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https://www.readbyqxmd.com/read/28549377/biocompatibility-of-liposome-nanocarriers-in-the-rat-inner-ear-after-intratympanic-administration
#1
Jing Zou, Hao Feng, Rohit Sood, Paavo K J Kinnunen, Ilmari Pyykko
Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28545460/intraperitoneal-implantation-of-life-long-telemetry-transmitters-in-three-rehabilitated-harbor-seal-pups
#2
Markus Horning, Martin Haulena, Justin F Rosenberg, Chad Nordstrom
BACKGROUND: Pinnipeds, including many phocid species of concern, are inaccessible and difficult to monitor for extended periods using conventional, externally attached telemetry devices that are shed during the annual molt. Archival satellite transmitters were implanted intraperitoneally into three stranded Pacific harbor seal pups (Phoca vitulina richardii) that completed rehabilitation, to evaluate the viability of this surgical technique for the deployment of life long telemetry devices in phocids...
May 25, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28545143/haemophilus-parasuis-cytolethal-distending-toxin-induces-cell-cycle-arrest-and-p53-dependent-apoptosis
#3
Gang Li, Hui Niu, Yanhe Zhang, Yanling Li, Fang Xie, Paul R Langford, Siguo Liu, Chunlai Wang
Haemophilus parasuis is the causative agent of Glasser's disease in pigs. Cytolethal distending toxin (CDT) is an important virulence factor of H. parasuis. It is composed of three subunits: CdtA, CdtB and CdtC and all were successfully expressed in soluble form in Escherichia coli when the signal peptides were removed. Purified CdtB had DNase activity, i.e. caused DNA double strand damage, in vitro and in vivo prior to cell arrest and apoptosis. Flow cytometry analysis showed CdtB alone could induce cell cycle arrest and apoptosis in PK-15 porcine kidney and pulmonary alveolar macrophage (PAM) cells, which could be enhanced by CdtA or/and CdtC...
2017: PloS One
https://www.readbyqxmd.com/read/28535307/intergenerational-impact-of-paternal-lifetime-exposures-to-both-folic-acid-deficiency-and-supplementation-on-reproductive-outcomes-and-imprinted-gene-methylation
#4
Lundi Ly, Donovan Chan, Mahmoud Aarabi, Mylène Landry, Nathalie A Behan, Amanda J MacFarlane, Jacquetta Trasler
STUDY QUESTION: Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? SUMMARY ANSWER: Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation...
May 23, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28526979/the-probabilities-of-one-and-multi-track-events-for-modeling-radiation-induced-cell-kill
#5
Uwe Schneider, Fabiano Vasi, Jürgen Besserer
In view of the clinical importance of hypofractionated radiotherapy, track models which are based on multi-hit events are currently reinvestigated. These models are often criticized, because it is believed that the probability of multi-track hits is negligible. In this work, the probabilities for one- and multi-track events are determined for different biological targets. The obtained probabilities can be used with nano-dosimetric cluster size distributions to obtain the parameters of track models. We quantitatively determined the probabilities for one- and multi-track events for 100, 500 and 1000 keV electrons, respectively...
May 19, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28526807/dihydroartemisinin-induces-autophagy-dependent-death-in-human-tongue-squamous-cell-carcinoma-cells-through-dna-double-strand-break-mediated-oxidative-stress
#6
Xinli Shi, Li Wang, Xiaoming Li, Jing Bai, Jianchun Li, Shenghao Li, Zeming Wang, Mingrui Zhou
Dihydroartemisinin is an effective antimalarial agent with multiple biological activities. In the present investigation, we elucidated its therapeutic potential and working mechanism on human tongue squamous cell carcinoma (TSCC). It was demonstrated that dihydroartemisinin could significantly inhibit cell growth in a dose- and time-dependent manner by the Cell Counting Kit-8 and colony formation assay in vitro. Meanwhile, autophagy was promoted in the Cal-27 cells treated by dihydroartemisinin, evidenced by increased LC3B-II level, increased autophagosome formation, and increased Beclin-1 level compared to dihydroartemisinin-untreated cells...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526682/aeroallergens-induce-reactive-oxygen-species-production-and-dna-damage-and-dampen-antioxidant-responses-in-bronchial-epithelial-cells
#7
Tze Khee Chan, W S Daniel Tan, Hong Yong Peh, W S Fred Wong
Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#8
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28524082/cellular-repair-of-dna-dna-cross-links-induced-by-1-2-3-4-diepoxybutane
#9
Lisa N Chesner, Amanda Degner, Dewakar Sangaraju, Shira Yomtoubian, Susith Wickramaratne, Bhaskar Malayappan, Natalia Tretyakova, Colin Campbell
Xenobiotic-induced interstrand DNA-DNA cross-links (ICL) interfere with transcription and replication and can be converted to toxic DNA double strand breaks. In this work, we investigated cellular responses to 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) cross-links induced by 1,2,3,4-diepoxybutane (DEB). High pressure liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI⁺-MS/MS) assays were used to quantify the formation and repair of bis-N7G-BD cross-links in wild-type Chinese hamster lung fibroblasts (V79) and the corresponding isogenic clones V-H1 and V-H4, deficient in the XPD and FANCA genes, respectively...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28521363/a-cisplatin-derivative-tetra-pt-bpy-as-an-oncotherapeutic-agent-for-targeting-alt-cancer
#10
Xiao-Hui Zheng, Xin Nie, Yiming Fang, Zepeng Zhang, Yingnan Xiao, Zongwan Mao, Haiying Liu, Jian Ren, Feng Wang, Lixin Xia, Junjiu Huang, Yong Zhao
Background: In approximately 15% of human cancers, telomere length is maintained independently of telomerase by the homologous recombination (HR)-mediated alternative lengthening of telomeres (ALT) pathway. Whether the ALT pathway can be exploited for therapeutic treatment remains unknown. The purpose of this study is to develop oncotherapeutic agent to target ALT cancers. Methods: Surface plasmon resonance assay, antibody to G-quadruplex, and fluorescence in situ hybridization (FISH) were used to discover Tetra-Pt(bpy), a cisplatin derivative that specifically targets telomeric G-quadruplex...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28515885/evaluating-morphometric-and-metabolic-markers-of-body-condition-in-a-small-cetacean-the-harbor-porpoise-phocoena-phocoena
#11
Joanna L Kershaw, Meredith Sherrill, Nicholas J Davison, Andrew Brownlow, Ailsa J Hall
Mammalian body condition is an important individual fitness metric as it affects both survival and reproductive success. The ability to accurately measure condition has key implications for predicting individual and population health, and therefore monitoring the population-level effects of changing environments. No consensus currently exists on the best measure to quantitatively estimate body condition in many species, including cetaceans. Here, two measures of body condition were investigated in the harbor porpoise (Phocoena phocoena)...
May 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28511573/inhibition-of-pkr-ameliorates-lipopolysaccharide-induced-acute-lung-injury-by-suppressing-nf-%C3%AE%C2%BAb-pathway-in-mice
#12
Yinjiao Li, Jinglei Xiao, Yongchang Tan, Jun Wang, Yan Zhang, Xiaoming Deng, Yan Luo
Acute lung injury (ALI) is characterized by dramatic lung inflammation and alveolar epithelial cell death. Although protein kinase R (PKR) (double-stranded RNA-activated serine/threonine kinase) has been implicated in inflammatory response to bacterial cell wall components, whether it plays roles in lipopolysaccharide (LPS)-induced ALI remains unclear. This study was aimed to reveal whether and how PKR was involved in LPS-induced ALI pathology and the potential effects of its specific inhibitor, C16 (C13H8N4OS)...
May 17, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28497687/eukaryotic-translesion-dna-synthesis-on-the-leading-and-lagging-strands-unique-detours-around-the-same-obstacle
#13
Mark Hedglin, Stephen J Benkovic
During S-phase, minor DNA damage may be overcome by DNA damage tolerance (DDT) pathways that bypass such obstacles, postponing repair of the offending damage to complete the cell cycle and maintain cell survival. In translesion DNA synthesis (TLS), specialized DNA polymerases replicate the damaged DNA, allowing stringent DNA synthesis by a replicative polymerase to resume beyond the offending damage. Dysregulation of this DDT pathway in human cells leads to increased mutation rates that may contribute to the onset of cancer...
May 12, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28485930/reactivity-and-cross-linking-of-5-terminal-abasic-sites-within-dna
#14
Suzanne J Admiraal, Patrick J O'Brien
Nicking of the DNA strand immediately upstream of an internal abasic (AP) site produces 5'-terminal abasic (dRp) DNA. Both the intact and the nicked abasic species are reactive intermediates along the DNA base excision repair (BER) pathway and can be derailed by side reactions. Aberrant accumulation of the 5'-terminal abasic intermediate has been proposed to lead to cell death, so we explored its reactivity and compared it to the reactivity of the better-characterized internal abasic intermediate. We find that the 5'-terminal abasic group cross-links with the exocyclic amine of a nucleotide on the opposing strand to form an interstrand DNA-DNA cross-link (ICL)...
May 9, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28484023/coronavirus-nonstructural-protein-15-mediates-evasion-of-dsrna-sensors-and-limits-apoptosis-in-macrophages
#15
Xufang Deng, Matthew Hackbart, Robert C Mettelman, Amornrat O'Brien, Anna M Mielech, Guanghui Yi, C Cheng Kao, Susan C Baker
Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28475874/unprotected-replication-forks-are-converted-into-mitotic-sister-chromatid-bridges
#16
Anissia Ait Saada, Ana Teixeira-Silva, Ismail Iraqui, Audrey Costes, Julien Hardy, Giulia Paoletti, Karine Fréon, Sarah A E Lambert
Replication stress and mitotic abnormalities are key features of cancer cells. Temporarily paused forks are stabilized by the intra-S phase checkpoint and protected by the association of Rad51, which prevents Mre11-dependent resection. However, if a fork becomes dysfunctional and cannot resume, this terminally arrested fork is rescued by a converging fork to avoid unreplicated parental DNA during mitosis. Alternatively, dysfunctional forks are restarted by homologous recombination. Using fission yeast, we report that Rad52 and the DNA binding activity of Rad51, but not its strand-exchange activity, act to protect terminally arrested forks from unrestrained Exo1-nucleolytic activity...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28475451/postmortem-findings-in-cetaceans-found-stranded-in-the-pelagos-sanctuary-italy-2007-2014
#17
Federica Giorda, Marco Ballardini, Giovanni Di Guardo, Maria Domenica Pintore, Carla Grattarola, Barbara Iulini, Walter Mignone, Maria Goria, Laura Serracca, Katia Varello, Alessandro Dondo, Pier Luigi Acutis, Fulvio Garibaldi, Frine Eleonora Scaglione, Andrea Gustinelli, Sandro Mazzariol, Cristina Esmeralda Di Francesco, Cristiana Tittarelli, Cristina Casalone, Alessandra Pautasso
Between 2007 and 2014, 83 cetaceans were found stranded along the Ligurian coast of Italy, in the Pelagos Sanctuary, the largest marine protected area in the Mediterranean basin. Forty-nine (59%) were submitted to complete or partial necropsy, depending on the conservation status of the carcass. Based on gross and histological pathology and ancillary testing, the cause of death was determined and categorized as anthropogenic or natural (i.e., nonanthropogenic) in origin for 33 animals (67%) and of undetermined origin in the remaining 16 (33%)...
May 5, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28474844/one-pot-synthesis-of-multiple-protein-encapsulated-dna-flowers-and-their-application-in-intracellular-protein-delivery
#18
Eunjung Kim, Limor Zwi-Dantsis, Natalie Reznikov, Catherine S Hansel, Shweta Agarwal, Molly M Stevens
Inspired by biological systems, many biomimetic methods suggest fabrication of functional materials with unique physicochemical properties. Such methods frequently generate organic-inorganic composites that feature highly ordered hierarchical structures with intriguing properties, distinct from their individual components. A striking example is that of DNA-inorganic hybrid micro/nanostructures, fabricated by the rolling circle technique. Here, a novel concept for the encapsulation of bioactive proteins in DNA flowers (DNF) while maintaining the activity of protein payloads is reported...
May 5, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28468581/a-new-insight-on-reciprocal-relationship-between-microrna-expression-and-epigenetic-modifications-in-human-lung-cancer
#19
Roghayeh Sheervalilou, Sakine Shirvaliloo, Sedigheh Fekri Aval, Amir Mahdi Khamaneh, Akbar Sharifi, Khalil Ansarin, Nosratollah Zarghami
Lung cancer stands among the leading causes of cancer-related death in the world. Although the molecular network implicated in lung cancer development is extensively revealed, the mortality rate is only slightly improved. MicroRNAs are small, endogenous single-stranded evolutionary conserved non-coding RNAs which involve in a wide variety of biological processes including cell growth, proliferation, metabolism, and differentiation. MicroRNAs, as novel biomarkers, have multiple functions in normal lung tissue development, and aberrant expression profiles of certain microRNAs could induce lung tumorigenesis...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28467801/inhibition-of-exportin-1-function-results-in-rapid-cell-cycle-associated-dna-damage-in-cancer-cells
#20
Russell T Burke, Joshua M Marcus, James D Orth
Selective inhibitors of nuclear export (SINE) are small molecules in development as anti-cancer agents. The first-in-class SINE, selinexor, is in clinical trials for blood and solid cancers. Selinexor forms a covalent bond with exportin-1 at cysteine-528, and blocks its ability to export cargos. Previous work has shown strong cell cycle effects and drug-induced cell death across many different cancer-derived cell lines. Here, we report strong cell cycle-associated DNA double-stranded break formation upon the treatment of cancer cells with SINE...
April 12, 2017: Oncotarget
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