Base de dados : MEDLINE
Pesquisa : D02.092.782.258 [Categoria DeCS]
Referências encontradas : 2776 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 278 ir para página                         

  1 / 2776 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29284118
[Au] Autor:Uematsu A; Kido K; Manabe E; Takeda H; Takahashi H; Hayashi M; Imai Y; Sawasaki T
[Ad] Endereço:Division of Cell-Free Sciences, Proteo-Science Center (PROS), Ehime University, Japan.
[Ti] Título:DANFIN functions as an inhibitor of transcription factor NF-κB and potentiates the antitumor effect of bortezomib in multiple myeloma.
[So] Source:Biochem Biophys Res Commun;495(3):2289-2295, 2018 01 15.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nuclear factor-κB (NF-κB) proteins are transcription factors that play key roles in regulating most immune responses and cell death. Constitutively active NF-κB has been shown to exhibit chemoresistance by inducing anti-apoptosis in tumor cells. Multiple myeloma is known as a constitutive NF-κB activating disease, and the proteasome inhibitor bortezomib is used to treat multiple myeloma and mantle cell lymphoma. We demonstrate here that DANFIN (N,N'-bis-(2,4-dimethyl-phenyl)-ethane-1,2-diamine) functions as an inhibitor of the p65 family proteins and induces chemosensitization to bortezomib in multiple myeloma. DANFIN was found to be an inhibitor of interactions between p65 and IκBα without the inhibition of the DNA binding activity of the p65 protein. In addition, DANFIN affected the IκBα binding region in Rel Homology Domain (RHD) and suppressed the nuclear translocalization of the p65 protein in cells. Furthermore, in multiple myeloma cells, DANFIN suppressed the expression level of NF-κB target genes and induced apoptosis. The combination therapy of DANFIN with bortezomib dramatically enhanced the apoptosis of multiple myeloma cells and indicated a remarkable anti-tumor effect in a multiple-myeloma xenograft mouse model.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Apoptose/efeitos dos fármacos
Bortezomib/administração & dosagem
Diaminas/administração & dosagem
Mieloma Múltiplo/tratamento farmacológico
Mieloma Múltiplo/metabolismo
NF-kappa B/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Sinergismo Farmacológico
Feminino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Mieloma Múltiplo/patologia
Fatores de Transcrição/metabolismo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Diamines); 0 (N,N'-bis-(2,4-dimethyl-phenyl)-ethane-1,2-diamine); 0 (NF-kappa B); 0 (Transcription Factors); 69G8BD63PP (Bortezomib)
[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:171229
[St] Status:MEDLINE


  2 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28688958
[Au] Autor:Popadyuk II; Markov AV; Babich VO; Salomatina OV; Logashenko EB; Zenkova MA; Salakhutdinov NF
[Ad] Endereço:N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, 9, Lavrent'ev ave., Novosibirsk 630090, Russian Federation. Electronic address: popadyuk@nioch.nsc.ru.
[Ti] Título:Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine moieties at the C-3 position: Synthesis and evaluation of anti-proliferative activity.
[So] Source:Bioorg Med Chem Lett;27(16):3755-3759, 2017 08 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A new library of deoxycholic acid derivatives bearing nitrogen-containing moieties at the C-3 position was synthesised from epoxy derivative 1 via an epoxide ring-opening reaction promoted by aliphatic or cyclic diamines and fully characterised by NMR and mass-spectroscopy. The synthesised compounds were screened for cytotoxicity against four human tumour cell lines. The results showed that some of the novel diamine-bearing derivatives displayed improved anti-proliferative activities over the parent compound DCA. Among them, a 1-methylpiperazine containing compound (6) showed promising activity and the highest selectivity against tumour cells of enterohepatic origin (HepG2: IC =3.6µM, SI=9.0; HuTu-80: IC =4.6µM, SI=6.9) and was identified as a lead molecule.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Ácido Desoxicólico/farmacologia
Diaminas/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Ácido Desoxicólico/síntese química
Ácido Desoxicólico/química
Diaminas/síntese química
Diaminas/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Diamines); 005990WHZZ (Deoxycholic Acid)
[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:170710
[St] Status:MEDLINE


  3 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28636676
[Au] Autor:Newman M; Halter L; Lim A; Lardelli M
[Ad] Endereço:Alzheimer's Disease Genetics Laboratory, Centre for Molecular Pathology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
[Ti] Título:Mitochondrion to endoplasmic reticulum apposition length in zebrafish embryo spinal progenitors is unchanged in response to perturbations associated with Alzheimer's disease.
[So] Source:PLoS One;12(6):e0179859, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD). The length of mitochondrion-endoplasmic reticulum (M-ER) appositions is increased in Psen1-/-/Psen2-/- double knockout murine embryonic fibroblasts and in fibroblasts from AD-affected individuals. Development of an easily accessible, genetically manipulable, in vivo system for studying M-ER appositions would be valuable so we attempted to manipulate M-ER apposition length in zebrafish (Danio rerio) embryos. We injected fertilized zebrafish eggs with antisense morpholino oligonucleotides (MOs) that inhibit expression of zebrafish familial AD gene orthologues psen1 and psen2. Furthermore, we treated zebrafish embryos with DAPT (a highly specific γ-secretase inhibitor) or with sodium azide (to mimic partially hypoxic conditions). We then analyzed M-ER apposition in an identified, presumably proliferative neural cell type using electron microscopy. Our analysis showed no significant differences in M-ER apposition lengths at 48 hours post fertilization (hpf) between psen1 & psen2 MO co-injected embryos, embryos treated with DAPT, or sodium azide, and control embryos. Instead, the distribution of M-ER apposition lengths into different length classes was close to identical. However, this indicates that it is feasible to reproducibly measure M-ER size distributions in zebrafish embryos. While our observations differ from those of murine and human studies, this may be due to differences in cellular differentiation and metabolic state, cell age, or species-specific responses. In particular, by focusing on a presumably proliferative embryonic cell type, we may have selected a cell heavily already reliant on anaerobic glycolysis and less responsive to factors affecting M-ER apposition. Future examination of more differentiated, more secretory cell types may reveal measurable responses of M-ER apposition to environmental and genetic manipulation.
[Mh] Termos MeSH primário: Retículo Endoplasmático/metabolismo
Mitocôndrias/metabolismo
[Mh] Termos MeSH secundário: Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores
Secretases da Proteína Precursora do Amiloide/metabolismo
Animais
Tamanho Corporal/efeitos dos fármacos
Diaminas/toxicidade
Embrião não Mamífero/citologia
Embrião não Mamífero/efeitos dos fármacos
Retículo Endoplasmático/efeitos dos fármacos
Seres Humanos
Camundongos
Microscopia Eletrônica de Transmissão
Mitocôndrias/efeitos dos fármacos
Oligonucleotídeos Antissenso/metabolismo
Presenilina-1/antagonistas & inibidores
Presenilina-1/genética
Presenilina-1/metabolismo
Presenilina-2/antagonistas & inibidores
Presenilina-2/genética
Presenilina-2/metabolismo
Azida Sódica/toxicidade
Coluna Vertebral/citologia
Células-Tronco/citologia
Células-Tronco/metabolismo
Tiazóis/toxicidade
Peixe-Zebra
Proteínas de Peixe-Zebra/antagonistas & inibidores
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (24-diamino-5-phenylthiazole); 0 (Diamines); 0 (Oligonucleotides, Antisense); 0 (Presenilin-1); 0 (Presenilin-2); 0 (Thiazoles); 0 (Zebrafish Proteins); 0 (presenilin 1 protein, zebrafish); 0 (presenilin 2 protein, zebrafish); 968JJ8C9DV (Sodium Azide); EC 3.4.- (Amyloid Precursor Protein Secretases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179859


  4 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28601529
[Au] Autor:Gahan JM; Schnitzler CE; DuBuc TQ; Doonan LB; Kanska J; Gornik SG; Barreira S; Thompson K; Schiffer P; Baxevanis AD; Frank U
[Ad] Endereço:Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
[Ti] Título:Functional studies on the role of Notch signaling in Hydractinia development.
[So] Source:Dev Biol;428(1):224-231, 2017 08 01.
[Is] ISSN:1095-564X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The function of Notch signaling was previously studied in two cnidarians, Hydra and Nematostella, representing the lineages Hydrozoa and Anthozoa, respectively. Using pharmacological inhibition in Hydra and a combination of pharmacological and genetic approaches in Nematostella, it was shown in both animals that Notch is required for tentacle morphogenesis and for late stages of stinging cell maturation. Surprisingly, a role for Notch in neural development, which is well documented in bilaterians, was evident in embryonic Nematostella but not in adult Hydra. Adult neurogenesis in the latter seemed to be unaffected by DAPT, a drug that inhibits Notch signaling. To address this apparent discrepancy, we studied the role of Notch in Hydractinia echinata, an additional hydrozoan, in all life stages. Using CRISPR-Cas9 mediated mutagenesis, transgenesis, and pharmacological interference we show that Notch is dispensable for Hydractinia normal neurogenesis in all life stages but is required for the maturation of stinging cells and for tentacle morphogenesis. Our results are consistent with a conserved role for Notch in morphogenesis and nematogenesis across Cnidaria, and a lineage-specific loss of Notch dependence in neurogenesis in hydrozoans.
[Mh] Termos MeSH primário: Extremidades/embriologia
Hidrozoários/embriologia
Neurogênese/fisiologia
Receptores Notch/metabolismo
[Mh] Termos MeSH secundário: Animais
Sistemas CRISPR-Cas/genética
Diaminas/farmacologia
Feminino
Hidrozoários/genética
Hibridização In Situ
Masculino
Mutagênese/genética
Neurogênese/genética
Receptores Notch/antagonistas & inibidores
Receptores Notch/genética
Transdução de Sinais/genética
Tiazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (24-diamino-5-phenylthiazole); 0 (Diamines); 0 (Receptors, Notch); 0 (Thiazoles)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170612
[St] Status:MEDLINE


  5 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28526405
[Au] Autor:Liu Z; Li C; Meng X; Bai Y; Qi J; Wang J; Zhou Q; Zhang W; Zhang X
[Ad] Endereço:Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital,
[Ti] Título:Hypoxia-inducible factor-lα mediates aggrecan and collagen Π expression via NOTCH1 signaling in nucleus pulposus cells during intervertebral disc degeneration.
[So] Source:Biochem Biophys Res Commun;488(3):554-561, 2017 Jul 01.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although hypoxia-inducible factor-lα (HIF-lα) has been reported to have an important role in the metabolism and synthesis of the extracellular matrix (ECM) of nucleus pulposus cells (NPCs), the underlying mechanism has not been fully clarified. Here, we show for the first time that NOTCH1 expression is decreased in NPs isolated from degenerated human intervertebral discs (IVDs), as well as in the NPs of NP-specific HIF-1α mice. Our study reveals that overexpression of HIF-1α leads to increased expression of NOTCH1, the NOTCH1 ligand JAGGED1, and its target gene hairy and enhancer of split-1 (HES1), while also upregulating collagen Π and aggrecan expression in human NPCs. Importantly, these changes in expression are significantly suppressed by the NOTCH1 inhibitor DAPT. In parallel with changes in collagen Π and aggrecan expression, inhibition of the HIF-1α-NOTCH1 pathway altered ECM turnover by suppressing expression of the matrix metalloproteinases MMP1 and MMP13, while increasing the expression of tissue inhibitor of metalloproteinase-1 (TIMP1). Lastly, activation of NOTCH1 via JAGGED1 in human NPCs isolated from degenerated IVDs restored collagen Π and aggrecan expression. Therefore, our study shows that HIF-1α regulates collagen Π and aggrecan expression through NOTCH1 signaling and implicate NOTCH1 as a potential therapeutic target in disc degeneration.
[Mh] Termos MeSH primário: Agrecanas/metabolismo
Colágeno Tipo II/metabolismo
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Degeneração do Disco Intervertebral/metabolismo
Núcleo Pulposo/metabolismo
Receptor Notch1/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Agrecanas/antagonistas & inibidores
Agrecanas/genética
Animais
Células Cultivadas
Colágeno Tipo II/antagonistas & inibidores
Colágeno Tipo II/genética
Diaminas/farmacologia
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores
Subunidade alfa do Fator 1 Induzível por Hipóxia/deficiência
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Masculino
Camundongos
Camundongos Knockout
Meia-Idade
Núcleo Pulposo/citologia
Núcleo Pulposo/efeitos dos fármacos
Receptor Notch1/antagonistas & inibidores
Receptor Notch1/genética
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
Relação Estrutura-Atividade
Tiazóis/farmacologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (24-diamino-5-phenylthiazole); 0 (Aggrecans); 0 (Collagen Type II); 0 (Diamines); 0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (NOTCH1 protein, human); 0 (Receptor, Notch1); 0 (Thiazoles)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170521
[St] Status:MEDLINE


  6 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28445410
[Au] Autor:Micheletti G; Bordoni S; Chugunova E; Boga C
[Ad] Endereço:Department of Industrial Chemistry 'Toso Montanari', Alma Mater Studiorum Università di Bologna Viale Del Risorgimento, Bologna 4402136, Italy. gabriele.micheletti3@unibo.it.
[Ti] Título:C-C Coupling Reactions between Benzofurazan Derivatives and 1,3-Diaminobenzenes.
[So] Source:Molecules;22(5), 2017 Apr 26.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Aromatic substitution reactions between 1,3-diaminobenzene and chloronitrobenzofurazan derivatives have never been reported so far. The aim of the current study was to synthesize novel electron-donor and -acceptor architectures of interest in applied fields and to provide new insights on the nucleophilic behavior of 1,3-diaminobenzenes. The reaction of 1,3-dipiperidinyl-, 1,3-dimorpholinyl-, 1,3-dipyrrolidinyl-, or 1,3-dimethylamino-benzene with 7-chloro-4,6-dinitrobenzofuroxan or with a series of chloro-nitrobenzofurazans has been carried out in mild conditions. The partners reactivity has been investigated by monitoring the reaction course through ¹H-NMR spectroscopy. The reaction occurred in a regioselective way, providing in good yields the novel C-C coupling compounds. Indications on the reactivity behavior for the studied nucleophiles have been relieved.
[Mh] Termos MeSH primário: Derivados de Benzeno/química
Benzofuranos/química
Diaminas/química
[Mh] Termos MeSH secundário: Simportadores de Próton-Fosfato
Teoria Quântica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzene Derivatives); 0 (Benzofurans); 0 (Diamines); 0 (Proton-Phosphate Symporters)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


  7 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28371583
[Au] Autor:Tomazin U; Groselj U; Pockaj M; Pozgan F; Stefane B; Svete J
[Ad] Endereço:Faculty of Chemistry and Chemical Technology, University of Ljubljana , Vecna pot 113, SI-1000 Ljubljana, Slovenia.
[Ti] Título:Combinatorial Synthesis of Acacen-Type Ligands and Their Coordination Compounds.
[So] Source:ACS Comb Sci;19(6):386-396, 2017 Jun 12.
[Is] ISSN:2156-8944
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A highly modular synthetic method for the preparation of acacen-type ligands and their coordination compounds was developed. A series of 46 acacen-type ligands were synthesized by a combinatorial acid-catalyzed transamination between six primary diamines and eight enaminones. The bis-enaminone products were used as tetradentate ligands for coordination of copper(II), nickel(II), cobalt(II), and palladium(II). Dependence of the preferred E- or Z-configuration of the enaminone ligand on the α-substituent of the enaminone moiety in solution was determined by NMR and confirmed by X-ray diffraction. The copper(II) complexes were tested for their suitability as catalysts in 3 + 2 cycloaddition of azomethine imine to methyl propiolate.
[Mh] Termos MeSH primário: Técnicas de Química Combinatória/métodos
Complexos de Coordenação/síntese química
Pentanonas/síntese química
[Mh] Termos MeSH secundário: Catálise
Cobalto/química
Complexos de Coordenação/química
Cobre/química
Cristalografia por Raios X
Diaminas/síntese química
Diaminas/química
Ligantes
Níquel/química
Paládio/química
Pentanonas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Diamines); 0 (Ligands); 0 (Pentanones); 3G0H8C9362 (Cobalt); 46R950BP4J (acetylacetone); 5TWQ1V240M (Palladium); 789U1901C5 (Copper); 7OV03QG267 (Nickel)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1021/acscombsci.7b00027


  8 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28246378
[Au] Autor:Takehana Y; Umekita M; Hatano M; Kato C; Sawa R; Igarashi M
[Ad] Endereço:Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
[Ti] Título:Fradiamine A, a new siderophore from the deep-sea actinomycete Streptomyces fradiae MM456M-mF7.
[So] Source:J Antibiot (Tokyo);70(5):611-615, 2017 May.
[Is] ISSN:0021-8820
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:New bioactive substances were identified from several marine actinomycetes strains by LC-HRESI-MS based non-targeted metabolomics. A new siderophore and its derivative, named fradiamines A and B, were isolated from the extract of the deep-sea actinomycetes Streptomyces fradiae MM456M-mF7 by Diaion CHP-20P, Sephadex LH-20 column chromatography and HPLC. Fradiamine A was a new compound, but fradiamine B was previously patented as a sweetness enhancer. Their structures were determined by NMR and LC-HRESI-MS/MS analysis. Fradiamines A and B contained two alkyl amines asymmetrically bonded to citrate, a type of structure derived from actinomycetes and other bacteria and rarely observed in siderophores. Fradiamines A and B showed moderate antibiotic activity against Clostridium difficile with IC values of 32 and 8 µg ml , respectively.
[Mh] Termos MeSH primário: Acetatos/farmacologia
Antibacterianos/farmacologia
Clostridium difficile/efeitos dos fármacos
Diaminas/farmacologia
Sideróforos/farmacologia
Streptomyces/metabolismo
[Mh] Termos MeSH secundário: Acetatos/química
Acetatos/isolamento & purificação
Antibacterianos/química
Antibacterianos/isolamento & purificação
Cromatografia Líquida
Diaminas/química
Diaminas/isolamento & purificação
Concentração Inibidora 50
Espectroscopia de Ressonância Magnética
Espectrometria de Massas
Sideróforos/química
Sideróforos/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Anti-Bacterial Agents); 0 (Diamines); 0 (Siderophores); 0 (fradiamine A)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170620
[Lr] Data última revisão:
170620
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170302
[St] Status:MEDLINE
[do] DOI:10.1038/ja.2017.26


  9 / 2776 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28238274
[Au] Autor:Singla DK; Wang J; Singla R
[Ad] Endereço:Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
[Ti] Título:Primary human monocytes differentiate into M2 macrophages and involve Notch-1 pathway.
[So] Source:Can J Physiol Pharmacol;95(3):288-294, 2017 Mar.
[Is] ISSN:1205-7541
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:The current study investigates whether inhibiting the Notch-1 signaling pathway in primary human monocytes enhances M2 macrophage differentiation. We generated a primary human monocyte cell culture model to understand the effect of the Notch-1 signaling pathway. Monocytes were treated with Notch-1 inhibitors DAPT or siRNA. Our data show that there was a significant increase in the M1 macrophage population demonstrated by iNOS marker in the primary human monocytes treated with apoptotic-conditioned medium (ACM). Next, the levels of pro-inflammatory cytokines IL-6 and MCP-1, as well as TNF-α, increased in ACM media (p < 0.05). Furthermore, M1 macrophages and pro-inflammatory cytokines were reduced following DAPT or siRNA treatment. Comparatively, there was a significant increase in M2 macrophages, as demonstrated by an increase in CD206 and arginase-1 positive cells treated with DAPT or siRNA (p < 0.05). Furthermore, a significant increase in the associated anti-inflammatory cytokines IL-10 and IL-1RA was also observed with respect to control groups (p < 0.05). We conclude that blocking the Notch-1 pathway with DAPT or siRNA attenuates pro-inflammatory cytokines, enhances M2 macrophage differentiation, and increases anti-inflammatory cytokines in primary human monocytes. As a result, Notch-1 pathway inhibition has potential therapeutic applications of inflammatory disease.
[Mh] Termos MeSH primário: Diferenciação Celular
Macrófagos/metabolismo
Monócitos/metabolismo
Receptor Notch1/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Apoptose
Arginase/metabolismo
Biomarcadores/metabolismo
Diferenciação Celular/efeitos dos fármacos
Células Cultivadas
Citocinas/metabolismo
Diaminas/farmacologia
Seres Humanos
Mediadores da Inflamação/metabolismo
Lectinas Tipo C/metabolismo
Macrófagos/efeitos dos fármacos
Lectinas de Ligação a Manose/metabolismo
Monócitos/efeitos dos fármacos
Monócitos/patologia
Óxido Nítrico Sintase Tipo II/metabolismo
Fenótipo
Cultura Primária de Células
Interferência de RNA
Receptor Notch1/antagonistas & inibidores
Receptor Notch1/genética
Receptores de Superfície Celular/metabolismo
Transdução de Sinais/efeitos dos fármacos
Tiazóis/farmacologia
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (24-diamino-5-phenylthiazole); 0 (Biomarkers); 0 (Cytokines); 0 (Diamines); 0 (Inflammation Mediators); 0 (Lectins, C-Type); 0 (Mannose-Binding Lectins); 0 (NOTCH1 protein, human); 0 (Receptor, Notch1); 0 (Receptors, Cell Surface); 0 (Thiazoles); 0 (mannose receptor); EC 1.14.13.39 (NOS2 protein, human); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 3.5.3.1 (Arginase); EC 3.5.3.1 (arginase I, human)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170321
[Lr] Data última revisão:
170321
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE
[do] DOI:10.1139/cjpp-2016-0319


  10 / 2776 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28152430
[Au] Autor:Wang M; Yang J; Yuan M; Xue L; Li H; Tian C; Wang X; Liu J; Zhang Z
[Ad] Endereço:Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
[Ti] Título:Synthesis and antiproliferative activity of a series of novel 6-substituted pyrido[3,2-d]pyrimidines as potential nonclassical lipophilic antifolates targeting dihydrofolate reductase.
[So] Source:Eur J Med Chem;128:88-97, 2017 Mar 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Dihydrofolate reductase (DHFR) has been a well-recognized target for the treatment of many diseases. Based on 8,10-dideazaminopterins, which are classical antifolates that potently inhibit DHFR, we have designed a series of novel 2,4-diamino-6-substituted pyrido[3,2-d]pyrimidines. By removing the glutamate moiety and introducing lipophilic groups, we hoped to improve passive diffuse through the cell membranes. The target compounds were efficiently synthesized using one-pot procedure and evaluated in vitro for DHFR inhibition and antitumor activity. Compounds 5e, 5h, 5i and 5k were the most potent inhibitors of recombinant human DHFR (rhDHFR) with IC values in the range 0.2-1.0 µM. Analysis using flow cytometric indicated that the effect of compound 5k on cell cycle progression was linked to induction of S phase arrest. Compounds 5g, 5h, 5i and 5k showed broad spectrum antitumor activity against four different tumor cell lines, with IC values in the range 0.07-23 µM. Molecular docking investigations showed that the trimethoyphenyl ring of compound 5k occupied a position near the cofactor-binding site in the rhDHFR-inhibitor complex, with close intermolecular contacts with Asp21, Phe31, Ser59, Ile60 and Pro61.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Diaminas/farmacologia
Antagonistas do Ácido Fólico/farmacologia
Pirimidinas/química
Tetra-Hidrofolato Desidrogenase/química
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Ciclo Celular/efeitos dos fármacos
Diaminas/síntese química
Ensaios de Seleção de Medicamentos Antitumorais
Antagonistas do Ácido Fólico/síntese química
Seres Humanos
Modelos Moleculares
Simulação de Acoplamento Molecular
Estrutura Molecular
Neoplasias/tratamento farmacológico
Neoplasias/patologia
Pirimidinas/síntese química
Pirimidinas/farmacologia
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2,4-diamino-6-(3-methoxylstyryl)pyrido(3,2-d)pyrimidine); 0 (2,4-diamino-6-(4-fluorostyryl)pyrido(3,2-d)pyrimidine); 0 (Antineoplastic Agents); 0 (Diamines); 0 (Folic Acid Antagonists); 0 (Pyrimidines); EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170418
[Lr] Data última revisão:
170418
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE



página 1 de 278 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde