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https://www.readbyqxmd.com/read/29352505/p53-independent-noxa-induction-by-cisplatin-is-regulated-by-atf3-atf4-in-head-and-neck-squamous-cell-carcinoma-cells
#1
Kanika Sharma, Thien-Trang Vu, Wade Cook, Mitra Naseri, Kevin Zhan, Wataru Nakajima, Hisashi Harada
The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family-dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of pro-apoptotic BCL-2 family protein, Noxa, that can bind to the pro-survival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death...
January 19, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29352449/continuous-exposure-to-microplastics-does-not-cause-physiological-effects-in-the-cultivated-mussel-perna-perna
#2
Marina F M Santana, Fabiana T Moreira, Camilo D S Pereira, Denis M S Abessa, Alexander Turra
The environmental impact of microplastics is a challenging theme, especially under realistic experimental conditions. We investigated physiological responses to 0.1-1.0 μm PVC particles intake by the mussel Perna perna after a relative long-term exposure (90 days) at a less extreme concentration compared with previous studies (0.125 g/L). Microplastic intake was inferred by the presence of PVC in the feces of mussels, and physiological damages were assessed through ingestion rate, assimilation efficiency, growth rate, cellular and molecular biomarkers (lysosomal integrity, lipid peroxidation, and DNA damage), and condition index...
January 19, 2018: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/29352261/insight-into-the-role-of-pikk-family-members-and-nf-%C3%B0%C2%BAb-in-dnadamage-induced-senescence-and-senescence-associated-secretory-phenotype-of-colon-cancer-cells
#3
Anna Strzeszewska, Olga Alster, Grażyna Mosieniak, Agata Ciolko, Ewa Sikora
Senescence of cancer cells is an important outcome of treatment of many cancer types. Cell senescence is a permanent cell cycle arrest induced by stress conditions, including DNA damage. DNA damage activates DNA damage response (DDR), which involves members of the phosphatidylinositol 3-kinase-related kinase (PIKK) superfamily: protein kinases ATM, ATR, and DNA-PKcs. The so-far collected data indicate that ATM, with its downstream targets CHK2, p53, and p21, is the key protein involved in DDR-dependent senescence...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#4
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352181/samhd1-is-recurrently-mutated-in-t-cell-prolymphocytic-leukemia
#5
Patricia Johansson, Ludger Klein-Hitpass, Axel Choidas, Peter Habenberger, Bijan Mahboubi, Baek Kim, Anke Bergmann, René Scholtysik, Martina Brauser, Anna Lollies, Reiner Siebert, Thorsten Zenz, Ulrich Dührsen, Ralf Küppers, Jan Dürig
T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated...
January 19, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29352124/hbv-infection-potentiates-resistance-to-s-phase-arrest-inducing-chemotherapeutics-by-inhibiting-chk2-pathway-in-diffuse-large-b-cell-lymphoma
#6
Xinying Zhao, Xudong Guo, Libo Xing, Wenqin Yue, Haisen Yin, Miaoxia He, Jianmin Wang, Jianmin Yang, Jie Chen
A considerable number of diffuse large B-cell lymphoma (DLBCL) patients are infected with hepatitis B virus (HBV), which is correlated with their poor outcomes. However, the role of HBV infection in DLBCL treatment failure remains poorly understood. Here, our data demonstrated that HBV infection was closely associated with poorer clinical prognosis independent of its hepatic dysfunction in germinal center B-cell type (GCB type) DLBCL patients. Interestingly, we found that DLBCL cells expressing hepatitis B virus X protein (HBX) did not exhibit enhanced cell growth but did show reduced sensitivity to methotrexate (MTX) and cytarabine (Ara-C), which induced S-phase arrest...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352098/dna-damage-response-selected-review-and-neurologic-implications
#7
Elizabeth A Coon, Eduardo E Benarroch
No abstract text is available yet for this article.
January 19, 2018: Neurology
https://www.readbyqxmd.com/read/29351884/crucial-role-of-chelatable-iron-in-silver-nanoparticles-induced-dna-damage-and-cytotoxicity
#8
Agnieszka Grzelak, Maria Wojewódzka, Sylwia Meczynska-Wielgosz, Mariusz Zuberek, Dominika Wojciechowska, Marcin Kruszewski
Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O2•-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H2O2 instead of O2•-, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity...
January 9, 2018: Redox Biology
https://www.readbyqxmd.com/read/29351627/repair-kinetics-of-dna-double-strand-breaks-and-incidence-of-apoptosis-in-mouse-neural-stem-progenitor-cells-and-their-differentiated-neurons-exposed-to-ionizing-radiation
#9
Hiroki Kashiwagi, Kazunori Shiraishi, Kenta Sakaguchi, Tomoya Nakahama, Seiji Kodama
Neuronal loss leads to neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such as DNA double-strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it remains largely unknown whether the DSB repair ability of neurons is more efficient compared with that of other cells. Here, we investigated the repair kinetics of X-ray-induced DSBs in mouse neural cells by scoring the number of phosphorylated 53BP1 foci post irradiation...
January 17, 2018: Journal of Radiation Research
https://www.readbyqxmd.com/read/29351587/heat-exposure-induces-oxidative-stress-and-dna-damage-in-the-male-germ-line
#10
Brendan J Houston, Brett Nixon, Jacinta H Martin, Geoffry N D E Iuliis, Elizabeth G Bromfield, Kristen E McEwen, R John Aitkena
The reproductive consequences of global warming are not currently understood. In order to address this issue we have examined the reproductive consequences of exposing male mice to a mild heat stress. For this purpose, adult male mice were exposed to an elevated ambient temperature of 35°C under two exposure models. The first involved acute exposure for 24 hours, followed by recovery periods of between 1 day and 6 weeks. The alternative heating regimen involved a daily exposure of 8 hours for periods of 1 or 2 weeks...
January 17, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29351567/whole-thorax-irradiation-of-non-human-primates-induces-persistent-nuclear-damage-and-gene-expression-changes-in-peripheral-blood-cells
#11
Shanaz A Ghandhi, Helen C Turner, Igor Shuryak, Gregory O Dugan, J Daniel Bourland, John D Olson, Janet A Tooze, Shad R Morton, Ines Batinic-Haberle, J Mark Cline, Sally A Amundson
We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals...
2018: PloS One
https://www.readbyqxmd.com/read/29351565/sumo-targeting-of-a-stress-tolerant-ulp1-sumo-protease
#12
Jennifer Peek, Catherine Harvey, Dreux Gray, Danny Rosenberg, Likhitha Kolla, Reuben Levy-Myers, Rui Yin, Jonathan L McMurry, Oliver Kerscher
SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1...
2018: PloS One
https://www.readbyqxmd.com/read/29351515/understanding-key-mechanisms-of-exercise-induced-cardiac-protection-to-mitigate-disease-current-knowledge-and-emerging-concepts
#13
Bianca C Bernardo, Jenny Y Y Ooi, Kate L Weeks, Natalie L Patterson, Julie R McMullen
The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29351465/emerging-potential-benefits-of-modulating-nad-metabolism-in-cardiovascular-disease
#14
Daniel S Matasic, Charles Brenner, Barry London
Nicotinamide adenine dinucleotide (NAD+) and related metabolites are central mediators of fuel oxidation and bioenergetics within cardiomyocytes. Additionally, NAD+ is required for the activity of multifunctional enzymes including sirtuins and poly(ADP-ribose) polymerases (PARPs) that regulate post-translational modifications, DNA damage responses, and calcium signaling. Recent research indicates that NAD+ participates in a multitude of processes dysregulated in cardiovascular diseases. Therefore, supplementation of NAD+ precursors including nicotinamide riboside (NR) that boost or replete the NAD+ metabolome may be cardioprotective...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351455/thrombosis-systemic-and-cardiac-oxidative-stress-and-dna-damage-induced-by-pulmonary-exposure-to-diesel-exhaust-particles-and-the-effect-of-nootkatone-thereon
#15
Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Badreldin H Ali
Adverse cardiovascular effects of particulate air pollution persist even at lower concentrations than those of the current air quality limit. Therefore, identification of safe and effective measures against particles-induced cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit with diverse bioactivities including anti-inflammatory and antioxidant effects. However, its protective effect on the cardiovascular injury induced by diesel exhaust particles (DEP) has not been studied before...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351274/dna-polymerase-iv-primarily-operates-outside-of-dna-replication-forks-in-escherichia-coli
#16
Sarah S Henrikus, Elizabeth A Wood, John P McDonald, Michael M Cox, Roger Woodgate, Myron F Goodman, Antoine M van Oijen, Andrew Robinson
In Escherichia coli, damage to the chromosomal DNA induces the SOS response, setting in motion a series of different DNA repair and damage tolerance pathways. DNA polymerase IV (pol IV) is one of three specialised DNA polymerases called into action during the SOS response to help cells tolerate certain types of DNA damage. The canonical view in the field is that pol IV primarily acts at replisomes that have stalled on the damaged DNA template. However, the results of several studies indicate that pol IV also acts on other substrates, including single-stranded DNA gaps left behind replisomes that re-initiate replication downstream of a lesion, stalled transcription complexes and recombination intermediates...
January 19, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29351238/telomeres-implications-for-cancer-development
#17
REVIEW
Aina Bernal, Laura Tusell
Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR). This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350491/reproductive-toxic-impact-of-subchronic-treatment-with-combined-butylparaben-and-triclosan-in-weanling-male-rats
#18
Madeha A Riad, Marwa M Abd-Rabo, Samy A Abd El Aziz, Adel M El Behairy, Mohamed M Badawy
The effect of treatment with combined butylparaben and triclosan on male gonadal toxicity in weanling rats was investigated. All treated groups experienced atrophy in the ventral prostate and seminal vesicle, likewise significant depletion in the number and motility of sperm. Given individually or combined butylparaben and triclosan, significantly decreased testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Individual treatment with tested compounds caused significant elevation in the E2 level, whereas combined treatment did not alter the E2 level...
January 19, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29350405/reactive-oxygen-species-induced-parthanatos-of-immunocytes-by-human-cytomegalovirus-associated-substance
#19
Jung Heon Kim, Jiyeon Kim, Jin Roh, Chan-Sik Park, Ju-Young Seoh, Eung-Soo Hwang
Previous studies examined various immune evasion strategies of human cytomegalovirus (HCMV) to understand HCMV pathogenesis. Although the mechanism that underlies immunocyte destruction near HCMV-infected lesions has yet to be established, we show that substances produced by HCMV-infected cells induce death in several types of immunocytes, but not in fibroblasts or astrocytomas. These substances contain HCMV proteins and were termed HCMV-associated insoluble substance (HCMVAIS). We characterized this mechanism of cell death induced by HCMVAIS to understand the death of immunocytes near HCMV-infected lesions...
January 19, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29350299/mutagenicity-cytotoxic-and-antioxidant-activities-of-ricinus-communis-different-parts
#20
Mazhar Abbas, Abid Ali, Muhammad Arshad, Asia Atta, Zahed Mehmood, Imtiaz Mahmood Tahir, Munawar Iqbal
Ricinus communis (castor plant) is a potent medicinal plant, which is commonly used in the treatment of various ailments. The present study was conducted to appraise the cytotoxicity and mutagenicity of R. communis along with antioxidant and antimicrobial activities. Cytotoxicity was evaluated by hemolytic and brine shrimp assays, whereas Ames test (TA98 and TA100) was used for mutagenicity evaluation. Plant different parts were extracted in methanol by shaking, sonication and Soxhlet extraction methods. The R...
January 19, 2018: Chemistry Central Journal
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