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Dna decoy

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https://www.readbyqxmd.com/read/28903493/editor-s-highlight-formulation-and-toxicology-evaluation-of-the-intrathecal-ayx1-dna-decoy-in-sprague-dawley-rats
#1
Julien Mamet, David C Yeomans, Tony L Yaksh, Donald C Manning, Scott Harris
The longevity of pain after surgery is debilitating and limits the recovery of patients. AYX1 is a double-stranded, unprotected, 23 base-pair oligonucleotide designed to reduce acute post-surgical pain and prevent its chronification with a single intrathecal perioperative dose. AYX1 mimics the DNA sequence normally bound by EGR1 on chromosomes, a transcription factor transiently induced in the dorsal root ganglia-spinal cord network following a noxious input. AYX1 binds to EGR1 and prevents it from launching waves of gene regulation that are necessary to maintain pain over time...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28878400/thiamine-antagonists-trigger-p53-dependent-apoptosis-in-differentiated-sh-sy5y-cells
#2
Sergiy Chornyy, Yulia Parkhomenko, Nataliya Chorna
Accumulating evidences suggest that p53 is a key coordinator of cellular events triggered by oxidative stress often associated with the impairment in thiamine metabolism and its functions. However, there are limited data regarding the pursuant feedback between p53 transactivation and thiamine homeostasis. Impairment in thiamine metabolism can be induced experimentally via interference with the thiamine uptake and/or inhibition of the thiamin pyrophosphate-dependent enzymes using thiamine antagonists - amprolium (AM), oxythiamine (OT) or pyrithiamine (PT)...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865342/inclusion-of-oligonucleotide-antimicrobials-in-biocompatible-cationic-liposomes-a-structural-study
#3
Marianna Mamusa, Francesco Barbero, Costanza Montis, Laura Cutillo, Ana Gonzalez-Paredes, Debora Berti
HYPOTHESIS: Transcription factor decoys (TFD) are short oligonucleotides designed to block essential genetic pathways in bacteria and defeat resistant infections. TFD protection in biological fluids and their delivery to the site of infection require formulation in appropriate delivery systems. In this work, we build on a classical phosphatidylcholine/phosphatidylethanolamine (POPC/DOPE) scaffold to design TFD-loaded cationic liposomes by combining the DNA-complexing abilities of a bolaamphiphile, (1,1'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride (12-bis-THA), with the biocompatible cationic lipid ethyl-phosphatidylcholine (DPePC)...
August 24, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28833847/simultaneous-targeted-inhibition-of-sox2-oct4-transcription-factors-using-decoy-oligodeoxynucleotides-to-repress-stemness-properties-in-mouse-embryonic-stem-cells
#4
Behrooz Johari, Jamil Zargan
Transcriptional master regulators like Sox2 and Oct4, which are expressed in various human tumors, have been shown to cause tumor growth promotion as well as epithelial dysplasia by means of interfering with progenitor cell differentiation. In order to investigate the potential of Sox2-Oct4 transcription factor decoy (TFD) strategy for differentiation therapy, mouse embryonic stem cells (mESCs) were used in this study as a model of cancer stem cells (CSCs). Sox2-Oct4 complex decoy ODNs (cd-ODNs) were designed according to their elements in the promoter region of Sox2 gene...
August 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28815539/long-noncoding-rnas-in-plants
#5
Hsiao-Lin V Wang, Julia A Chekanova
The eukaryotic genomes are pervasively transcribed. In addition to protein-coding RNAs, thousands of long noncoding RNAs (lncRNAs) modulate key molecular and biological processes. Most lncRNAs are found in the nucleus and associate with chromatin, but lncRNAs can function in both nuclear and cytoplasmic compartments. Emerging work has found that many lncRNAs regulate gene expression and can affect genome stability and nuclear domain organization both in plant and in the animal kingdom. Here, we describe the major plant lncRNAs and how they act, with a focus on research in Arabidopsis thaliana and our emerging understanding of lncRNA functions in serving as molecular sponges and decoys, functioning in regulation of transcription and silencing, particularly in RNA-directed DNA methylation, and in epigenetic regulation of flowering time...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815537/from-heterochromatin-to-long-noncoding-rnas-in-drosophila-expanding-the-arena-of-gene-function-and-regulation
#6
Subhash C Lakhotia
Recent years have witnessed a remarkable interest in exploring the significance of pervasive noncoding transcripts in diverse eukaryotes. Classical cytogenetic studies using the Drosophila model system unraveled the perplexing attributes and "functions" of the "gene"-poor heterochromatin. Recent molecular studies in the fly model are likewise revealing the very diverse and significant roles played by long noncoding RNAs (lncRNAs) in development, gene regulation, chromatin organization, cell and nuclear architecture, etc...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814144/-express-intrathecal-administration-of-ayx2-dna-decoy-produces-a-long-term-pain-treatment-in-rat-models-of-chronic-pain-by-inhibiting-the-klf6-klf9-and-klf15-transcription-factors
#7
Julien Mamet, Michael Klukinov, Scott Harris, Donald C Manning, Simon Xie, Conrado Pascual, Bradley K Taylor, Renee R Donahue, David C Yeomans
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28700344/decoy-receptor-1-dcr1-promoter-hypermethylation-and-response-to-irinotecan-in-metastatic-colorectal-cancer
#8
Linda J W Bosch, Geert Trooskens, Petur Snaebjornsson, Veerle M H Coupé, Sandra Mongera, Josien C Haan, Susan D Richman, Miriam Koopman, Jolien Tol, Tim de Meyer, Joost Louwagie, Luc Dehaspe, Nicole C T van Grieken, Bauke Ylstra, Henk M W Verheul, Manon van Engeland, Iris D Nagtegaal, James G Herman, Philip Quirke, Matthew T Seymour, Cornelis J A Punt, Wim van Criekinge, Beatriz Carvalho, Gerrit A Meijer
Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients.Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI))...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28678467/a-two-photon-photocleavable-linker-for-triggering-light-induced-strand-breaks-in-oligonucleotides
#9
Xenia M M Weyel, Manuela A H Fichte, Alexander Heckel
We synthesized a two-photon-sensitive photocleavable linker based on the 7-diethylaminocoumarin structure and introduced it successfully into DNA strands. First, we demonstrated the inducibility of strand scissions upon irradiation at 365 nm. To verify and visualize the two-photon activity, we used a fluorescence assay based on a DNA strand displacement immobilized in a hydrogel. Additionally, we investigated its use in a new class of DNA decoys that are able to catch and release nuclear factor κB (NF-κB) by using light as an external trigger signal...
July 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28642036/transcription-factor-decoy-technology-a-therapeutic-update
#10
REVIEW
Markus Hecker, Andreas H Wagner
Targeting transcription factors represents one possibility to interfere with a known activated regulatory pathway that promotes disease. Double-stranded transcription factor decoy (TFD) oligodeoxynucleotides (ODN) are therapeutic drug candidates, which are able to specifically target and neutralize key transcription factors involved in the pathogenesis of a given disease. These short double-stranded TFD molecules mimic the consensus DNA binding site of a specific transcription factor in the promoter region of its target genes...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28617169/the-frequency-and-associated-factors-for-bk-virus-infection-in-a-center-performing-mainly-living-kidney-transplantations
#11
Selma Alagoz, Mert Kuskucu, Sibel Gulcicek, Serkan Feyyaz Yalin, Meric Oruc, Kenan Midilli, Erkan Yılmaz, Mehmet Riza Altiparmak, Nurhan Seyahi
PURPOSE: BK virus (BKV) nephropathy has increasingly become an important cause of morbidity in renal transplant recipients. We evaluated the frequency and associated factors for BKV infection in a center performing mainly living donor transplantations over a long time period. METHODS: One hundred consecutive renal transplant patients were included. Quarterly visits were planned to examine urine for decoy cells and to measure the BKV DNA in the blood and urine. Renal biopsy was performed in case of deteriorated allograft function...
June 2017: Progress in Transplantation
https://www.readbyqxmd.com/read/28486614/potential-role-of-dna-methylation-as-a-facilitator-of-target-search-processes-for-transcription-factors-through-interplay-with-methyl-cpg-binding-proteins
#12
Catherine A Kemme, Rolando Marquez, Ross H Luu, Junji Iwahara
Eukaryotic genomes contain numerous non-functional high-affinity sequences for transcription factors. These sequences potentially serve as natural decoys that sequester transcription factors. We have previously shown that the presence of sequences similar to the target sequence could substantially impede association of the transcription factor Egr-1 with its targets. In this study, using a stopped-flow fluorescence method, we examined the kinetic impact of DNA methylation of decoys on the search process of the Egr-1 zinc-finger protein...
July 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28484853/protein-sequestration-as-a-normal-function-of-long-noncoding-rnas-and-a-pathogenic-mechanism-of-rnas-containing-nucleotide-repeat-expansions
#13
REVIEW
Ginny R Morriss, Thomas A Cooper
An emerging class of long noncoding RNAs (lncRNAs) function as decoy molecules that bind and sequester proteins thereby inhibiting their normal functions. Titration of proteins by lncRNAs has wide-ranging effects affecting nearly all steps in gene expression. While decoy lncRNAs play a role in normal physiology, RNAs expressed from alleles containing nucleotide repeat expansions can be pathogenic due to protein sequestration resulting in disruption of normal functions. This review focuses on commonalities between decoy lncRNAs that regulate gene expression by competitive inhibition of protein function through sequestration and specific examples of nucleotide repeat expansion disorders mediated by toxic RNA that sequesters RNA-binding proteins and impedes their normal functions...
May 8, 2017: Human Genetics
https://www.readbyqxmd.com/read/28394696/pharmacology-pharmacokinetics-and-metabolism-of-the-dna-decoy-ayx1-for-the-prevention-of-acute-and-chronic-post-surgical-pain
#14
Julien Mamet, Scott Harris, Michael Klukinov, David C Yeomans, Renee R Donahue, Brad K Taylor, Kelly Eddinger, Tony Yaksh, Donald C Manning
Background AYX1 is an unmodified DNA-decoy designed to reduce acute post-surgical pain and its chronification with a single intrathecal dose at the time of surgery. AYX1 inhibits the transcription factor early growth response protein 1, which is transiently induced at the time of injury and triggers gene regulation in the dorsal root ganglia and spinal cord that leads to long-term sensitization and pain. This work characterizes the AYX1 dose-response profile in rats and the link to AYX1 pharmacokinetics and metabolism in the cerebrospinal fluid, dorsal root ganglia, and spinal cord...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28088582/ripk1-protects-hepatocytes-from-kupffer-cells-mediated-tnf-induced-apoptosis-in-mouse-models-of-pamp-induced-hepatitis
#15
Aveline Filliol, Claire Piquet-Pellorce, Céline Raguénès-Nicol, Sarah Dion, Muhammad Farooq, Catherine Lucas-Clerc, Peter Vandenabeele, Mathieu J M Bertrand, Jacques Le Seyec, Michel Samson
BACKGROUND & AIMS: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of pathogen associated molecular patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the receptor interacting protein kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/27959934/mice-with-an-n-ethyl-n-nitrosourea-enu-induced-tyr209asn-mutation-in-natriuretic-peptide-receptor-3-npr3-provide-a-model-for-kyphosis-associated-with-activation-of-the-mapk-signaling-pathway
#16
Christopher T Esapa, Sian E Piret, M Andrew Nesbit, Nellie Y Loh, Gethin Thomas, Peter I Croucher, Matthew A Brown, Steve D M Brown, Roger D Cox, Rajesh V Thakker
Non-syndromic kyphosis is a common disorder that is associated with significant morbidity and has a strong genetic involvement; however, the causative genes remain to be identified, as such studies are hampered by genetic heterogeneity, small families and various modes of inheritance. To overcome these limitations, we investigated 12 week old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments including dysmorphology, radiography, and dual-energy X-ray absorptiometry...
2016: PloS One
https://www.readbyqxmd.com/read/27899652/production-of-dna-minicircles-less-than-250-base-pairs-through-a-novel-concentrated-dna-circularization-assay-enabling-minicircle-design-with-nf-%C3%AE%C2%BAb-inhibition-activity
#17
Thomas Thibault, Jeril Degrouard, Patrick Baril, Chantal Pichon, Patrick Midoux, Jean-Marc Malinge
Double-stranded DNA minicircles of less than 1000 bp in length have great interest in both fundamental research and therapeutic applications. Although minicircles have shown promising activity in gene therapy thanks to their good biostability and better intracellular trafficking, minicircles down to 250 bp in size have not yet been investigated from the test tube to the cell for lack of an efficient production method. Herein, we report a novel versatile plasmid-free method for the production of DNA minicircles comprising fewer than 250 bp...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27893463/inhibition-of-the-gas6-axl-pathway-augments-the-efficacy-of-chemotherapies
#18
Mihalis S Kariolis, Yu Rebecca Miao, Anh Diep, Shannon E Nash, Monica M Olcina, Dadi Jiang, Douglas S Jones, Shiven Kapur, Irimpan I Mathews, Albert C Koong, Erinn B Rankin, Jennifer R Cochran, Amato J Giaccia
The AXL receptor and its activating ligand, growth arrest-specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. However, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. Here, we have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27804999/overexpression-of-soluble-rage-in-mesenchymal-stem-cells-enhances-their-immunoregulatory-potential-for-cellular-therapy-in-autoimmune-arthritis
#19
Min-Jung Park, Seung Hoon Lee, Su-Jin Moon, Jung-Ah Lee, Eun-Jung Lee, Eun-Kyung Kim, Jin-Sil Park, Jennifer Lee, Jun-Ki Min, Seok Jung Kim, Sung-Hwan Park, Mi-La Cho
Mesenchymal stem cells (MSCs) are attractive agents for cellular therapy in rheumatoid arthritis (RA). The receptor for advanced glycation end products (RAGE) serves as a pattern recognition receptor for endogenous inflammatory ligands. Soluble RAGE (sRAGE) is a truncated form of RAGE that functions as a decoy and acts as an anti-inflammatory molecule. The aim of this study was to determine whether sRAGE has therapeutic effects and the mechanisms active in sRAGE-overexpressing MSCs (sRAGE-MSCs) in an experimental model of RA...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27723319/protein-dynamics-and-contact-topology-reveal-protein-dna-binding-orientation
#20
Aravind Chandrasekaran, Justin Chan, Carmay Lim, Lee-Wei Yang
Structure-encoded conformational dynamics are crucial for biomolecular functions. However, there is insufficient evidence to support the notion that dynamics play a role in guiding protein-nucleic acid interactions. Here, we show that protein-DNA docking orientation is a function of protein intrinsic dynamics, but the binding site itself does not display unique patterns in the examined spectrum of motions. This revelation is made possible by a novel technique that locates "dynamics interfaces" in proteins across which protein parts are anticorrelated in their slowest dynamics...
November 8, 2016: Journal of Chemical Theory and Computation
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