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Dna decoy

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 plays 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 anti-correlated in their slowest dynamics...
October 10, 2016: Journal of Chemical Theory and Computation
Zhipeng Wang, Davit A Potoyan, Peter G Wolynes
Eukaryotic transcription factors in the NF-κB family are central components of an extensive genetic network that activates cellular responses to inflammation and to a host of other external stressors. This network consists of feedback loops that involve the inhibitor IκBα, numerous downstream functional targets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-κB becomes oscillatory, and temporal patterns of NF-κB pulses appear to govern the patterns of downstream gene expression needed for immune response...
September 2016: Journal of the Royal Society, Interface
Amanda L Edwards, Dimphna H Meijer, Rachel M Guerra, Remco J Molenaar, John A Alberta, Federico Bernal, Gregory H Bird, Charles D Stiles, Loren D Walensky
Basic helix-loop-helix (bHLH) transcription factors play critical roles in organism development and disease by regulating cell proliferation and differentiation. Transcriptional activity, whether by bHLH homo- or heterodimerization, is dependent on protein-protein and protein-DNA interactions mediated by α-helices. Thus, α-helical decoys have been proposed as potential targeted therapies for pathologic bHLH transcription. Here, we developed a library of stabilized α-helices of OLIG2 (SAH-OLIG2) to test the capacity of hydrocarbon-stapled peptides to disrupt OLIG2 homodimerization, which drives the development and chemoresistance of glioblastoma multiforme, one of the deadliest forms of human brain cancer...
October 4, 2016: ACS Chemical Biology
Sonya VanPatten, Shan Sun, Mingzhu He, Kai Fan Cheng, Ahmad Altiti, Angelos Papatheodorou, Czeslawa Kowal, Venkatesh Jeganathan, James M Crawford, Ona Bloom, Bruce T Volpe, Christian Grant, Nathalie Meurice, Thomas R Coleman, Betty Diamond, Yousef Al-Abed
Systemic lupus erythematosus is an autoimmune disease that can affect numerous tissues and is characterized by the production of nuclear antigen-directed autoantibodies (e.g., anti-dsDNA). Using a combination of virtual and ELISA-based screens, we made the intriguing discovery that several HIV-protease inhibitors can function as decoy antigens to specifically inhibit the binding of anti-dsDNA antibodies to target antigens such as dsDNA and pentapeptide DWEYS. Computational modeling revealed that HIV-protease inhibitors comprised structural features present in DWEYS and predicted that analogues containing more flexible backbones would possess preferred binding characteristics...
October 13, 2016: Journal of Medicinal Chemistry
Yang-Ye Hu, Yuan Wang, Shuang Liang, Xue-Li Yu, Lei Zhang, Lin-Yin Feng, Yi Feng
Over-activated microglia during stroke has been documented to aggravate brain damage. Our previous studies showed that senkyunolide I (SEI) exerted anti-inflammatory effects against endotoxin insult in vitro and ameliorative effects on cerebral ischemia/reperfusion (I/R) injury in vivo. Using oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic stroke, we here investigated the anti-inflammatory effect of SEI on microglial cells and explored the underlying mechanisms. OGD for 3h followed by reoxygenation for 12h significantly enhanced the release of pro-inflammatory cytokines and expressions of inflammation-related enzymes in BV-2 cells, which was inhibited by pretreatment with SEI...
August 11, 2016: Brain Research
A D Ranzi, G O Introíni, J C Prolla, R Brackmann, N C Bassani, A C Pasqualotto, C G Bica
OBJECTIVE: The purpose of the present, prospective, cohort study was to monitor urine cytology samples from recipients of renal transplants to search for the occurrence of decoy cells and degenerated inclusion-bearing cells with an aim to correlate the existence of these cells with molecular detection of polyomavirus BK (BKV) DNA in urine. MATERIAL AND METHODS: This study included patients who underwent renal transplantation. Patients had their urine tested quarterly, during the first year post-transplantation, for the presence of decoy cells and degenerated cells, as well as by quantitative determination of BKV load in the urine and plasma...
August 8, 2016: Cytopathology: Official Journal of the British Society for Clinical Cytology
Catherine A Kemme, Dan Nguyen, Abhijnan Chattopadhyay, Junji Iwahara
Eukaryotic genomic DNA contains numerous high-affinity sites for transcription factors. Only a small fraction of these sites directly regulates target genes. Other high-affinity sites can serve as naturally present decoys that sequester transcription factors. Such natural decoys in genomic DNA may provide novel regulatory mechanisms for transcription factors.
August 7, 2016: Transcription
Jingqiu Li, Haihua Tian, Jie Yang, Zhaohui Gong
The revolutionary findings in nonprotein-coding part of human genome analysis have revealed a large number of RNA transcripts longer than 200 nucleotides that lack coding protein function, termed long noncoding RNAs (lncRNAs). Recently, accumulating shreds of evidence suggest that lncRNAs are widely distributed in human genome and deeply involved in cellular activities such as cell growth, proliferation, and apoptosis. Generally, lncRNAs regulate cell behaviors by targeting cell cycle-associated cyclins, cyclin-dependent kinases (CDKs), and/or CDK inhibitors...
September 2016: DNA and Cell Biology
Xin Liu, Guo Fu, Zhenyu Ji, Xiabing Huang, Cong Ding, Hui Jiang, Xiaolong Wang, Mingxuan Du, Ting Wang, Qiaozhen Kang
Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy...
August 2016: Inflammation
Jing Hu, Daniah Al-Waili, Aishlin Hassan, Guo-Chang Fan, Mei Xin, Jiukuan Hao
The present study generated a novel DNA complex to specifically target endothelial NF-κB to inhibit cerebral vascular inflammation. This DNA complex (GS24-NFκB) contains a DNA decoy which inhibits NF-κB activity, and a DNA aptamer (GS-24), a ligand of transferrin receptor (TfR), which allows for targeted delivery of the DNA decoy into cells. The results indicate that GS24-NFκB was successfully delivered into a murine brain-derived endothelial cell line, bEND5, and inhibited inflammatory responses induced by tumor necrosis factor α (TNF-α) or oxygen-glucose deprivation/re-oxygenation (OGD/R) via down-regulation of the nuclear NF-κB subunit, p65, as well as its downstream inflammatory cytokines, inter-cellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1)...
August 4, 2016: Neuroscience
N H Abd Ellah, L Taylor, N Ayres, M M Elmahdy, G N Fetih, H N Jones, E A Ibrahim, G M Pauletti
Multidrug resistance (MDR), a major cause for chemotherapy failure, has been linked to upregulation of ATP-dependent membrane efflux systems that limit intracellular accumulation of cytotoxic anticancer agents. P-glycoprotein (P-gp) encoded by the human ABCB1 gene was the first efflux transporter identified to contribute to MDR. ABCB1 gene expression is correlated with constitutive activation of the NF-κB signaling pathway in tumor cells. The objective of this research is to modulate P-gp activity in colon cancer cells using NF-κB decoy oligodeoxynucleotides (ODNs) that are effectively delivered into the nucleus of colorectal cancer cells by self-assembling nonviral nanoparticles comprising the novel poly[N-(2-hydroxypropyl)methacrylamide]-poly(N,N-dimethylaminoethylmethacrylate) diblock copolymer (pHPMA-b-pDMAEMA)...
May 2016: Cancer Gene Therapy
Kannan Sridharan, Nithya Jaideep Gogtay
Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are simple linear polymers that have been the subject of considerable research in the last two decades and have now moved into the realm of being stand-alone therapeutic agents. Much of this has stemmed from the appreciation that they carry out myriad functions that go beyond mere storage of genetic information and protein synthesis. Therapy with nucleic acids either uses unmodified DNA or RNA or closely related compounds. From both a development and regulatory perspective, they fall somewhere between small molecules and biologics...
September 2016: British Journal of Clinical Pharmacology
Nicholas B Struntz, Daniel A Harki
Catch and release DNA decoys (CRDDs) are a new class of non-natural DNA probes that capture and dissociate from DNA-binding proteins using a light trigger. Photolytic cleavage of non-natural nucleobases in the CRDD yields abasic sites and truncation products that lower the affinity of the CRDD for its protein target. Herein, we demonstrate the ability of the first-generation CRDD to bind and release NF-κB proteins. This platform technology should be applicable to other DNA-binding proteins by modification of the target sequence...
June 17, 2016: ACS Chemical Biology
Taseem A Mokhdomi, Shoiab Bukhari, Naveed Anjum Chikan, Asif Amin, Asrar H Wafai, Sajad H Wani, Nisar A Chowdri, Raies A Qadri
Vascular endothelial growth factor receptor 1 (VEGFR-1) has been implicated in diverse pathologies, including cancers. Although VEGFR-1 is considered as functionally impaired kinase, its decoy characteristics make it an important regulator of VEGFR-mediated signaling, particularly in tumor angiogenesis. VEGFR-1 conveys signaling via its tyrosine kinase (TK) domain whose activation is regulated by phosphorylation of specific tyrosine residues. Thus dysregulation of VEGFR-1 signaling, as reported in most of the cancers, might be a consequence of altered phosphorylation that could be attributed to genotypic variations in its TK domain...
August 2016: European Journal of Human Genetics: EJHG
I V Kryvdiuk, D O Minchenko, N A Hlushchak, O O Ratushna, L L Karbovskyi, O H Minchenko
Inhibition of IRE1 (inositol requiring enzyme-1), the major signaling pathway of endoplasmic reticulm stress, significantly decreases glioma cell proliferation and tumor growth. We have studied the expression of TNFα-related genes and effect of glucose deprivation on these gene expressions in U87 glioma cells over-expressing dominant-negative IRE1 defective in both kinase and endonuclease (dn-IRE1) activity of IRE1 with hopes of elucidating its contribution to IRE1 mediated glioma growth. We have demonstrated that glucose deprivation condition leads to down-regulation of the expression of TNFRSF11B, TNFRSF1A, TNFRSF10D/TRAILR4, and LITAF genes and up-regulation of TNFRSF10B/TRAILR2/DR5 gene at the mRNA level in control glioma cells...
November 2015: Ukrainian Biochemical Journal
Marianna Mamusa, Claudio Resta, Francesco Barbero, Davide Carta, Doroty Codoni, Kostas Hatzixanthis, Michael McArthur, Debora Berti
Bacterial resistance to antimicrobials is a global threat that requires development of innovative therapeutics that circumvent its onset. The use of Transcription Factor Decoys (TFDs), DNA fragments that act by blocking essential transcription factors in microbes, represents a very promising approach. TFDs require appropriate carriers to protect them from degradation in biological fluids and transfect them through the bacterial cell wall into the cytoplasm, their site of action. Here we report on a bolaform cationic surfactant, [12-bis-THA]Cl2, with proven transfection activity in vivo...
July 1, 2016: Colloids and Surfaces. B, Biointerfaces
Michele Olivieri, Matteo Ferro, Sara Terreri, Montano Durso, Alessandra Romanelli, Concetta Avitabile, Ottavio De Cobelli, Anna Messere, Dario Bruzzese, Ivan Vannini, Luciana Marinelli, Ettore Novellino, Wei Zhang, Mariarosaria Incoronato, Gennaro Ilardi, Stefania Staibano, Laura Marra, Renato Franco, Sisto Perdonà, Daniela Terracciano, Bogdan Czerniak, Giovanna L Liguori, Vincenza Colonna, Muller Fabbri, Ferdinando Febbraio, George A Calin, Amelia Cimmino
Ultraconserved regions (UCRs) have been shown to originate non-coding RNA transcripts (T-UCRs) that have different expression profiles and play functional roles in the pathophysiology of multiple cancers. The relevance of these functions to the pathogenesis of bladder cancer (BlCa) is speculative. To elucidate this relevance, we first used genome-wide profiling to evaluate the expression of T-UCRs in BlCa tissues. Analysis of two datasets comprising normal bladder tissues and BlCa specimens with a custom T-UCR microarray identified ultraconserved RNA (uc...
April 12, 2016: Oncotarget
Miriam Klaus, Nina Prokoph, Mathias Girbig, Xuecong Wang, Yong-Heng Huang, Yogesh Srivastava, Linlin Hou, Kamesh Narasimhan, Prasanna R Kolatkar, Mathias Francois, Ralf Jauch
The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75Å presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone...
May 5, 2016: Nucleic Acids Research
Tomohiro Shiraki, Akiko Tsuzuki, Fumiyuki Toshimitsu, Naotoshi Nakashima
For the first time, the thermodynamics are described for the formation of double-stranded DNA (ds-DNA)-single-walled carbon nanotube (SWNT) hybrids. This treatment is applied to the exchange reaction of sodium cholate (SC) molecules on SWNTs and the ds-DNAs d(A)20 -d(T)20 and nuclear factor (NF)-κB decoy. UV/Vis/near-IR spectroscopy with temperature variations was used for analyzing the exchange reaction on the SWNTs with four different chiralities: (n,m)=(8,3), (6,5), (7,5), and (8,6). Single-stranded DNAs (ss-DNAs), including d(A)20 and d(T)20, are also used for comparison...
March 24, 2016: Chemistry: a European Journal
Mark R Pickard, Gwyn T Williams
Growth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone-sensitive and -insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA...
March 1, 2016: Oncotarget
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