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https://www.readbyqxmd.com/read/28346906/long-term-exposure-to-high-air-pollution-induces-cumulative-dna-damages-in-traffic-policemen
#1
Chaochao Tan, Shijie Lu, Yupeng Wang, Yan Zhu, Ting Shi, Mingyue Lin, Zhonghua Deng, Zhu Wang, Nana Song, Shuna Li, Pingting Yang, Liyan Yang, Yuanyuan Liu, Zhiheng Chen, Keqian Xu
The specific effects of long-term exposure to high air pollution on human health and biological remain unclear. To explore the adverse health effects as well as biological mechanisms and biomarkers for durative exposure to air pollution, 183 traffic policemen and 88 office policemen were enrolled in this study. The concentration of PM2.5 in both the traffic and office policemen's working environments were obtained. Detailed personal questionnaires were completed and levels of inflammation, oxidative stress and DNA damage markers of all participants were analyzed in this study...
March 24, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28346709/synthetic-%C3%AE-nitrostyrene-derivative-cyt-rx20-as-inhibitor-of-oral-cancer-cell-proliferation-and-tumor-growth-through-glutathione-suppression-and-reactive-oxygen-species-induction
#2
Yen-Yun Wang, Yuk-Kwan Chen, Ya-Ling Hsu, Wen-Chin Chiu, Chun-Hao Tsai, Stephen Chu-Sung Hu, Pei-Wen Hsieh, Shyng-Shiou F Yuan
BACKGROUND: The β-nitrostyrene family possesses anticancer properties. In this study, β-nitrostyrene derivative CYT-Rx20 (3'-hydroxy-4'-methoxy-β-methyl-β-nitrostyrene) was synthesized and investigated its anticancer activity in oral cancer. METHODS: Anticancer activity of CYT-Rx20 and the underlying mechanisms were analyzed using cell viability assay, reactive oxygen species (ROS) generation assay, fluorescence-activated cell sorter analysis, annexin V staining, comet assay, glutathione (GSH)/glutathione disulfide (GSSG) ratio, immunoblotting, soft agar assay, nude mice xenograft study, and immunohistochemistry...
March 27, 2017: Head & Neck
https://www.readbyqxmd.com/read/28346693/using-a-novel-nqo1-bioactivatable-drug-beta-lapachone-arq761-to-enhance-chemotherapeutic-effects-by-metabolic-modulation-in-pancreatic-cancer
#3
Muhammad Shaalan Beg, Xiumei Huang, Molly A Silvers, David E Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J Deberardinis, Matthew E Merritt, Xian-Jin Xie, Richard Leff, Daniel Laheru, David A Boothman
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H2 O2 ) levels; normal tissues are spared by low NQO1 and high catalase expression...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28346524/rare-mutations-and-potentially-damaging-missense-variants-in-genes-encoding-fibrillar-collagens-and-proteins-involved-in-their-production-are-candidates-for-risk-for-preterm-premature-rupture-of-membranes
#4
Bhavi P Modi, Maria E Teves, Laurel N Pearson, Hardik I Parikh, Piya Chaemsaithong, Nihar U Sheth, Timothy P York, Roberto Romero, Jerome F Strauss
Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth with ~ 40% of preterm births being associated with PPROM and occurs in 1% - 2% of all pregnancies. We hypothesized that multiple rare variants in fetal genes involved in extracellular matrix synthesis would associate with PPROM, based on the assumption that impaired elaboration of matrix proteins would reduce fetal membrane tensile strength, predisposing to unscheduled rupture. We performed whole exome sequencing (WES) on neonatal DNA derived from pregnancies complicated by PPROM (49 cases) and healthy term deliveries (20 controls) to identify candidate mutations/variants...
2017: PloS One
https://www.readbyqxmd.com/read/28346474/the-microrna-205-5p-is-correlated-to-metastatic-potential-of-21t-series-a-breast-cancer-progression-model
#5
L Stankevicins, A Barat, P Dessen, Y Vassetzky, C V de Moura Gallo
MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression...
2017: PloS One
https://www.readbyqxmd.com/read/28346446/dengue-virus-ns2b-protein-targets-cgas-for-degradation-and-prevents-mitochondrial-dna-sensing-during-infection
#6
Sebastian Aguirre, Priya Luthra, Maria T Sanchez-Aparicio, Ana M Maestre, Jenish Patel, Francise Lamothe, Anthony C Fredericks, Shashank Tripathi, Tongtong Zhu, Jessica Pintado-Silva, Laurence G Webb, Dabeiba Bernal-Rubio, Alexander Solovyov, Benjamin Greenbaum, Viviana Simon, Christopher F Basler, Lubbertus C F Mulder, Adolfo García-Sastre, Ana Fernandez-Sesma
During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection...
March 27, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28346444/genetic-variants-associated-with-mosaic-y-chromosome-loss-highlight-cell-cycle-genes-and-overlap-with-cancer-susceptibility
#7
Daniel J Wright, Felix R Day, Nicola D Kerrison, Florian Zink, Alexia Cardona, Patrick Sulem, Deborah J Thompson, Svanhvit Sigurjonsdottir, Daniel F Gudbjartsson, Agnar Helgason, J Ross Chapman, Steve P Jackson, Claudia Langenberg, Nicholas J Wareham, Robert A Scott, Unnur Thorsteindottir, Ken K Ong, Kari Stefansson, John R B Perry
The Y chromosome is frequently lost in hematopoietic cells, which represents the most common somatic alteration in men. However, the mechanisms that regulate mosaic loss of chromosome Y (mLOY), and its clinical relevance, are unknown. We used genotype-array-intensity data and sequence reads from 85,542 men to identify 19 genomic regions (P < 5 × 10(-8)) that are associated with mLOY. Cumulatively, these loci also predicted X chromosome loss in women (n = 96,123; P = 4 × 10(-6)). Additional epigenome-wide methylation analyses using whole blood highlighted 36 differentially methylated sites associated with mLOY...
March 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28346378/dna-repair-pathway-alterations-in-bladder-cancer
#8
REVIEW
Kent W Mouw
Most bladder tumors have complex genomes characterized by a high mutation burden as well as frequent copy number alterations and chromosomal rearrangements. Alterations in DNA repair pathways-including the double-strand break (DSB) and nucleotide excision repair (NER) pathways-are present in bladder tumors and may contribute to genomic instability and drive the tumor phenotype. DNA damaging such as cisplatin, mitomycin C, and radiation are commonly used in the treatment of muscle-invasive or metastatic bladder cancer, and several recent studies have linked specific DNA repair pathway defects with sensitivity to DNA damaging-based therapy...
March 27, 2017: Cancers
https://www.readbyqxmd.com/read/28346321/growth-arrest-and-dna-damage-inducible-protein-45%C3%AE-mediated-dna-demethylation-of-voltage-dependent-t-type-calcium-channel-3-2-subunit-enhances-neuropathic-allodynia-after-nerve-injury-in-rats
#9
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, An-Sheng Lee, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Growth arrest and DNA-damage-inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage-inducible protein 45β-dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. METHODS: Adult male Sprague-Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage-inducible protein 45β messenger RNA-targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage-inducible protein 45β, Ro 25-6981 (an NR2B-bearing N-methyl-D-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings...
March 27, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28345889/ape1-accelerates-turnover-of-hogg1-by-preventing-retrograde-binding-to-the-abasic-site-product
#10
Alexandre Esadze, Gaddiel Rodriguez, Shannen Lee Cravens, James T Stivers
A major product of oxidative DNA damage is 8-oxoguanine. In humans, 8-oxoguanine DNA Glycosylase (hOGG1) facilitates removal of these lesions, producing an abasic (AP) site in the DNA that is subsequently incised by AP-endonuclease 1 (APE1). APE1 stimulates turnover of several glycosylases by accelerating rate-limiting product release. However, there have been conflicting accounts of whether hOGG1 follows a similar mechanism. In pre-steady state kinetic measurements, we found that addition of APE1 had no effect on the rapid burst phase of 8-oxoguanine excision by hOGG1, but accelerated steady-state turnover (kcat) by ~10-fold...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28345663/nuclear-localization-of-beclin-1-promotes-radiation-induced-dna-damage-repair-independent-of-autophagy
#11
Fei Xu, Yixuan Fang, Lili Yan, Lan Xu, Suping Zhang, Yan Cao, Li Xu, Xiaoying Zhang, Jialing Xie, Gaoyue Jiang, Chaorong Ge, Ni An, Daohong Zhou, Na Yuan, Jianrong Wang
Beclin 1 is a well-established core mammalian autophagy protein that is embryonically indispensable and has been presumed to suppress oncogenesis via an autophagy-mediated mechanism. Here, we show that Beclin 1 is a prenatal primary cytoplasmic protein but rapidly relocated into the nucleus during postnatal development in mice. Surprisingly, deletion of beclin1 in in vitro human cells did not block an autophagy response, but attenuated the expression of several DNA double-strand break (DSB) repair proteins and formation of repair complexes, and reduced an ability to repair DNA in the cells exposed to ionizing radiation (IR)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345622/comprehensive-track-structure-based-evaluation-of-dna-damage-by-light-ions-from-radiotherapy-relevant-energies-down-to-stopping
#12
W Friedland, E Schmitt, P Kundrát, M Dingfelder, G Baiocco, S Barbieri, A Ottolenghi
Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25-256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345606/53bp1-contributes-to-regulation-of-autophagic-clearance-of-mitochondria
#13
Cha Kyung Youn, Hong Beum Kim, Ting Ting Wu, Sanggon Park, Sung Il Cho, Jung-Hee Lee
Autophagy, the primary recycling pathway within cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the cellular response to stress. Here we provide evidence that 53BP1, a DNA damage response protein, is involved in regulating mitochondrial clearance from the cell via a type of autophagy termed mitophagy. We found that when either human or mouse cells were 53BP1-deficient, there was an increase in mitochondrial abnormalities, as observed through staining intensity, aggregation, and increased mass...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345531/polyphenols-in-preventing-endothelial-dysfunction
#14
Sylwia Biegańska-Hensoldt, Danuta Rosołowska-Huszcz
One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions. Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties...
March 27, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28345375/the-chemo-prophylactic-efficacy-of-an-ethanol-moringa-oleifera-leaf-extract-against-hepatocellular-carcinoma-in-rats
#15
Kadry M Sadek, Tarek K Abouzed, Reham Abouelkhair, Sherif Nasr
CONTEXT: Hepatocellular carcinoma (HCC) is among the most well-known threatening tumours around the world, and the outlook remains bleak. Moringa oleifera Lam. (Moringaceae) exhibits antitumor, antioxidant and hepatoprotective properties. OBJECTIVES: To assess the chemo-prophylactic proficiency and other likely activities of Moringa oleifera leaf ethanol extract (MOLEE) against diethyl nitrosamine (DEN)-induced HCC. MATERIALS AND METHODS: Wistar rats were gastrogavaged with MOLEE (500 mg/kg) for one week and then gastrogavaged with MOLEE and DEN (10 mg/kg) for the following 16 weeks...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28345297/residual-cdk1-2-activity-after-dna-damage-promotes-senescence
#16
Erik Müllers, Helena Silva Cascales, Kamila Burdova, Libor Macurek, Arne Lindqvist
In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage until terminal cell cycle exit. This low level of Cdk activity not only allows cell cycle progression, but also promotes cell cycle exit at a decision point in G2 phase. We find that residual Cdk1/2 activity is required for efficient p21 production, allowing for nuclear sequestration of Cyclin B1, subsequent APC/C(C)(dh1) -dependent degradation of mitotic inducers and induction of senescence...
March 26, 2017: Aging Cell
https://www.readbyqxmd.com/read/28345120/fission-yeast-srm1-is-involved-in-stress-response-and-cell-cycle
#17
Aslıhan Örs Gevrekci
Polyamines are well-conserved, multifunctional polycations that contribute to a number of processes in the cells such as cell cycle, apoptosis, stress response, and gene expression. Therefore, polyamine levels should be kept under strict regulation by specific polyamine transporters and polyamine synthases. In this study, the aim is to experimentally characterize a predicted spermidine synthase gene srm1, which was identified upon sequence similarity, in fission yeast Schizosaccharomyces pombe. In an attempt to understand the role of this gene in cell cycle and stress response, deletion mutant of srm1 was generated and analyzed in terms of cell cycle regulation and environmental stress response...
March 27, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28344868/langerhans-cells-and-nk-cells-cooperate-in-the-inhibition-of-chemical-skin-carcinogenesis
#18
Daniela Ortner, Christoph H Tripp, Kerstin Komenda, Sandrine Dubrac, Bernhard Zelger, Martin Hermann, Wolfgang Doppler, Piotr Z Tymoszuk, Louis Boon, Björn E Clausen, Patrizia Stoitzner
Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the initiation of chemical carcinogenesis with DMBA remain elusive. Here, we discovered that natural killer (NK) cells and Langerhans cells (LC) cooperate to impair this oncogenic process in murine skin...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344198/radiosensitizing-effect-of-p2x7-receptor-antagonist-on-melanoma-in-vitro-and-in-vivo
#19
Keisuke Tanamachi, Keisuke Nishino, Natsuki Mori, Toshihiro Suzuki, Sei-Ichi Tanuma, Ryo Abe, Mitsutoshi Tsukimoto
Melanoma is highly malignant, and generally exhibits radioresistance, responding poorly to radiation therapy. We previously reported that activation of P2X7, P2Y6, and P2Y12 receptors is involved in the DNA damage response after γ-irradiation of human lung adenocarcinoma A549 cells. However, it is not clear whether these receptors are also involved in the case of melanoma cells, although P2X7 receptor is highly expressed in various cancers, including melanoma. Here, we show that P2X7 receptor antagonist enhances radiation-induced cytotoxicity in B16 melanoma cells in vitro and in vivo...
March 24, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28343997/dna-double-strand-breaks-and-aurora-b-mislocalization-induced-by-exposure-of-early-mitotic-cells-to-h2o2-appear-to-increase-chromatin-bridges-and-resultant-cytokinesis-failure
#20
Min-Guk Cho, Ju-Hyun Ahn, Hee-Song Choi, Jae-Ho Lee
Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated. Here, using time-lapse analysis of asynchronously growing cells and immunocytochemical analyses of synchronized cells, we found that hydrogen peroxide (H2O2) treatment at early mitosis (primarily prometaphase) significantly induced cytokinesis failure...
March 24, 2017: Free Radical Biology & Medicine
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