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  1 / 1981 MEDLINE  
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[PMID]:29214531
[Au] Autor:Zhang J; Liang L; Guan X; Deng R; Qu H; Huang D; Xu S; Liang C; Xu W
[Ad] Endereço:State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun, Jilin, 130012, China.
[Ti] Título:In situ, accurate, surface-enhanced Raman scattering detection of cancer cell nucleus with synchronous location by an alkyne-labeled biomolecular probe.
[So] Source:Anal Bioanal Chem;410(2):585-594, 2018 Jan.
[Is] ISSN:1618-2650
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A surface-enhanced Raman scattering (SERS) method for in situ detection and analysis of the intranuclear biomolecular information of a cell has been developed based on a small, biocompatible, nuclear-targeting alkyne-tagged deoxyribonucleic acid (DNA) probe (5-ethynyl-2'-deoxyuridine, EDU) that can specially accumulate in the cell nucleus during DNA replications to precisely locate the nuclear region without disturbance in cell biological activities and functions. Since the specific alkyne group shows a Raman peak in the Raman-silent region of cells, it is an interior label to visualize the nuclear location synchronously in real time when measuring the SERS spectra of a cell. Because no fluorescent-labeled dyes were used for locating cell nuclei, this method is simple, nondestructive, non- photobleaching, and valuable for the in situ exploration of vital physiological processes with DNA participation in cell organelles. Graphical abstract A universal strategy was developed to accurately locate the nuclear region and obtain precise molecular information of cell nuclei by SERS.
[Mh] Termos MeSH primário: Alquinos/análise
Núcleo Celular/patologia
Desoxiuridina/análogos & derivados
Neoplasias/patologia
[Mh] Termos MeSH secundário: Núcleo Celular/química
Desoxiuridina/análise
Seres Humanos
Células MCF-7
Microscopia de Fluorescência/métodos
Neoplasias/química
Imagem Óptica/métodos
Análise Espectral Raman/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkynes); G373S00W2J (5-ethynyl-2'-deoxyuridine); W78I7AY22C (Deoxyuridine)
[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:171208
[St] Status:MEDLINE
[do] DOI:10.1007/s00216-017-0761-4


  2 / 1981 MEDLINE  
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[PMID]:28966282
[Au] Autor:Ito Y; Matsuo M; Osawa T; Hari Y
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Tokushima Bunri University.
[Ti] Título:Triplex- and Duplex-Forming Abilities of Oligonucleotides Containing 2'-Deoxy-5-trifluoromethyluridine and 2'-Deoxy-5-trifluoromethylcytidine.
[So] Source:Chem Pharm Bull (Tokyo);65(10):982-988, 2017.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:A facile synthesis of 2'-deoxy-5-trifluoromethyluridine and 2'-deoxy-5-trifluoromethylcytidine phosphoramidites from commercially available 2'-deoxyuridine and 2'-deoxycytidine was achieved, respectively. The obtained phosphoramidites were incorporated into oligonucleotides, and their binding affinity to double-stranded DNA (dsDNA) and single-stranded RNA (ssRNA) was evaluated by UV-melting experiments. The triplex-forming abilities of oligonucleotides including 5-trifluoromethylpyrimidine nucleobases with dsDNA were decreased. Especially, the stability of the triplex containing a trifluoromethylcytosine ( C)-GC base triplet was low, likely due to the low pK of protonated C by the electron-withdrawing trifluoromethyl group. A slight decrease in stability of the duplex formed with ssRNA by oligonucleotides including 5-trifluoromethylpyrimidine nucleobases was only observed, suggesting that they might be applicable to various ssRNA-targeted technologies using features of fluorine atoms.
[Mh] Termos MeSH primário: Desoxicitidina/análogos & derivados
Desoxiuridina/análogos & derivados
Oligonucleotídeos/síntese química
[Mh] Termos MeSH secundário: Pareamento de Bases
DNA/química
DNA/metabolismo
Cinética
Desnaturação de Ácido Nucleico/efeitos da radiação
RNA/química
RNA/metabolismo
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oligonucleotides); 0 (triplex DNA); 0W860991D6 (Deoxycytidine); 63231-63-0 (RNA); 9007-49-2 (DNA); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00530


  3 / 1981 MEDLINE  
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[PMID]:28622881
[Au] Autor:Pinho P; Kalayanov G; Westerlind H; Rosenquist Å; Wähling H; Sund C; Almeida M; Ayesa S; Tejbrant J; Targett-Adams P; Eneroth A; Lindqvist A
[Ad] Endereço:Medivir AB, Box 1086, 141 22 Huddinge, Sweden. Electronic address: pedro.pinho@medivir.com.
[Ti] Título:Discovery of ß-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of hepatitis C virus replication.
[So] Source:Bioorg Med Chem Lett;27(15):3468-3471, 2017 08 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Discovery of sofosbuvir has radically changed hepatitis C treatment and nucleoside/tide NS5B inhibitors are now viewed as one of the key components in combination therapies with other direct-acting antiviral agents. As part of our program to identify new nucleoside inhibitors of HCV replication, we now wish to report on the discovery of ß-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of HCV replication. Although, cytidine analogues have long been recognized to be metabolized to both cytidine and uridine triphosphates through the action of cytidine deaminase, uridine analogues are generally believed to produce exclusively uridine triphosphate. Detailed investigation of the intracellular metabolism of our newly discovered uridine prodrugs, as well as of sofosbuvir, has now revealed the formation of both uridine and cytidine triphosphates. This occurs, not only in vitro in cell lines, but also in vivo upon oral dosing to dogs.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Desoxiuridina/análogos & derivados
Hepacivirus/efeitos dos fármacos
Hepatite C/tratamento farmacológico
Pró-Fármacos/farmacologia
Proteínas não Estruturais Virais/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antivirais/química
Antivirais/metabolismo
Células Cultivadas
Desoxiuridina/química
Desoxiuridina/metabolismo
Desoxiuridina/farmacologia
Cães
Descoberta de Drogas
Hepacivirus/fisiologia
Hepatite C/virologia
Hepatócitos/metabolismo
Hepatócitos/virologia
Seres Humanos
Pró-Fármacos/química
Pró-Fármacos/metabolismo
Proteínas não Estruturais Virais/metabolismo
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (NS-5 protein, hepatitis C virus); 0 (Prodrugs); 0 (Viral Nonstructural Proteins); 4753-04-2 (2'-chloro-2'-deoxyuridine); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170618
[St] Status:MEDLINE


  4 / 1981 MEDLINE  
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[PMID]:28583799
[Au] Autor:Hasegawa Y; Takada T; Nakamura M; Yamana K
[Ad] Endereço:Department of Materials Science and Chemistry, University of Hyogo, 2167 Shosha, Himeji 671-2280, Japan.
[Ti] Título:Ferrocene conjugated oligonucleotide for electrochemical detection of DNA base mismatch.
[So] Source:Bioorg Med Chem Lett;27(15):3555-3557, 2017 08 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We describe the synthesis, binding, and electrochemical properties of ferrocene-conjugated oligonucleotides (Fc-oligos). The key step for the preparation of Fc-oligos contains the coupling of vinylferrocene to 5-iododeoxyuridine via Heck reaction. The Fc-conjugated deoxyuridine phosphoramidite was used in the Fc-oligonucleotide synthesis. We show that thiol-modified Fc-oligos deposited onto gold electrodes possess potential ability in electrochemical detection of DNA base mismatch.
[Mh] Termos MeSH primário: Pareamento Incorreto de Bases
DNA/genética
Desoxiuridina/análogos & derivados
Técnicas Eletroquímicas/métodos
Compostos Ferrosos/química
Oligonucleotídeos/química
[Mh] Termos MeSH secundário: Sequência de Bases
DNA/química
Eletrodos
Ouro/química
Idoxuridina/química
Metalocenos
Compostos de Vinila/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ferrous Compounds); 0 (Metallocenes); 0 (Oligonucleotides); 0 (Vinyl Compounds); 1271-51-8 (vinylferrocene); 7440-57-5 (Gold); 9007-49-2 (DNA); LGP81V5245 (Idoxuridine); U96PKG90JQ (ferrocene); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE


  5 / 1981 MEDLINE  
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[PMID]:28570836
[Au] Autor:Czarny P; Merecz-Sadowska A; Majchrzak K; Jablkowski M; Szemraj J; Sliwinski T; Karwowski B
[Ad] Endereço:1 Department of Medical Biochemistry, Medical University of Lodz , Lodz, Poland .
[Ti] Título:The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells.
[So] Source:DNA Cell Biol;36(7):535-540, 2017 Jul.
[Is] ISSN:1557-7430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Núcleo Celular/efeitos dos fármacos
Reparo do DNA
DNA/genética
Leucócitos Mononucleares/efeitos dos fármacos
Mitocôndrias/efeitos dos fármacos
[Mh] Termos MeSH secundário: Anilidas/farmacologia
Carbamatos/farmacologia
Núcleo Celular/metabolismo
Núcleo Celular/virologia
DNA/metabolismo
Quebras de DNA de Cadeia Dupla
DNA Glicosilases/genética
DNA Glicosilases/metabolismo
DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética
DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo
Desoxiuridina/metabolismo
Quimioterapia Combinada
Endonucleases/genética
Endonucleases/metabolismo
Expressão Gênica
Hepacivirus/efeitos dos fármacos
Hepacivirus/crescimento & desenvolvimento
Hepatite C Crônica/tratamento farmacológico
Hepatite C Crônica/virologia
Interações Hospedeiro-Patógeno
Seres Humanos
Leucócitos Mononucleares/metabolismo
Leucócitos Mononucleares/virologia
Compostos Macrocíclicos/farmacologia
Mitocôndrias/metabolismo
Mitocôndrias/virologia
Mimetismo Molecular
Cultura Primária de Células
Ribavirina/farmacologia
Ritonavir/farmacologia
Sulfonamidas/farmacologia
Uracila/análogos & derivados
Uracila/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-267); 0 (ABT-333); 0 (ABT-450); 0 (Anilides); 0 (Antiviral Agents); 0 (Carbamates); 0 (Macrocyclic Compounds); 0 (Sulfonamides); 49717AWG6K (Ribavirin); 56HH86ZVCT (Uracil); 9007-49-2 (DNA); EC 3.1.- (Endonucleases); EC 3.2.2.- (DNA Glycosylases); EC 3.2.2.- (oxoguanine glycosylase 1, human); EC 4.2.99.18 (APEX1 protein, human); EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase); O3J8G9O825 (Ritonavir); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1089/dna.2017.3653


  6 / 1981 MEDLINE  
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[PMID]:28477555
[Au] Autor:Fu Q; Lyu D; Zhang L; Qin Z; Tang Q; Yin H; Lou X; Chen Z; Yao K
[Ad] Endereço:Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang Province, China.
[Ti] Título:Airborne particulate matter (PM2.5) triggers autophagy in human corneal epithelial cell line.
[So] Source:Environ Pollut;227:314-322, 2017 Aug.
[Is] ISSN:1873-6424
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To investigate particulate matter (PM2.5)-induced damage to human corneal epithelial cells (HCECs) and to determine the underlying mechanisms. METHODS: HCECs were exposed to PM2.5 at a series of concentrations for various periods. Cell viability was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was evaluated via 5-ethynyl-2'-deoxyuridine (EdU) analysis, while autophagy was determined by immunofluorescence and Western blot. RESULTS: PM2.5-induced cell damage of HCECs occurred in a time- and dose-dependent manner. Decreased cell viability and proliferation as well as increased apoptosis were observed in HCECs after PM2.5 exposure for 24 h. Autophagy in HCECs was slightly inhibited in the early stage (before 4 h) of exposure but significantly activated in the late stage (after 24 h), as evidenced by a decrease in the former and increase in the latter of the expression of the autophagy-associated markers LC3B, ATG5, and BECN1. Interestingly, rapamycin, an autophagy activator, attenuated early-stage but aggravated late-stage PM2.5-induced cell damage, suggesting that the role of autophagy in HCECs may change over time during PM2.5 exposure. In addition, in the early stage, the expression of LC3B and ATG5 increased in cells co-treated with rapamycin and PM2.5 compared to rapamycin-only or PM2.5-only treated cells, suggesting that autophagy may benefit cell viability after PM2.5 exposure. CONCLUSIONS: The results indicate the potential role of autophagy in the treatment of PM2.5-induced ocular corneal diseases and provide direct evidence for the cytotoxicity, possibly involving an autophagic process, of PM2.5 in HCECs.
[Mh] Termos MeSH primário: Poluentes Atmosféricos/toxicidade
Material Particulado/toxicidade
[Mh] Termos MeSH secundário: Apoptose
Autofagia
Linhagem Celular
Proliferação Celular
Sobrevivência Celular
Desoxiuridina/análogos & derivados
Células Epiteliais/metabolismo
Seres Humanos
Sais de Tetrazólio
Tiazóis
Testes de Toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Air Pollutants); 0 (Particulate Matter); 0 (Tetrazolium Salts); 0 (Thiazoles); EUY85H477I (thiazolyl blue); G373S00W2J (5-ethynyl-2'-deoxyuridine); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170507
[St] Status:MEDLINE


  7 / 1981 MEDLINE  
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[PMID]:28431244
[Au] Autor:García-González AP; Ritter AD; Shrestha S; Andersen EC; Yilmaz LS; Walhout AJM
[Ad] Endereço:Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
[Ti] Título:Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics.
[So] Source:Cell;169(3):431-441.e8, 2017 Apr 20.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT). We find numerous bacterial nucleotide metabolism genes that affect drug efficacy in C. elegans. Surprisingly, we find that 5-FU and FUDR act through bacterial ribonucleotide metabolism to elicit their cytotoxic effects in C. elegans rather than by thymineless death or DNA damage. Our study provides a blueprint for characterizing the role of bacteria in the host response to chemotherapeutics.
[Mh] Termos MeSH primário: Antineoplásicos/metabolismo
Caenorhabditis elegans/microbiologia
Comamonas/metabolismo
Escherichia coli/metabolismo
Microbioma Gastrointestinal
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Camptotecina/metabolismo
Camptotecina/farmacologia
Neoplasias Colorretais/tratamento farmacológico
Comamonas/genética
Desoxiuridina/análogos & derivados
Desoxiuridina/metabolismo
Desoxiuridina/farmacologia
Dieta
Escherichia coli/genética
Fluoruracila/metabolismo
Fluoruracila/farmacologia
Seres Humanos
Modelos Animais
Nucleosídeos de Pirimidina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-fluoro-2'-deoxyuridine); 0 (Antineoplastic Agents); 0 (Pyrimidine Nucleosides); U3P01618RT (Fluorouracil); W78I7AY22C (Deoxyuridine); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE


  8 / 1981 MEDLINE  
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[PMID]:28301746
[Au] Autor:Syed A; Smith EA
[Ad] Endereço:Department of Chemistry, Iowa State University, Ames, Iowa 50011; email: wrtaleem@iastate.edu , esmith1@iastate.edu.
[Ti] Título:Raman Imaging in Cell Membranes, Lipid-Rich Organelles, and Lipid Bilayers.
[So] Source:Annu Rev Anal Chem (Palo Alto Calif);10(1):271-291, 2017 Jun 12.
[Is] ISSN:1936-1335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Raman-based optical imaging is a promising analytical tool for noninvasive, label-free chemical imaging of lipid bilayers and cellular membranes. Imaging using spontaneous Raman scattering suffers from a low intensity that hinders its use in some cellular applications. However, developments in coherent Raman imaging, surface-enhanced Raman imaging, and tip-enhanced Raman imaging have enabled video-rate imaging, excellent detection limits, and nanometer spatial resolution, respectively. After a brief introduction to these commonly used Raman imaging techniques for cell membrane studies, this review discusses selected applications of these modalities for chemical imaging of membrane proteins and lipids. Finally, recent developments in chemical tags for Raman imaging and their applications in the analysis of selected cell membrane components are summarized. Ongoing developments toward improving the temporal and spatial resolution of Raman imaging and small-molecule tags with strong Raman scattering cross sections continue to expand the utility of Raman imaging for diverse cell membrane studies.
[Mh] Termos MeSH primário: Membrana Celular/química
Bicamadas Lipídicas/química
Análise Espectral Raman/métodos
[Mh] Termos MeSH secundário: Animais
Biomarcadores/química
Biomarcadores/metabolismo
Desoxiuridina/química
Grafite/química
Seres Humanos
Nanotubos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (Lipid Bilayers); 7782-42-5 (Graphite); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1146/annurev-anchem-061516-045317


  9 / 1981 MEDLINE  
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[PMID]:28278052
[Au] Autor:Liu Z; Xu D; Wang S; Chen Y; Li Z; Gao X; Jiang L; Tang Y; Peng Y
[Ad] Endereço:a Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology , Chongqing Medical University , Chongqing , P.R. China.
[Ti] Título:Astrocytes induce proliferation of oligodendrocyte progenitor cells via connexin 47-mediated activation of the ERK/Id4 pathway.
[So] Source:Cell Cycle;16(7):714-722, 2017 Apr 03.
[Is] ISSN:1551-4005
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The proliferative ability of oligodendrocyte progenitor cells (OPCs) varied markedly under different culture conditions. Astrocytes (ASTs) have been verified to play a major role in regulating the proliferation of OPCs through direct contact. However, the mechanisms have not been fully clarified. To investigate the effect and mechanism under AST and OPC co-culture conditions, we analyzed all connexins comprehensively in OPCs under OPC mono-culture, AST-secreted cell factor co-culture and AST-OPC direct-contact co-culture, and found that significantly differentially expressed Cx47 was the most significant. To assess whether Cx47 plays a role in proliferation, Cx47 siRNA were conducted. The result indicates that the cell cycle of OPCs was changed, and the cell proliferation was markedly inhibited. Kyoto Encyclopedia of Genes and Genomes (KEGG) predictive analysis suggested that Cx47 regulate cell cycle and proliferation by Ca activation of ERK1/2. To verify the prediction, flow cytometry, confocal microscopy, 5-ethynyl-2'-deoxyuridine (EdU), polymerase chain reaction (RT-PCR) and western blot were used. The results show that interference of Cx47 led to decreased Ca concentrations, lower p-ERK 1/2 levels, reduced transcription factor inhibitor of DNA binding 4 (Id4) expression, arrested cell cycle and reduced OPCs proliferative ability. Additionally, blocking ERK1/2 signaling caused decreased Id4 expression, arrested cell cycle in G1 phase, and reduced OPCs proliferative ability. In conclusion, ASTs can cause Ca signaling activation, ERK1/2 phosphorylation, and Id4 expression stimulation in OPCs, inducing proliferation of these cells, mainly through Cx47.
[Mh] Termos MeSH primário: Astrócitos/citologia
Conexinas/metabolismo
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Proteínas Inibidoras de Diferenciação/metabolismo
Sistema de Sinalização das MAP Quinases
Oligodendroglia/citologia
Células-Tronco/citologia
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Astrócitos/metabolismo
Cálcio/metabolismo
Sinalização do Cálcio
Ciclo Celular
Proliferação Celular
Técnicas de Cocultura
Desoxiuridina/análogos & derivados
Desoxiuridina/metabolismo
Oligodendroglia/metabolismo
Fosforilação
RNA Interferente Pequeno/metabolismo
Ratos Sprague-Dawley
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Connexins); 0 (Idb4 protein, rat); 0 (Inhibitor of Differentiation Proteins); 0 (RNA, Small Interfering); 0 (connexin 47); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); G373S00W2J (5-ethynyl-2'-deoxyuridine); SY7Q814VUP (Calcium); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.1080/15384101.2017.1295183


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[PMID]:28258952
[Au] Autor:Lin G; Reed-Maldonado AB; Wang B; Lee YC; Zhou J; Lu Z; Wang G; Banie L; Lue TF
[Ad] Endereço:Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.
[Ti] Título:In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy.
[So] Source:J Sex Med;14(4):493-501, 2017 Apr.
[Is] ISSN:1743-6109
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We previously reported that progenitor cells, or stem cells, exist within penile tissue. We hypothesized that acoustic wave stimulation by low-intensity extracorporeal shockwave therapy (Li-ESWT) would activate local stem or progenitor cells within the penis, producing regenerative effects. AIMS: To study the feasibility of in situ penile progenitor cell activation by Li-ESWT. METHODS: We performed a cohort analysis of young and middle-age male Sprague-Dawley rats treated with 5-ethynyl-2'-deoxyuridine (EdU) pulse followed by Li-ESWT. In addition, Li-ESWT was applied to cultured Schwann cells and endothelial cells to study the molecular mechanism involved in cell proliferation. Thirty minutes before Li-ESWT, each rat received an intraperitoneal injection of EdU. Li-ESWT was applied to the penis at very low (0.02 mJ/mm at 3 Hz for 300 pulses) or low (0.057 mJ/mm at 3 Hz for 500 pulses) energy levels. The endothelial and Schwann cells were treated with very low energy (0.02 mJ/mm at 3 Hz for 300 pulses) in vitro. OUTCOMES: At 48 hours or 1 week after Li-ESWT, penile tissues were harvested for histologic study to assess EdU and Ki-67 cells, and cell proliferation, Ki-67 expression, Erk1/2 phosphorylation, translocation, and angiogenesis were examined in cultured Schwann and endothelial cells after Li-ESWT. RESULTS: Li-ESWT significantly increased EdU cells within penile erectile tissues (P < .01) at 48 hours and 1 week. There were more cells activated in young animals than in middle-age animals, and the effect depended on dosage. Most activated cells were localized within subtunical spaces. In vitro studies indicated that Li-ESWT stimulated cell proliferation through increased phosphorylation of Erk1/2. CLINICAL TRANSLATION: The present results provide a possible explanation for the clinical benefits seen with Li-ESWT. STRENGTHS AND LIMITATIONS: The main limitation of the present project was the short period of study and the animal model used. Li-ESWT could be less effective in improving erectile function in old animals because of the decreased number and quality of penile stem or progenitor cells associated with aging. CONCLUSION: Li-ESWT activation of local penile progenitor cells might be one of the mechanisms that contribute to the beneficial effects of shockwave treatment for erectile dysfunction, which represents a non-invasive alternative to exogenous stem cell therapy. Lin G, Reed-Maldonado AB, Wang B, et al. In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy. J Sex Med 2017;14:493-501.
[Mh] Termos MeSH primário: Desoxiuridina/análogos & derivados
Disfunção Erétil/terapia
Ondas de Choque de Alta Energia/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Desoxiuridina/uso terapêutico
Modelos Animais de Doenças
Células Endoteliais/metabolismo
Disfunção Erétil/metabolismo
Seres Humanos
Masculino
Ratos
Ratos Sprague-Dawley
Células de Schwann/metabolismo
Células-Tronco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
G373S00W2J (5-ethynyl-2'-deoxyuridine); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170305
[St] Status:MEDLINE



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