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Hiroyasu Sakai, Ken Sato, Fumiaki Sato, Yuki Kai, Kazutaka Mandokoro, Kenjiro Matsumoto, Shinichi Kato, Tetsuro Yumoto, Minoru Narita, Yoshihiko Chiba
OBJECTIVES: Contact dermatitis model involving repeated application of hapten is used as a tool to assess dermatitis, as characterized by thickening. Involvement of cell proliferation, elicited by repeated hapten-stimulation, in this swelling has been unclear. Curcumin is reported to reduce inflammation. We examined involvement of cell proliferation and the role of extracellular regulated kinase (ERK) in 2,4,6-trinitrochlorobenzene (TNCB) challenge-induced ear swelling. We also examined the effects of curcumin in this model...
April 12, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Keith M Godfrey, Wayne Cutfield, Shiao-Yng Chan, Philip N Baker, Yap-Seng Chong
BACKGROUND: Improved maternal nutrition and glycaemic control before and during pregnancy are thought to benefit the health of the mother, with consequent benefits for infant body composition and later obesity risk. Maternal insulin resistance and glycaemia around conception and in early pregnancy may be key determinants of maternal physiology and placental function, affecting fetal nutrient supply and maternal-feto-placental communications throughout gestation, with implications for later postnatal health...
March 20, 2017: Trials
Janelle Mapes, Quanxi Li, Athilakshmi Kannan, Lavanya Anandan, Mary Laws, John P Lydon, Indrani C Bagchi, Milan K Bagchi
In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1), expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation...
March 2017: PLoS Genetics
Yadav Wagley, Ping-Yee Law, Li-Na Wei, Horace H Loh
Since the discovery of μ-opioid receptor (MOR) gene two decades ago, various regulatory factors have been shown to interact with the MOR promoter and modulate transcript levels. However, the majority of early transcriptional studies on MOR gene have not addressed how intracellular signaling pathways mediate extracellular modulators. In this study, we demonstrate that MOR epigenetic regulation requires multiple coordinated signals converging at the MOR promoter, involving mitogen-activated protein kinase (MAPK) activation and mitogen- and stress-activated protein kinase 1 (MSK1)-ranges of intracellular signaling pathways similar to those activated by opioid agonists...
April 2017: Molecular Pharmacology
Said Khelwatty, Sharadah Essapen, Izhar Bagwan, Margaret Green, Alan Seddon, Helmout Modjtahedi
Anti-EGFR mAbs cetuximab and panitumumab are routinely used for the treatment of patients with KRAS-wild type metastatic colorectal cancer (mCRC). However, in some patients their efficacy remains modest and with no clear association between the EGFR protein expression determined by PharmDx™ kit, and response to anti-EGFR therapies. Therefore, we investigated the relative expression and predictive value of wild-type EGFR (wtEGFR), mutated EGFRvIII and EGFR ligand proteins in mCRC patients treated with cetuximab...
January 31, 2017: Oncotarget
Bhuminder Singh, Graham Carpenter, Robert J Coffey
Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN). Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR...
2016: F1000Research
Jeffrey S Boyles, Shane Atwell, Zhanna Druzina, Josef G Heuer, Derrick R Witcher
Recent studies have implicated a role of the epidermal growth factor receptor (EGFR) pathway in kidney disease. Skin toxicity associated with therapeutics which completely block the EGFR pathway precludes their use in chronic dosing. Therefore, we developed antibodies which specifically neutralize the EGFR ligands TGFα (transforming growth factor-alpha) and epiregulin but not EGF (epidermal growth factor), amphiregulin, betacellulin, HB-EGF (heparin-binding epidermal growth factor), or epigen. The epitope of one such neutralizing antibody, LY3016859, was characterized in detail to elucidate the structural basis for ligand specificity...
November 2016: Protein Science: a Publication of the Protein Society
Lenka Tesarova, Pavel Simara, Stanislav Stejskal, Irena Koutna
The potential clinical applications of human induced pluripotent stem cells (hiPSCs) are limited by genetic and epigenetic variations among hiPSC lines and the question of their equivalency with human embryonic stem cells (hESCs). We used MethylScreen technology to determine the DNA methylation profile of pluripotency and differentiation markers in hiPSC lines from different source cell types compared to hESCs and hiPSC source cells. After derivation, hiPSC lines compromised a heterogeneous population characterized by variable levels of aberrant DNA methylation...
2016: PloS One
Kylie Vuong, Bruce K Armstrong, Elisabete Weiderpass, Eiliv Lund, Hans-Olov Adami, Marit B Veierod, Jennifer H Barrett, John R Davies, D Timothy Bishop, David C Whiteman, Catherine M Olsen, John L Hopper, Graham J Mann, Anne E Cust, Kevin McGeechan
IMPORTANCE: Identifying individuals at high risk of melanoma can optimize primary and secondary prevention strategies. OBJECTIVE: To develop and externally validate a risk prediction model for incident first-primary cutaneous melanoma using self-assessed risk factors. DESIGN, SETTING, AND PARTICIPANTS: We used unconditional logistic regression to develop a multivariable risk prediction model. Relative risk estimates from the model were combined with Australian melanoma incidence and competing mortality rates to obtain absolute risk estimates...
August 1, 2016: JAMA Dermatology
Juliette Dabin, Anna Fortuny, Sophie E Polo
Organism viability relies on the stable maintenance of specific chromatin landscapes, established during development, that shape cell functions and identities by driving distinct gene expression programs. Yet epigenome maintenance is challenged during transcription, replication, and repair of DNA damage, all of which elicit dynamic changes in chromatin organization. Here, we review recent advances that have shed light on the specialized mechanisms contributing to the restoration of epigenome structure and function after DNA damage in the mammalian cell nucleus...
June 2, 2016: Molecular Cell
Andrew X Zhu, Yoon-Koo Kang, Olivier Rosmorduc, T R Jeffry Evans, Armando Santoro, Paul Ross, Edward Gane, Arndt Vogel, Michael Jeffers, Gerold Meinhardt, Carol E A Peña
PURPOSE: Sorafenib is the current standard therapy for advanced hepatocellular carcinoma, but validated biomarkers predicting clinical outcomes are lacking. This study aimed to identify biomarkers predicting prognosis and/or response to sorafenib, with or without erlotinib, in hepatocellular carcinoma patients from the phase III SEARCH trial. EXPERIMENTAL DESIGN: A total of 720 patients were randomized to receive oral sorafenib 400 mg twice daily plus erlotinib 150 mg once daily or placebo...
October 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
M Fernanda Lima-Costa, James Macinko, Juliana Vaz de Mello Mambrini, Sérgio Viana Peixoto, Alexandre Costa Pereira, Eduardo Tarazona-Santos, Antonio Luiz Pinho Ribeiro
BACKGROUND: The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged ≥ 60 years) of the Bambui (Brazil) population-based cohort study of aging...
May 2016: PLoS Neglected Tropical Diseases
Elena Loche, Susan E Ozanne
Obesity and its related metabolic comorbidities can be inherited across generations through non-genetic mechanisms. In a recent report, Huypens et al., using an in vitro fertilization approach, provide evidence that exposure to a high-fat diet modifies egg and sperm epigenetic information, rendering the progeny more prone to obesity.
June 2016: Trends in Endocrinology and Metabolism: TEM
Tom Ronan, Jennifer L Macdonald-Obermann, Lorel Huelsmann, Nicholas J Bessman, Kristen M Naegle, Linda J Pike
The EGF receptor can bind seven different agonist ligands. Although each agonist appears to stimulate the same suite of downstream signaling proteins, different agonists are capable of inducing distinct responses in the same cell. To determine the basis for these differences, we used luciferase fragment complementation imaging to monitor the recruitment of Cbl, CrkL, Gab1, Grb2, PI3K, p52 Shc, p66 Shc, and Shp2 to the EGF receptor when stimulated by the seven EGF receptor ligands. Recruitment of all eight proteins was rapid, dose-dependent, and inhibited by erlotinib and lapatinib, although to differing extents...
March 11, 2016: Journal of Biological Chemistry
Weihua Wen, Lin Lu, Yuefeng He, Huirong Cheng, Fang He, Shuqiao Cao, Liang Li, Li Xiong, Tangchun Wu
Arsenic (As) metabolites could induce methylation changes of DNA and base modifications of p53, which play role in the toxicity of As. LincRNAs should play a key regulatory role in the p53 transcriptional response. There were 43 workers producing As trioxide, 36 workers who stopped exposure to As trioxide about 85 days ago, and 24 individuals as control group. Three As species in urine were measured, and primary and secondary methylation indexes, iAs%, MMA% and DMA% were calculated. RT-PCR was performed to detect the expression of 7 LincRNAs and the base modifications of exon 5, 6, 7, and 8 of p53...
February 25, 2016: Chemico-biological Interactions
M Fernanda Lima-Costa, Juliana Vaz de Mello Mambrini, Maria Lea Corrêa Leite, Sérgio Viana Peixoto, Josélia Oliveira Araújo Firmo, Antônio Ignácio de Loyola Filho, Mateus H Gouveia, Thiago P Leal, Alexandre Costa Pereira, James Macinko, Eduardo Tarazona-Santos
The study objective is to examine the role of African genome origin on baseline and 11-year blood pressure trajectories in community-based ethnoracially admixed older adults in Brazil. Data come from 1272 participants (aged ≥60 years) of the Bambui cohort study of aging during 11 years of follow-up. Outcome measures were systolic blood pressure, diastolic blood pressure, and hypertension control. Potential confounding variables were demographic characteristics, socioeconomic position (schooling and household income), and health indicators (smoking, sedentary lifestyle, high-density lipoprotein cholesterol, waist circumference, diabetes mellitus, and cardiovascular diseases), including antihypertensive drug use...
February 2016: Hypertension
M Fernanda Lima-Costa, James Macinko, Juliana Vaz de Melo Mambrini, Cibele C Cesar, Sérgio V Peixoto, Wagner C S Magalhães, Bernardo L Horta, Mauricio Barreto, Erico Castro-Costa, Josélia O A Firmo, Fernando A Proietti, Thiago Peixoto Leal, Maira R Rodrigues, Alexandre Pereira, Eduardo Tarazona-Santos
BACKGROUND: Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. MATERIALS/METHODS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians...
2015: PloS One
Gauri M Ugale, Nagaraj B Kalburgi, Shivaprasad Bilichodmath, Shivaraj B Warad, Mahesh S Ugale, Arati C Koregol, Shobha C Bijjargi
BACKGROUND: The host immune response to bacterial dental plaque determines periodontal disease susceptibility by increasing the secretion of inflammatory cytokines. The Epidermal Growth Factor family cytokines stimulate proliferation and keratinization of cells in dermis and oral epithelium. Epidermal Growth Factor family consists of Amphiregulin, Betacellulin, Epiregulin, Epigen, Heparin binding Epidermal Growth Factor like growth factor and transforming Growth Factor-alpha. AIM: The current study aimed to investigate expression of Betacellulin in chronic periodontitis patients with and without type 2 diabetes mellitus and thereby assessing role of betacellulin in periodontal health and disease...
November 2015: Journal of Clinical and Diagnostic Research: JCDR
Yong Li, Stefan W Stoll, Sahil Sekhon, Caroline Talsma, Maya I Camhi, Jennifer L Jones, Sylviane Lambert, Hue Marley, Laure Rittié, Marina Grachtchouk, Yi Fritz, Nicole L Ward, James T Elder
To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5' and 3' untranslated region sequences (AREG-UTR) led to a >10-fold increase in hAREG expression compared to an otherwise-identical construct containing only the coding region (AREG-CDR). AREG-UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG-CDR mice...
March 2016: Experimental Dermatology
Bonnie Edwards, John Lesnick, Jing Wang, Nga Tang, Carl Peters
Epigenetics continues to emerge as an important target class for drug discovery and cancer research. As programs scale to evaluate many new targets related to epigenetic expression, new tools and techniques are required to enable efficient and reproducible high-throughput epigenetic screening. Assay miniaturization increases screening throughput and reduces operating costs. Echo liquid handlers can transfer compounds, samples, reagents, and beads in submicroliter volumes to high-density assay formats using only acoustic energy-no contact or tips required...
February 2016: Journal of Laboratory Automation
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