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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]:27777628
[Au] Autor:Brueckner L; van Arensbergen J; Akhtar W; Pagie L; van Steensel B
[Ad] Endereço:Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands.
[Ti] Título:High-throughput assessment of context-dependent effects of chromatin proteins.
[So] Source:Epigenetics Chromatin;9:43, 2016.
[Is] ISSN:1756-8935
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chromatin proteins control gene activity in a concerted manner. We developed a high-throughput assay to study the effects of the local chromatin environment on the regulatory activity of a protein of interest. The assay combines a previously reported multiplexing strategy based on barcoded randomly integrated reporters with Gal4-mediated tethering. We applied the assay to heterochromatin protein 1a (HP1a), which is mostly known as a repressive protein but has also been linked to transcriptional activation. RESULTS: Recruitment to over 1000 genomic locations revealed that HP1a is a potent repressor able to silence even highly expressing reporter genes. However, the local chromatin context can modulate HP1a function. In pericentromeric regions, HP1a-induced repression was enhanced by twofold. In regions marked by a H3K36me3-rich chromatin signature, HP1a-dependent silencing was significantly decreased. We found no evidence for an activating function of HP1a in our experimental system. Furthermore, we did not observe stable transmission of repression over mitotic divisions after loss of targeted HP1a. CONCLUSIONS: The multiplexed tethered reporter assay should be applicable to a large number of chromatin proteins and will be a useful tool to dissect combinatorial regulatory interactions in chromatin.
[Mh] Termos MeSH primário: Cromatina/metabolismo
Proteínas Cromossômicas não Histona/genética
Proteínas de Drosophila/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Proteínas Cromossômicas não Histona/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Inativação Gênica
Histonas/metabolismo
Plasmídeos/genética
Plasmídeos/metabolismo
Elongação da Transcrição Genética
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromatin); 0 (Chromosomal Proteins, Non-Histone); 0 (Drosophila Proteins); 0 (GAL4 protein, Drosophila); 0 (Histones); 0 (Transcription Factors)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180310
[Lr] Data última revisão:
180310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29429182
[Au] Autor:Niu JT; Liu SG; Huang YW; Li C
[Ad] Endereço:Department of Otorhinolaryngology Head and Neck Surgery, Second Hospital, Tianjin Medical University, Tianjin 300221, China.
[Ti] Título:[The effect of miR-497 on laryngeal squamous cell carcinoma invasion through modulating PlexinA4].
[So] Source:Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi;53(2):124-130, 2018 Feb 07.
[Is] ISSN:1673-0860
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To study the roles of miR-497 and PlexinA4 in the progression of laryngeal squamous cell carcinoma. The expressions of miR-497 and PlexinA4 in fresh tumor specimens and adjacent normal mucosa tissues as well as in cell lines of laryngeal squamous cell carcinoma (LSCC) were detected with qRT-PCR and immunohistochemistry. The association of miR-497 and PlexinA4 expressions with clinicopathologic factors and their prognostic values in LSCC were evaluated PlexinA4 siRNA and pcDNA3.1 (+ )/PlexinA4 plasmid were transfected into the LSCC and measured by Transwell to evaluate their effect on the invasion of LSCC. miR-497 was low expression in LSCC, which related to pathological differentiation, while PlexinA4 mRNA was high expression in LSCC. Kaplan-Meier method showed that the prognosis of patients with high miR-497 expression was better than that of patients with low miR-497 expression (χ(2)=10.342, =0.001); . Cox regression analysis showed that miR-497 was an independent prognostic factor for LSCC. The double luciferase reporter gene showed that the variation of the fluorescence activity of wild type PlexinA4 was significantly different from that of the control group ( <0.01). In Hep-2 and TU212 cell line, the number of cells with PlexinA4 siRNA passing through the compartments was 70.00±10.85 and 85.00±6.45, significantly higher than control ( values were 30.251 and 23.936, both <0.05), the number of cells with pcDNA3.1 (+ ) /PlexinA4 was 170.56±11.95 and 142.00±10.43, also significantly less than control (F values were 35.104 and 29.643, both <0.05). The expression of miR-497 in LSCC is decreased, indicating poor prognosis, which is as an independent risk factor for prognosis of LSCC. miR-497 may modulate LSCC invasion through PlexinA4.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/metabolismo
Neoplasias Laríngeas/metabolismo
MicroRNAs/metabolismo
Receptores de Superfície Celular/metabolismo
[Mh] Termos MeSH secundário: Carcinoma de Células Escamosas/patologia
Proliferação Celular
Progressão da Doença
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Mucosa Laríngea/metabolismo
Neoplasias Laríngeas/mortalidade
Neoplasias Laríngeas/patologia
Prognóstico
RNA Interferente Pequeno
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN497 microRNA, human); 0 (MicroRNAs); 0 (Plxna4 protein, human); 0 (RNA, Small Interfering); 0 (Receptors, Cell Surface)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.1673-0860.2018.02.008


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[PMID]:28453731
[Au] Autor:Demolli S; Doddaballapur A; Devraj K; Stark K; Manavski Y; Eckart A; Zehendner CM; Lucas T; Korff T; Hecker M; Massberg S; Liebner S; Kaluza D; Boon RA; Dimmeler S
[Ad] Endereço:Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany.
[Ti] Título:Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D.
[So] Source:Cardiovasc Res;113(6):681-691, 2017 May 01.
[Is] ISSN:1755-3245
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aims: Vessel maturation involves the recruitment of mural cells such as pericytes and smooth muscle cells. Laminar shear stress is a major trigger for vessel maturation, but the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs (miRs) are small non-coding RNAs, which post-transcriptionally control gene expression. The aim of the present study was to unveil the mechanism by which shear stress-regulated microRNAs contribute to vessel maturation. Methods and results: Here, we show that laminar shear stress increased miR-27a and miR-27b expression in vitro and in ex vivo in mouse femoral artery explants. Overexpression of miR-27b in endothelial cells increased pericyte adhesion and pericyte recruitment in vitro. In vitro barrier function of endothelial-pericyte co-cultures was augmented by miR-27b overexpression, whereas inhibition of miR-27a/b reduced adhesion and pericyte coverage and decreased barrier functions. In vivo, pharmacological inhibition of miR-27a/b by locked nucleic acid antisense oligonucleotides significantly reduced pericyte coverage and increased water content in the murine uterus. MiR-27b overexpression repressed semaphorins (SEMA), which mediate repulsive signals, and the vessel destabilizing human but not mouse Angiopoietin-2 (Ang-2). Silencing of SEMA6A and SEMA6D rescued the reduced pericyte adhesion by miR-27 inhibition. Furthermore, inhibition of SEMA6D increased barrier function of an endothelial-pericyte co-culture in vitro. Conclusion: The present study demonstrates for the first time that shear stress-regulated miR-27b promotes the interaction of endothelial cells with pericytes, partly by repressing SEMA6A and SEMA6D.
[Mh] Termos MeSH primário: Encéfalo/irrigação sanguínea
Comunicação Celular
Movimento Celular
Células Endoteliais/metabolismo
Mecanotransdução Celular
Microvasos/metabolismo
Pericitos/metabolismo
Semaforinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Técnicas de Cocultura
Células Endoteliais da Veia Umbilical Humana/metabolismo
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
MicroRNAs/genética
MicroRNAs/metabolismo
Interferência de RNA
Semaforinas/genética
Estresse Mecânico
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN27 microRNA, human); 0 (MicroRNAs); 0 (Mirn27 microRNA, mouse); 0 (SEMA6A protein, human); 0 (Sema6a protein, mouse); 0 (Sema6d protein, mouse); 0 (Semaphorins)
[Em] Mês de entrada:1802
[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/cvr/cvx032


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[PMID]:28468789
[Au] Autor:Bobi J; Solanes N; Fernández-Jiménez R; Galán-Arriola C; Dantas AP; Fernández-Friera L; Gálvez-Montón C; Rigol-Monzó E; Agüero J; Ramírez J; Roqué M; Bayés-Genís A; Sánchez-González J; García-Álvarez A; Sabaté M; Roura S; Ibáñez B; Rigol M
[Ad] Endereço:August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Institut de Malalties Cardiovasculars, Hospital Clínic de Barcelona, Universitat de Barcelona, Spain.
[Ti] Título:Intracoronary Administration of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction.
[So] Source:J Am Heart Assoc;6(5), 2017 May 03.
[Is] ISSN:2047-9980
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. METHODS AND RESULTS: Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6±6% versus 55.9±5.7% in vehicle; =0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; =0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; =0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; =0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118±18 versus 92.4±24.3 vessels/mm in vehicle; =0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. CONCLUSIONS: In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. No effect on left ventricular volumes or ejection fraction was observed.
[Mh] Termos MeSH primário: Tecido Adiposo/citologia
Circulação Coronária
Transplante de Células-Tronco Mesenquimais/métodos
Células Mesenquimais Estromais
Infarto do Miocárdio/cirurgia
Disfunção Ventricular Esquerda/cirurgia
Função Ventricular Esquerda
[Mh] Termos MeSH secundário: Proteínas Angiogênicas/metabolismo
Animais
Células Cultivadas
Angiografia por Tomografia Computadorizada
Angiografia Coronária/métodos
Citocinas/metabolismo
Modelos Animais de Doenças
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Imagem por Ressonância Magnética
Masculino
Transplante de Células-Tronco Mesenquimais/efeitos adversos
Células Mesenquimais Estromais/metabolismo
Tomografia Computadorizada Multidetectores
Infarto do Miocárdio/diagnóstico por imagem
Infarto do Miocárdio/metabolismo
Infarto do Miocárdio/fisiopatologia
Miocárdio/metabolismo
Miocárdio/patologia
Neovascularização Fisiológica
Imagem de Perfusão/métodos
Recuperação de Função Fisiológica
Regeneração
Sus scrofa
Fatores de Tempo
Transfecção
Transplante Homólogo
Disfunção Ventricular Esquerda/diagnóstico por imagem
Disfunção Ventricular Esquerda/metabolismo
Disfunção Ventricular Esquerda/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenic Proteins); 0 (Cytokines); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


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[PMID]:28743825
[Au] Autor:Navarro Negredo P; Edgar JR; Wrobel AG; Zaccai NR; Antrobus R; Owen DJ; Robinson MS
[Ad] Endereço:Cambridge Institute for Medical Research, University of Cambridge, Cambridge, England, UK.
[Ti] Título:Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting.
[So] Source:J Cell Biol;216(9):2927-2943, 2017 Sep 04.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1. In vitro experiments showed that the basic patch on µ1 that interacts with the Nef acidic cluster also contributes to the binding of endogenous acidic cluster proteins. Surprisingly, µ1 mutant proteins lacking the basic patch and/or the tyrosine-based motif binding pocket could rescue the µ1 knockout phenotype completely. In contrast, these mutants failed to rescue Nef-induced down-regulation of MHC class I, suggesting a possible mechanism for attacking the virus while sparing the host cell.
[Mh] Termos MeSH primário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Subunidades mu do Complexo de Proteínas Adaptadoras/metabolismo
Vesículas Revestidas por Clatrina/metabolismo
HIV-1/metabolismo
Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/química
Complexo 1 de Proteínas Adaptadoras/genética
Subunidades mu do Complexo de Proteínas Adaptadoras/química
Subunidades mu do Complexo de Proteínas Adaptadoras/genética
Sistemas CRISPR-Cas
Citometria de Fluxo
Técnicas de Silenciamento de Genes
Genótipo
Células HEK293
HIV-1/genética
Células HeLa
Antígenos de Histocompatibilidade Classe I/genética
Antígenos de Histocompatibilidade Classe I/metabolismo
Interações Hospedeiro-Patógeno
Seres Humanos
Modelos Moleculares
Mutação
Fenótipo
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Transporte Proteico
Relação Estrutura-Atividade
Fatores de Tempo
Transfecção
Produtos do Gene nef do Vírus da Imunodeficiência Humana/química
Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AP1M1 protein, human); 0 (Adaptor Protein Complex 1); 0 (Adaptor Protein Complex mu Subunits); 0 (Histocompatibility Antigens Class I); 0 (nef Gene Products, Human Immunodeficiency Virus); 0 (nef protein, Human immunodeficiency virus 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201602058


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[PMID]:28448657
[Au] Autor:Drögemöller BI; Monzon JG; Bhavsar AP; Borrie AE; Brooks B; Wright GEB; Liu G; Renouf DJ; Kollmannsberger CK; Bedard PL; Aminkeng F; Amstutz U; Hildebrand CA; Gunaretnam EP; Critchley C; Chen Z; Brunham LR; Hayden MR; Ross CJD; Gelmon KA; Carleton BC
[Ad] Endereço:Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
[Ti] Título:Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer.
[So] Source:JAMA Oncol;3(11):1558-1562, 2017 Nov 01.
[Is] ISSN:2374-2445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Cisplatin-induced ototoxic effects are an important complication that affects testicular cancer survivors as a consequence of treatment. The identification of genetic variants associated with this adverse drug reaction will further our mechanistic understanding of its development and potentially lead to strategies to prevent ototoxic effects. Objective: To identify the genetic variants associated with cisplatin-induced ototoxic effects in adult testicular cancer patients. Design, Setting, and Participants: This retrospective study was performed by the Canadian Pharmacogenomics Network for Drug Safety using patients recruited from 5 adult oncology treatment centers across Canada. Male patients who were 17 years or older, diagnosed with germ cell testicular cancer, and previously treated with cisplatin-based chemotherapy were recruited from July 2009 to April 2013 using active surveillance methodology. Cisplatin-induced ototoxic effects were independently diagnosed by 2 audiologists. Patients were genotyped for 7907 variants using a custom pharmacogenomic array. Logistic regression was used to identify genetic variants that were significantly associated with ototoxic effects. The validity of these findings was confirmed through independent replication and cell-based functional assays. Exposures: Cisplatin-based chemotherapy. Main Outcomes and Measures: Cisplatin-induced ototoxic effects. Results: After exclusions, 188 patients (median [interquartile range] age, 31 [24-39] years) were enrolled in this study to form the discovery and replication cohorts. Association and fine-mapping analyses identified a protein-coding variant, rs4788863 in SLC16A5, that was associated with protection against cisplatin-induced ototoxic effects in 2 independent cohorts (combined cohort: odds ratio, 0.06; 95% CI, 0.02-0.22; P = 2.17 × 10-7). Functional validation of this transporter gene revealed that in vitro SLC16A5-silencing altered cellular responses to cisplatin treatment, supporting a role for SLC16A5 in the development of cisplatin-induced ototoxic effects. These results were further supported by the literature, which provided confirmatory evidence for the role that SLC16A5 plays in hearing. Conclusions and Relevance: This study has identified a novel association between protein-coding variation in SLC16A5 and cisplatin-induced ototoxic effects. These findings have provided insight into the molecular mechanisms of this adverse drug reaction in adult patients with germ cell testicular cancer. Given that previous studies have shown that cimetidine, an SLC16A5-inhibitor, prevents murine cisplatin-induced ototoxic effects, the findings from this study have important implications for otoprotectant strategies in humans.
[Mh] Termos MeSH primário: Antineoplásicos/efeitos adversos
Cisplatino/efeitos adversos
Perda Auditiva/induzido quimicamente
Perda Auditiva/genética
Transportadores de Ácidos Monocarboxílicos/genética
Variantes Farmacogenômicos
Neoplasias Testiculares/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Canadá
Relação Dose-Resposta a Droga
Predisposição Genética para Doença
Células HeLa
Perda Auditiva/diagnóstico
Perda Auditiva/metabolismo
Seres Humanos
Modelos Logísticos
Masculino
Transportadores de Ácidos Monocarboxílicos/efeitos dos fármacos
Transportadores de Ácidos Monocarboxílicos/metabolismo
Farmacogenética
Testes Farmacogenômicos
Fenótipo
Interferência de RNA
Estudos Retrospectivos
Fatores de Risco
Transfecção
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Monocarboxylic Acid Transporters); 0 (SLC16A5 protein, human); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1001/jamaoncol.2017.0502


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[PMID]:29220646
[Au] Autor:Hu P; Fabyanic E; Kwon DY; Tang S; Zhou Z; Wu H
[Ad] Endereço:Department of Genetics, University of Pennsylvania, Philadelphia PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA 19104, USA.
[Ti] Título:Dissecting Cell-Type Composition and Activity-Dependent Transcriptional State in Mammalian Brains by Massively Parallel Single-Nucleus RNA-Seq.
[So] Source:Mol Cell;68(5):1006-1015.e7, 2017 Dec 07.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Massively parallel single-cell RNA sequencing can precisely resolve cellular diversity in a high-throughput manner at low cost, but unbiased isolation of intact single cells from complex tissues such as adult mammalian brains is challenging. Here, we integrate sucrose-gradient-assisted purification of nuclei with droplet microfluidics to develop a highly scalable single-nucleus RNA-seq approach (sNucDrop-seq), which is free of enzymatic dissociation and nucleus sorting. By profiling ∼18,000 nuclei isolated from cortical tissues of adult mice, we demonstrate that sNucDrop-seq not only accurately reveals neuronal and non-neuronal subtype composition with high sensitivity but also enables in-depth analysis of transient transcriptional states driven by neuronal activity, at single-cell resolution, in vivo.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Córtex Cerebral/metabolismo
Sequenciamento de Nucleotídeos em Larga Escala
Neurônios/metabolismo
RNA/genética
Convulsões/genética
Análise de Sequência de RNA/métodos
Análise de Célula Única/métodos
Transcrição Genética
[Mh] Termos MeSH secundário: Animais
Núcleo Celular/patologia
Centrifugação com Gradiente de Concentração
Córtex Cerebral/patologia
Córtex Cerebral/fisiopatologia
Modelos Animais de Doenças
Células-Tronco Embrionárias Humanas/metabolismo
Seres Humanos
Cinética
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Técnicas Analíticas Microfluídicas
Células NIH 3T3
Inibição Neural
Neurônios/patologia
Pentilenotetrazol
RNA/metabolismo
Convulsões/metabolismo
Convulsões/patologia
Convulsões/fisiopatologia
Transmissão Sináptica
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
63231-63-0 (RNA); WM5Z385K7T (Pentylenetetrazole)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:27775991
[Au] Autor:Kan B; Yang L; Wen YJ; Yang JR; Niu T; Li J; Deng HX; Wei W; Chen LG; Zhang Q; Wang W; Wei YQ
[Ad] Endereço:aState Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy bDepartment of Emergency, West China Hospital, Sichuan University, Chengdu cSchool of Pharmaceutical Sciences, Tsinghua University, Beijing dState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, People's Republic of China.
[Ti] Título:Irradiated VEGF164-modified tumor cell vaccine protected mice from the parental tumor challenge.
[So] Source:Anticancer Drugs;28(2):197-205, 2017 02.
[Is] ISSN:1473-5741
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Vascular endothelial growth factor (VEGF) is an important regulating molecule of angiogenesis in tumor formation and progression. Cancer cells always secrete VEGF to stimulate angiogenesis that facilitate growth and invasion of the tumor. In this study, we established a VEGF164 overexpressing LL/2 lung cancer cell model and found that the postirradiated VEGF164-modified tumor cells protected the host against the challenge with LL/2 wild-type tumor cells. Histochemical assay showed that there were large areas of tumor necrosis with macrophage infiltration in the mice vaccinated with the VEGF164-modified tumor vaccine. T-cells isolated from the vaccinated mice showed cytotoxicity against the parental tumor cells in a dose-dependent manner. Meanwhile, sera from the mice vaccinated with LL/2-VEGF164 showed higher titers of antibodies against parental tumor cells compared with the nonvaccinated groups. Our results indicated that VEGF164-modified tumor vaccine could modulate host antitumor immune response and hold therapeutic potential for cancer.
[Mh] Termos MeSH primário: Vacinas Anticâncer/imunologia
Imunoterapia Adotiva/métodos
Neoplasias Pulmonares/imunologia
Neoplasias Pulmonares/terapia
Fator A de Crescimento do Endotélio Vascular/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Vacinas Anticâncer/genética
Relação Dose-Resposta Imunológica
Feminino
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Linfócitos T Citotóxicos/imunologia
Transfecção
Fator A de Crescimento do Endotélio Vascular/biossíntese
Fator A de Crescimento do Endotélio Vascular/genética
Fator A de Crescimento do Endotélio Vascular/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cancer Vaccines); 0 (Vascular Endothelial Growth Factor A); 0 (vascular endothelial growth factor A, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1097/CAD.0000000000000447


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[PMID]:29352320
[Au] Autor:Zhou X; Desai R; Zhang Y; Stec WJ; Miller KW; Jounaidi Y
[Ad] Endereço:Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
[Ti] Título:High-level production and purification in a functional state of an extrasynaptic gamma-aminobutyric acid type A receptor containing α4ß3δ subunits.
[So] Source:PLoS One;13(1):e0191583, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The inhibitory γ-aminobutyric acid type A receptors are implicated in numerous physiological processes, including cognition and inhibition of neurotransmission, rendering them important molecular targets for many classes of drugs. Functionally, the entire GABAAR family of receptors can be subdivided into phasic, fast acting synaptic receptors, composed of α-, ß- and γ-subunits, and tonic extrasynaptic receptors, many of which contain the δ-subunit in addition to α- and ß-subunits. Whereas the subunit arrangement of the former group is agreed upon, that of the αßδ GABAARs remains unresolved by electrophysiological and pharmacological research. To resolve such issues will require biophysical techniques that demand quantities of receptor that have been previously unavailable. Therefore, we have engineered a stable cell line with tetracycline inducible expression of human α4-, ß3- and N-terminally Flag-tagged δ-subunits. This cell line achieved a specific activity between 15 and 20 pmol [3H]muscimol sites/mg of membrane protein, making it possible to obtain 1 nmole of purified α4ß3δ GABAAR from sixty 15-cm culture dishes. When induced, these cells exhibited agonist-induced currents with characteristics comparable to those previously reported for this receptor and a pharmacology that included strong modulation by etomidate and the δ-subunit-specific ligand, DS2. Immunoaffinity purification and reconstitution in CHAPS/asolectin micelles resulted in the retention of equilibrium allosteric interactions between the separate agonist, anesthetic and DS2 sites. Moreover, all three subunits retained glycosylation. The establishment of this well-characterized cell line will allow molecular level studies of tonic receptors to be undertaken.
[Mh] Termos MeSH primário: Receptores de GABA-A/biossíntese
[Mh] Termos MeSH secundário: Fenômenos Eletrofisiológicos
Células HEK293
Seres Humanos
Cinética
Engenharia de Proteínas
Subunidades Proteicas
Ensaio Radioligante
Receptores de GABA-A/genética
Receptores de GABA-A/isolamento & purificação
Proteínas Recombinantes de Fusão/biossíntese
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/isolamento & purificação
Transfecção
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Protein Subunits); 0 (Receptors, GABA-A); 0 (Recombinant Fusion Proteins); 56-12-2 (gamma-Aminobutyric Acid)
[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:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191583



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