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[PMID]:29183759
[Au] Autor:Kim HJ; Lee E; Lee M; Ahn S; Kim J; Liu J; Jin SH; Ha J; Bae IH; Lee TR; Noh M
[Ad] Endereço:Basic Research and Innovation Division, AmorePacific Corporation R&D Center, Yongin, Gyeounggi-do 17074, Republic of Korea.
[Ti] Título:Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes.
[So] Source:Toxicol Appl Pharmacol;338:174-181, 2018 01 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Benzophenone-3 (BP-3), which is extensively used in organic sunscreen, has phototoxic potential in human skin. Phosphodiesterase 4B (PDE4B) has a well-established role in inflammatory responses in immune cells. Currently, it is unknown if PDE4B is associated with BP-3-induced phototoxicity in normal human keratinocytes (NHKs). We found that BP-3 significantly increased PDE4B expression in ultraviolet B (UVB)-irradiated NHKs. Notably, BP-8, a sunscreen agent that shares the 2-hydroxy-4-methoxyphenyl methanone moiety with BP-3, also upregulated PDE4B expression in NHKs. Upon UVB irradiation, BP-3 upregulated the expression of pro-inflammatory factors, such as prostaglandin endoperoxide synthase 2, tumor necrosis factor α, interleukin 8, and S100A7, and downregulated the level of cornified envelope associated proteins, which are important in the development of the epidermal permeability barrier. The additive effects of UVB-activated BP-3 on the expression of both pro-inflammatory mediators and cornified envelope associated proteins were antagonized by treatment with the PDE4 inhibitor rolipram. The BP-3 and UVB co-stimulation-induced PDE4B upregulation and its association with the upregulation of pro-inflammatory mediators and the downregulation of epidermal differentiation markers were confirmed in a reconstituted three dimensional human epidermis model. Therefore, PDE4B has a role in the mechanism of BP-3-induced phototoxicity.
[Mh] Termos MeSH primário: Benzofenonas/toxicidade
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/fisiologia
Dermatite Fototóxica/etiologia
Queratinócitos/efeitos dos fármacos
[Mh] Termos MeSH secundário: AMP Cíclico/fisiologia
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética
Dinoprostona/biossíntese
Seres Humanos
Interleucina-8/biossíntese
Fator de Necrose Tumoral alfa/biossíntese
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzophenones); 0 (Interleukin-8); 0 (Tumor Necrosis Factor-alpha); 95OOS7VE0Y (oxybenzone); E0399OZS9N (Cyclic AMP); EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4); K7Q1JQR04M (Dinoprostone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE


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[PMID]:28821467
[Au] Autor:Kim J; Lee PG; Jung EO; Kim BG
[Ad] Endereço:Department of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
[Ti] Título:In vitro characterization of CYP102G4 from Streptomyces cattleya: A self-sufficient P450 naturally producing indigo.
[So] Source:Biochim Biophys Acta;1866(1):60-67, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Self-sufficient CYP102As possess outstanding hydroxylating activity to fatty acids such as myristic acid. Other CYP102 subfamily members share substrate specificity of CYP102As, but, occasionally, unusual characteristics of its own subfamily have been found. In this study, only one self-sufficient cytochrome P450 from Streptomyces cattleya was renamed from CYP102A_scat to CYP102G4, purified and characterized. UV-Vis spectrometry pattern, FAD/FMN analysis, and protein sequence comparison among CYP102s have shown that CYP102 from Streptomyces cattleya belongs to CYP102G subfamily. It showed hydroxylation activity toward fatty acids generating ω-1, ω-2, and ω-3-hydroxyfatty acids, which is similar to the general substrate specificity of CYP102 family. Unexpectedly, however, expression of CYP102G4 showed indigo production in LB medium batch flask culture, and high catalytic activity (k /K ) for indole was measured as 6.14±0.10min mM . Besides indole, CYP102G4 was able to hydroxylate aromatic compounds such as flavone, benzophenone, and chloroindoles. Homology model has shown such ability to accept aromatic compounds is due to its bigger active site cavity. Unlike other CYP102s, CYP102G4 did not have biased cofactor dependency, which was possibly determined by difference in NAD(P)H binding residues (Ala984, Val990, and Tyr1064) compared to CYP102A1 (Arg966, Lys972 and Trp1046). Overall, a self-sufficient CYP within CYP102G subfamily was characterized using purified enzymes, which appears to possess unique properties such as an only prokaryotic CYP naturally producing indigo.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
Ácidos Graxos/metabolismo
Índigo Carmim/metabolismo
NADPH-Ferri-Hemoproteína Redutase/metabolismo
Streptomyces/enzimologia
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Benzofenonas/metabolismo
Domínio Catalítico
Clonagem Molecular
Sistema Enzimático do Citocromo P-450/química
Sistema Enzimático do Citocromo P-450/genética
Escherichia coli/genética
Escherichia coli/metabolismo
Ácidos Graxos/química
Flavonas/metabolismo
Expressão Gênica
Hidroxilação
Indóis/metabolismo
Cinética
Modelos Moleculares
NADP/química
NADP/metabolismo
NADPH-Ferri-Hemoproteína Redutase/química
NADPH-Ferri-Hemoproteína Redutase/genética
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Streptomyces/genética
Homologia Estrutural de Proteína
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Benzophenones); 0 (Fatty Acids); 0 (Flavones); 0 (Indoles); 0 (Recombinant Proteins); 53-59-8 (NADP); 701M4TTV9O (benzophenone); 8724FJW4M5 (indole); 9035-51-2 (Cytochrome P-450 Enzyme System); D3741U8K7L (Indigo Carmine); EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase); EC 1.6.2.4 (flavocytochrome P450 BM3 monoxygenases); S2V45N7G3B (flavone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE


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[PMID]:28884584
[Au] Autor:Hussain H; Al-Sadi AM; Schulz B; Steinert M; Khan A; Green IR; Ahmed I
[Ad] Endereço:UoN Chair of Oman's Medicinal Plants & Marine Natural Products, University of Nizwa, PO Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of Oman.
[Ti] Título:A fruitful decade for fungal polyketides from 2007 to 2016: antimicrobial activity, chemotaxonomy and chemodiversity.
[So] Source:Future Med Chem;9(14):1631-1648, 2017 Sep.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The last three decades have shown that the fungi can be 'biofactories' of novel, bioactive secondary metabolites that produce numerous natural products with novel skeletons and biological activities. Particularly in the last 10 years, large numbers of antimicrobial fungal secondary metabolites have been discovered. This review provides an overview of key, defining developments of the last 10 years regarding the discovery of antimicrobial activity, chemotaxonomy and chemodiversity of fungal polyketides.
[Mh] Termos MeSH primário: Anti-Infecciosos/química
Fungos/química
Policetídeos/química
[Mh] Termos MeSH secundário: Antraquinonas/química
Antraquinonas/isolamento & purificação
Antraquinonas/farmacologia
Anti-Infecciosos/isolamento & purificação
Anti-Infecciosos/farmacologia
Benzofenonas/química
Benzofenonas/isolamento & purificação
Benzofenonas/farmacologia
Cumarínicos/química
Cumarínicos/isolamento & purificação
Cumarínicos/farmacologia
Depsídeos/química
Depsídeos/isolamento & purificação
Depsídeos/farmacologia
Fungos/metabolismo
Bactérias Gram-Negativas/efeitos dos fármacos
Bactérias Gram-Positivas/efeitos dos fármacos
Lactonas/química
Lactonas/isolamento & purificação
Lactonas/farmacologia
Policetídeos/isolamento & purificação
Policetídeos/farmacologia
Pironas/química
Pironas/isolamento & purificação
Pironas/farmacologia
Xantonas/química
Xantonas/isolamento & purificação
Xantonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Anti-Infective Agents); 0 (Benzophenones); 0 (Coumarins); 0 (Depsides); 0 (Lactones); 0 (Polyketides); 0 (Pyrones); 0 (Xanthones); 3580-77-6 (depsidone); 701M4TTV9O (benzophenone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0028


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[PMID]:28799017
[Au] Autor:Archana G; Dhodapkar R; Kumar A
[Ad] Endereço:Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, 440010, India.
[Ti] Título:Ecotoxicological risk assessment and seasonal variation of some pharmaceuticals and personal care products in the sewage treatment plant and surface water bodies (lakes).
[So] Source:Environ Monit Assess;189(9):446, 2017 Aug 10.
[Is] ISSN:1573-2959
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This paper reports the seasonal variation and environmental quality control data for five fingerprint pharmaceuticals and personal care products (PPCPs) (acetaminophen ciprofloxacin, caffeine, irgasan and benzophenone) in the influent and the effluent of the sewage treatment plant (STP) and surface water bodies (six major lakes) in and around Nagpur, one of the "A class city" in the central India over a period of 1 year. The target compounds were analysed using developed offline solid-phase extraction (SPE) coupled with reversed phase high-performance liquid chromatography (RP-HPLC-PDA) method. All the five PPCPs were found in the influent, whereas four were found in the effluent of the STP. However, in the surface water bodies, three PPCPs were detected in all the seasons. Above PPCPs were present in the concentration range of 1-174 µg L in the surface water bodies, 12-373 µg L in the influent and 11-233 µg L in the effluent of the STP. Amongst the five PPCPs, caffeine was found to be in higher concentration as compared to others. The seasonal trends indicate higher concentrations of PPCPs in summer season and lowest in the rainy season. Additionally, physico-chemical characterisations (inorganic and organic parameters) of the collected samples were performed to access the anthropogenic pollution. Ecotoxicological risk assessment was done to appraise the degree of toxicity of the targeted compounds. Hazard quotient (HQ) values were found to be < 1 indicating no adverse effect on the targeted organism.
[Mh] Termos MeSH primário: Cosméticos/análise
Monitoramento Ambiental
Lagos/química
Preparações Farmacêuticas/análise
Eliminação de Resíduos Líquidos
Águas Residuais/química
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Benzofenonas
Carbanilidas
Cromatografia de Fase Reversa
Cidades
Ecotoxicologia
Índia
Medição de Risco
Estações do Ano
Esgotos/análise
Extração em Fase Sólida
Purificação da Água/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzophenones); 0 (Carbanilides); 0 (Cosmetics); 0 (Pharmaceutical Preparations); 0 (Sewage); 0 (Waste Water); 0 (Water Pollutants, Chemical); 701M4TTV9O (benzophenone); I5ZZY3DC5G (cloflucarban)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170812
[St] Status:MEDLINE
[do] DOI:10.1007/s10661-017-6148-3


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[PMID]:28774630
[Au] Autor:Yang F; Wei D; Xiao M; Sun X; Guo Q; Liu Y; Du Y
[Ad] Endereço:State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: yangfan715@mails.ucas.ac.cn.
[Ti] Título:The chlorination transformation characteristics of benzophenone-4 in the presence of iodide ions.
[So] Source:J Environ Sci (China);58:93-101, 2017 Aug.
[Is] ISSN:1001-0742
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Benzophenone-type UV filters are a group of compounds widely used to protect human skin from damage of UV irradiation. Benzophenone-4 (BP-4) was targeted to explore its transformation behaviors during chlorination disinfection treatment in the presence of iodide ions. With the help of ultra performance liquid phase chromatograph and high-resolution quadrupole time-of-flight mass spectrometer, totally fifteen halogenated products were identified, and five out of them were iodinated products. The transformation mechanisms of BP-4 involved electrophilic substitution generating mono- or di-halogenated products, which would be oxidized into esters and further hydrolyzed into phenolic derivatives. The desulfonation and decarboxylation were observed in chlorination system either. Obeying the transformation pathways, five iodinated products formed. The pH conditions of chlorination system determined the reaction types of transformation and corresponding species of products. The more important was that, the acute toxicity had significant increase after chlorination treatment on BP-4, especially in the presence of iodide ions. When the chlorination treatment was performed on ambient water spiked with BP-4 and iodide ions, iodinated by-products could be detected.
[Mh] Termos MeSH primário: Benzofenonas/química
Iodetos/química
Modelos Químicos
Protetores Solares/química
Poluentes Químicos da Água/química
[Mh] Termos MeSH secundário: Benzofenonas/análise
Desinfecção
Halogenação
Protetores Solares/análise
Raios Ultravioleta
Poluentes Químicos da Água/análise
Purificação da Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzophenones); 0 (Iodides); 0 (Sunscreening Agents); 0 (Water Pollutants, Chemical); 1W6L629B4K (sulisobenzone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE


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[PMID]:28754541
[Au] Autor:Yuan H; Zhao J; Wang M; Khan SI; Zhai C; Xu Q; Huang J; Peng C; Xiong G; Wang W; Khan IA
[Ad] Endereço:TCM and Ethnomedicine Innovation & Development Laboratory, Sino-Pakistan TCM and Ethnomedicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, People's Republic of China; National Center for Natural Products Research, Research Institute of Pharmaceutic
[Ti] Título:Benzophenone glycosides from the flower buds of Aquilaria sinensis.
[So] Source:Fitoterapia;121:170-174, 2017 Sep.
[Is] ISSN:1873-6971
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Four new benzophenone glycosides named as aquilaside A-D (1-4) along with five known compounds (5-9) were isolated from the methanol extract of the flower buds of Aquilaria sinensis. Their structures were elucidated on the basis of 1D and 2D NMR and mass spectroscopic analyses. All purified compounds were evaluated for their anti-inflammatory and cytotoxic activities. Aquilasides B and C displayed moderate cytotoxicity against SK-MEL cells with IC of 17.0 and 12.0µM and weak NF-κB inhibitive activity at 100µM with 30% and 60%, respectively.
[Mh] Termos MeSH primário: Benzofenonas/química
Flores/química
Glicosídeos/química
Thymelaeaceae/química
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios/química
Anti-Inflamatórios/isolamento & purificação
Antineoplásicos Fitogênicos/química
Antineoplásicos Fitogênicos/isolamento & purificação
Benzofenonas/isolamento & purificação
Linhagem Celular Tumoral
Glicosídeos/isolamento & purificação
Seres Humanos
Camundongos
Estrutura Molecular
NF-kappa B/antagonistas & inibidores
Óxido Nítrico Sintase Tipo II/antagonistas & inibidores
Estresse Oxidativo/efeitos dos fármacos
Extratos Vegetais/química
Células RAW 264.7
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antineoplastic Agents, Phytogenic); 0 (Benzophenones); 0 (Glycosides); 0 (NF-kappa B); 0 (Plant Extracts); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170730
[St] Status:MEDLINE


  7 / 2712 MEDLINE  
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[PMID]:28729053
[Au] Autor:Youn UJ; Sripisut T; Miklossy G; Turkson J; Laphookhieo S; Chang LC
[Ad] Endereço:Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States; Division of Life Sciences, Korea Polar Research Institute, KIOST, Incheon 21990, Republic of Korea.
[Ti] Título:Bioactive polyprenylated benzophenone derivatives from the fruits extracts of Garcinia xanthochymus.
[So] Source:Bioorg Med Chem Lett;27(16):3760-3765, 2017 08 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Two new polycyclic prenylated xanthones (1 and 2) and a new phenylpropanoid glycoside (3), along with seven known compounds (4-10) were isolated from the fruits of Garcinia xanthochymus. The structures were elucidated by 1D- and 2D-NMR, and HRMS experiments. The isolates were evaluated for their inhibitory effects against the viability of U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbor an aberrantly active signal transducer and exhibit activation of transcription 3 (STAT3), and compared to normal NIH3T3 mouse fibroblasts. Among the isolates, compounds 1, 2, 5, and 6-9 inhibited the viability of glioma cancer cells with IC values in the range of 1.6-6.5µM. Furthermore, treatment of U251MG with 6 and 7 inhibited intracellular STAT3 tyrosine phosphorylation and glioma cell migration in vitro, respectively.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia
Benzofenonas/farmacologia
Frutas/química
Garcinia/química
[Mh] Termos MeSH secundário: Animais
Antineoplásicos Fitogênicos/química
Antineoplásicos Fitogênicos/isolamento & purificação
Benzofenonas/química
Benzofenonas/isolamento & purificação
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Camundongos
Estrutura Molecular
Células NIH 3T3
Fosforilação/efeitos dos fármacos
Fator de Transcrição STAT3/antagonistas & inibidores
Fator de Transcrição STAT3/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Benzophenones); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human)
[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:170722
[St] Status:MEDLINE


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[PMID]:28728896
[Au] Autor:Huang X; Huang R; Gou S; Wang Z; Liao Z; Wang H
[Ad] Endereço:Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.
[Ti] Título:Platinum(IV) complexes conjugated with phenstatin analogue as inhibitors of microtubule polymerization and reverser of multidrug resistance.
[So] Source:Bioorg Med Chem;25(17):4686-4700, 2017 Sep 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pt(IV) complexes comprising a phenstatin analogue, as dual-targeting Pt(IV) prodrug, were designed and synthesized. They were found not only to carry the DNA binding platinum warhead into the tumor cells, but also to have a small molecular unit to inhibit tubulin polymerization. In vitro evaluation results revealed that Pt(IV) complexes showed better and more potent activity against the test human cancer cells including cisplatin resistant cell lines than their corresponding Pt(II) counterparts. In addition, the Pt(IV) derivative of cisplatin, complex 10, exhibited highly selective inhibition in human cancer cells and displayed no obvious toxicity to two human normal cell lines, respectively. Mechanism study suggested that complex 10 induced cell-cycle arrest at the G2/M phase and caused apoptotic cell death of human lung cancer NCI-H460 cells through the mitochondrial mediated pathway. Moreover, complex 10 effectively inhibited the tumor growth in the NCI-H460 xenograft model.
[Mh] Termos MeSH primário: Benzofenonas/química
Complexos de Coordenação/química
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Platina/química
Moduladores de Tubulina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Sítios de Ligação
Linhagem Celular Tumoral
Cisplatino/toxicidade
Desenho de Drogas
Ensaios de Seleção de Medicamentos Antitumorais
Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos
Seres Humanos
Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos
Camundongos Endogâmicos BALB C
Camundongos Nus
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Simulação de Dinâmica Molecular
Neoplasias/tratamento farmacológico
Neoplasias/patologia
Estrutura Terciária de Proteína
Ratos
Espécies Reativas de Oxigênio/metabolismo
Transplante Heterólogo
Tubulina (Proteína)/metabolismo
Moduladores de Tubulina/química
Moduladores de Tubulina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzophenones); 0 (Coordination Complexes); 0 (Reactive Oxygen Species); 0 (Tubulin); 0 (Tubulin Modulators); 0 (phenstatin); 49DFR088MY (Platinum); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE


  9 / 2712 MEDLINE  
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[PMID]:28686747
[Au] Autor:Quintana AM; Hernandez JA; Gonzalez CG
[Ad] Endereço:Department of Biological Sciences, University of Texas El Paso, El Paso, TX, United States of America.
[Ti] Título:Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development.
[So] Source:PLoS One;12(7):e0180856, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions. Moreover, we utilized loss of function analysis and pharmacological inhibition to determine the extent of sonic hedgehog (Shh) signaling in animals with aberrant cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway, results in craniofacial abnormalities via defects in cranial neural crest cell differentiation. Furthermore targeted pharmacological inhibition of the cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants. These data raise the possibility that deficiencies in cholesterol modulate chondrocyte differentiation by a combination of Shh independent and Shh dependent mechanisms. Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms.
[Mh] Termos MeSH primário: Colesterol/biossíntese
Anormalidades Craniofaciais/genética
Proteínas Hedgehog/genética
Hidroximetilglutaril-CoA Redutases/genética
Hidroximetilglutaril-CoA Sintase/genética
Terpenos/metabolismo
Proteínas de Peixe-Zebra/genética
Proteína GLI1 em Dedos de Zinco/genética
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Atorvastatina Cálcica/farmacologia
Benzofenonas/farmacologia
Padronização Corporal/efeitos dos fármacos
Padronização Corporal/genética
Diferenciação Celular/efeitos dos fármacos
Condrócitos/efeitos dos fármacos
Condrócitos/metabolismo
Condrócitos/patologia
Anormalidades Craniofaciais/metabolismo
Anormalidades Craniofaciais/patologia
Embrião não Mamífero
Inibidores Enzimáticos/farmacologia
Regulação da Expressão Gênica no Desenvolvimento
Proteínas Hedgehog/metabolismo
Seres Humanos
Hidroximetilglutaril-CoA Redutases/metabolismo
Hidroximetilglutaril-CoA Sintase/metabolismo
Crista Neural/efeitos dos fármacos
Crista Neural/metabolismo
Crista Neural/patologia
Piperidinas/farmacologia
Piridinas/farmacologia
Transdução de Sinais
Terpenos/antagonistas & inibidores
Peixe-Zebra
Proteínas de Peixe-Zebra/metabolismo
Proteína GLI1 em Dedos de Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Benzophenones); 0 (Enzyme Inhibitors); 0 (Hedgehog Proteins); 0 (Piperidines); 0 (Pyridines); 0 (Shha protein, zebrafish); 0 (Terpenes); 0 (Zebrafish Proteins); 0 (Zinc Finger Protein GLI1); 161582-11-2 (Ro 48-8071); 48A5M73Z4Q (Atorvastatin Calcium); 97C5T2UQ7J (Cholesterol); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 2.3.3.10 (HMGCS1 protein, human); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); IOW153004F (lonafarnib)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180856


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[PMID]:28554026
[Au] Autor:Campos D; Gravato C; Fedorova G; Burkina V; Soares AMVM; Pestana JLT
[Ad] Endereço:Departamento de Biologia & CESAM, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
[Ti] Título:Ecotoxicity of two organic UV-filters to the freshwater caddisfly Sericostoma vittatum.
[So] Source:Environ Pollut;228:370-377, 2017 Sep.
[Is] ISSN:1873-6424
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Organic ultraviolet filters (UV-filters) used for protection against radiation in personal care products and other materials (e.g. textiles, plastic products) are considered emerging contaminants of aquatic ecosystem. Benzophenone-3 (BP3) and 3-(4-methylbenzylidene)camphor (4-MBC) are the most commonly used organic UV-filters and have been reported in freshwater environments due to contamination through discharges from wastewater treatment plants and swimming pools or by direct contamination from recreational activities. Our aim was to evaluate the ecotoxicological effects of these UV-filters using the freshwater caddisfly Sericostoma vittatum' biochemical biomarkers and energy processing related endpoints (feeding behaviour, energy reserves and cellular metabolism). In laboratory trials, both compounds induced feeding inhibition of S. vittatum at 3.55 mg/kg of BP3 and at concentrations ≥2.57 mg/kg of 4-MBC, decreased carbohydrates content at 3.55 and 6.95 mg/kg of BP3 and 4-MBC respectively, and increased total glutathione levels at concentrations ≥1.45 and 1.35 mg/kg of BP3 and 4-MBC respectively. No significant effects were observed on endpoints associated with oxidative stress, antioxidant defences, phase II biotransformation or neurotoxicity after exposure to the two UV-filters. Our results show that environmental relevant concentrations of BP3 and 4-MBC, can negatively impact freshwater insects and demonstrate the importance of monitoring the ecological effects of organic UV-filters using non-model invertebrate species.
[Mh] Termos MeSH primário: Insetos/fisiologia
Protetores Solares/toxicidade
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Animais
Benzofenonas/toxicidade
Cânfora/análogos & derivados
Cânfora/toxicidade
Água Doce
Piscinas
Poluentes Químicos da Água/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzophenones); 0 (Sunscreening Agents); 0 (Water Pollutants, Chemical); 76-22-2 (Camphor); 8I3XWY40L9 (enzacamene); 95OOS7VE0Y (oxybenzone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE



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