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DNA damage response

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https://www.readbyqxmd.com/read/28822844/a-ph-sensitive-methenamine-mandelate-loaded-nanoparticle-induces-dna-damage-and-apoptosis-of-cancer-cells
#1
Linhua Zhang, Wenbo Hao, Lv Xu, Yongfeng Gao, Xusheng Wang, Dunwan Zhu, Zhuo Chen, Xudong Zhang, Hongbo Chen, Lin Mei
Methenamine mandelate is a urinary antibacterial agent, which can be converted to formaldehyde in urine that has a relatively low pH of average 5.5-6.8. Here, we prepare a pH-sensitive PLGA-based nanoparticle containing both methenamine mandelate and NaHCO3. Methenamine mandelate/NaHCO3-coloaded nanoparticle could enter cells via endosome/lysosome pathway. The pH in lysosomes and endo-lysosomes is approximately 5.0. In the acidic environment, NaHCO3 reacts with proton and produce CO2 bubbles, which burst nanoparticles and lead to the rapidly release of methenamine mandelate...
August 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28822748/systematical-exploration-of-transcription-factors-in-cardiomyocytes-against-hydrogen-peroxide-induced-oxidative-stress-by-danhong-injection
#2
Jingjing Zhang, Feifei Guo, Junying Wei, Minghua Xian, Shihuan Tang, Ye Zhao, Mingwei Liu, Lei Song, Ya Geng, Hongjun Yang, Chen Ding, Luqi Huang
Oxidative stress plays a vital role in many pathological processes of the cardiovascular diseases. However, the underlying mechanism remains unclear, especially on a transcription factor (TF) level. In this study, a new method, concatenated tandem array of consensus transcription factor response elements (catTFREs), and an Illumina-based RNA-seq technology were integrated and then combined with a network pharmacology strategy to systematically investigate the role of TFs in hydrogen peroxide (H2O2)-induced oxidative stress in cardiomyocytes; the damage was then rescued by Danhong injection (DHI), a Chinese standardized product approved for cardiovascular diseases treatment...
August 16, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28822740/is-dna-damage-indispensable-for-stress-induced-senescence
#3
REVIEW
Anna Bielak-Zmijewska, Grazyna Mosieniak, Ewa Sikora
Cellular senescence is a fundamental trait of many eukaryotic organisms. Senescent cells participate both in the developmental program and in normal ageing and age-related diseases. Senescence of proliferation-prone cells is a state of permanent cell cycle arrest accompanied by metabolic activity manifested by high secretion levels of numerous factors, including pro-inflammatory ones. It seems that cell senescence is a stress response. There are many intrinsic and extrinsic stress inducers which can elicit cell senescence...
August 16, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28821750/rap1-and-cdc13-have-complementary-roles-in-preventing-exonucleolytic-degradation-of-telomere-5-ends
#4
Rikard Runnberg, Saishyam Narayanan, Marita Cohn
Telomere DNA ends with a single-stranded 3' overhang. Long 3' overhangs may cause aberrant DNA damage responses and accelerate telomere attrition, which is associated with cancer and aging, respectively. Genetic studies have indicated several important players in preventing 5' end hyper-resection, yet detailed knowledge about the molecular mechanism in which they act is still lacking. Here, we use an in vitro DNA 5' end protection assay, to study how N. castellii Cdc13 and Rap1 protect against 5' exonucleolytic degradation by λ-exonuclease...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821559/synergy-of-wee1-and-mtor-inhibition-in-mutant-kras-driven-lung-cancers
#5
Josephine Hai, Shengwu Liu, Lauren Bufe, Khanh Do, Ting Chen, Xiaoen Wang, Christine Ng, Shuai Li, Ming-Sound Tsao, Geoffrey I Shapiro, Kwok-Kin Wong
Purpose:KRAS-activating mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multi-targeted therapy may offer a plausible strategy to effectively treat KRAS-driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential therapy for lung cancers harboring KRAS mutations. <p>Experimental Design: We investigated the synergistic effect of combining mTOR and WEE1 inhibitors on cell viability, apoptosis, and DNA damage repair response using a panel of human KRAS-mutant and wild type NSCLC cell lines and patient-derived xenograft cell lines...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821289/transcriptome-wide-analyses-indicate-mitochondrial-responses-to-particulate-air-pollution-exposure
#6
Ellen Winckelmans, Tim S Nawrot, Maria Tsamou, Elly Den Hond, Willy Baeyens, Jos Kleinjans, Wouter Lefebvre, Nicolas Van Larebeke, Martien Peusens, Michelle Plusquin, Hans Reynders, Greet Schoeters, Charlotte Vanpoucke, Theo M de Kok, Karen Vrijens
BACKGROUND: Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM10 exposure. METHODS: Whole genome gene expression was measured in peripheral blood of 98 adults (49% women). We performed linear regression analyses stratified by sex and adjusted for individual and temporal characteristics to investigate alterations in gene expression induced by short-term (week before blood sampling) and medium-term (month before blood sampling) PM10 exposure...
August 18, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28821159/inhibition-of-dna-pk-enhances-chemosensitivity-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-to-doxorubicin
#7
Fatemeh Alikarami, Majid Safa, Mohammad Faranoush, Parisa Hayat, Ahmad Kazemi
DNA damage repair pathways greatly affect the response to genotoxic drugs in cancer cells, so inhibition of such pathways could be a potentially useful strategy to enhance chemosensitivity. DNA-dependent protein kinase (DNA-PK) plays a crucial role in the repair of DNA double-strand breaks (DSBs) that are probably one of the most detrimental types of DNA damage. It has been shown that DNA-PK is highly expressed in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Less well appreciated was the effect of DNA-PK inhibition on sensitivity of BCP-ALL cells to DNA-damaging agents...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28820495/human-papillomavirus-and-the-dna-damage-response-exploiting-host-repair-pathways-for-viral-replication
#8
REVIEW
Chelsey C Spriggs, Laimonis A Laimins
High-risk human papillomaviruses (HPVs) are the causative agents of cervical and other genital cancers. In addition, HPV infections are associated with the development of many oropharyngeal cancers. HPVs activate and repress a number of host cellular pathways to promote their viral life cycles, including those of the DNA damage response. High-risk HPVs activate the ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) DNA damage repair pathways, which are essential for viral replication (particularly differentiation-dependent genome amplification)...
August 18, 2017: Viruses
https://www.readbyqxmd.com/read/28820390/small-molecule-inhibitors-of-dna-pk-for-tumor-sensitization-to-anticancer-therapy
#9
M Pospisilova, M Seifrtova, M Rezacova
The most sensitive cell structure - a DNA molecule, is the common target of cancer therapy. DNA damage response (controlled by enzymes from the phosphatidylinositol 3-kinase-related kinases family - PIKK) presents many encouraging targets for improving both conventional cytotoxic anticancer therapy and individualized monotherapy. DNA-dependent protein kinase (DNA-PK) is a member of the PIKK superfamily and plays an important role in the detection and repair of DNA double-strand breaks via the non-homologous end-joining pathway...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820388/blockade-of-the-lrp16-pkr-nf-%C3%AE%C2%BAb-signaling-axis-sensitizes-colorectal-carcinoma-cells-to-dna-damaging-cytotoxic-therapy
#10
Xiaolei Li, Zhiqiang Wu, Xiaojing An, Qian Mei, Miaomiao Bai, Leena Hanski, Xiang Li, Tero Ahola, Weidong Han
Acquired therapeutic resistance by tumors is a substantial impediment to reducing the morbidity and mortality that are attributable to human malignancies. The mechanisms responsible for the dramatic shift between chemosensitivity and chemoresistance in colorectal carcinoma have not been defined. Here, we report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKβ, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-κB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28819745/bioassessment-of-the-effluents-discharged-from-two-export-oriented-industrial-zones-located-in-kelani-river-basin-sri-lanka-using-erythrocytic-responses-of-the-fish-nile-tilapia-oreochromis-niloticus
#11
C K Hemachandra, A Pathiratne
Complex effluents originating from diverse industrial processes in industrial zones could pose cytotoxic/genotoxic hazards to biota in the receiving ecosystems which cannot be revealed by conventional monitoring methods. This study assessed potential cytotoxicity/genotoxicity of treated effluents of two industrial zones which are discharged into Kelani river, Sri Lanka combining erythrocytic abnormality tests and comet assay of the tropical model fish, Nile tilapia. Exposure of fish to the effluents induced erythrocytic DNA damage and deformed erythrocytes with serrated membranes, vacuolations, nuclear buds and micronuclei showing cytotoxic/genotoxic hazards in all cases...
August 17, 2017: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28819638/connecting-androgen-receptor-signaling-and-the-dna-damage-response-development-of-new-therapies-for-advanced-prostate-cancer
#12
Timothy C Thompson, Likun Li
Androgen receptor-mediated cell signaling involves complex molecular pathways that are interconnected with DNA damage response, including replication stress-driven DNA repair. Understanding the relationships between androgen receptor signaling and DNA damage response at the molecular level will likely lead to novel and effective combination therapy for advanced prostate cancer.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28819136/the-possible-molecular-mechanisms-of-bisphenol-a-action-on-porcine-early-embryonic-development
#13
Jing Guo, Ming-Hui Zhao, Kyung-Tae Shin, Ying-Jie Niu, Yong-Dae Ahn, Nam-Hyung Kim, Xiang-Shun Cui
Bisphenol A (BPA) is an environmental contaminant widely used in the plastic industry. BPA has been demonstrated to be an endocrine disruptor and has an adverse effect on the embryonic development of mammals. However, the mechanism of action of BPA is limited. In this study, we investigated the role and mechanism of BPA in porcine embryonic development. First, the parthenotes were treated with different concentrations of BPA. We found that blastocyst formation was impaired and the parthenotes were arrested at the 4-cell stage after treatment with 100 μm BPA...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818740/assessment-of-genotoxicity-of-four-volatile-pollutants-from-cigarette-smoke-based-on-the-in-vitro-%C3%AE-h2ax-assay-using-high-content-screening
#14
Sen Zhang, Huan Chen, An Wang, Yong Liu, Hongwei Hou, Qingyuan Hu
To evaluate the genotoxic effects of formaldehyde, acetaldehyde, acrolein and benzene on A549 cells, the in vitro γH2AX assay was used in combination with high content screening (HCS) technology. All aldehydes showed a significant genotoxicity in a dose/time-dependent effect on the induction of γH2AX. Benzene failed to show a significant genotoxicity based on the γH2AX assay. However, hydroquinone (one of metabolites of benzene) showed a significant genotoxicity in vitro. Based on the dose-response of γH2AX and Hill model, the ability to induce DNA double-strand break can be evaluated as acrolein>formaldehyde>acetaldehyde>benzene...
July 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28818686/methyleugenol-and-selected-oxidative-metabolites-affect-dna-damage-signalling-pathways-and-induce-apoptosis-in-human-colon-tumour-ht29-cells
#15
Isabel Anna Maria Groh, Melanie Esselen
Previously the food carcinogen methyleugenol was found to be cytotoxic and genotoxic in multiple cell lines and in primary hepatocytes. In this study, the question addressed was whether methyleugenol and the selected oxidative metabolites, 1'-hydroxymethyleugenol, methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol trigger a DNA damage response in the human colon carcinoma HT29 cell line. Most notably investigations by flow cytometry revealed that the metabolites induce an accumulation of HT29 cells in the G2 phase of the cell cycle...
August 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28818588/comprehensive-analysis-of-fly-ash-induced-changes-in-physiological-growth-parameters-dna-damage-and-oxidative-stress-over-the-life-cycle-of-brassica-juncea-and-brassica-alba
#16
Aditi Jana, Manosij Ghosh, Arpita De, Sonali Sinha, Manivannan Jothiramajayam, Anita Mukherjee
Fly ash (FA) being a heterogeneous mixture of heavy metal affects plant system in various ways. Previous studies have shown bioaccumulation of toxic metals in the plants and disturbance in cellular activities. Here, we have studied the impacts of FA treatment through the life cycle of economically important, annual crop plant mustard (Brassica juncea and Brassica alba). Result revealed that FA did not alter germination rate and photosynthetic pigment levels. Tolerance index of B. juncea was higher compared to B...
August 8, 2017: Chemosphere
https://www.readbyqxmd.com/read/28818580/effects-of-sulfur-mustard-on-mesenchymal-stem-cells
#17
Annette Schmidt, Steinritz Dirk, Rothmiller Simone, Thiermann Horst, Scherer A Michael
Chronic wound healing disorders that occur as a result of a sulfur mustard (SM) exposure present a particular challenge. These chronic wounds are similar to other chronic wounds. In the past, it has been shown that mesenchymal stem cells (MSC) play an important role in the healing of chronic wounds. An important property to support wound healing is their ability to migrate. However, we were able to show that SM leads to a reduction in MSC migration even at low concentrations. Currently, exposed MSCs are still able to differentiate...
August 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28816208/pm2-5-exposure-elicits-oxidative-stress-responses-and-mitochondrial-apoptosis-pathway-activation-in-hacat-keratinocytes
#18
Rong Hu, Xiao-Yuan Xie, Si-Ka Xu, Ya-Ning Wang, Ming Jiang, Li-Rong Wen, Wei Lai, Lei Guan
BACKGROUND: PM2.5 (aerodynamic diameter ≤ 2.5 μm) is a dominant and ubiquitous air pollutant that has become a global concern as PM2.5 exposure has been linked to many adverse health effects including cardiovascular and pulmonary diseases. Emerging evidence supports a correlation between increased air PM2.5 levels and skin disorders although reports on the underlying pathophysiological mechanisms are limited. Oxidative stress is the most common mechanism of PM2.5-induced adverse health effects...
August 14, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28814798/genetic-polymorphisms-of-lncrna-p53-regulatory-network-genes-are-associated-with-concurrent-chemoradiotherapy-toxicities-and-efficacy-in-nasopharyngeal-carcinoma-patients
#19
Youhong Wang, Zhen Guo, Yu Zhao, Yi Jin, Liang An, Bin Wu, Zhaoqian Liu, Xiaoping Chen, Xiang Chen, Honghao Zhou, Hui Wang, Wei Zhang
The relevance of the transcription factor p53 in cancer is inarguable, and numerous lncRNAs are involved in the p53 regulatory network as either regulators or effectors, triggering a transcriptional response that causes either cell arrest or apoptosis following DNA damage in a p53-dependent manner. Despite the fact that the therapeutic response is improved in NPC, heterogeneity among people remains with regard to the susceptibility of adverse effects and the efficacy of treatments. Therefore, we analysed eight potentially functional SNPs of five genes in the lncRNA-p53 regulatory network in a discovery cohort of 505 NPC patients...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814116/the-dark-side-of-the-ring-role-of-the-dna-sliding-surface-of-pcna
#20
Matteo De March, Alfredo De Biasio
The proliferating cell nuclear antigen (PCNA) sliding clamp lies at the heart of the accurate duplication of eukaryotic genomes. While the outer surface of the PCNA ring interacts with polymerases and other factors, the role of the inner wall facing the DNA is elusive. Recent evidence shows that conserved basic residues in the PCNA central channel create a specific surface that recognizes the DNA backbone and enables the clamp to slide by rotationally tracking the DNA helix. The sliding surface can be modulated (i) through lysine acetylation, which triggers PCNA degradation during nucleotide excision repair (NER) and stimulates repair by homologous recombination (HR) or (ii) through binding of the protein factor p15(PAF), which turns off DNA lesion bypass...
August 17, 2017: Critical Reviews in Biochemistry and Molecular Biology
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