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https://www.readbyqxmd.com/read/29786770/the-extract-of-leonurus-sibiricus-transgenic-roots-with-atpap1-transcriptional-factor-induces-apoptosis-via-dna-damage-and-down-regulation-of-selected-epigenetic-factors-in-human-cancer-cells
#1
Przemysław Sitarek, Tomasz Kowalczyk, Simona Santangelo, Adam J Białas, Monika Toma, Joanna Wieczfinska, Tomasz Śliwiński, Ewa Skała
The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels...
May 21, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29786074/constitutive-interferon-signaling-maintains-critical-threshold-of-mlkl-expression-to-license-necroptosis
#2
Joseph Sarhan, Beiyun C Liu, Hayley I Muendlein, Chi G Weindel, Irina Smirnova, Amy Y Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A Fitzgerald, Alexander Poltorak
Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785486/radiation-induced-bystander-effect-in-large-japanese-field-mouse-apodemus-speciosus-embryonic-cells
#3
Kentaro Ariyoshi, Tomisato Miura, Kosuke Kasai, Nakata Akifumi, Yohei Fujishima, Mitsuaki A Yoshida
Although evidence suggests that ionizing radiation can induce the bystander effect (radiation-induced bystander effect: RIBE) in cultured cells or mouse models, it is unclear whether the effect occurs in cells of wild animals. We investigated medium-mediated bystander micronucleus (MN) formation and DNA damage in un-irradiated cells from a large Japanese field mouse (Apodemus speciosus). We isolated four clones of A. speciosus embryonic fibroblasts (A603-1, A603-2, A603-3, and A603-4) derived from the same mother, and examined their radiation sensitivity using the colony-forming assay...
May 22, 2018: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29785231/advantages-of-evaluating-%C3%AE-h2ax-induction-in-non-clinical-drug-development
#4
REVIEW
Shigeki Motoyama, Akira Takeiri, Kenji Tanaka, Asako Harada, Kaori Matsuzaki, Junko Taketo, Saori Matsuo, Etsuko Fujii, Masayuki Mishima
γH2AX, the phosphorylated form of a histone variant H2AX at Ser 139, is already widely used as a biomarker to research the fundamental biology of DNA damage and repair and to assess the risk of environmental chemicals, pollutants, radiation, and so on. It is also beginning to be used in the early non-clinical stage of pharmaceutical drug development as an in vitro tool for screening and for mechanistic studies on genotoxicity. Here, we review the available information on γH2AX-based test systems that can be used to develop drugs and present our own experience of practically applying these systems during the non-clinical phase of drug development...
2018: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/29785172/graft-versus-host-disease-from-basic-pathogenic-principles-to-dna-damage-response-and-cellular-senescence
#5
REVIEW
Adam Kuba, Ludek Raida
Graft versus host disease (GVHD), a severe immunogenic complication of allogeneic hematopoietic stem cell transplantation (HSCT), represents the most frequent cause of transplant-related mortality (TRM). Despite a huge progress in HSCT techniques and posttransplant care, GVHD remains a significant obstacle in successful HSCT outcome. This review presents a complex summary of GVHD pathogenesis with focus on references considering basic biological processes such as DNA damage response and cellular senescence.
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29785130/human-herpesvirus-6-pneumonitis-in-a-patient-with-follicular-lymphoma-following-immunochemotherapy-with-rituximab
#6
Saeko Kuwahara-Ota, Yoshiaki Chinen, Yoshimi Mizuno, Tomoko Takimoto-Shimomura, Yayoi Matsumura-Kimoto, Kazuna Tanba, Taku Tsukamoto, Shinsuke Mizutani, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Junya Kuroda
Primary infection with human herpesvirus-6 (HHV-6) commonly occurs at an early age in children, most often at 3 years of age, and is associated with childhood diseases, such as exanthema subitum, hepatitis, febrile convulsions, or encephalitis. However, the virus occasionally reactivates from its latent state in immunosuppressed adults, especially post-transplant, resulting in serious disseminated, sometimes life-threatening end-organ complications. Herein, we report a case of a 68-year-old man with relapsed follicular lymphoma who developed HHV-6 pneumonitis...
2018: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29785044/the-live-cell-dna-stain-sir-hoechst-induces-dna-damage-responses-and-impairs-cell-cycle-progression
#7
Onur Sen, Adrian T Saurin, Jonathan M G Higgins
SiR-Hoechst (SiR-DNA) is a far-red fluorescent DNA probe being used widely for time-lapse imaging of living cells that is reported to be minimally toxic at concentrations as high as 10-25 µM. However, measuring nuclear import of Cyclin B1, inhibition of mitotic entry, and the induction of γH2AX foci in cultured human cells reveals that SiR-Hoechst induces DNA damage responses and G2 arrest at concentrations well below 1 µM. SiR-Hoechst is useful for live cell imaging, but it should be used with caution and at the lowest practicable concentration...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784880/arginine-methylation-of-translocated-in-liposarcoma-tls-inhibits-its-binding-to-long-noncoding-rna-abrogating-tls-mediated-repression-of-cbp-p300-activity
#8
Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa
Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29784807/oocyte-stage-specific-effects-of-mtor-determine-granulosa-cell-fate-and-oocyte-quality-in-mice
#9
Jing Guo, Teng Zhang, Yueshuai Guo, Tao Sun, Hui Li, Xiaoyun Zhang, Hong Yin, Guangyi Cao, Yaoxue Yin, Hao Wang, Lanying Shi, Xuejiang Guo, Jiahao Sha, John J Eppig, You-Qiang Su
MTOR (mechanistic target of rapamycin) is a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation. Here we show that conditional knockout (cKO) of Mtor in either primordial or growing oocytes caused infertility but differentially affected oocyte quality, granulosa cell fate, and follicular development. cKO of Mtor in nongrowing primordial oocytes caused defective follicular development leading to progressive degeneration of oocytes and loss of granulosa cell identity coincident with the acquisition of immature Sertoli cell-like characteristics...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784452/regulation-of-the-oxidative-balance-with-coenzyme-q10-sensitizes-human-glioblastoma-cells-to-radiation-and-temozolomide
#10
Javier Frontiñán-Rubio, Raquel María Santiago-Mora, Consuelo María Nieva-Velasco, Gustavo Ferrín, Alicia Martínez-González, María Victoria Gómez, María Moreno, Julia Ariza, Eva Lozano, Jacinto Arjona-Gutiérrez, Antonio Gil-Agudo, Manuel De la Mata, Milica Pesic, Juan Ramón Peinado, José M Villalba, Luis Pérez-Romasanta, Víctor M Pérez-García, Francisco J Alcaín, Mario Durán-Prado
OBJECTIVES: To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. MATERIAL AND METHODS: Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2 - ) and H2 O2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time...
May 18, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29784358/short-probe-based-duplex-specific-nuclease-signal-amplification-strategy-enables-imaging-of-endogenous-micrornas-in-living-cells-with-ultrahigh-specificity
#11
Yingjun Ma, Jun Chen, Danping Chen, Yuzhi Xu, Li Zhang, Zong Dai, Xiaoyong Zou
Specific nucleic acids amplification at a constant and mild temperature is important for imaging assay of endogenous microRNAs (miRNAs) in living cells. Duplex-specific nuclease (DSN) is attractive in one-step isothermal assay of miRNA; however, its intrinsic limitations of low amplification specificity and high reaction temperature greatly restrict the application scope. Herein, we present a short-probe-based DSN signal amplification (spDSNSA) strategy enabling analysis of miRNAs at body temperature with significantly high specificity...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29784069/first-molecular-phylogeny-of-agrilus-coleoptera-buprestidae-the-largest-genus-on-earth-with-dna-barcode-database-for-forestry-pest-diagnostics
#12
I Kelnarova, E Jendek, V V Grebennikov, L Bocak
All more than 3000 species of Agrilus beetles are phytophagous and some cause economically significant damage to trees and shrubs. Facilitated by international trade, Agrilus species regularly invade new countries and continents. This necessitates a rapid identification of Agrilus species, as the first step for subsequent protective measures. This study provides the first DNA reference library for ~100 Agrilus species from the Northern Hemisphere based on three mitochondrial markers: cox1-5' (DNA barcode fragment), cox1-3', and rrnL...
May 22, 2018: Bulletin of Entomological Research
https://www.readbyqxmd.com/read/29784019/the-parp-inhibitor-olaparib-potentiates-the-effect-of-the-dna-damaging-agent-doxorubicin-in-osteosarcoma
#13
Hye Jeong Park, Jun Sang Bae, Kyoung Min Kim, Young Jae Moon, See-Hyoung Park, Sang Hoon Ha, Usama Khamis Hussein, Zhongkai Zhang, Ho Sung Park, Byung-Hyun Park, Woo Sung Moon, Jung Ryul Kim, Kyu Yun Jang
BACKGROUND: PARP1 facilitates the recovery of DNA-damaged cells by recruiting DNA damage response molecules such as γH2AX and BRCA1/2, and plays a role in resistance to antitumor therapies. Therefore, PARP inhibition being evaluated as an anti-cancer therapy. However, there are limited studies regrading PARP inhibition in osteosarcoma. METHODS: We evaluated the expression of DNA damage response molecules in 35 human osteosarcomas and investigated the effects of co-treatment of the PARP inhibitor, olaparib, and doxorubicin in osteosarcoma cells...
May 21, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29783987/an-updated-review-of-the-genotoxicity-of-respirable-crystalline-silica
#14
REVIEW
Paul J A Borm, Paul Fowler, David Kirkland
Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not conclusive in either of the IARC reviews, although a proposal for mode of actions was made in an extensive review of the genotoxicity of CS by Borm, Tran and Donaldson in 2011 [3]. The present study identified 141 new papers from search strings related to genotoxicity of respirable CS (RCS) since 2011 and, of these, 17 relevant publications with genotoxicity data were included in this detailed review...
May 21, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29783948/expansion-of-the-sos-regulon-of-vibrio-cholerae-through-extensive-transcriptome-analysis-and-experimental-validation
#15
Evelyne Krin, Sebastian Aguilar Pierlé, Odile Sismeiro, Bernd Jagla, Marie-Agnès Dillies, Hugo Varet, Oihane Irazoki, Susana Campoy, Zoé Rouy, Stéphane Cruveiller, Claudine Médigue, Jean-Yves Coppée, Didier Mazel
BACKGROUND: The SOS response is an almost ubiquitous response of cells to genotoxic stresses. The full complement of genes in the SOS regulon for Vibrio species has only been addressed through bioinformatic analyses predicting LexA binding box consensus and in vitro validation. Here, we perform whole transcriptome sequencing from Vibrio cholerae treated with mitomycin C as an SOS inducer to characterize the SOS regulon and other pathways affected by this treatment. RESULTS: Comprehensive transcriptional profiling allowed us to define the full landscape of promoters and transcripts active in V...
May 21, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29783721/azd1775-increases-sensitivity-to-olaparib-and-gemcitabine-in-cancer-cells-with-p53-mutations
#16
Xiangbing Meng, Jianling Bi, Yujun Li, Shujie Yang, Yuping Zhang, Mary Li, Haitao Liu, Yiyang Li, Megan E Mcdonald, Kristina W Thiel, Kuo-Kuang Wen, Xinhao Wang, Meng Wu, Kimberly K Leslie
Tumor suppressor p53 is responsible for enforcing cell cycle checkpoints at G1/S and G2/M in response to DNA damage, thereby allowing both normal and tumor cells to repair DNA before entering S and M. However, tumor cells with absent or mutated p53 are able to activate alternative signaling pathways that maintain the G2/M checkpoint, which becomes uniquely critical for the survival of such tumor cells. We hypothesized that abrogation of the G2 checkpoint might preferentially sensitize p53-defective tumor cells to DNA-damaging agents and spare normal cells with intact p53 function...
May 19, 2018: Cancers
https://www.readbyqxmd.com/read/29781987/retrospective-microrna-sequencing-complementary-dna-library-preparation-protocol-using-formalin-fixed-paraffin-embedded-rna-specimens
#17
Olivier Loudig, Christina Liu, Thomas Rohan, Iddo Z Ben-Dov
-Archived, clinically classified formalin-fixed paraffin-embedded (FFPE) tissues can provide nucleic acids for retrospective molecular studies of cancer development. By using non-invasive or pre-malignant lesions from patients who later develop invasive disease, gene expression analyses may help identify early molecular alterations that predispose to cancer risk. It has been well described that nucleic acids recovered from FFPE tissues have undergone severe physical damage and chemical modifications, which make their analysis difficult and generally requires adapted assays...
May 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781766/significant-suppression-of-ct-radiation-induced-dna-damage-in-normal-human-cells-by-the-prc-210-radioprotector
#18
Frank Jermusek, Chelsea Benedict, Emma Dreischmeier, Michael Brand, Michael Uder, Justin J Jeffery, Frank N Ranallo, William E Fahl
While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants...
May 21, 2018: Radiation Research
https://www.readbyqxmd.com/read/29781764/charged-iron-particles-found-in-galactic-cosmic-rays-are-potent-inducers-of-epithelial-ovarian-tumors
#19
Birendra Mishra, Gregory W Lawson, Ryan Ripperdan, Laura Ortiz, Ulrike Luderer
Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer...
May 21, 2018: Radiation Research
https://www.readbyqxmd.com/read/29780750/the-luxs-ai-2-quorum-sensing-system-of-streptococcus-pneumoniae-is-required-to-cause-disease-and-to-regulate-virulence-and-metabolism-related-genes-in-a-rat-model-of-middle-ear-infection
#20
Mukesh K Yadav, Jorge E Vidal, Yoon Y Go, Shin H Kim, Sung-Won Chae, Jae-Jun Song
Objective: Streptococcus pneumoniae colonizes the nasopharynx of children, and from nasopharynx it could migrate to the middle ear and causes acute otitis media (AOM). During colonization and AOM, the pneumococcus forms biofilms. In vitro biofilm formation requires a functional LuxS/AI-2 quorum-sensing system. We investigated the role of LuxS/AI-2 signaling in pneumococcal middle ear infection, and identified the genes that are regulated by LuxS/AI-2 during pneumococcal biofilm formation. Methods: Streptococcus pneumoniae D39 wild-type and an isogenic D39Δ luxS strain were utilized to evaluate in vitro biofilm formation, and in vivo colonization and epithelial damage using a microtiter plate assay and a rat model of pneumococcal middle ear infection, respectively...
2018: Frontiers in Cellular and Infection Microbiology
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