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https://www.readbyqxmd.com/read/28449123/capturing-a-mammalian-dna-polymerase-extending-from-an-oxidized-nucleotide
#1
Amy M Whitaker, Mallory R Smith, Matthew A Schaich, Bret D Freudenthal
The oxidized nucleotide, 8-oxo-7,8-dihydro-2΄-deoxyguanosine (8-oxoG), is one of the most abundant DNA lesions. 8-oxoG plays a major role in tumorigenesis and human disease. Biological consequences of 8-oxoG are mediated in part by its insertion into the genome, making it essential to understand how DNA polymerases handle 8-oxoG. Insertion of 8-oxoG is mutagenic when opposite adenine but not when opposite cytosine. However, either result leads to DNA damage at the primer terminus (3΄-end) during the succeeding insertion event...
April 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28448902/surface-modified-tio2-nanoparticles-with-ascorbic-acid-antioxidant-properties-and-efficiency-against-dna-damage-in-vitro
#2
Vladan Bajić, Biljana Spremo-Potparević, Lada Živković, Andrea Čabarkapa, Jelena Kotur-Stevuljević, Esma Isenović, Dušan Sredojević, Ivana Vukoje, Vesna Lazić, S Phillip Ahrenkiel, Jovan M Nedeljković
The antigenotoxic and antioxidative properties of surface-modified TiO2 nanoparticles (NPs) with ascorbic acid (AA) were compared with those of constituents (free AA and bare TiO2 NPs). Colloids consisting of the TiO2 NPs with anatase crystal structure were prepared by acidic hydrolysis of TiCl4. The synthesized TiO2 NPs were characterized using transmission electron microscopy and X-ray diffraction analysis. The charge transfer (CT) complex formation between surface Ti atoms and AA is indicated by immediate appearance of red color...
April 14, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28448866/function-of-microrna-143-in-different-signal-pathways-in-cancer-new-insights-into-cancer-therapy
#3
REVIEW
Leila Karimi, Behzad Mansoori, Dariush Shanebandi, Ali Mohammadi, Mahyar Aghapour, Behzad Baradaran
MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28448742/choreography-of-parental-histones-in-damaged-chromatin
#4
Juliette Dabin, Sophie E Polo
In the cell nucleus, DNA repair machineries operate on a chromatin substrate, whose integrity is key for preserving cell functions and identity. Yet, it is still unclear how the epigenetic information conveyed by chromatin is maintained during the DNA repair process. We recently characterized the dynamics of parental histones coupled to UV-C damage repair in human cells, providing insights into how the pre-damage chromatin state may be restored. Here, we summarize our main findings and discuss them in the context of epigenome maintenance following DNA damage...
February 23, 2017: Nucleus
https://www.readbyqxmd.com/read/28448462/targeting-the-atr-chk1-axis-in-cancer-therapy
#5
REVIEW
Stuart Rundle, Alice Bradbury, Yvette Drew, Nicola J Curtin
Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation...
April 27, 2017: Cancers
https://www.readbyqxmd.com/read/28448444/role-of-the-vanins-myeloperoxidase-axis-in-colorectal-carcinogenesis
#6
REVIEW
Francesco Mariani, Luca Roncucci
The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS) and mutagenic species...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28448084/dna-damage-copper-and-lead-associates-with-cognitive-function-among-older-adults
#7
A Meramat, N F Rajab, S Shahar, R A Sharif
BACKGROUND: A cross sectional study was conducted in a group of 317 subjects older than 60 in Malaysia, aimed to determine risk factors associated with cognitive impairment in older adults, focusing on trace elements and DNA damage. METHOD: Cognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28448050/single-molecule-analysis-of-laser-localized-psoralen-adducts
#8
Jing Huang, Himabindu Gali, Julia Gichimu, Marina A Bellani, Durga Pokharel, Manikandan Paramasivam, Michael M Seidman
The DNA Damage Response (DDR) has been extensively characterized in studies of double strand breaks (DSBs) induced by laser micro beam irradiation in live cells. The DDR to helix distorting covalent DNA modifications, including interstrand DNA crosslinks (ICLs), is not as well defined. We have studied the DDR stimulated by ICLs, localized by laser photoactivation of immunotagged psoralens, in the nuclei of live cells. In order to address fundamental questions about adduct distribution and replication fork encounters, we combined laser localization with two other technologies...
April 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28448022/development-of-an-economical-dna-delivery-system-by-acufection-and-its-application-to-skin-research
#9
Yu-Jei Lin, Tsung-Lin Lee, Chia-Chi Ku
Dysregulation of immune response in skin is associated with numerous human skin disorders. Direct transfer of immune-related genes into skin tissue is a fascinating approach to investigate immune modulation of cutaneous inflammation in mouse models of human diseases. Here we present a cost-effective protocol that delivered naked DNA in mouse skin and leads to transgene expression. The method is coined "acufection", denoting acupuncture-mediated DNA transfection. To perform acufection, mouse skin was first infused with DNA in phosphate-buffered saline (PBS) and then pricked lightly with a bundle of acupuncture needles to facilitate the absorption of DNA and transfection into cells...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447907/nanotherapy-of-cancer-by-photoelectrons-emitted-from-the-surface-of-nanoparticles-exposed-to-nonionizing-ultraviolet-radiation
#10
Renat R Letfullin, Thomas F George
AIM: We introduce a new method for selectively destroying cancer cell organelles by electrons emitted from the surface of intracellularly localized nanoparticles exposed to the nonionizing ultraviolet (UV) radiation. METHODS: We propose to target cancerous intracellular organelles by nanoparticles and expose them to UV radiation with energy density safe for healthy tissue. RESULTS: We simulate the number of photoelectrons produced by the nanoparticles made of various metals and radii, calculate their kinetic energy and compare it to the threshold energy for producing biological damage...
April 27, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28447739/neural-precursor-cell-expressed-developmentally-downregulated-8%C3%A2-activating-enzyme-inhibitor-mln4924-sensitizes-colorectal-cancer-cells-to-oxaliplatin-by-inducing-dna-damage-g2-cell-cycle-arrest-and-apoptosis
#11
Wanwei Zheng, Zhongguang Luo, Jun Zhang, Pei Min, Wenshuai Li, Diannan Xu, Ziqiang Zhang, Panpan Xiong, Hong Liang, Jie Liu
Oxaliplatin-based chemotherapy is a primary treatment for patients with metastatic colorectal cancer (CRC); however, its efficacy is limited. Therefore, novel therapeutic agents are urgently required. MLN4924 is a first‑in‑class inhibitor of neural precursor cell expressed, developmentally downregulated 8 (NEDD8)‑activating enzyme E1, and has entered various phase‑I/II clinical trials for cancer therapy due to its significant anticancer efficacy. The aim of the present study was to examine the synergistic effect and underlying mechanisms of MLN4924 and oxaliplatin combined treatment for CRC...
March 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447610/parp3-is-a-promoter-of-chromosomal-rearrangements-and-limits-g4-dna
#12
Tovah A Day, Jacob V Layer, J Patrick Cleary, Srijoy Guha, Kristen E Stevenson, Trevor Tivey, Sunhee Kim, Anna C Schinzel, Francesca Izzo, John Doench, David E Root, William C Hahn, Brendan D Price, David M Weinstock
Chromosomal rearrangements are essential events in the pathogenesis of both malignant and nonmalignant disorders, yet the factors affecting their formation are incompletely understood. Here we develop a zinc-finger nuclease translocation reporter and screen for factors that modulate rearrangements in human cells. We identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell types. We focus on PARP3 as it is dispensable for murine viability and has druggable catalytic activity...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447517/hepatoprotective-potential-of-phyllanthus-muellarianus-leaf-extract-studies-on-hepatic-oxidative-stress-and-inflammatory-biomarkers
#13
Taofeek O Ajiboye, Fatimah M Ahmad, Airat O Daisi, Aminat A Yahaya, Oluwayemisi B Ibitoye, Hamdalat F Muritala, Taofik O Sunmonu
CONTEXT: Leaves of Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) are widely used in the management of liver disorders in Nigeria. However, no there is no scientific validation to support this use. OBJECTIVE: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was investigated in acetaminophen-induced liver injury mice. MATERIALS AND METHODS: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was evaluated in acetaminophen-induced hepatic damage in Swiss albino mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28447447/nuclear-targeting-gold-nanorods-for-extremely-low-nir-activated-photothermal-therapy
#14
Limin Pan, Jianan Liu, Jianlin Shi
Photo-related nanomedicine is of particular interest as an emerging paradigm toward precise cancer therapy, as demonstrated by the recent developments of photothermal therapy (PTT), an emerging technique employing light converting agents to burn cancerous cells by over-dosed optical energy-converted heat. However, most of the laser irradiations needed for effective PTT significantly exceed the maximal permissible power density in human skin, which is likely to damage surrounding normal tissues. Herein, we report a strategy of intranuclear PTT of cancer enabled by nuclear-targeted delivery of gold nanorods of ~ 10...
April 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28447339/activity-of-anti-inflammatory-analgesic-and-antigenotoxic-of-the-aqueous-flower-extracts-of-opuntia-microdasys-lem-pfeiff
#15
Hassiba Chahdoura, Safia El Bok, Taoufik Refifa, Khaoula Adouni, Fethia Khemiss, Habib Mosbah, Mossadok Ben-Attia, Guido Flamini, Lotfi Achour
OBJECTIVES: The aim of this study was to evaluate the analgesic and the anti-inflammatory activity of Opuntia microdasys at post flowering stage, F3 (OMF3) in rat and, in other hand, its antigenotoxic effects by the Allium cepa test. METHODS: OMF3 extracts were screened for activity of analgesic and anti-inflammatory using, respectively, the acetic acid writhing test in mice and the carrageenan-induced paw oedema assay in rats. The antigenotoxic has been evaluated by A...
April 26, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28446826/a-systematic-and-mechanistic-review-on-the-phytopharmacological-properties-of-alhagi-species
#16
REVIEW
Mohammad Hossein Asghari, Marjan Fallah, Milad Moloudizargari, Fatemeh Mehdikhani, Peyman Sepehrnia, Bigard Moradi
Alhagi species are well known in Iran (locally known as Khar Shotor) and other parts of Asia as a popular folk medicine. Recent research has shown extensive pharmacological effects of these species. This paper is a comprehensive review of the phytopharmacological effects and traditional uses of Alhagi species and their active constituents with special attention to the responsible mechanisms, effective dosages and routes of administration. The Alhagi species studied in this paper include: A. maurorum, A. camelorum, A...
October 2016: Ancient Science of Life
https://www.readbyqxmd.com/read/28446751/crl4b-dcaf11-e3-ligase-targets-p21-for-degradation-to-control-cell-cycle-progression-in-human-osteosarcoma-cells
#17
Zhi Chen, Kun Wang, Canglong Hou, Kaibiao Jiang, Bin Chen, Jianwei Chen, Lifeng Lao, Lie Qian, Guibin Zhong, Zude Liu, Caiguo Zhang, Hongxing Shen
Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446681/minute-virus-of-mice-mvm-inhibits-transcription-of-the-cyclin-b1-gene-during-infection
#18
Matthew S Fuller, Kinjal Majumder, David J Pintel
Replication of minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus then exploits to prepare the nuclear environment for effective parvovirus takeover. An essential aspect of the MVM-induced DDR is the establishment of a potent pre-mitotic block, which we previously found to be independent of activated p21 and ATR/Chk1 signaling. This arrest, unlike others previously reported, depends upon the significant, specific depletion of cyclin B1 and its encoding RNA, which precludes cyclin B1/CDK1 complex function thus preventing mitotic entry...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446670/collateral-damage-during-dengue-virus-infection-making-sense-of-dna-by-cgas
#19
Sebastian Aguirre, Ana Fernandez-Sesma
Early sensing of viral components or infection-induced tissue damage, is a prerequisite for the successful control of pathogenic viruses by the host innate immune system. Recent results from our laboratory show how immune cells use the DNA sensing machinery to detect intracellular damage generated early during infection with an RNA virus, namely dengue virus (DENV). Conversely, we found that DENV can efficiently dismantle this sensing mechanism by targeting the cyclic GMP-AMP synthase (cGAS) and the stimulator of interferon gene (STING); two crucial host factors involved in DNA detection and type I interferon (IFN) production...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446595/dna-damage-signaling-mediates-the-functional-antagonism-between-replicative-senescence-and-terminal-muscle-differentiation
#20
Lucia Latella, Alessandra Dall'Agnese, Francesca Boscolo Sesillo, Chiara Nardoni, Marianna Cosentino, Armin Lahm, Alessandra Sacco, Pier Lorenzo Puri
The molecular determinants of muscle progenitor impairment to regenerate aged muscles are currently unclear. We show that, in a mouse model of replicative senescence, decline in muscle satellite cell-mediated regeneration coincides with activation of DNA damage response (DDR) and impaired ability to differentiate into myotubes. Inhibition of DDR restored satellite cell differentiation ability. Moreover, in replicative human senescent fibroblasts, DDR precluded MYOD-mediated activation of the myogenic program...
April 1, 2017: Genes & Development
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