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https://www.readbyqxmd.com/read/28099491/death-of-monocytes-through-oxidative-burst-of-macrophages-and-neutrophils-killing-in-trans
#1
Viviane Ponath, Bernd Kaina
Monocytes and their descendants, macrophages, play a key role in the defence against pathogens. They also contribute to the pathogenesis of inflammatory diseases. Therefore, a mechanism maintaining a balance in the monocyte/macrophage population must be postulated. Our previous studies have shown that monocytes are impaired in DNA repair, rendering them vulnerable to genotoxic stress while monocyte-derived macrophages are DNA repair competent and genotoxic stress-resistant. Based on these findings, we hypothesized that monocytes can be selectively killed by reactive oxygen species (ROS) produced by activated macrophages...
2017: PloS One
https://www.readbyqxmd.com/read/28098415/intracranial-aav-ifn-%C3%AE-gene-therapy-eliminates-invasive-xenograft-glioblastoma-and-improves-survival-in-orthotopic-syngeneic-murine-model
#2
Dwijit GuhaSarkar, James Neiswender, Qin Su, Guangping Gao, Miguel Sena-Esteves
The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard-of-care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon-beta (IFN-β) gene therapy by locally administered adeno-associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models...
November 9, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#3
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28095450/non-lytic-egression-of-infectious-bursal-disease-virus-ibdv-particles-from-infected-cells
#4
Fernando Méndez, Nicolás Romero, Liliana L Cubas, Laura R Delgui, Dolores Rodríguez, José F Rodríguez
Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is responsible for a devastating immunosuppressive disease affecting juvenile domestic chickens. IBDV particles are naked icosahedrons enclosing a bipartite double-stranded RNA genome harboring three open reading frames (ORF). One of these ORFs codes for VP5, a non-structural polypeptide dispensable for virus replication in tissue culture but essential for IBDV pathogenesis. Using two previously described recombinant viruses, whose genomes differ in a single nucleotide, expressing or not the VP5 polypeptide, we have analyzed the role of this polypeptide during the IBDV replication process...
2017: PloS One
https://www.readbyqxmd.com/read/28087073/abnormal-mortality-of-octopus-after-a-storm-water-event-accumulated-lead-and-lead-isotopes-as-fingerprints
#5
J Raimundo, F Ruano, J Pereira, M Mil-Homens, P Brito, C Vale, M Caetano
Octopus vulgaris is a sedentary organism that inhabits coastal waters being exposed to anthropogenic compounds. Lead concentration in coastal environments reflects many processes and activities namely weathering, industrial and domestic discharges, and atmospheric deposition. Since lead isotopic composition is little affected by kinetic processes occurring between source and sink, its signature has been used to identify different Pb sources. After a short-term heavy rainfall, hundreds of octopus appeared dead in two Portuguese coastal areas...
January 10, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28081154/sensitization-of-radioresistant-prostate-cancer-cells-by-resveratrol-isolated-from-arachis-hypogaea-stems
#6
Yu-An Chen, Hsiu-Man Lien, Min-Chuan Kao, U-Ging Lo, Li-Chiung Lin, Chun-Jung Lin, Sheau-Jiun Chang, Chia-Chang Chen, Jer-Tsong Hsieh, Ho Lin, Chih-Hsin Tang, Chih-Ho Lai
Resveratrol (RV, 3,4',5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28079299/a-platinum-blue-complex-exerts-its-cytotoxic-activity-via-dna-damage-and-induces-apoptosis-in-cancer-cells
#7
Zelal Adiguzel, Seniz Ozalp-Yaman, Gokalp Celik, Safia Salem, Tugba Bagci-Onder, Filiz Senbabaoglu, Yüksel Cetin, Ceyda Acilan
Here, we describe the characteristics of a Pt-blue complex [Pt4 (2-atp)8 (H2 O)(OH)] (2-atp: 2-aminothiophenol) as a prodrug for its DNA-binding properties and its use in cancer therapy. The nature of the interaction between the Pt-blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single and double stranded breaks (DBS) on DNA in vitro, but no DSBs in cells...
January 12, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#8
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28077781/effects-of-an-unusual-poison-identify-a-lifespan-role-for-topoisomerase-2-in-saccharomyces-cerevisiae
#9
Gregory Tombline, Jonathan I Millen, Bogdan Polevoda, Matan Rapaport, Bonnie Baxter, Michael Van Meter, Matthew Gilbertson, Joe Madrey, Gary A Piazza, Lynn Rasmussen, Krister Wennerberg, E Lucile White, John L Nitiss, David S Goldfarb
A progressive loss of genome maintenance has been implicated as both a cause and consequence of aging. Here we present evidence supporting the hypothesis that an age-associated decay in genome maintenance promotes aging in Saccharomyces cerevisiae (yeast) due to an inability to sense or repair DNA damage by topoisomerase 2 (yTop2). We describe the characterization of LS1, identified in a high throughput screen for small molecules that shorten the replicative lifespan of yeast. LS1 accelerates aging without affecting proliferative growth or viability...
January 5, 2017: Aging
https://www.readbyqxmd.com/read/28077560/mechanistic-insights-into-type-i-toxin-antitoxin-systems-in-helicobacter-pylori-the-importance-of-mrna-folding-in-controlling-toxin-expression
#10
Hélène Arnion, Dursun Nizam Korkut, Sara Masachis Gelo, Sandrine Chabas, Jérémy Reignier, Isabelle Iost, Fabien Darfeuille
Type I toxin-antitoxin (TA) systems have been identified in a wide range of bacterial genomes. Here, we report the characterization of a new type I TA system present on the chromosome of the major human gastric pathogen, Helicobacter pylori We show that the aapA1 gene encodes a 30 amino acid peptide whose artificial expression in H. pylori induces cell death. The synthesis of this toxin is prevented by the transcription of an antitoxin RNA, named IsoA1, expressed on the opposite strand of the toxin gene. We further reveal additional layers of post-transcriptional regulation that control toxin expression: (i) transcription of the aapA1 gene generates a full-length transcript whose folding impedes translation (ii) a 3' end processing of this message generates a shorter transcript that, after a structural rearrangement, becomes translatable (iii) but this rearrangement also leads to the formation of two stem-loop structures allowing formation of an extended duplex with IsoA1 via kissing-loop interactions...
January 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28070110/melatonin-suppresses-methamphetamine-triggered-endoplasmic-reticulum-stress-in-c6-cells-glioma-cell-lines
#11
Wanida Tungkum, Pichaya Jumnongprakhon, Chainarong Tocharus, Piyarat Govitrapong, Jiraporn Tocharus
Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28068995/mobility-as-a-predictor-of-all-cause-mortality-in-older-men-and-women-11-8%C3%A2-year-follow-up-in-the-troms%C3%A3-study
#12
Astrid Bergland, Lone Jørgensen, Nina Emaus, Bjørn Heine Strand
BACKGROUND: Disability in older adults is associated with loss of independence, institutionalization, and death. The aim of this study was to study the association between the Timed Up and Go (TUG) test and all-cause mortality in a population-based sample of older men and women. METHODS: Our study population was home dwellers aged 65 and above, who participated in the fifth wave of the Tromsø study. This study included the TUG test and a range of lifestyle and mortality predictors...
January 10, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28068427/s1-type-endonuclease-2-in-dedifferentiating-arabidopsis-protoplasts-translocation-to-the-nucleus-in-senescing-protoplasts-is-associated-with-de-glycosylation
#13
Yemima Givaty-Rapp, Narendra Singh Yadav, Asif Khan, Gideon Grafi
Cell dedifferentiation characterizes the transition of leaf cells to protoplasts and is accompanied by global chromatin decondensation. Here we show that in Arabidopsis, chromocentric chromatin undergoes prompt and gradual decondensation upon protoplasting. We hypothesized that prompt chromatin decondensation is unlikely to be driven solely by epigenetic means and other factors might be involved. We investigated the possibility that S1-type endonucleases are involved in prompt chromatin decondensation via their capability to target and cleave unpaired regions within superhelical DNA, leading to chromatin relaxation...
2017: PloS One
https://www.readbyqxmd.com/read/28061446/%C3%AE-40p53-is-involved-in-the-inactivation-of-autophagy-and-contributes-to-inhibition-of-cell-death-in-hct116-%C3%AE-40p53-cells
#14
Yunjin Zang, Ying Shi, Kai Liu, Luxin Qiao, Xianghua Guo, Dexi Chen
Δ40p53 is an isoform of wild-type p53 (wtp53). Here, we assessed whether Δ40p53 has the same functions as wild-type p53 in the regulation of cell death and autophagy. First, we used HCT116 (p53+/+) and H1299 (p53-free) cells to produce two cell lines (HCT116-Δ40p53 and H1299-Δ40p53) that express exogenous Δ40p53 but not wtp53. By using these cell lines, we determined that Δ40p53 inhibited starvation-induced autophagy, as does wtp53. This inhibition arises from both Δ40p53 and wtp53 having 3'-5' exonuclease activity, which reduces the levels of double-stranded RNA (dsRNA) and then inhibits PKR/eIF2α-induced autophagy in cells exposed to starvation...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061443/mhy1485-ameliorates-uv-induced-skin-cell-damages-via-activating-mtor-nrf2-signaling
#15
Bo Yang, Qiu-Yun Xu, Chun-Yan Guo, Jin-Wen Huang, Shu-Mei Wang, Yong-Mei Li, Ying Tu, Li He, Zhi-Gang Bi, Chao Ji, Bo Cheng
Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060411/scarless-cas9-assisted-recombineering-no-scar-in-escherichia-coli-an-easy-to-use-system-for-genome-editing
#16
Christopher R Reisch, Kristala L J Prather
The discovery and development of genome editing systems that leverage the site-specific DNA endonuclease system CRISPR/Cas9 has fundamentally changed the ease and speed of genome editing in many organisms. In eukaryotes, the CRISPR/Cas9 system utilizes a "guide" RNA to enable the Cas9 nuclease to make a double-strand break at a particular genome locus, which is repaired by non-homologous end joining (NHEJ) repair enzymes, often generating random mutations in the process. A specific alteration of the target genome can also be generated by supplying a DNA template in vivo with a desired mutation, which is incorporated by homology-directed repair...
January 5, 2017: Current Protocols in Molecular Biology
https://www.readbyqxmd.com/read/28059653/sulforaphane-suppresses-the-growth-of-glioblastoma-cells-glioblastoma-stem-cell-like-spheroids-and-tumor-xenografts-through-multiple-cell-signaling-pathways
#17
Khadijeh Bijangi-Vishehsaraei, M Reza Saadatzadeh, Haiyan Wang, Angie Nguyen, Malgorzata M Kamocka, Wenjing Cai, Aaron A Cohen-Gadol, Stacey L Halum, Jann N Sarkaria, Karen E Pollok, Ahmad R Safa
OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28051860/cytotoxicity-and-mechanism-of-action-of-the-marine-derived-fungal-metabolite-trichodermamide-b-and-synthetic-analogues
#18
Petra E Jans, Adelphe M Mfuh, Hadi D Arman, Corena V Shaffer, Oleg V Larionov, Susan L Mooberry
The trichodermamides are modified dipeptides isolated from a wide variety of fungi, including Trichoderma virens. Previous studies reported that trichodermamide B (2) initiated cytotoxicity in HCT-116 colorectal cancer cells, while trichodermamide A (1) was devoid of activity. We recently developed an efficient total synthesis for the trichodermamides A-C (1-3). Multiple intermediates and analogues were produced, and they were evaluated for biological effects to identify additional structure-activity relationships and the possibility that a simplified analogue would retain the biological effects of 2...
January 4, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28049740/resolvase-osgen1-mediates-dna-repair-by-homologous-recombination
#19
Chong Wang, James Higgins, Yi He, Pingli Lu, Dabing Zhang, Wanqi Liang
Yen1/GEN1 are canonical Holliday Junction (HJ) resolvases that belong to the RAD2/XPG family. In eukaryotes, such as budding yeast, mice, worms, and humans, Yen1/GEN1 work together with Mus81-Mms4/MUS81-EME1 and Slx1-Slx4/SLX1-SLX4 in DNA repair by homologous recombination to maintain genome stability. In plants, the biological function of Yen1/GEN1 remains largely unclear. In this study, we characterized the loss of function mutants of OsGEN1 and OsSEND1, a pair of paralogs of Yen1/GEN1 in rice. We first investigated the role of OsGEN1 during meiosis and found a reduction in chiasma frequency by ~6% in osgen1 mutants, compared to wild type, suggesting a possible involvement of OsGEN1 in the formation of crossovers...
January 3, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28049724/endonuclease-eepd1-is-a-gatekeeper-for-repair-of-stressed-replication-forks
#20
Hyun-Suk Kim, Jac A Nickoloff, Yuehan Wu, Elizabeth A Williamson, Gurjit Singh Sidhu, Brian L Reinert, Aruna S Jaiswal, Gayathri Srinivasan, Bhavita Patel, Kimi Kong, Sandeep Burma, Suk-Hee Lee, Robert A Hromas
Replication is not as continuous as once thought, with DNA damage frequently stalling replication forks. Aberrant repair of stressed replication forks can result in cell death or genome instability and resulting transformation to malignancy. Stressed replication forks are most commonly repaired via homologous recombination (HR), which begins with end resection, mediated by exonuclease complexes, one of which contains Exo1. However, Exo1 requires free DNA ends upon which to act, and these are not commonly present in non-reversed stalled replication forks...
January 3, 2017: Journal of Biological Chemistry
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