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[PMID]:28458037
[Au] Autor:Okesli A; Khosla C; Bassik MC
[Ad] Endereço:Departments of Chemistry, Genetics, and Chemical Engineering, and Stanford ChEM-H, Stanford University, Stanford, CA 94305, United States.
[Ti] Título:Human pyrimidine nucleotide biosynthesis as a target for antiviral chemotherapy.
[So] Source:Curr Opin Biotechnol;48:127-134, 2017 Dec.
[Is] ISSN:1879-0429
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The development of broad-spectrum, host-acting antiviral therapies remains an important but elusive goal in anti-infective drug discovery. To replicate efficiently, viruses not only depend on their hosts for an adequate supply of pyrimidine nucleotides, but also up-regulate pyrimidine nucleotide biosynthesis in infected cells. In this review, we outline our understanding of mammalian de novo and salvage metabolic pathways for pyrimidine nucleotide biosynthesis. The available spectrum of experimental and FDA-approved drugs that modulate individual steps in these metabolic pathways is also summarized. The logic of a host-acting combination antiviral therapy comprised of inhibitors of dihydroorotate dehydrogenase and uridine/cytidine kinase is discussed.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Inibidores Enzimáticos/uso terapêutico
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores
Nucleotídeos de Pirimidina/biossíntese
Vírus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Seres Humanos
Vírus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Enzyme Inhibitors); 0 (Pyrimidine Nucleotides); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.5.2 (dihydroorotate dehydrogenase)
[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:170502
[St] Status:MEDLINE


  2 / 2652 MEDLINE  
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[PMID]:29024632
[Au] Autor:Zheng X; Ning C; Dong Y; Zhao P; Li J; Fan Z; Li J; Yu Y; Mrode R; Liu JF
[Ad] Endereço:National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
[Ti] Título:Quantitative proteome analysis of bovine mammary gland reveals protein dynamic changes involved in peak and late lactation stages.
[So] Source:Biochem Biophys Res Commun;494(1-2):292-297, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mammary gland is an important organ for milk synthesis and secretion. It undergoes dramatic physiological changes to adapt the shift from peak to late lactation stage. Protein plays a final very vital role in many life functions, and the protein changes during different lactation stages potentially reflect the biology of lactation and the functions of mammary gland in cows. In current study, we adopted tandem mass tags label-based quantitative analysis technique and to investigate proteome changes occurring in bovine mammary gland from peak to late lactation stages. A total of 3753 proteins from mammary tissues taken at two lactation points from four individual cows by biopsy were quantified, out of which 179 proteins were expressed differentially between two stages. We observed five new DEPs (AACS, DHCR7, GSTM3, SFRP1 and SFRP4) and nine functional well-studies known proteins (PLIN2, LPIN1, PLIN3, GSN, CD74, MMP2, SOD1, SOD3 and GPX3) related to milk performance and mammary morphology. Bioinformatics analyses of the DEPs showed a majority of the up-regulated proteins during late lactation stage were related to apoptosis and immune process, while the downregulated proteins were mainly involved in localization, lipid metabolic and transport process. This suggests that the mammary gland can adapt to different molecular functions according to the biological need of the animal. From the integrated analysis of the differentially expressed proteins with known quantitative trait loci and genome-wide association study data, we identified 95 proteins may potentially affect milking performance. We expect findings in this study could be a valuable resource for future studies investigating the bovine proteome and functional studies.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica no Desenvolvimento
Lactação/genética
Glândulas Mamárias Animais/metabolismo
Proteoma/genética
Locos de Características Quantitativas
[Mh] Termos MeSH secundário: Animais
Apoptose
Bovinos
Feminino
Ontologia Genética
Glutationa Transferase/genética
Glutationa Transferase/imunologia
Imunidade Inata
Isoenzimas/genética
Isoenzimas/imunologia
Glândulas Mamárias Animais/crescimento & desenvolvimento
Metaloproteinase 2 da Matriz/genética
Metaloproteinase 2 da Matriz/imunologia
Anotação de Sequência Molecular
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/imunologia
Perilipinas/genética
Perilipinas/imunologia
Proteoma/imunologia
Proteômica
Superóxido Dismutase/genética
Superóxido Dismutase/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Perilipins); 0 (Proteome); EC 1.15.1.1 (Superoxide Dismutase); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase); EC 2.5.1.18 (Glutathione Transferase); EC 2.5.1.18 (glutathione transferase M3-3); EC 3.4.24.24 (Matrix Metalloproteinase 2)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE


  3 / 2652 MEDLINE  
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[PMID]:28927883
[Au] Autor:Pang XY; Wang S; Jurczak MJ; Shulman GI; Moise AR
[Ad] Endereço:Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA.
[Ti] Título:Retinol saturase modulates lipid metabolism and the production of reactive oxygen species.
[So] Source:Arch Biochem Biophys;633:93-102, 2017 Nov 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Retinol saturase (RetSat) catalyzes the saturation of double bonds of all-trans-retinol leading to the production of dihydroretinoid metabolites. Beside its role in retinoid metabolism, there is evidence that RetSat modulates the cellular response to oxidative stress and plays critical roles in adipogenesis and the accumulation of lipids. Here, we explore the relationship between RetSat, lipid metabolism and oxidative stress using in vitro and in vivo models with altered expression of RetSat. Our results reveal that RetSat is a potent modulator of the cellular response to oxidative stress and the generation of reactive oxygen species (ROS). The levels of reactive aldehydes products of lipid peroxidation, as measured based on thiobarbituric acid reactivity, are increased in RetSat overexpressing cells and, conversely, reduced in cells and tissues with reduced or absent expression of RetSat compared to controls. Despite increased weight gain, neutral lipid accumulation and alterations in hepatic lipid composition, RetSat mice exhibit normal responses to insulin. In conclusion, our findings further expand upon the role of RetSat in oxidative stress and lipid metabolism and could provide insight in the significance of alterations of RetSat expression as observed in metabolic disorders.
[Mh] Termos MeSH primário: Ácidos Graxos/metabolismo
Fibroblastos/enzimologia
Metabolismo dos Lipídeos/genética
Fígado/enzimologia
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Peso Corporal/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Embrião de Mamíferos
Fibroblastos/citologia
Expressão Gênica
Insulina/farmacologia
Metabolismo dos Lipídeos/efeitos dos fármacos
Fígado/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Células NIH 3T3
Estresse Oxidativo
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/deficiência
Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Insulin); 0 (Reactive Oxygen Species); 0 (Thiobarbituric Acid Reactive Substances); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.- (retinol saturase (all trans retinol 13,14 reductase), mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE


  4 / 2652 MEDLINE  
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[PMID]:28886093
[Au] Autor:Peláez-García A; Yébenes L; Berjón A; Angulo A; Zamora P; Sánchez-Méndez JI; Espinosa E; Redondo A; Heredia-Soto V; Mendiola M; Feliú J; Hardisson D
[Ad] Endereço:Department of Pathology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
[Ti] Título:Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer.
[So] Source:PLoS One;12(9):e0183452, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas. METHODS: Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score). RESULTS: The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)). CONCLUSIONS: This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Receptor ErbB-2/metabolismo
Receptores Estrogênicos/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Ligação ao Cálcio/metabolismo
Calmodulina/metabolismo
Proteínas de Transporte/metabolismo
Receptor gp130 de Citocina/metabolismo
Proteínas da Matriz Extracelular/metabolismo
Feminino
Glicoproteínas/metabolismo
Seres Humanos
Imuno-Histoquímica
Técnicas In Vitro
Proteínas Inibidoras de Apoptose/metabolismo
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Antígeno Ki-67/metabolismo
Meia-Idade
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Proteínas/metabolismo
Receptores de Progesterona/metabolismo
Proteínas Ribossômicas/metabolismo
Enzimas de Conjugação de Ubiquitina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AZGP1 protein, human); 0 (BIRC5 protein, human); 0 (CALM2 protein, human); 0 (Calcium-Binding Proteins); 0 (Calmodulin); 0 (Carrier Proteins); 0 (Extracellular Matrix Proteins); 0 (Glycoproteins); 0 (IL6ST protein, human); 0 (Inhibitor of Apoptosis Proteins); 0 (Intercellular Signaling Peptides and Proteins); 0 (Ki-67 Antigen); 0 (Proteins); 0 (RPL37A protein, human); 0 (Receptors, Estrogen); 0 (Receptors, Progesterone); 0 (Ribosomal Proteins); 0 (STC2 protein, human); 0 (matrix Gla protein); 0 (ornithine decarboxylase antizyme); 133483-10-0 (Cytokine Receptor gp130); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase); EC 2.3.2.23 (UBE2C protein, human); EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes); EC 2.7.10.1 (Receptor, ErbB-2)
[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:170909
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183452


  5 / 2652 MEDLINE  
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[PMID]:28782186
[Au] Autor:Sowaileh MF; Hazlitt RA; Colby DA
[Ad] Endereço:Department of BioMolecular Sciences, University of Mississippi, University, MS, 38677, USA.
[Ti] Título:Application of the Pentafluorosulfanyl Group as a Bioisosteric Replacement.
[So] Source:ChemMedChem;12(18):1481-1490, 2017 Sep 21.
[Is] ISSN:1860-7187
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The success of fluorinated molecules in drug design has led medicinal chemists to search for new fluorine-containing substituents. A major recently developed group is the pentafluorosulfanyl group. This group is stable under physiological conditions and displays unique physical and chemical properties. There are currently few synthetic methods to install the SF group, yet efforts to integrate this group into lead optimization continue unabated. Typically, the SF group has been used as a replacement for trifluoromethyl, tert-butyl, halogen, or nitro groups. In this review, the use of the SF group as a bioisosteric replacement for each of these three functionalities is compared and contrasted across various groups of biologically active molecules. The organization and presentation of these data should be instructive to medicinal chemists considering to design synthetic strategies to access SF -substituted molecules.
[Mh] Termos MeSH primário: Sulfetos/química
Compostos de Enxofre/química
[Mh] Termos MeSH secundário: Antiprotozoários/química
Antiprotozoários/farmacologia
Desenho de Drogas
Ácido Flufenâmico/análogos & derivados
Ácido Flufenâmico/farmacologia
Halogenação
NADH NADPH Oxirredutases/antagonistas & inibidores
NADH NADPH Oxirredutases/metabolismo
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Plasmodium falciparum/efeitos dos fármacos
Plasmodium falciparum/enzimologia
Ligação Proteica
Receptores de Canabinoides/química
Receptores de Canabinoides/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Receptors, Cannabinoid); 0 (Sulfides); 0 (Sulfur Compounds); 60GCX7Y6BH (Flufenamic Acid); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.5.2 (dihydroorotate dehydrogenase); EC 1.6.- (NADH, NADPH Oxidoreductases); EC 1.8.1.12 (trypanothione reductase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170808
[St] Status:MEDLINE
[do] DOI:10.1002/cmdc.201700356


  6 / 2652 MEDLINE  
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[PMID]:28728845
[Au] Autor:Park AK; Kim H; Kim IS; Roh SJ; Shin SC; Lee JH; Park H; Kim HW
[Ad] Endereço:Unit of Polar Genomics, Korea Polar Research Institute, Incheon 21990, South Korea.
[Ti] Título:Crystal structure of cis-dihydrodiol naphthalene dehydrogenase (NahB) from Pseudomonas sp. MC1: Insights into the early binding process of the substrate.
[So] Source:Biochem Biophys Res Commun;491(2):403-408, 2017 Sep 16.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The bacterial strain Pseudomonas sp. MC1 harbors an 81-kb metabolic plasmid, which encodes enzymes involved in the conversion of naphthalene to salicylate. Of these, the enzyme NahB (cis-dihydrodiol naphthalene dehydrogenase), which catalyzes the second reaction of this pathway, binds to various substrates such as cis-1,2-dihydro-1,2-dihydroxy-naphthalene (1,2-DDN), cis-2,3-dihydro-2,3-dihydroxybiphenyl (2,3-DDB), and 3,4-dihydro-3,4-dihydroxy-2,2',5,5'-tetrachlorobiphenyl (3,4-DD-2,2',5-5-TCB). However, the mechanism underlying its broad substrate specificity is unclear owing to the lack of structural information. Here, we determined the first crystal structures of NahB in the absence and presence of NAD and 2,3-dihydroxybiphenyl (2,3-DB). Structure analysis suggests that the flexible substrate-binding loop allows NahB to accommodate diverse substrates. Furthermore, we defined the initial steps of substrate recognition and identified the early substrate-binding site in the substrate recognition process through the complex structure with ligands.
[Mh] Termos MeSH primário: Compostos de Bifenilo/química
Catecóis/química
Naftóis/química
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química
Bifenilos Policlorados/química
Pseudomonas/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Sítios de Ligação
Compostos de Bifenilo/metabolismo
Catecóis/metabolismo
Clonagem Molecular
Cristalografia por Raios X
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Modelos Moleculares
Naftóis/metabolismo
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Bifenilos Policlorados/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Pseudomonas/enzimologia
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biphenyl Compounds); 0 (Catechols); 0 (Naphthols); 0 (Recombinant Proteins); 1133-63-7 (2,3-dihydroxybiphenyl); 2R5017T335 (1,2-dihydroxynaphthalene); DFC2HB4I0K (Polychlorinated Biphenyls); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.29 (cis-1,2-dihydro-1,2-dihydroxynaphthalene dehydrogenase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE


  7 / 2652 MEDLINE  
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[PMID]:28669445
[Au] Autor:McConkey GA; Bedingfield PTP; Burrell DR; Chambers NC; Cunningham F; Prior TJ; Fishwick CWG; Boa AN
[Ad] Endereço:School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
[Ti] Título:Interconvertible geometric isomers of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors exhibit multiple binding modes.
[So] Source:Bioorg Med Chem Lett;27(16):3878-3882, 2017 08 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Two new tricyclic ß-aminoacrylate derivatives (2e and 3e) have been found to be inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) with Ki 0.037 and 0.15µM respectively. H and C NMR spectroscopic data show that these compounds undergo ready cis-trans isomerisation at room temperature in polar solvents. In silico docking studies indicate that for both molecules there is neither conformation nor double bond configuration which bind preferentially to PfDHODH. This flexibility is favourable for inhibitors of this channel that require extensive positioning to reach their binding site.
[Mh] Termos MeSH primário: Acrilatos/farmacologia
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores
Plasmodium falciparum/enzimologia
[Mh] Termos MeSH secundário: Acrilatos/síntese química
Acrilatos/química
Relação Dose-Resposta a Droga
Simulação de Acoplamento Molecular
Estrutura Molecular
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acrylates); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.5.2 (dihydroorotate dehydrogenase)
[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:170704
[St] Status:MEDLINE


  8 / 2652 MEDLINE  
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[PMID]:28668836
[Au] Autor:Feng X; Matsuo K; Zhang T; Hu Y; Mays AC; Browne JD; Zhou X; Sullivan CA
[Ad] Endereço:Department of Otolaryngology, Wake Forest School of Medicine, Winston-Salem, NC, U.S.A. xfeng@wakehealth.edu csulliva@wakehealth.edu.
[Ti] Título:MicroRNA Profiling and Target Genes Related to Metastasis of Salivary Adenoid Cystic Carcinoma.
[So] Source:Anticancer Res;37(7):3473-3481, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Perineural invasion and distant metastasis lead to a poor prognosis of adenoid cystic carcinoma and there is no effective therapy available. MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression, which can be biomarkers or therapeutic targets for certain cancer types. We aimed to identify miRNAs and their target genes possibly involved in metastasis of salivary gland adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: Using Nanostring nCounter analysis, we examined miRNA expression in two SACC cell lines: SACC-83 and SACC-LM, with low and high lung metastasis rates, respectively. We then verified the differentially expressed miRNAs with real-time polymerase chain reaction in the cell lines and in tumor samples from patients with SACC. miRNA target-gene expression was also analyzed. RESULTS: SACC-83 showed higher gene expression of miR-130a, miR-342, and miR-205; SACC-LM showed higher gene expression of miR-99a and miR-155. In human tissue, miR-205 was highly expressed in the primary SACC, while miR-155 and miR-342 were highly expressed in recurrent SACC. Six predicted target genes of miRNA-155 and miR-99a linked to tumorigenesis were further analyzed and RNA expression of ubiquitin-like modifier activating enzyme 2 (UBA2) was higher in SACC than normal salivary gland tissue, and higher in primary compared to recurrent SACC (p<0.05). RNA expression of retinoic acid receptors (RARS) was higher in tissue from primary than recurrent SACC and normal salivary gland (p<0.05), but that in recurrent SACC was not significantly higher than normal salivary gland tissue. RNA expression of minichromosome maintenance 8 homologous recombination repair factor (MCM8) and 24-dehydrocholesterol reductase (DHCR24) was higher in primary SACC than normal salivary gland tissue (p<0.05). CONCLUSION: miR-99a, miR-155, miR-130a, miR-342, and miR-205 may play a role in metastasis of SACC. MiR-155 may be involved in SACC metastasis through UBA2 pathways, and UBA2 may function as a biomarker/mediator of SACC metastasis.
[Mh] Termos MeSH primário: Carcinoma Adenoide Cístico/genética
MicroRNAs/genética
Neoplasias das Glândulas Salivares/genética
[Mh] Termos MeSH secundário: Biomarcadores Tumorais/genética
Carcinogênese/genética
Linhagem Celular Tumoral
Expressão Gênica/genética
Seres Humanos
Proteínas de Manutenção de Minicromossomo/genética
Proteínas do Tecido Nervoso/genética
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Receptores do Ácido Retinoico/genética
Glândulas Salivares/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (MicroRNAs); 0 (Nerve Tissue Proteins); 0 (Receptors, Retinoic Acid); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.- (DHCR24 protein, human); EC 3.6.4.12 (MCM8 protein, human); EC 3.6.4.12 (Minichromosome Maintenance Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE


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[PMID]:28666740
[Au] Autor:Reis RAG; Calil FA; Feliciano PR; Pinheiro MP; Nonato MC
[Ad] Endereço:Department of Chemistry, Georgia State University, Atlanta, GA 30302, United States.
[Ti] Título:The dihydroorotate dehydrogenases: Past and present.
[So] Source:Arch Biochem Biophys;632:175-191, 2017 Oct 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The flavoenzyme dihydroorotate dehydrogenase catalyzes the stereoselective oxidation of (S)-dihydroorotate to orotate in the fourth of the six conserved enzymatic reactions involved in the de novo pyrimidine biosynthetic pathway. Inhibition of pyrimidine metabolism by selectively targeting DHODHs has been exploited in the development of new therapies against cancer, immunological disorders, bacterial and viral infections, and parasitic diseases. Through a chronological narrative, this review summarizes the efforts of the scientific community to achieve our current understanding of structural and biochemical properties of DHODHs. It also attempts to describe the latest advances in medicinal chemistry for therapeutic development based on the selective inhibition of DHODH, including an overview of the experimental techniques used for ligand screening during the process of drug discovery.
[Mh] Termos MeSH primário: Flavoproteínas
Oxirredutases atuantes sobre Doadores de Grupo CH-CH
[Mh] Termos MeSH secundário: Animais
Infecções Bacterianas/tratamento farmacológico
Infecções Bacterianas/enzimologia
Descoberta de Drogas
Inibidores Enzimáticos/química
Inibidores Enzimáticos/uso terapêutico
Flavoproteínas/antagonistas & inibidores
Flavoproteínas/química
Flavoproteínas/metabolismo
Seres Humanos
Doenças do Sistema Imune/tratamento farmacológico
Doenças do Sistema Imune/enzimologia
Neoplasias/tratamento farmacológico
Neoplasias/enzimologia
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Doenças Parasitárias/tratamento farmacológico
Doenças Parasitárias/enzimologia
Pirimidinas/química
Pirimidinas/metabolismo
Viroses/tratamento farmacológico
Viroses/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Flavoproteins); 0 (Pyrimidines); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.5.2 (dihydroorotate dehydrogenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170702
[St] Status:MEDLINE


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[PMID]:28575224
[Au] Autor:Moon RJ; Harvey NC; Cooper C; D'Angelo S; Curtis EM; Crozier SR; Barton SJ; Robinson SM; Godfrey KM; Graham NJ; Holloway JW; Bishop NJ; Kennedy S; Papageorghiou AT; Schoenmakers I; Fraser R; Gandhi SV; Prentice A; Inskip HM; Javaid MK; Maternal Vitamin D Osteoporosis Study Trial Group
[Ad] Endereço:Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton SO16 6YD, United Kingdom.
[Ti] Título:Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants.
[So] Source:J Clin Endocrinol Metab;102(8):2941-2949, 2017 Aug 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Design: Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Setting: Hospital antenatal clinics. Participants: In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. Main Outcome Measure: 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [ß represents the change in 25(OH)D per additional common allele]. Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [ß = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (ß = -5.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (ß = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Conclusions: Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.
[Mh] Termos MeSH primário: Colecalciferol/uso terapêutico
Deficiência de Vitamina D/prevenção & controle
Vitaminas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Alelos
Colestanotriol 26-Mono-Oxigenase/genética
Família 2 do Citocromo P450/genética
Suplementos Nutricionais
Método Duplo-Cego
Feminino
Genótipo
Seres Humanos
Modelos Lineares
Análise Multivariada
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Polimorfismo de Nucleotídeo Único
Gravidez
Resultado do Tratamento
Vitamina D/análogos & derivados
Vitamina D/sangue
Proteína de Ligação a Vitamina D/genética
Vitamina D3 24-Hidroxilase/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Vitamin D-Binding Protein); 0 (Vitamins); 1406-16-2 (Vitamin D); 1C6V77QF41 (Cholecalciferol); 64719-49-9 (25-hydroxyvitamin D); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 1.14.14.24 (CYP2R1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase); EC 1.14.15.16 (CYP24A1 protein, human); EC 1.14.15.16 (Vitamin D3 24-Hydroxylase); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00682



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