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https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#1
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#2
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27891208/endogenous-n-3-fatty-acids-alleviate-carbon-tetrachloride-induced-acute-liver-injury-in-fat-1-transgenic-mice
#3
Ruibing Feng, Meng Wang, Chunyan Yan, Peng Li, Meiwan Chen, Chengwei He, Jian-Bo Wan
n-3 polyunsaturated fatty acids (PUFAs) are beneficial for numerous models of liver diseases. The probable protective effects of n-3 PUFA against carbon-tetrachloride- (CCl4-) induced acute liver injury were evaluated in a fat-1 transgenic mouse that synthesizes endogenous n-3 from n-6 PUFA. Fat-1 mice and their WT littermates were fed a modified AIN93 diet containing 10% corn oil and were injected intraperitoneally with a single dose of CCl4 or vehicle. CCl4 challenge caused severe liver injury in WT mice, as indicated by serum parameters and histopathological changes, which were remarkably ameliorated in fat-1 mice...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27889639/sulforaphane-is-a-nrf2-independent-inhibitor-of-mitochondrial-fission
#4
Gary B O'Mealey, William L Berry, Scott M Plafker
The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN), an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1) cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1...
November 21, 2016: Redox Biology
https://www.readbyqxmd.com/read/27888130/protective-role-of-phenylalanine-on-the-ros-induced-oxidative-damage-apoptosis-and-tight-junction-damage-via-nrf2-tor-and-nf-%C3%AE%C2%BAb-signalling-molecules-in-the-gill-of-fish
#5
Lin Feng, Wen Li, Yang Liu, Wei-Dan Jiang, Sheng-Yao Kuang, Pei Wu, Jun Jiang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study explored the possible preventive effects of dietary phenylalanine (Phe) on antioxidant responses, apoptosis and tight junction protein transcription in the gills of young grass carp (Ctenopharyngodon idella). Fish were fed six different experimental diets containing graded levels of Phe (3.4-16.8 g kg(-1)) for 8 weeks. The results showed that Phe deficiency induced protein oxidation and lipid peroxidation by decreasing the glutathione content and the activities and mRNA levels of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) in fish gill (P < 0...
November 23, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27854327/visualization-of-oxidative-stress-induced-by-experimental-periodontitis-in-keap1-dependent-oxidative-stress-detector-luciferase-mice
#6
Kota Kataoka, Daisuke Ekuni, Takaaki Tomofuji, Koichiro Irie, Muneyoshi Kunitomo, Yoko Uchida, Daiki Fukuhara, Manabu Morita
The aim of this study was to investigate whether a Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mouse model would be useful for the visualization of oxidative stress induced by experimental periodontitis. A ligature was placed around the mandibular first molars for seven days to induce periodontitis. Luciferase activity was measured with an intraperitoneal injection of d-luciferin on days 0, 1, and 7. The luciferase activity in the periodontitis group was significantly greater than that in the control group at seven days...
November 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27853236/regulation-of-sirt1-nrf2-tnf-%C3%AE-signaling-pathway-by-luteolin-is-critical-to-attenuate-acute-mercuric-chloride-exposure-induced-hepatotoxicity
#7
Daqian Yang, Xiao Tan, Zhanjun Lv, Biying Liu, Ruiqi Baiyun, Jingjing Lu, Zhigang Zhang
Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27847554/nrf2-and-notch-signaling-in-lung-cancer-near-the-crossroad
#8
REVIEW
Angelo Sparaneo, Federico Pio Fabrizio, Lucia Anna Muscarella
The transcription factor Nrf2 (NF-E2 related factor 2) is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements) in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27832175/rnai-screen-for-nrf2-inducers-identifies-targets-that-rescue-primary-lung-epithelial-cells-from-cigarette-smoke-induced-radical-stress
#9
Frances-Rose Schumacher, Steffen Schubert, Michael Hannus, Birte Sönnichsen, Carina Ittrich, Stefan Kreideweiss, Thimo Kurz, Jörg F Rippmann
Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent condition characterized by inflammation and progressive obstruction of the airways. At present, there is no treatment that suppresses the chronic inflammation of the disease, and COPD patients often succumb to the condition. Excessive oxidative stress caused by smoke inhalation is a major driving force of the disease. The transcription factor NRF2 is a critical player in the battle against oxidative stress and its function is impaired in COPD...
2016: PloS One
https://www.readbyqxmd.com/read/27825853/nrf2-signaling-pathway-pivotal-roles-in-inflammation
#10
REVIEW
Syed Minhaj Uddin Ahmed, Lin Luo, Akhileshwar Namani, Xiu Jun Wang, Xiuwen Tang
Inflammation is the most common feature of many chronic diseases and complications, while playing critical roles in carcinogenesis. Several studies have demonstrated that Nrf2 contributes to the anti-inflammatory process by orchestrating the recruitment of inflammatory cells and regulating gene expression through the antioxidant response element (ARE). The Keap1 (Kelch-like ECH-associated protein)/Nrf2 (NF-E2 p45-related factor 2)/ARE signaling pathway mainly regulates anti-inflammatory gene expression and inhibits the progression of inflammation...
November 4, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27824068/sulforaphane-improves-ischemia-induced-detrusor-overactivity-by-downregulating-the-enhancement-of-associated-endoplasmic-reticulum-stress-autophagy-and-apoptosis-in-rat-bladder
#11
Huai-Ching Tai, Shiu-Dong Chung, Chiang-Ting Chien, Hong-Jeng Yu
Atherosclerosis-associated pelvic ischemia has been reported to be a risk factor for bladder dysfunction and subsequent lower urinary tract symptoms (LUTS) in the elderly population. However, the molecular mechanisms of this association remain unclear. We hypothesized that stress-induced cellular responses might play a role in the pathogenesis of ischemia-induced bladder dysfunction. In the present study, the animal model of bladder ischemia was induced by bilateral partial arterial occlusion (BPAO) in rats...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821350/exposure-to-mercuric-chloride-induces-developmental-damage-oxidative-stress-and-immunotoxicity-in-zebrafish-embryos-larvae
#12
Qun-Fang Zhang, Ying-Wen Li, Zhi-Hao Liu, Qi-Liang Chen
Mercury (Hg) is a widespread environmental pollutant that can produce severe negative effects on fish even at very low concentrations. However, the mechanisms underlying inorganic Hg-induced oxidative stress and immunotoxicity in the early development stage of fish still need to be clarified. In the present study, zebrafish (Danio rerio) embryos were exposed to different concentrations of Hg(2+) (0, 1, 4 and 16μg/L; added as mercuric chloride, HgCl2) from 2h post-fertilization (hpf) to 168hpf. Developmental parameters and total Hg accumulation were monitored during the exposure period, and antioxidant status and the mRNA expression of genes related to the innate immune system were examined at 168hpf...
December 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27816475/proteomics-analysis-of-dendritic-cell-activation-by-contact-allergens-reveals-possible-biomarkers-regulated-by-nrf2
#13
Franz Mussotter, Janina Melanie Tomm, Zeina El Ali, Marc Pallardy, Saadia Kerdine-Römer, Mario Götz, Martin von Bergen, Andrea Haase, Andreas Luch
Allergic contact dermatitis is a widespread disease with high clinical relevance affecting approximately 20% of the general population. Typically, contact allergens are low molecular weight electrophilic compounds which can activate the Keap1/Nrf2 pathway. We performed a proteomics study to reveal possible biomarkers for dendritic cell (DC) activation by contact allergens and to further elucidate the role of Keap1/Nrf2 signaling in this process. We used bone marrow derived dendritic cells (BMDCs) of wild-type (nrf2(+/+)) and Nrf2 knockout (nrf2(-/-)) mice and studied their response against the model contact sensitizers 2,4-dinitrochlorobenzene (DNCB), cinnamaldehyde (CA) and nickel(II) sulfate by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS)...
December 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27815660/mitochondrial-phosphatase-pgam5-regulates-keap1-mediated-bcl-xl-degradation-and-controls-cardiomyocyte-apoptosis-driven-by-myocardial-ischemia-reperfusion-injury
#14
Chen Yang, Xiaojuan Liu, Fangfang Yang, Weixun Zhang, Zihao Chen, Daliang Yan, Qingsheng You, Xiang Wu
Phosphoglycerate mutase 5 (PGAM5) is a mitochondrial membrane protein that plays crucial roles in necroptosis and apoptosis. Though PGAM5 is known to be required for inducing intrinsic apoptosis through interacting with BCL2 associated X protein (Bax) and dynamin-related protein 1 (Drp1), the expression and role of PGAM5 in cardiomyocyte apoptosis driven by myocardial ischemia/reperfusion injury(MIRI) has not been studied. The present study shows that PGAM5 expression decreased after MIRI in vivo, positively correlated with Bcl-xL expression, negatively correlated with Kelch-ECH associating protein 1 (Keap1) expression...
November 4, 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27814396/chronic-activation-of-hepatic-nrf2-has-no-major-effect-on-fatty-acid-and-glucose-metabolism-in-adult-mice
#15
Sebastian Brachs, Angelika F Winkel, James Polack, Hui Tang, Maria Brachs, Daniel Margerie, Bodo Brunner, Kerstin Jahn-Hofmann, Hartmut Ruetten, Joachim Spranger, Dieter Schmoll
The transcription factor NF-E2-related factor 2 (Nrf2) induces cytoprotective genes, but has also been linked to the regulation of hepatic energy metabolism. In order to assess the pharmacological potential of hepatic Nrf2 activation in metabolic disease, Nrf2 was activated over 7 weeks in mice on Western diet using two different siRNAs against kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2. Whole genome expression analysis followed by pathway analysis demonstrated successful knock-down of Keap1 expression and induction of Nrf2-dependent genes involved in anti-oxidative stress defense and biotransformation, proving the activation of Nrf2 by the siRNAs against Keap1...
2016: PloS One
https://www.readbyqxmd.com/read/27806574/ado-keto-reductase-regulation-by-the-nrf2-system-implications-for-stress-response-chemotherapy-drug-resistance-and-carcinogenesis
#16
Trevor M Penning
Human Aldo-Keto Reductases are NAD(P)H dependent oxidoreductases that convert aldehydes and ketones to primary and secondary alcohols for subsequent conjugation reactions and can be referred to as "phase 1" enzymes. Among all the human genes regulated by the Keap1/Nrf2 pathway they are consistently the most overexpressed in response to Nrf2 activators. While these enzymes play clear cytoprotective roles and deal effectively with carbonyl stress, their up-regulation by the Keap1/Nrf2 pathway also has a potential dark-side, which can lead to chemotherapeutic drug resistance, and the metabolic activation of lung carcinogens (e...
November 3, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27805827/nrf2-activation-as-a-key-event-triggered-by-skin-sensitisers-the-development-of-the-stable-keratinosens-reporter-gene-assay
#17
REVIEW
Andreas Natsch, Roger Emter
The 21st century paradigm for toxicology and the adverse outcome pathway concept envisage a future toxicology largely based on mechanistic in vitro assays and relying mainly on cellular models. In the skin sensitisation field, this concept was not intuitive at the beginning. Given the high structural diversity of skin sensitising molecules, classical receptor binding as the molecular initiating event in a cell-based assay could be excluded from the start, leaving the question of how cells could sense potential skin sensitising chemicals and be able to differentiate them from non-sensitisers...
October 2016: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/27804998/keap1-hypomorphism-protects-against-ischemic-and-obstructive-kidney-disease
#18
Roderick J Tan, Dionysios V Chartoumpekis, Brittney M Rush, Dong Zhou, Haiyan Fu, Thomas W Kensler, Youhua Liu
The Keap1/Nrf2 pathway is a master regulator of antioxidant, anti-inflammatory, and other cytoprotective mechanisms important in protection from kidney disease. For the first time in kidney disease, we describe the use of Keap1 hypomorphic mice, which possess Nrf2 hyperactivation. We exposed these mice and wild type controls to ischemia/reperfusion injury (IRI). The initial tubular injury at 24 hours post-IRI appeared to be unaffected, with the only observed difference being a decrease in inflammatory cytokine expression in the hypomorphs...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799074/activation-of-the-keap1-nrf2-stress-response-pathway-in-autophagic-vacuolar-myopathies
#19
Steve Duleh, Xianhong Wang, Allison Komirenko, Marta Margeta
Nrf2 (nuclear factor [erythroid-derived 2]-like 2; the transcriptional master regulator of the antioxidant stress response) is regulated through interaction with its cytoplasmic inhibitor Keap1 (Kelch-like ECH-associated protein 1), which under basal conditions targets Nrf2 for proteasomal degradation. Sequestosome 1 (SQSTM1)/p62-a multifunctional adapter protein that accumulates following autophagy inhibition and can serve as a diagnostic marker for human autophagic vacuolar myopathies (AVMs)-was recently shown to compete with Nrf2 for Keap1 binding, resulting in activation of the Nrf2 pathway...
October 31, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27781231/genistein-promotes-the-metabolic-transformation-of-acetaminophen-to-glucuronic-acid-in-human-l-o2-hepg2-and-hep3b-cells-via-the-nrf2-keap1-pathway
#20
Fan Yuan-Jing, Wei Wei, Luo Jian-Ping, Jin Yu-Xia, Dai Zi-Ling
This study aimed to explore the effects of genistein on regulating the activation of UGTs via the Nrf2/Keap1 pathway and to elucidate the underlying mechanisms of detoxification and hepatic protection. Experiments monitoring genistein-induced protection against acetaminophen-induced cell damage were performed in L-02, HepG2 and Hep3b cells. The results of the MTT, AST, ALT, LDH, GSH and GSSG assays showed that genistein evidently protected the cells from acetaminophen-induced injury in a dose-dependent manner...
October 26, 2016: Food & Function
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