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[PMID]: 29184402 [Au] Autor: Wu X; Wang L; Qiu Y; Zhang B; Hu Z; Jin R [Ad] Endereço: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan. [Ti] Título: Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia. [So] Source: Int J Nanomedicine;12:8025-8034, 2017. [Is] ISSN: 1178-2013 [Cp] País de publicação: New Zealand [La] Idioma: eng [Ab] Resumo: T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores Nanopartículas/química Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico [Mh] Termos MeSH secundário: Animais Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem Compostos de Bifenilo/administração & dosagem Compostos de Bifenilo/farmacologia Liberação Controlada de Fármacos Sinergismo Farmacológico Feminino Seres Humanos Células Jurkat Ácido Láctico/química Camundongos Nanopartículas/administração & dosagem Nitrofenóis/administração & dosagem Nitrofenóis/farmacologia Piperazinas/administração & dosagem Piperazinas/farmacologia Ácido Poliglicólico/química Sulfonamidas/administração & dosagem Sulfonamidas/farmacologia Ensaios Antitumorais Modelo de Xenoenxerto [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (ABT-737); 0 (Biphenyl Compounds); 0 (Nitrophenols); 0 (Piperazines); 0 (Sulfonamides); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); EC 2.7.11.1 (IRAK1 protein, human); EC 2.7.11.1 (IRAK4 protein, human); EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180305 [Lr] Data última revisão: 180305 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171130 [St] Status: MEDLINE [do] DOI: 10.2147/IJN.S146875

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[PMID]: 29372687 [Au] Autor: Stefaniková A; Klacanová K; Pilchová I; Hatok J; Racay P [Ad] Endereço: 1 Department of Medical Biochemistry Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. racay@jfmed.uniba.sk. [Ti] Título: Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737. [So] Source: Gen Physiol Biophys;36(5):539-547, 2017 Dec. [Is] ISSN: 0231-5882 [Cp] País de publicação: Slovakia [La] Idioma: eng [Ab] Resumo: Colorectal carcinoma (CRC) that represents one of the major causes for cancer-related death in humans is often associated with over-expression of anti-apoptotic proteins of Bcl-2 family. The aim of presented study was to determine the effect of ABT-737 inhibitor of anti-apoptotic proteins Bcl-2, Bcl-XL and Bcl-w as well as cyclin-dependent kinase 2 (CDK2) inhibitor SU9516 alone and in combination with ABT-737 on survival of colorectal cell lines HT29 and Caco-2. We have shown that both Caco-2 and HT29 cells that are relatively resistant to ABT-737 are also partially sensitive to SU9516, which increased sensitivity of Caco-2 but not HT29 cells to ABT-737. Increased sensitivity of Caco-2 cells to ABT-737 after addition of SU9516 correlated well with SU9516-induced decrease of Mcl-1 expression while we have not observed downregulation of Mcl-1 after the treatment of HT29 cells with SU9516. Instead of this, we have shown that treatment of HT29 cells with SU9516 is associated with decreased expression of tumour suppressor protein p53. Our findings provide a rationale for clinical use of Bcl-2 family inhibitors in combination with CDK2 inhibitors for treatment of Mcl-1-dependent colorectal tumours associated with expression of Bcl-2, Bcl-XL and Bcl-w proteins. In addition, we have shown potential of CDK2 inhibitors for treatment of tumours expressing R273H mutant p53. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem Compostos de Bifenilo/administração & dosagem Neoplasias Colorretais/tratamento farmacológico Neoplasias Colorretais/enzimologia Quinase 2 Dependente de Ciclina/antagonistas & inibidores Imidazóis/administração & dosagem Indóis/administração & dosagem Nitrofenóis/administração & dosagem Sulfonamidas/administração & dosagem [Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/química Compostos de Bifenilo/química Células CACO-2 Sobrevivência Celular/efeitos dos fármacos Neoplasias Colorretais/patologia Relação Dose-Resposta a Droga Sinergismo Farmacológico Células HT29 Seres Humanos Nitrofenóis/química Piperazinas/administração & dosagem Piperazinas/química Sulfonamidas/química Resultado do Tratamento [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (ABT-737); 0 (BH3 Interacting Domain Death Agonist Protein); 0 (BID protein, human); 0 (Biphenyl Compounds); 0 (Imidazoles); 0 (Indoles); 0 (Nitrophenols); 0 (Piperazines); 0 (SU 9516); 0 (Sulfonamides); EC 2.7.11.22 (CDK2 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 2) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180223 [Lr] Data última revisão: 180223 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180127 [St] Status: MEDLINE [do] DOI: 10.4149/gpb_2017030

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[PMID]: 29272851 [Au] Autor: Zaheer Z [Ad] Endereço: Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21413, Saudi Arabia. Electronic address: zzkhan@kau.edu.sa. [Ti] Título: Biogenic synthesis, optical, catalytic, and in vitro antimicrobial potential of Ag-nanoparticles prepared using Palm date fruit extract. [So] Source: J Photochem Photobiol B;178:584-592, 2018 Jan. [Is] ISSN: 1873-2682 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: Silver nanoparticles (AgNPs) have been synthesized via green route using an aqueous extract of Palm date fruit pericarp extract. The appearance of the yellow color and the surface resonance plasmon (SRP) band at around 400-450nm in UV-Visible spectroscopy initially reveals the formation of AgNPs. The particle size, crystalline nature, and size distribution was confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) ring patterns, energy dispersive X-ray spectroscopy (EDX), dynamic light scattering (DLS) techniques. The particles size ranged ca. 3nm to 30nm and are spherical in shape. The microbial activity of biogenic AgNPs was tested on clinical multiple drug resistance Staphylococcus aureus, Escherichia coli and Candida albicans reference strain. Zones of inhibition growth increases with [AgNPs]. The results suggest that the particle tested in this study certainly mediate the inhibition of bacterial and fungus growth. To overcome the serious problems related to environment like discharge of hazardous chemicals to water bodies, AgNPs have been found to be very important in the catalytic degradation of 4-nitrophenol. The rate of degradation strongly depends on the sun light exposure. Based on the chemical and kinetic studies, an attempt has been made to elucidate the mechanism of AgNPs formation. [Mh] Termos MeSH primário: Anti-Infecciosos/síntese química Nanopartículas Metálicas/química Phoeniceae/química Prata/química [Mh] Termos MeSH secundário: Anti-Infecciosos/química Anti-Infecciosos/farmacologia Candida albicans/efeitos dos fármacos Catálise Difusão Dinâmica da Luz Escherichia coli/efeitos dos fármacos Frutas/química Frutas/metabolismo Química Verde Nanopartículas Metálicas/toxicidade Microscopia Eletrônica de Varredura Nitrofenóis/química Tamanho da Partícula Phoeniceae/metabolismo Fotólise/efeitos da radiação Extratos Vegetais/química Espectrometria por Raios X Espectrofotometria Staphylococcus aureus/efeitos dos fármacos Luz Solar Ressonância de Plasmônio de Superfície [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Infective Agents); 0 (Nitrophenols); 0 (Plant Extracts); 3M4G523W1G (Silver); Y92ZL45L4R (4-nitrophenol) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180212 [Lr] Data última revisão: 180212 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171223 [St] Status: MEDLINE

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[PMID]: 28782938 [Au] Autor: Yang X; Luo MJ; Yeung ACM; Lewis PJ; Chan PKS; Ip M; Ma C [Ad] Endereço: Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital , Shatin, Hong Kong. [Ti] Título: First-In-Class Inhibitor of Ribosomal RNA Synthesis with Antimicrobial Activity against Staphylococcus aureus. [So] Source: Biochemistry;56(38):5049-5052, 2017 Sep 26. [Is] ISSN: 1520-4995 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: We report the discovery of the first bacterial ribosomal RNA (rRNA) synthesis inhibitor that has specific antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). A pharmacophore model was constructed on the basis of the protein-protein interaction between essential bacterial rRNA transcription factors NusB and NusE and employed for an in silico screen to identify potential leads. One compound, (E)-2-{[(3-ethynylphenyl)imino]methyl}-4-nitrophenol (MC4), demonstrated antimicrobial activity against a panel of S. aureus strains, including MRSA, without significant toxicity to mammalian cells. MC4 resulted in a decrease in the rRNA level in bacteria, and the target specificity of MC4 was confirmed at the molecular level. Results obtained from this work validated the bacterial rRNA transcription machinery as a novel antimicrobial target. This approach may be extended to other factors in rRNA transcription, and MC4 could be applied as a chemical probe to dissect the relationship among MRSA infection, MRSA growth rate, and rRNA synthesis, in addition to its therapeutic potential. [Mh] Termos MeSH primário: Antibacterianos/farmacologia Hidrazonas/farmacologia Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos Nitrofenóis/farmacologia RNA Ribossômico/antagonistas & inibidores [Mh] Termos MeSH secundário: Antibacterianos/efeitos adversos Proteínas de Bactérias/química Proteínas de Bactérias/metabolismo Simulação por Computador Avaliação Pré-Clínica de Medicamentos/métodos Proteínas de Escherichia coli/química Proteínas de Escherichia coli/metabolismo Hidrazonas/química Staphylococcus aureus Resistente à Meticilina/genética Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento Testes de Sensibilidade Microbiana Nitrofenóis/química Conformação Proteica RNA Ribossômico/biossíntese RNA Ribossômico/genética Proteínas Ribossômicas/química Proteínas Ribossômicas/metabolismo Fatores de Transcrição/química Fatores de Transcrição/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (2-(((3-ethynylphenyl)imino)methyl)-4-nitrophenol); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Escherichia coli Proteins); 0 (Hydrazones); 0 (Nitrophenols); 0 (NusB protein, E coli); 0 (RNA, Ribosomal); 0 (Ribosomal Proteins); 0 (Transcription Factors); 0 (ribosomal protein S10) [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: 170808 [St] Status: MEDLINE [do] DOI: 10.1021/acs.biochem.7b00349

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[PMID]: 28764053 [Au] Autor: Ahn-Jarvis JH; Teegarden MD; Schwartz SJ; Lee K; Vodovotz Y [Ad] Endereço: College of Dentistry, The Ohio State University, 3173 Postle Hall, 305 West 12th Avenue, Columbus, OH 43210, United States. Electronic address: ahn-jarvis.1@osu.edu. [Ti] Título: Modulating conversion of isoflavone glycosides to aglycones using crude beta-glycosidase extracts from almonds and processed soy. [So] Source: Food Chem;237:685-692, 2017 Dec 15. [Is] ISSN: 0308-8146 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Food processing alters the physicochemical state of soy which can enhance chemical and enzymatic conversion of isoflavones to their aglycone forms. This study investigated the role of ß-glycosidase from processed soy-ingredient mixture (SIM) or almonds, and examined the impact of isoflavone composition in mediating conversion to aglycones. ß-Glycosidase activity was quantified using p-nitrophenol-ß-d-glucopyranoside and SIM isoflavone extracts. Almond ß-glycosidase activity was significantly (p<0.001) reduced after roasting (99% reduction) or steaming (97% reduction) compared to raw almonds. SIM ß-glycosidase activity, however, increased, with steaming by 66% (p<0.001) and with roasting by 52% (p=0.022), compared to raw SIM. After incubation with ß-glycosidase, percentage of aglycone (total aglycone/total isoflavones) in SIM isoflavone extracts increased significantly in raw (35%), fermented (48%), roasted (88%) and steamed (91%) SIM, compared to their initial (∼5%) compositions. Manipulation of ß-glycosidase activity and isoflavone composition can be used to modulate aglycone content in soy food products. [Mh] Termos MeSH primário: Glicosídeo Hidrolases/metabolismo Glicosídeos/metabolismo Prunus dulcis [Mh] Termos MeSH secundário: Isoflavonas Nitrofenóis [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Glycosides); 0 (Isoflavones); 0 (Nitrophenols); EC 3.2.1.- (Glycoside Hydrolases); Y92ZL45L4R (4-nitrophenol) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171107 [Lr] Data última revisão: 171107 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170803 [St] Status: MEDLINE

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[PMID]: 28732333 [Au] Autor: Meijide J; Rosales E; Pazos M; Sanromán MA [Ad] Endereço: Department of Chemical Engineering University of Vigo, Isaac Newton Building, Campus As Lagoas, Marcosende, 36310, Vigo, Spain. [Ti] Título: p-Nitrophenol degradation by electro-Fenton process: Pathway, kinetic model and optimization using central composite design. [So] Source: Chemosphere;185:726-736, 2017 Oct. [Is] ISSN: 1879-1298 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The chemical process scale-up, from lab studies to industrial production, is challenging and requires deep knowledge of the kinetic model and the reactions that take place in the system. This knowledge is also useful in order to be employed for the reactor design and the determination of the optimal operational conditions. In this study, a model substituted phenol such as p-nitrophenol was degraded by electro-Fenton process and the reaction products yielded along the treatment were recorded. The kinetic model was developed using Matlab software and was based on main reactions that occurred until total mineralization which allowed predicting the degradation pathway under this advanced oxidation process. The predicted concentration profiles of p-nitrophenol, their intermediates and by-products in electro-Fenton process were validated with experimental assays and the results were consistent. Finally, based on the developed kinetic model the degradation process was optimized using central composite design taking as key parameters the ferrous ion concentration and current density. [Mh] Termos MeSH primário: Modelos Químicos Nitrofenóis/química Poluentes Químicos da Água/química [Mh] Termos MeSH secundário: Peróxido de Hidrogênio/química Ferro/química Cinética Oxirredução Fenol/química Poluentes Químicos da Água/análise [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Nitrophenols); 0 (Water Pollutants, Chemical); 339NCG44TV (Phenol); BBX060AN9V (Hydrogen Peroxide); E1UOL152H7 (Iron); Y92ZL45L4R (4-nitrophenol) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171017 [Lr] Data última revisão: 171017 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170722 [St] Status: MEDLINE

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[PMID]: 28686427 [Au] Autor: Yang J; Pignatello JJ; Pan B; Xing B [Ad] Endereço: Faculty of Environmental Science & Engineering, Kunming University of Science & Technology , Kunming 650500, P. R. China. [Ti] Título: Degradation of p-Nitrophenol by Lignin and Cellulose Chars: H O -Mediated Reaction and Direct Reaction with the Char. [So] Source: Environ Sci Technol;51(16):8972-8980, 2017 Aug 15. [Is] ISSN: 1520-5851 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Chars and other black carbons are reactive toward certain compounds. Such reactivity has been attributed to reduction of O by persistent free radicals in the solid to H O , which then back-reacts with the solid to generate reactive oxygen species (ROS; especially HO ). We studied the decomposition of p-nitrophenol (PNP) by pure lignin and cellulose chars aged in moist air or a vacuum at room temperature for up to a month. In air, the chars chemisorbed oxygen, a portion of which was liberated as H O when the char was submerged in water. The evolved H O was simultaneously decomposed by the char. PNP reacted predominantly in the sorbed state and only reduction products (phenol, catechol) were identified. Aging the char in air sharply (within hours) reduced H O -producing capacity and free radical concentration, but more gradually reduced PNP decay rate over the month-long period. PNP decay was only modestly suppressed (12-30%) by H O removal (catalase), and had little effect on the free radical signal (<6 radicals annihilated per 1000 PNP reacted). Contrasting with previous studies, the results show that direct reaction of PNP with char predominates over H O -dependent reactions, and the vast majority of direct-reacting sites are nonradical in character. Nonradical sites are also responsible in part for H O decomposition; in fact, H O pretreatment depleted PNP reactive sites. Lignin char was generally more reactive than cellulose char. The Fe impurity in lignin played no role. The results are relevant to the fate of pollutants in black carbon-rich environments and the use of carbons in remediation. [Mh] Termos MeSH primário: Celulose Lignina [Mh] Termos MeSH secundário: Peróxido de Hidrogênio Nitrofenóis [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Nitrophenols); 9004-34-6 (Cellulose); 9005-53-2 (Lignin); BBX060AN9V (Hydrogen Peroxide); Y92ZL45L4R (4-nitrophenol) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171106 [Lr] Data última revisão: 171106 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170708 [St] Status: MEDLINE [do] DOI: 10.1021/acs.est.7b01087

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[PMID]: 28678475 [Au] Autor: Chu Y; Williams NH; Hengge AC [Ad] Endereço: Department of Chemistry and Biochemistry, Utah State University , Logan, Utah 84322-0300, United States. [Ti] Título: Transition States and Control of Substrate Preference in the Promiscuous Phosphatase PP1. [So] Source: Biochemistry;56(30):3923-3933, 2017 Aug 01. [Is] ISSN: 1520-4995 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Catalytically promiscuous enzymes are an attractive frontier for biochemistry, because enzyme promiscuities not only plausibly explain enzyme evolution through the mechanism of gene duplication but also could provide an efficient route to changing the catalytic function of proteins by mimicking this evolutionary process. PP1γ is an effectively promiscuous phosphatase for the hydrolysis of both monoanionic and dianionic phosphate ester-based substrates. In addition to its native phosphate monoester substrate, PP1γ catalyzes the hydrolysis of aryl methylphosphonates, fluorophosphate esters, phosphorothioate esters, and phosphodiesters, with second-order rate accelerations that fall within the narrow range of 10 -10 . In contrast to the different transition states in the uncatalyzed hydrolysis reactions of these substrates, PP1γ catalyzes their hydrolysis through similar transition states. PP1γ does not catalyze the hydrolysis of a sulfate ester, which is unexpected. The PP1γ active site is tolerant of variations in the geometry of bound ligands, which permit the effective catalysis even of substrates whose steric requirements may result in perturbations to the positioning of the transferring group, both in the initial enzyme-substrate complex and in the transition state. The conservative mutation of arginine 221 to lysine results in a mutant that is a more effective catalyst toward monoanionic substrates. The surprising conversion of substrate preference lends support to the notion that mutations following gene duplication can result in an altered enzyme with different catalytic capabilities and preferences and may provide a pathway for the evolution of new enzymes. [Mh] Termos MeSH primário: Modelos Moleculares Proteína Fosfatase 1/metabolismo [Mh] Termos MeSH secundário: Substituição de Aminoácidos Arginina/química Ligação Competitiva Biocatálise Domínio Catalítico Inibidores Enzimáticos/farmacologia Estabilidade Enzimática Evolução Molecular Seres Humanos Ligações de Hidrogênio Hidrólise Ligantes Lisina/química Conformação Molecular Mutagênese Sítio-Dirigida Mutação Nitrofenóis/química Nitrofenóis/metabolismo Organofosfonatos/química Organofosfonatos/metabolismo Compostos Organofosforados/química Compostos Organofosforados/metabolismo Compostos Organotiofosforados/química Compostos Organotiofosforados/metabolismo Proteína Fosfatase 1/antagonistas & inibidores Proteína Fosfatase 1/química Proteína Fosfatase 1/genética Proteínas Recombinantes/química Proteínas Recombinantes/metabolismo Especificidade por Substrato [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (4-nitrophenyl phosphorothioate); 0 (Enzyme Inhibitors); 0 (Ligands); 0 (Nitrophenols); 0 (Organophosphonates); 0 (Organophosphorus Compounds); 0 (Organothiophosphorus Compounds); 0 (Recombinant Proteins); 330-13-2 (nitrophenylphosphate); 94ZLA3W45F (Arginine); EC 3.1.3.16 (PPP1CC protein, human); EC 3.1.3.16 (Protein Phosphatase 1); K3Z4F929H6 (Lysine) [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: 170706 [St] Status: MEDLINE [do] DOI: 10.1021/acs.biochem.7b00441

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[PMID]: 28672209 [Au] Autor: Ji Y; Wang L; Jiang M; Lu J; Ferronato C; Chovelon JM [Ad] Endereço: College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: yuefeiji@njau.edu.cn. [Ti] Título: The role of nitrite in sulfate radical-based degradation of phenolic compounds: An unexpected nitration process relevant to groundwater remediation by in-situ chemical oxidation (ISCO). [So] Source: Water Res;123:249-257, 2017 Oct 15. [Is] ISSN: 1879-2448 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: As promising in-situ chemical oxidation (ISCO) technologies, sulfate radical-based advanced oxidation processes (SR-AOPs) are applied in wastewater treatment and groundwater remediation in recent years. In this contribution, we report for the first time that, thermally activated persulfate oxidation of phenol in the presence of nitrite (NO ), an anion widely present in natural waters, could lead to the formation of nitrated by-products including 2-nitrophenol (2-NP), 4-nitrophenol (4-NP), 2,4-dinitrophenol (2,4-DNP), and 2,6-dinitrophenol (2,6-DNP). Nitrogen dioxide radical (NO ), arising from SO scavenging by NO , was proposed to be involved in the formation of nitrophenols as a nitrating agent. It was observed that nitrophenols accounted for approximately 70% of the phenol transformed under reaction conditions of [NO ] = 200 µM, [PS] = 2 mM and temperature of 50 °C. Increasing the concentration of NO remarkably enhanced the formation of nitrophenols but did not affect the transformation rate of phenol significantly. The degradation of phenol and the formation of nitrophenols were significantly influenced by persulfate dosage, solution pH and natural organic matter (NOM). Further studies on the degradation of other phenolic compounds, including 4-chlorophenol (4-CP), 4-hydroxybenzoic acid (4-HBA), and acetaminophen (ATP), verified the formation of their corresponding nitrated by-products as well. Therefore, formation of nitrated by-products is probably a common but overlooked phenomenon during SO -based oxidation of phenolic compounds in the presence of NO . Nitroaromatic compounds are well known for their carcinogenicity, mutagenicity and genotoxicity, and are potentially persistent in the environment. The formation of nitrated organic by-products in SR-AOPs should be carefully scrutinized, and risk assessment should be carried out to assess possible health and ecological impacts. [Mh] Termos MeSH primário: Água Subterrânea Nitrofenóis/química Poluentes Químicos da Água [Mh] Termos MeSH secundário: Nitritos Oxirredução Sulfatos/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Nitrites); 0 (Nitrophenols); 0 (Sulfates); 0 (Water Pollutants, Chemical); 0 (sulfate radical); F4QM4I92KC (2,6-dinitrophenol) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171013 [Lr] Data última revisão: 171013 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170704 [St] Status: MEDLINE

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[PMID]: 28663253 [Au] Autor: Choo HJ; Kholmukhamedov A; Zhou C; Jobe S [Ad] Endereço: From the BloodCenter of Wisconsin, Milwaukee (A.K., S.J.); Emory University School of Medicine, Department of Pediatrics and Children's Healthcare of Atlanta, GA (H.-J.C., C.Z., S.J.); Emory University, School of Medicine, Department of Cell Biology, Atlanta, GA (H.-J.C.); and Medical College of Wis [Ti] Título: Inner Mitochondrial Membrane Disruption Links Apoptotic and Agonist-Initiated Phosphatidylserine Externalization in Platelets. [So] Source: Arterioscler Thromb Vasc Biol;37(8):1503-1512, 2017 Aug. [Is] ISSN: 1524-4636 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo. APPROACH AND RESULTS: Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption. In both ABT-737 (apoptotic) and agonist (necrotic)-treated platelets, phosphatidylserine externalization was temporally correlated with IMM disruption. Agonist stimulation resulted in rapid cyclophilin D-dependent IMM disruption that coincided with phosphatidylserine exposure. ABT-737 treatment caused rapid cytochrome c release, eventually followed by caspase-dependent IMM disruption that again closely coincided with phosphatidylserine exposure. A nonmitochondrial and integrin-mediated mechanism has been implicated in the formation of a novel phosphatidylserine-externalizing platelet subpopulation. Using image cytometry, this subpopulation is demonstrated to be the result of the interaction of an aggregatory platelet and a procoagulant platelet rather than indicative of a novel intracellular mechanism regulating platelet phosphatidylserine externalization. Using electron microscopy, similar interactions between aggregatory and procoagulant platelets are demonstrated in vitro and in vivo within a mesenteric vein hemostatic thrombus. CONCLUSIONS: Platelet phosphatidylserine externalization is closely associated with the mitochondrial event of IMM disruption identifying a common pathway in phosphatidylserine-externalizing platelets. The limited interaction of procoagulant platelets and integrin-active aggregatory platelets identifies a potential mechanism for procoagulant platelet retention within the hemostatic thrombus. [Mh] Termos MeSH primário: Apoptose Plaquetas/metabolismo Mitocôndrias/metabolismo Membranas Mitocondriais/metabolismo Fosfatidilserinas/sangue Agregação Plaquetária Trombose Venosa/sangue [Mh] Termos MeSH secundário: Animais Apoptose/efeitos dos fármacos Compostos de Bifenilo/farmacologia Coagulação Sanguínea/efeitos dos fármacos Plaquetas/efeitos dos fármacos Plaquetas/ultraestrutura Caspases/sangue Venenos de Crotalídeos/farmacologia Ciclofilinas/sangue Ciclofilinas/genética Citocromos c/sangue Modelos Animais de Doenças Genótipo Integrinas/sangue Cinética Lectinas Tipo C Camundongos Knockout Mitocôndrias/efeitos dos fármacos Mitocôndrias/ultraestrutura Membranas Mitocondriais/efeitos dos fármacos Necrose Nitrofenóis/farmacologia Fenótipo Piperazinas/farmacologia Agregação Plaquetária/efeitos dos fármacos Transdução de Sinais Sulfonamidas/farmacologia Trombina/farmacologia Trombose Venosa/genética Trombose Venosa/patologia Proteína Killer-Antagonista Homóloga a bcl-2/sangue Proteína Killer-Antagonista Homóloga a bcl-2/genética Proteína X Associada a bcl-2/sangue Proteína X Associada a bcl-2/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (ABT-737); 0 (Bak1 protein, mouse); 0 (Bax protein, mouse); 0 (Biphenyl Compounds); 0 (Crotalid Venoms); 0 (Integrins); 0 (Lectins, C-Type); 0 (Nitrophenols); 0 (Phosphatidylserines); 0 (Piperazines); 0 (Sulfonamides); 0 (bcl-2 Homologous Antagonist-Killer Protein); 0 (bcl-2-Associated X Protein); 37206-04-5 (convulxin); 9007-43-6 (Cytochromes c); EC 3.4.21.5 (Thrombin); EC 3.4.22.- (Caspases); EC 5.2.1.- (Cyclophilins); EC 5.2.1.8 (cyclophilin D) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170819 [Lr] Data última revisão: 170819 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170701 [St] Status: MEDLINE [do] DOI: 10.1161/ATVBAHA.117.309473

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