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[PMID]:29392424
[Au] Autor:Shahkarami S; Mehrasa R; Younesian S; Yaghmaie M; Chahardouli B; Vaezi M; Rezaei N; Nikbakht M; Alimoghaddam K; Ghavamzadeh A; Tavakkoly-Bazzaz J; Ghaffari SH
[Ad] Endereço:Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Minimal residual disease (MRD) detection using rearrangement of immunoglobulin/T cell receptor genes in adult patients with acute lymphoblastic leukemia (ALL).
[So] Source:Ann Hematol;97(4):585-595, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:MRD detection with allele-specific oligonucleotide-quantitative polymerase chain reaction (ASO-qPCR) and using clone-specific immunoglobulin/T cell receptor rearrangements is considered as a powerful prognostic factor in acute lymphoblastic leukemia (ALL). In the present study, we evaluated an ASO-qPCR assay for MRD quantification in peripheral blood (PB) samples of adult patients with ALL. DNA was isolated from PB samples of patients with newly diagnosed ALL. They were first investigated by multiplex-PCR assay to identify V/J usage. An ASO-qPCR technique was then applied for 2.5-year monthly MRD quantification for detection of patient-specific Ig/TCR receptor rearrangements as a molecular target. From 98 patients who were diagnosed as ALL, 72 (73.5%) were enrolled in the present study for MRD detection. MRD was successfully quantified in patients with 1-month interval time. MRD level at the end of induction therapy up to day 88 was the only significant prognostic factor. Regarding MRD level, patients were categorized into two groups of low and high-risk. 2.5-year OS in all three time points (days 28, 58 and 88) were significantly lower in high-risk group (P < 0.008). The results of the 2.5-year MRD detection indicate that MRD level at the end of induction up to about 6 months after the first diagnosis was associated with clinical outcome. This study may highlight the usefulness of PB and the definitions of cut-off level for early prediction of relapse and for stratifying ALL patients. Short-interval time points and frequent PB sampling to monitor MRD level is suggested for early clinical relapse prediction and clinical management of the disease.
[Mh] Termos MeSH primário: Rearranjo Gênico do Linfócito T/efeitos dos fármacos
Quimioterapia de Indução
Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Alelos
Feminino
Seguimentos
Hospitais Universitários
Seres Humanos
Irã (Geográfico)
Masculino
Reação em Cadeia da Polimerase Multiplex
Proteínas de Neoplasias/química
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Neoplasia Residual/diagnóstico
Neoplasia Residual/genética
Neoplasia Residual/metabolismo
Neoplasia Residual/patologia
Oligonucleotídeos/química
Oligonucleotídeos/metabolismo
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Prognóstico
Estudos Prospectivos
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Medição de Risco
Análise de Sobrevida
Carga Tumoral/efeitos dos fármacos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (Oligonucleotides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3230-z


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[PMID]:29238194
[Au] Autor:Du C; Yan H; Liang J; Luo A; Wang L; Zhu J; Xiong H; Chen Y
[Ad] Endereço:Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan.
[Ti] Título:Polyethyleneimine-capped silver nanoclusters for microRNA oligonucleotide delivery and bacterial inhibition.
[So] Source:Int J Nanomedicine;12:8599-8613, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Efficient and safe nonviral gene delivery systems are a prerequisite for the clinical application of therapeutic genes. In this paper, polyethyleneimine-capped silver nanoclusters (PEI-AgNCs) were prepared for the purpose of microRNA (miRNA) delivery. The resultant PEI-AgNCs were characterized by a photoluminescence assay and transmission electron microscopy. A cytotoxicity assay showed that PEI-AgNCs exhibit relatively low cytotoxicity. Interestingly, PEI-AgNCs were confirmed to transfect miRNA mimics more effectively than PEI in HepG2 and 293A cells. In this regard, hsa-miR-21 or hsa-miR-221 mimics (miR-21/221m) were transported into HepG2 cells by using PEI-AgNCs. The miR-21/221 expression was determined post-transfection by quantitative real-time polymerase chain reaction. Compared with the negative control, PEI-AgNCs/miR-21/221m groups exhibited higher miR-21/221 levels. In addition, AgNCs endow PEI with stronger antibacterial activity, and this advantage provided PEI-AgNCs the potential to prevent bacterial contamination during the transfection process. Furthermore, we showed that PEI-AgNCs are viable nanomaterials for plain imaging of the cells by laser scanning confocal microscopy, indicating great potential as an ideal fluorescent probe to track the transfection behavior. These results demonstrated that PEI-AgNCs are promising and novel nonviral vectors for gene delivery.
[Mh] Termos MeSH primário: MicroRNAs/administração & dosagem
Nanoestruturas/química
Polietilenoimina/química
Prata/administração & dosagem
Transfecção/métodos
[Mh] Termos MeSH secundário: Antibacterianos/administração & dosagem
Antibacterianos/farmacologia
Escherichia coli/efeitos dos fármacos
Células HEK293
Células Hep G2
Seres Humanos
MicroRNAs/genética
Microscopia Confocal
Nanoestruturas/administração & dosagem
Oligonucleotídeos/administração & dosagem
Polietilenoimina/farmacologia
Reação em Cadeia da Polimerase em Tempo Real
Prata/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (MIRN21 microRNA, human); 0 (MIRN221 microRNA, human); 0 (MicroRNAs); 0 (Oligonucleotides); 3M4G523W1G (Silver); 9002-98-6 (Polyethyleneimine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S146968


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[PMID]:28453765
[Au] Autor:Marafini I; Monteleone I; Dinallo V; Di Fusco D; De Simone V; Laudisi F; Fantini MC; Di Sabatino A; Pallone F; Monteleone G
[Ad] Endereço:Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
[Ti] Título:CCL20 Is Negatively Regulated by TGF-ß1 in Intestinal Epithelial Cells and Reduced in Crohn's Disease Patients With a Successful Response to Mongersen, a Smad7 Antisense Oligonucleotide.
[So] Source:J Crohns Colitis;11(5):603-609, 2017 May 01.
[Is] ISSN:1876-4479
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background and Aims: The chemokine CCL20 is over-produced in epithelium of Crohn's disease [CD] patients and contributes to recruiting immune cells to inflamed gut. Tumour necrosis factor-α [TNF-α] is a powerful inducer of CCL20 in intestinal epithelial cells. In CD, high levels of Smad7 block the activity of transforming growth factor-ß1 [TGF-ß1], a negative regulator of TNF signalling. We investigated whether intestinal epithelial cell-derived CCL20 is negatively regulated by TGF-ß1 and whether Smad7 knock-down reduces CCL20 in CD. Methods: CCL20 was evaluated in NCM460, a normal colonic epithelial cell line, stimulated with TGF-ß1 and TNF-α, and in Smad7 over-expressing NCM460 cells. CCL20 and Smad7 expression were assessed in sections of CD intestinal specimens by immunochemistry, and in CD colonic explants treated with mongersen, a Smad7 antisense oligonucleotide. CCL20 was examined in serum samples taken from 95 of 166 active CD patients receiving mongersen or placebo for 2 weeks and participating in a phase II, multicentre, double-blind, placebo-controlled study. Results: CCL20 expression was increased by TNF-α, and this effect was inhibited by TGF-ß1 in NCM460 cells, but not in Smad7 over-expressing NCM460 cells. In CD, epithelium CCL20 and Smad7 co-localised, and treatment of CD explants with mongersen reduced CCL20 production. During follow-up, in responders to mongersen, serum CCL20 levels significantly decreased, whereas patients without response/remission to mongersen and placebo patients did not have change in CCL20. Conclusions: TGF-ß1 reduces intestinal epithelial cell-derived CCL20 production, an effect abrogated by Smad7. CD patients responding to mongersen demonstrated a reduction in serum CCL20.
[Mh] Termos MeSH primário: Quimiocina CCL20/metabolismo
Doença de Crohn/tratamento farmacológico
Mucosa Intestinal/metabolismo
Oligonucleotídeos/uso terapêutico
Proteína Smad7/antagonistas & inibidores
Fator de Crescimento Transformador beta1/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Quimiocina CCL20/sangue
Doença de Crohn/metabolismo
Método Duplo-Cego
Seres Humanos
Mucosa Intestinal/efeitos dos fármacos
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (CCL20 protein, human); 0 (Chemokine CCL20); 0 (GED0301); 0 (Oligonucleotides); 0 (SMAD7 protein, human); 0 (Smad7 Protein); 0 (Transforming Growth Factor beta1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/ecco-jcc/jjw191


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[PMID]:29248770
[Au] Autor:Hupert M; Elfgen A; Schartmann E; Schemmert S; Buscher B; Kutzsche J; Willbold D; Santiago-Schübel B
[Ad] Endereço:Forschungszentrum Jülich GmbH, Central Institute for Engineering, Analytics (ZEA-3), Jülich, Germany.
[Ti] Título:Development and validation of an UHPLC-ESI-QTOF-MS method for quantification of the highly hydrophilic amyloid-ß oligomer eliminating all-D-enantiomeric peptide RD2 in mouse plasma.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1073:123-129, 2018 Jan 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:During preclinical drug development, a method for quantification of unlabeled compounds in blood plasma samples from treatment or pharmacokinetic studies in mice is required. In the current work, a rapid, specific, sensitive and validated liquid chromatography mass-spectrometric UHPLC-ESI-QTOF-MS method was developed for the quantification of the therapeutic compound RD2 in mouse plasma. RD2 is an all-D-enantiomeric peptide developed for the treatment of Alzheimer's disease, a progressive neurodegenerative disease finally leading to dementia. Due to RD2's highly hydrophilic properties, the sample preparation and the chromatographic separation and quantification were very challenging. The chromatographic separation of RD2 and its internal standard were accomplished on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm particle size) within 6.5 min at 50 °C with a flow rate of 0.5 mL/min. Mobile phases consisted of water and acetonitrile with 1% formic acid and 0.025% heptafluorobutyric acid, respectively. Ions were generated by electrospray ionization (ESI) in the positive mode and the peptide was quantified by QTOF-MS. The developed extraction method for RD2 from mouse plasma revealed complete recovery. The linearity of the calibration curve was in the range of 5.3 ng/mL to 265 ng/mL (r > 0.999) with a lower limit of detection (LLOD) of 2.65 ng/mL and a lower limit of quantification (LLOQ) of 5.3 ng/mL. The intra-day and inter-day accuracy and precision of RD2 in plasma ranged from -0.54% to 2.21% and from 1.97% to 8.18%, respectively. Moreover, no matrix effects were observed and RD2 remained stable in extracted mouse plasma at different conditions. Using this validated bioanalytical method, plasma samples of unlabeled RD2 or placebo treated mice were analyzed. The herein developed UHPLC-ESI-QTOF-MS method is a suitable tool for the quantitative analysis of unlabeled RD2 in plasma samples of treated mice.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/sangue
Cromatografia Líquida de Alta Pressão/métodos
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/química
Peptídeos beta-Amiloides/isolamento & purificação
Animais
Interações Hidrofóbicas e Hidrofílicas
Limite de Detecção
Modelos Lineares
Masculino
Camundongos
Camundongos Transgênicos
Oligonucleotídeos/isolamento & purificação
Oligonucleotídeos/metabolismo
Reprodutibilidade dos Testes
Espectrometria de Massas por Ionização por Electrospray/métodos
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Oligonucleotides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE


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[PMID]:29443664
[Au] Autor:Mercuri E; Darras BT; Chiriboga CA; Day JW; Campbell C; Connolly AM; Iannaccone ST; Kirschner J; Kuntz NL; Saito K; Shieh PB; Tulinius M; Mazzone ES; Montes J; Bishop KM; Yang Q; Foster R; Gheuens S; Bennett CF; Farwell W; Schneider E; De Vivo DC; Finkel RS; CHERISH Study Group
[Ad] Endereço:From the Department of Pediatric Neurology, Catholic University, Rome (E.M., E.S.M.); the Department of Neurology, Boston Children's Hospital, Boston (B.T.D.), and Biogen, Cambridge (R.F., S.G., W.F.) - both in Massachusetts; the Departments of Neurology (C.A.C., J.M., D.C.D.), Pediatrics (C.A.C., D
[Ti] Título:Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.
[So] Source:N Engl J Med;378(7):625-635, 2018 02 15.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. RESULTS: In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS: Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537 .).
[Mh] Termos MeSH primário: Oligonucleotídeos Antissenso/uso terapêutico
Oligonucleotídeos/uso terapêutico
Atrofias Musculares Espinais da Infância/tratamento farmacológico
[Mh] Termos MeSH secundário: Idade de Início
Criança
Pré-Escolar
Método Duplo-Cego
Feminino
Seres Humanos
Lactente
Injeções Espinhais
Análise dos Mínimos Quadrados
Masculino
Destreza Motora
Oligonucleotídeos/efeitos adversos
Oligonucleotídeos Antissenso/efeitos adversos
Atrofias Musculares Espinais da Infância/fisiopatologia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Oligonucleotides); 0 (Oligonucleotides, Antisense); 0 (nusinersen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1710504


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[PMID]:29336444
[Au] Autor:Protopopova AD; Tsvetkov VB; Varizhuk AM; Barinov NA; Podgorsky VV; Klinov DV; Pozmogova GE
[Ad] Endereço:Biophysics Department, Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, 119435, Russia. klinov.dmitry@mail.ru pozmge@gmail.com.
[Ti] Título:The structural diversity of C-rich DNA aggregates: unusual self-assembly of beetle-like nanostructures.
[So] Source:Phys Chem Chem Phys;20(5):3543-3553, 2018 Jan 31.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We studied the ability of oligonucleotides C T (n = 2, 5, 7, 9, 12, 25) to form an intermolecular i-motif using circular dichroism, ultra-violet spectroscopy, nuclear magnetic resonance, high-resolution atomic force microscopy, high-performance liquid chromatography, and molecular dynamics simulations. The arrangement of single-stranded oligonucleotides in multimer i-motifs was very unusual: C-tracts of different oligonucleotides followed each other consecutively in order to fold into a closed intermolecular i-motif core with minimal loops (one cytidine in a loop spanning over a minor groove, three cytidines in a loop over a major groove); intact T-tracts protruded from predefined loci allowing visualization of beetle-like nanostructures by atomic force microscopy. The same structures were formed from analogous biotinylated oligonucleotides demonstrating one of the potential applications of such structures as carriers of multiple functional groups. Our findings open up possibilities for the rational design of pH-sensitive DNA aggregates and evaluation of the efficiency of their assembly.
[Mh] Termos MeSH primário: Nanoestruturas/química
Oligonucleotídeos/química
[Mh] Termos MeSH secundário: Sequência de Bases
Dicroísmo Circular
Microscopia de Força Atômica
Simulação de Dinâmica Molecular
Ressonância Magnética Nuclear Biomolecular
Conformação de Ácido Nucleico
Oligonucleotídeos/síntese química
Espectrofotometria Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oligonucleotides)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp05380k


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[PMID]:29351348
[Au] Autor:Jasinski M; Kulik M; Wojciechowska M; Stolarski R; Trylska J
[Ad] Endereço:Centre of New Technologies, University of Warsaw, Warsaw, Poland.
[Ti] Título:Interactions of 2'-O-methyl oligoribonucleotides with the RNA models of the 30S subunit A-site.
[So] Source:PLoS One;13(1):e0191138, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Synthetic oligonucleotides targeting functional regions of the prokaryotic rRNA could be promising antimicrobial agents. Indeed, such oligonucleotides were proven to inhibit bacterial growth. 2'-O-methylated (2'-O-Me) oligoribonucleotides with a sequence complementary to the decoding site in 16S rRNA were reported as inhibitors of bacterial translation. However, the binding mode and structures of the formed complexes, as well as the level of selectivity of the oligonucleotides between the prokaryotic and eukaryotic target, were not determined. We have analyzed three 2'-O-Me oligoribonucleotides designed to hybridize with the models of the prokaryotic rRNA containing two neighboring aminoglycoside binding pockets. One pocket is the paromomycin/kanamycin binding site corresponding to the decoding site in the small ribosomal subunit and the other one is the close-by hygromycin B binding site whose dynamics has not been previously reported. Molecular dynamics (MD) simulations, as well as isothermal titration calorimetry, gel electrophoresis and spectroscopic studies have shown that the eukaryotic rRNA model is less conformationally stable (in terms of hydrogen bonds and stacking interactions) than the corresponding prokaryotic one. In MD simulations of the eukaryotic construct, the nucleotide U1498, which plays an important role in correct positioning of mRNA during translation, is flexible and spontaneously flips out into the solvent. In solution studies, the 2'-O-Me oligoribonucleotides did not interact with the double stranded rRNA models but all formed stable complexes with the single-stranded prokaryotic target. 2'-O-Me oligoribonucleotides with one and two mismatches bound less tightly to the eukaryotic target. This shows that at least three mismatches between the 2'-O-Me oligoribonucleotide and eukaryotic rRNA are required to ensure target selectivity. The results also suggest that, in the ribosome environment, the strand invasion is the preferred binding mode of 2'-O-Me oligoribonucleotides targeting the aminoglycoside binding sites in 16S rRNA.
[Mh] Termos MeSH primário: Modelos Moleculares
Oligonucleotídeos/química
RNA Ribossômico 16S/química
[Mh] Termos MeSH secundário: Calorimetria
Eletroforese em Gel de Poliacrilamida
Espectrometria de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Oligonucleotides); 0 (RNA, Ribosomal, 16S)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191138


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[PMID]:29326044
[Au] Autor:Nigam R; Anindya R
[Ad] Endereço:Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Hyderabad 502285, Telangana, India.
[Ti] Título:Escherichia coli single-stranded DNA binding protein SSB promotes AlkB-mediated DNA dealkylation repair.
[So] Source:Biochem Biophys Res Commun;496(2):274-279, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Repair of alkylation damage in DNA is essential for maintaining genome integrity. Escherichia coli (E.coli) protein AlkB removes various alkyl DNA adducts including N1-methyladenine (N meA) and N3-methylcytosine (N meC) by oxidative demethylation. Previous studies showed that AlkB preferentially removes N meA and N meC from single-stranded DNA (ssDNA). It can also remove N meA and N meC from double-stranded DNA by base-flipping. Notably, ssDNA produced during DNA replication and recombination, remains bound to E. coli single-stranded DNA binding protein SSB and it is not known whether AlkB can repair methyl adduct present in SSB-coated DNA. Here we have studied AlkB-mediated DNA repair using SSB-bound DNA as substrate. In vitro repair reaction revealed that AlkB could efficiently remove N meC adducts inasmuch as DNA length is shorter than 20 nucleotides. However, when longer N meC-containing oligonuleotides were used as the substrate, efficiency of AlkB catalyzed reaction was abated compared to SSB-bound DNA substrate of identical length. Truncated SSB containing only the DNA binding domain could also support the stimulation of AlkB activity, suggesting the importance of SSB-DNA interaction for AlkB function. Using 70-mer oligonucleotide containing single N meC we demonstrate that SSB-AlkB interaction promotes faster repair of the methyl DNA adducts.
[Mh] Termos MeSH primário: Reparo do DNA
DNA Bacteriano/genética
Proteínas de Ligação a DNA/genética
Proteínas de Escherichia coli/genética
Escherichia coli/genética
Regulação Bacteriana da Expressão Gênica
Oxigenases de Função Mista/genética
[Mh] Termos MeSH secundário: Alquilação
DNA/genética
DNA/metabolismo
Adutos de DNA/química
Adutos de DNA/metabolismo
Dano ao DNA
Metilação de DNA
DNA Bacteriano/metabolismo
DNA de Cadeia Simples/genética
DNA de Cadeia Simples/metabolismo
Proteínas de Ligação a DNA/metabolismo
Escherichia coli/metabolismo
Proteínas de Escherichia coli/metabolismo
Cinética
Oxigenases de Função Mista/metabolismo
Oligonucleotídeos/química
Oligonucleotídeos/metabolismo
Oxirredução
Ligação Proteica
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA Adducts); 0 (DNA, Bacterial); 0 (DNA, Single-Stranded); 0 (DNA-Binding Proteins); 0 (Escherichia coli Proteins); 0 (Oligonucleotides); 0 (SSB protein, E coli); 9007-49-2 (DNA); EC 1.- (Mixed Function Oxygenases); EC 1.14.11.- (AlkB protein, E coli)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE


  9 / 19402 MEDLINE  
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[PMID]:29230469
[Au] Autor:van Rixel VHS; Moolenaar GF; Siegler MA; Messori L; Bonnet S
[Ad] Endereço:Leiden University, Leiden Institute of Chemistry, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands. bonnet@chem.leidenuniv.nl.
[Ti] Título:Controlling with light the interaction between trans-tetrapyridyl ruthenium complexes and an oligonucleotide.
[So] Source:Dalton Trans;47(2):507-516, 2018 Jan 02.
[Is] ISSN:1477-9234
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Three new trans-ruthenium(ii) complexes coordinated to tetrapyridyl ligands, namely [Ru(bapbpy)(dmso)Cl]Cl ([2]Cl), [Ru(bapbpy)(Hmte) ](PF ) ([3](PF ) ), and [Ru(biqbpy)(Hmte) ](PF ) ([4](PF ) ), were prepared as analogues of [Ru(biqbpy)(dmso)Cl]Cl ([1]Cl), a recently described photoactivated chemotherapy agent. The new complexes were characterized, and their crystal structures showed the distorted coordination octahedron typical of this family of complexes. Their photoreactivity in solution was analyzed by spectrophotometry and mass spectrometry, which showed that the sulfur ligand was substituted upon blue light irradiation. The binding of the ruthenium complexes to a reference single-stranded oligonucleotide (s( CTACGGTTTCAC )) was explored both in the dark and under light irradiation by gel electrophoresis and high-resolution mass spectrometry. While adduct formation in the dark was negligible for the four complexes, light irradiation led to the formation of adducts with one or two ruthenium centers per oligonucleotide. The absence of interactions in the dark and the presence of complex-oligonucleotide adducts demonstrate that visible light controls the interaction of these ruthenium complexes with nucleic acids.
[Mh] Termos MeSH primário: Luz
Oligonucleotídeos/química
Compostos Organometálicos/química
Piridinas/química
Rutênio/química
[Mh] Termos MeSH secundário: Sequência de Bases
Ligantes
Modelos Moleculares
Conformação Molecular
Oligonucleotídeos/genética
Compostos Organometálicos/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Oligonucleotides); 0 (Organometallic Compounds); 0 (Pyridines); 7UI0TKC3U5 (Ruthenium); NH9L3PP67S (pyridine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1039/c7dt03613b


  10 / 19402 MEDLINE  
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[PMID]:29230450
[Au] Autor:Ren W; Zheng K; Liao C; Yang J; Zhao J
[Ad] Endereço:Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. jzhao@iccas.ac.cn.
[Ti] Título:Charge evolution during the unfolding of a single DNA i-motif.
[So] Source:Phys Chem Chem Phys;20(2):916-924, 2018 Jan 03.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The effective charge and evolution of single chains of a DNA i-motif during its unfolding process are investigated at the single molecule level. Using fluorescence correlation spectroscopy and photon counting histograms, the single chain dimensions and electrical potential of cytosine-rich human telomeric oligonucleotides are monitored, during their unfolding from the i-motif to the random coil state. It is discovered that the effective charge density of the DNA chain is very sensitive to conformation changes and the results remarkably expose the existence of an intermediate state of the unfolding process. A huge difference in pH value exists in the vicinity of the DNA chain and the bulk solution, depending on the salt concentration, as reflected by a down-shift in the pH value of unfolding. The presence of an external salt in the solution helps to stabilize the i-motif structure at low pH values due to the reduction of the effective charge density. It can also destabilize the folded structure in the pH range of the conformation transition due to the elevation of the local pH value, encouraging the deprotonation of the cytosine groups. These results provide new information for understanding the structure and stability of i-motif DNA, and its biological function, as well as the building blocks for smart nanomaterials.
[Mh] Termos MeSH primário: DNA/química
Conformação de Ácido Nucleico
Motivos de Nucleotídeos
Dobramento de Proteína
Telômero/química
[Mh] Termos MeSH secundário: Citosina/química
Oligonucleotídeos
Desnaturação Proteica
Espectrometria de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oligonucleotides); 8J337D1HZY (Cytosine); 9007-49-2 (DNA)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp06235d



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