 15, 2016: Stem Cells and Development
Agustí Toll, Rocío Salgado, Blanca Espinet, Angel Díaz-Lagares, Eugenia Hernández-Ruiz, Evelyn Andrades, Juan Sandoval, Manel Esteller, Ramón M Pujol, Inmaculada Hernández-Muñoz
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and frequently progresses from an actinic keratosis (AK), a sun-induced keratinocyte intraepithelial neoplasia (KIN). Epigenetic mechanisms involved in the phenomenon of progression from AK to cSCC remain to be elicited. METHODS: Expression of microRNAs in sun-exposed skin, AK and cSCC was analysed by Agilent microarrays. DNA methylation of miR-204 promoter was determined by bisulphite treatment and pyrosequencing...
2016: Molecular Cancer
Jaya Mary Thomas, Sumi Surendran, Mathew Abraham, Arumugam Rajavelu, Chandrasekharan C Kartha
Vascular malformations are developmental congenital abnormalities of the vascular system which may involve any segment of the vascular tree such as capillaries, veins, arteries, or lymphatics. Arteriovenous malformations (AVMs) are congenital vascular lesions, initially described as "erectile tumors," characterized by atypical aggregation of dilated arteries and veins. They may occur in any part of the body, including the brain, heart, liver, and skin. Severe clinical manifestations occur only in the brain...
2016: Clinical Epigenetics
Carolina N Perdigoto, Katherine L Dauber, Carmit Bar, Pai-Chi Tsai, Victor J Valdes, Idan Cohen, Francis J Santoriello, Dejian Zhao, Deyou Zheng, Ya-Chieh Hsu, Elena Ezhkova
An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles...
July 2016: PLoS Genetics
Liisa Nissinen, Mehdi Farshchian, Pilvi Riihilä, Veli-Matti Kähäri
Epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing worldwide. Solar UV radiation is an important risk factor for cSCC and leads to genetic and epigenetic changes both in epidermal keratinocytes and dermal cells. Tumor cells in cutaneous cSCCs typically harbor several driver gene mutations, but epidermal keratinocytes in sun-exposed normal skin also contain mutations in these same genes. Therefore, alterations in the microenvironment of premalignant lesions are evidently required for their progression to invasive and metastatic cSCC...
September 2016: Cell and Tissue Research
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