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https://www.readbyqxmd.com/read/28931570/mitochondrial-dna-double-strand-breaks-in-oligodendrocytes-cause-demyelination-axonal-injury-and-cns-inflammation
#1
Pernille M Madsen, Milena Pinto, Shreyans Patel, Stephanie McCarthy, Han Gao, Mehran Taherian, Shaffiat Karmally, Claudia V Pereira, Galina Dvoriantchikova, Dmitry Ivanov, Kenji F Tanaka, Carlos T Moraes, Roberta Brambilla
Mitochondrial dysfunction has been implicated in the pathophysiology of neurodegenerative disorders, including multiple sclerosis (MS). To date, the investigation of mitochondrial dysfunction in MS has focused exclusively on neurons, with no studies exploring whether dysregulation of mitochondrial bioenergetics and/or genetics in oligodendrocytes might be associated with the etiopathogenesis of MS and other demyelinating syndromes. To address this question, we established a mouse model where mitochondrial DNA (mtDNA) double-strand breaks (DSB) were specifically induced in myelinating oligodendrocytes (PLP:mtPstI mice) by expressing a mitochondrial-targeted endonuclease, mtPstI, starting at 3 weeks of age...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28928376/oligo-fucoidan-prevents-il-6-and-ccl2-production-and-cooperates-with-p53-to-suppress-atm-signaling-and-tumor-progression
#2
Li-Mei Chen, Po-Yen Liu, Yen-An Chen, Hong-Yu Tseng, Pei-Chun Shen, Pai-An Hwang, Hsin-Ling Hsu
Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53(+/+)) or without (p53(-/-)) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928208/picornaviruses-and-apoptosis-subversion-of-cell-death
#3
REVIEW
Sarah N Croft, Erin J Walker, Reena Ghildyal
Infected cells can undergo apoptosis as a protective response to viral infection, thereby limiting viral infection. As viruses require a viable cell for replication, the death of the cell limits cellular functions that are required for virus replication and propagation. Picornaviruses are single-stranded RNA viruses that modify the host cell apoptotic response, probably in order to promote viral replication, largely as a function of the viral proteases 2A, 3C, and 3CD. These proteases are essential for viral polyprotein processing and also cleave cellular proteins...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28919714/radium-223-dichloride-for-prostate-cancer-treatment
#4
REVIEW
Emmanuel Deshayes, Mathieu Roumiguie, Constance Thibault, Philippe Beuzeboc, Florent Cachin, Christophe Hennequin, Damien Huglo, François Rozet, Diana Kassab-Chahmi, Xavier Rebillard, Nadine Houédé
Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo(®)) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919588/poly-i-c-delivery-into-j774-1-and-raw264-7-macrophages-induces-rapid-cell-death
#5
Cheah Wen Yapp, Amal Widaad Mohaimin, Adi Idris
BACKGROUND: Cytosolic double-stranded RNA (dsRNA) is an important 'molecular signature' for the detection of intracellular viral infections. Although intracellular dsRNA is a known potent inducer of apoptosis, the optimal time and dose for the onset of dsRNA-mediated apoptosis have not been studied in detail. OBJECTIVE: To perform an accurate temporal assessment of the cell death responses in dsRNA-dependent cytotoxicity. METHODS: Poly I:C (PIC), a synthetic dsRNA molecule was delivered intracellularly into J774...
September 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28916476/pharmacologic-ascorbate-induces-neuroblastoma-cell-death-by-hydrogen-peroxide-mediated-dna-damage-and-reduction-in-cancer-cell-glycolysis
#6
Enlong Ma, Ping Chen, Heather M Wilkins, Tao Wang, Russell H Swerdlow, Qi Chen
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and non-apoptotic and non-autophagic cell death. The mechanism of cytotoxicity is different when PARP-dependent DNA repair machinery is active or inhibited. Ascorbate-generated H2O2 damaged DNA, activated PARP, depleted NAD+, and reduced glycolysis flux...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28911117/structure-based-domain-assignment-in-leishmania-infantum-endog-characterization-of-a-ph-dependent-regulatory-switch-and-a-c-terminal-extension-that-largely-dictates-dna-substrate-preferences
#7
Cristina Oliva, Pedro A Sánchez-Murcia, Eva Rico, Ana Bravo, Margarita Menéndez, Federico Gago, Antonio Jiménez-Ruiz
Mitochondrial endonuclease G from Leishmania infantum (LiEndoG) participates in the degradation of double-stranded DNA (dsDNA) during parasite cell death and is catalytically inactive at a pH of 8.0 or above. The presence, in the primary sequence, of an acidic amino acid-rich insertion exclusive to trypanosomatids and its spatial position in a homology-built model of LiEndoG led us to postulate that this peptide stretch might act as a pH sensor for self-inhibition. We found that a LiEndoG variant lacking residues 145-180 is indeed far more active than its wild-type counterpart at pH values >7...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28911109/selective-tumor-cell-death-induced-by-irradiated-riboflavin-through-recognizing-dna-g-t-mismatch
#8
Yi Yuan, Yongyun Zhao, Lianqi Chen, Jiasi Wu, Gangyi Chen, Sheng Li, Jiawei Zou, Rong Chen, Jian Wang, Fan Jiang, Zhuo Tang
Riboflavin (vitamin B2) has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Our work reveals that riboflavin was able to recognize G-T mismatch specifically and induce single-strand breaks in duplex DNA targets efficiently under irradiation. In the presence of riboflavin, the photo-irradiation could induce the death of tumor cells that are defective in mismatch repair system selectively, highlighting the G-T mismatch as potential drug target for tumor cells...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28911066/prevention-of-chemotherapy-toxicity-by-agents-that-neutralize-or-degrade-cell-free-chromatin
#9
I Mittra, K Pal, N Pancholi, A Shaikh, B Rane, P Tidke, S Kirolikar, N K Khare, K Agrawal, H Nagare, N K Nair
Background: Toxicity associated with chemotherapy is a major therapeutic challenge and is caused by chemotherapy-induced DNA damage and inflammation. We have recently reported that cell-free chromatin (cfCh) fragments released from dying cells can readily enter into healthy cells of the body to integrate into their genomes and induce DNA double-strand breaks, apoptosis and inflammation in them. We hypothesized that much of the toxicity of chemotherapy might be due to release of large quantities of cfCh from dying cells that could trigger an exaggerated DNA damage, apoptotic and inflammatory response in healthy cells over and above that caused by the drugs themselves...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28905214/mir-217-5p-induces-apoptosis-by-directly-targeting-prkci-bag3-itgav-and-mapk1-in-colorectal-cancer-cells
#10
Marion Flum, Michael Kleemann, Helga Schneider, Benjamin Weis, Simon Fischer, René Handrick, Kerstin Otte
Apoptosis is a genetically directed process of programmed cell death. A variety of microRNAs (miRNAs), endogenous single-stranded non-coding RNAs of about 22 nucleotides in length have been shown to be involved in the regulation of the intrinsic or extrinsic apoptotic pathways. There is increasing evidence that the aberrant expression of miRNAs plays a causal role in the development of diseases such as cancer. This makes miRNAs promising candidate molecules as therapeutic targets or agents. MicroRNA (miR)-217-5p has been implicated in carcinogenesis of various cancer entities, including colorectal cancer...
September 14, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28904740/low-dose-ionizing-radiation-affects-mesenchymal-stem-cells-via-extracellular-oxidized-cell-free-dna-a-possible-mediator-of-bystander-effect-and-adaptive-response
#11
V A Sergeeva, E S Ershova, N N Veiko, E M Malinovskaya, A A Kalyanov, L V Kameneva, S V Stukalov, O A Dolgikh, M S Konkova, A V Ermakov, V P Veiko, V L Izhevskaya, S I Kutsev, S V Kostyuk
We have hypothesized that the adaptive response to low doses of ionizing radiation (IR) is mediated by oxidized cell-free DNA (cfDNA) fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production), induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis. We have demonstrated that treatment of mesenchymal stem cells (MSCs) with low doses of IR (10 cGy) leads to cell death of part of cell population and release of oxidized cfDNA...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28904004/jadomycins-inhibit-type-ii-topoisomerases-and-promote-dna-damage-and-apoptosis-in-multidrug-resistant-triple-negative-breast-cancer-cells
#12
Steven R Hall, Jay Toulany, Leah G Bennett, Camilo F Martinez-Farina, Andrew W Robertson, David L Jakeman, Kerry B Goralski
Jadomycins are natural products that kill drug-sensitive and multidrug resistant (MDR) breast cancer cells. To date the cytotoxic activity of jadomycins has never been tested in MDR breast cancer cells that are also triple-negative. Additionally, there is only a rudimentary understanding of how jadomycins cause cancer cell death, which includes the induction of intracellular reactive oxygen species (ROS). We first created a paclitaxel-resistant, triple-negative breast cancer cell line (231-TXL) from drug-sensitive MDA-MB-231 cells (231-CON)...
September 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28900603/a-nanocomplex-of-c60-fullerene-with-cisplatin-design-characterization-and-toxicity
#13
Svitlana Prylutska, Svitlana Politenkova, Kateryna Afanasieva, Volodymyr Korolovych, Kateryna Bogutska, Andriy Sivolob, Larysa Skivka, Maxim Evstigneev, Viktor Kostjukov, Yuriy Prylutskyy, Uwe Ritter
The self-organization of C60 fullerene and cisplatin in aqueous solution was investigated using the computer simulation, dynamic light scattering and atomic force microscopy techniques. The results evidence the complexation between the two compounds. The genotoxicity of С60 fullerene, Cis and their complex was evaluated in vitro with the comet assay using human resting lymphocytes and lymphocytes after blast transformation. The cytotoxicity of the mentioned compounds was estimated by Annexin V/PI double staining followed by flow cytometry...
2017: Beilstein Journal of Nanotechnology
https://www.readbyqxmd.com/read/28891354/brca2-protects-mammalian-cells-from-heat-shock
#14
Yosuke Nakagawa, Atsuhisa Kajihara, Akihisa Takahashi, Akiho S Murata, Masaya Matsubayashi, Soichiro S Ito, Ichiro Ota, Takahiko Nakagawa, Masatoshi Hasegawa, Tadaaki Kirita, Takeo Ohnishi, Eiichiro Mori
PURPOSE: Heat shock induces DNA double-strand breaks (DSBs) in mammalian cells. Mammalian cells are capable of repairing DSBs by utilising the homologous recombination (HR) pathway. Breast cancer susceptibility gene 2 (BRCA2) is known to regulate the HR pathway. Here, we investigate the role of BRCA2 in repairing DNA damage induced by heat shock. MATERIALS AND METHODS: Chinese hamster lung fibroblast cell lines and human tongue squamous cell carcinoma SAS cells were used...
September 10, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28882807/atlantic-salmon-endothelial-cells-from-the-heart-were-more-susceptible-than-fibroblasts-from-the-bulbus-arteriosus-to-four-rna-viruses-but-protected-from-two-viruses-by-dsrna-pretreatment
#15
Phuc H Pham, Winnie W L Tong, Ehab Misk, Ginny Jones, John S Lumsden, Niels C Bols
Heart diseases caused by viruses are major causes of Atlantic salmon aquaculture loss. Two Atlantic salmon cardiovascular cell lines, an endothelial cell line (ASHe) from the heart and a fibroblast cell line (BAASf) from the bulbus arteriosus, were evaluated for their response to four fish viruses, CSV, IPNV, VHSV IVa and VHSV IVb, and the innate immune agonist, double-stranded RNA mimic poly IC. All four viruses caused cytopathic effects in ASHe and BAASf. However, ASHe was more susceptible to all four viruses than BAASf...
September 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28868264/the-role-of-long-non-coding-rnas-in-the-repair-of-dna-double-strand-breaks
#16
REVIEW
Ali Dianatpour, Soudeh Ghafouri-Fard
DNA double strand breaks (DSBs) are abrasions caused in both strands of the DNA duplex following exposure to both exogenous and endogenous conditions. Such abrasions have deleterious effect in cells leading to genome rearrangements and cell death. A number of repair systems including homologous recombination (HR) and non-homologous end-joining (NHEJ) have been evolved to minimize the fatal effects of these lesions in cell. The role of protein coding genes in regulation of these pathways has been assessed previously...
2017: International Journal of Molecular and Cellular Medicine
https://www.readbyqxmd.com/read/28867769/transgenic-cotton-plants-expressing-the-hahr3-gene-conferred-enhanced-resistance-to-helicoverpa-armigera-and-improved-cotton-yield
#17
Qiang Han, Zhenzhen Wang, Yunxin He, Yehui Xiong, Shun Lv, Shupeng Li, Zhigang Zhang, Dewen Qiu, Hongmei Zeng
RNA interference (RNAi) has been developed as an efficient technology. RNAi insect-resistant transgenic plants expressing double-stranded RNA (dsRNA) that is ingested into insects to silence target genes can affect the viability of these pests or even lead to their death. HaHR3, a molt-regulating transcription factor gene, was previously selected as a target expressed in bacteria and tobacco plants to control Helicoverpa armigera by RNAi technology. In this work, we selected the dsRNA-HaHR3 fragment to silence HaHR3 in cotton bollworm for plant mediated-RNAi research...
August 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28862449/structures-of-a-dna-polymerase-inserting-therapeutic-nucleotide-analogues
#18
Matthew A Schaich, Mallory R Smith, Ashley S Cloud, Sean M Holloran, Bret D Freudenthal
Members of the nucleoside analogue class of cancer therapeutics compete with canonical nucleotides to disrupt numerous cellular processes, including nucleotide homeostasis, DNA and RNA synthesis, and nucleotide metabolism. Nucleoside analogues are triphosphorylated and subsequently inserted into genomic DNA, contributing to the efficacy of therapeutic nucleosides in multiple ways. In some cases, the altered base acts as a mutagen, altering the DNA sequence to promote cellular death; in others, insertion of the altered nucleotide triggers DNA repair pathways, which produce lethal levels of cytotoxic intermediates such as single and double stranded DNA breaks...
September 1, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28861811/differential-effects-of-antiretroviral-drugs-on-neurons-in-vitro-roles-for-oxidative-stress-and-integrated-stress-response
#19
Anna L Stern, Rebecca N Lee, Nina Panvelker, Jiean Li, Jenna Harowitz, Kelly L Jordan-Sciutto, Cagla Akay-Espinoza
Mounting evidence suggests that antiretroviral drugs may contribute to the persistence of HIV-associated neurocognitive disorders (HAND), which impact 30%-50% of HIV-infected patients in the post-antiretroviral era. We previously reported that two first generation HIV protease inhibitors, ritonavir and saquinavir, induced oxidative stress, with subsequent neuronal death in vitro, which was reversed by augmentation of the endogenous antioxidant response by monomethyl fumarate. We herein determined whether two newer-generation PIs, darunavir and lopinavir, were deleterious to neurons in vitro...
August 31, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28852760/an-aptamer-bio-barcode-abc-assay-using-spr-rnase-h-and-probes-with-rna-and-gold-nanorods-for-anti-cancer-drug-screening
#20
Jacky Fong-Chuen Loo, Chengbin Yang, Hing Lun Tsang, Pui Man Lau, Ken-Tye Yong, Ho Pui Ho, Siu Kai Kong
With modifications to an ultra-sensitive bio-barcode (BBC) assay, we have developed a next generation aptamer-based bio-barcode (ABC) assay to detect cytochrome-c (Cyto-c), a cell death marker released from cancer cells, for anti-cancer drug screening. An aptamer is a short single-stranded DNA selected from a synthetic DNA library that is capable of binding to its target with high affinity and specificity based on its unique DNA sequence and 3D structure after folding. Similar to the BBC assay, Cyto-c is captured by a micro-magnetic particle (MMP) coated with capturing antibodies (Ab) and an aptamer specifically against Cyto-c to form sandwich structures ([MMP-Ab]-[Cyto-c]-[Aptamer])...
August 30, 2017: Analyst
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