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[PMID]: 28729181 [Au] Autor: Yi M; Shin JG; Lee SJ [Ad] Endereço: Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, Busan, South Korea. [Ti] Título: Expression of CYP4V2 in human THP1 macrophages and its transcriptional regulation by peroxisome proliferator-activated receptor gamma. [So] Source: Toxicol Appl Pharmacol;330:100-106, 2017 Sep 01. [Is] ISSN: 1096-0333 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Because macrophages respond to a variety of pathological and pharmacological reagents, understanding the role of P450s in macrophages is important for therapeutic intervention. There has been a lack of research on CYP4 in macrophages, but fatty acid accumulation and lipid trafficking in macrophages have been suggested to be a main cause of atherosclerosis. All human CYP4 genes (n=12) were screened in THP1 macrophages by gene-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Only CYP4V2 exhibited strong expression of both mRNA and protein. Expression levels of both CYP4V2 mRNA and protein were significantly reduced after treatment with peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662. However, the expression levels of CYP4V2 were not changed by PPARα antagonist (GW6471) and liver X receptor alpha antagonist (22-S hydroxycholesterol). A metabolite of the CYP4V2 enzyme, 12-hydroxydodecanoic acid, was detected in THP1 macrophages, and this metabolite was significantly decreased after treatment with the PPARγ inhibitor GW9662 (>80% decreased, p<0.05). In summary, fatty acid metabolizing protein CYP4V2 was identified in human THP1 macrophages, and its expression was regulated by PPARγ. Further study is required to understand the role of CYP4V2 with regard to fat accumulation in the activated macrophage and atherosclerotic plaque development. [Mh] Termos MeSH primário: Família 4 do Citocromo P450/genética Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos Macrófagos/enzimologia PPAR alfa/farmacologia [Mh] Termos MeSH secundário: Anilidas/farmacologia Linhagem Celular Família 4 do Citocromo P450/biossíntese Ácidos Graxos/metabolismo Seres Humanos Hidroxicolesteróis/farmacologia Ácidos Láuricos/metabolismo Receptores X do Fígado/antagonistas & inibidores Macrófagos/efeitos dos fármacos PPAR alfa/antagonistas & inibidores PPAR alfa/genética RNA Mensageiro/biossíntese RNA Mensageiro/genética RNA Interferente Pequeno/genética Acetato de Tetradecanoilforbol/farmacologia Transcrição Genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (2-chloro-5-nitrobenzanilide); 0 (Anilides); 0 (Fatty Acids); 0 (Hydroxycholesterols); 0 (Lauric Acids); 0 (Liver X Receptors); 0 (PPAR alpha); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 1160N9NU9U (lauric acid); 17711-16-9 (22-hydroxycholesterol); 505-95-3 (12-hydroxydodecanoic acid); EC 1.14.13.- (CYP4V2 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4); NI40JAQ945 (Tetradecanoylphorbol Acetate) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170814 [Lr] Data última revisão: 170814 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170722 [St] Status: MEDLINE

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[PMID]: 28694203 [Au] Autor: Dong XW; Jia YL; Ge LT; Jiang B; Jiang JX; Shen J; Jin YC; Guan Y; Sun Y; Xie QM [Ad] Endereço: Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou 310058, China. [Ti] Título: Soluble epoxide hydrolase inhibitor AUDA decreases bleomycin-induced pulmonary toxicity in mice by inhibiting the p38/Smad3 pathways. [So] Source: Toxicology;389:31-41, 2017 Aug 15. [Is] ISSN: 1879-3185 [Cp] País de publicação: Ireland [La] Idioma: eng [Ab] Resumo: Bleomycin (BLM) has potent tumor cell-killing properties that have given it an important place in cancer chemotherapy, but pulmonary toxicity is its major adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to have protective effects in fibrosis models, but the effects of AUDA, an sEH inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be researched. In this study, we assessed the effects of AUDA on the BLM-induced pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-ß -induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in vitro by monitoring changes in pulmonary function, inflammatory response, fibrotic remodeling, and signaling pathways. AUDA was administered by intragastric administration (i.g) daily for three weeks, starting at seven days after intratracheal instillation of BLM. All examinations were performed 24h after the last i.g. In vivo, AUDA significantly improved BLM-induced decline in lung function and body weight, and inhibited inflammatory cell accumulation and the mRNA and protein expression of interleukin (IL)-1ß, TGF-ß , and matrix metalloproteinase 9 (MMP-9) in lung tissue. Moreover, AUDA attenuated BLM-induced deposition of collagen fibers, destruction of alveolar structures, and pulmonary parenchyma. Additionally, AUDA regulated the expression of α-smooth muscle actin (α-SMA) and E-cadherin by inhibiting the Smad3/p38 signaling pathway. In vitro, AUDA significantly inhibited TGF-ß -induced epithelial cells and fibroblast proliferation, reduced sEH expression and α-SMA expression, and increased epoxyeicosatrienoic acid (EET) levels and E-cadherin expression in epithelial cells. These effects were blocked by AUDA by downregulating the Smad3 and p38 signaling pathways. Taken together, these data indicate that treatment with sEH inhibitors may improve BLM-induced pulmonary toxicity. [Mh] Termos MeSH primário: Adamantano/análogos & derivados Bleomicina Inibidores Enzimáticos/farmacologia Epóxido Hidrolases/antagonistas & inibidores Ácidos Láuricos/farmacologia Pulmão/efeitos dos fármacos Fibrose Pulmonar/prevenção & controle Proteína Smad3/metabolismo Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo [Mh] Termos MeSH secundário: Adamantano/farmacologia Animais Biomarcadores/metabolismo Linhagem Celular Proliferação Celular/efeitos dos fármacos Colágeno/metabolismo Citocinas/metabolismo Citoproteção Modelos Animais de Doenças Relação Dose-Resposta a Droga Transição Epitelial-Mesenquimal/efeitos dos fármacos Epóxido Hidrolases/metabolismo Feminino Seres Humanos Mediadores da Inflamação/metabolismo Pulmão/enzimologia Pulmão/patologia Pulmão/fisiopatologia Camundongos Endogâmicos ICR Pneumonia/induzido quimicamente Pneumonia/enzimologia Pneumonia/prevenção & controle Fibrose Pulmonar/induzido quimicamente Fibrose Pulmonar/enzimologia Fibrose Pulmonar/patologia Transdução de Sinais/efeitos dos fármacos Fatores de Tempo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (12-(3-adamantan-1-ylureido)dodecanoic acid); 0 (Biomarkers); 0 (Cytokines); 0 (Enzyme Inhibitors); 0 (Inflammation Mediators); 0 (Lauric Acids); 0 (Smad3 Protein); 0 (Smad3 protein, mouse); 11056-06-7 (Bleomycin); 9007-34-5 (Collagen); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.3.2.- (Epoxide Hydrolases); PJY633525U (Adamantane) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170911 [Lr] Data última revisão: 170911 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170712 [St] Status: MEDLINE

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[PMID]: 28603981 [Au] Autor: Hsieh CH; Huang X; Amaya JA; Rutland CD; Keys CL; Groves JT; Austin RN; Makris TM [Ad] Endereço: Department of Chemistry and Biochemistry, University of South Carolina , Columbia, South Carolina 29208, United States. [Ti] Título: The Enigmatic P450 Decarboxylase OleT Is Capable of, but Evolved To Frustrate, Oxygen Rebound Chemistry. [So] Source: Biochemistry;56(26):3347-3357, 2017 Jul 05. [Is] ISSN: 1520-4995 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OleT is a cytochrome P450 enzyme that catalyzes the removal of carbon dioxide from variable chain length fatty acids to form 1-alkenes. In this work, we examine the binding and metabolic profile of OleT with shorter chain length (n ≤ 12) fatty acids that can form liquid transportation fuels. Transient kinetics and product analyses confirm that OleT capably activates hydrogen peroxide with shorter substrates to form the high-valent intermediate Compound I and largely performs C-C bond scission. However, the enzyme also produces fatty alcohol side products using the high-valent iron oxo chemistry commonly associated with insertion of oxygen into hydrocarbons. When presented with a short chain fatty acid that can initiate the formation of Compound I, OleT oxidizes the diagnostic probe molecules norcarane and methylcyclopropane in a manner that is reminiscent of reactions of many CYP hydroxylases with radical clock substrates. These data are consistent with a decarboxylation mechanism in which Compound I abstracts a substrate hydrogen atom in the initial step. Positioning of the incipient substrate radical is a crucial element in controlling the efficiency of activated OH rebound. [Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo Caproatos/metabolismo Caprilatos/metabolismo Sistema Enzimático do Citocromo P-450/metabolismo Ácidos Decanoicos/metabolismo Ácidos Láuricos/metabolismo Micrococcus/enzimologia Modelos Moleculares [Mh] Termos MeSH secundário: Proteínas de Bactérias/química Proteínas de Bactérias/genética Biocatálise Biocombustíveis/análise Caprilatos/química Carboxiliases/química Carboxiliases/genética Carboxiliases/metabolismo Domínio Catalítico Ciclopropanos/química Ciclopropanos/metabolismo Sistema Enzimático do Citocromo P-450/química Sistema Enzimático do Citocromo P-450/genética Ácidos Decanoicos/química Descarboxilação Guaiacol/metabolismo Peróxido de Hidrogênio/química Peróxido de Hidrogênio/metabolismo Ácidos Láuricos/química Conformação Molecular Oxirredução Especificidade por Substrato Terpenos/química Terpenos/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (Biofuels); 0 (Caproates); 0 (Caprylates); 0 (Cyclopropanes); 0 (Decanoic Acids); 0 (Lauric Acids); 0 (Terpenes); 1F8SN134MX (hexanoic acid); 4G9EDB6V73 (decanoic acid); 594-11-6 (1-methylcyclopropane); 6JKA7MAH9C (Guaiacol); 9035-51-2 (Cytochrome P-450 Enzyme System); BBX060AN9V (Hydrogen Peroxide); EC 4.1.1.- (Carboxy-Lyases); OBL58JN025 (octanoic acid); ZGC3T0R48Q (norcarane) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 171029 [Lr] Data última revisão: 171029 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170613 [St] Status: MEDLINE [do] DOI: 10.1021/acs.biochem.7b00338

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[PMID]: 28419122 [Au] Autor: Zeiger K; Popp J; Becker A; Hankel J; Visscher C; Klein G; Meemken D [Ad] Endereço: Institute for Food Quality and Food Safety, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, Hannover, Germany. [Ti] Título: Lauric acid as feed additive - An approach to reducing Campylobacter spp. in broiler meat. [So] Source: PLoS One;12(4):e0175693, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The increasing prevalence of Campylobacter spp. within broiler populations is a major problem for food safety and consumer protection worldwide. In vitro studies could already demonstrate that Campylobacter spp. are susceptible to lauric acid. The purpose of this study was to examine in vivo the influence of lauric acid as a feed additive on slaughter parameters, muscle fatty acid profile, meat quality traits and the reduction of Campylobacter coli in inoculated meat of Ross 308 (R308) and Hubbard JA 757 (HJA) broilers in three independent trials (n = 3). Although slaughter parameters did not show any significant differences, the fatty acid profile of both breeds revealed significantly higher lauric acid concentrations (P < 0.0001) in the Musculus pectoralis superficialis of treated broilers. Comparing both tested breeds, R308 test broilers had significantly higher lauric acid concentrations than HJA test broilers (P < 0.0001), indicating a higher conversion rate in those animals. The meat quality traits showed no differences in the R308 breed (P > 0.05), but HJA test broilers had higher values for drip loss, electrical conductivity, CIE color values L* and b*, and lower pH values. The inoculation trials of R308 showed that initial bacterial loads of 5.9 log10 cfu/g were reduced during six days of storage (4°C) to approximately 4.3 log10 cfu/g in the control groups compared to 3.5 log10 cfu/g in the treatment groups (P = 0.0295), which could be due to antimicrobial effects of lauric acid within the muscle. This study therefore suggests that lauric acid as a feed additive has the potential to improve food safety by reducing the numbers of Campylobacter coli in broiler meat. However, this effect seems to be dependent on the breed determining the feed intake capacity, the fat deposition and therefore the ability to incorporate lauric acid in the muscle. [Mh] Termos MeSH primário: Ração Animal Galinhas/metabolismo Aditivos Alimentares/metabolismo Ácidos Láuricos/metabolismo Carne/análise [Mh] Termos MeSH secundário: Animais Campylobacter/efeitos dos fármacos Campylobacter/fisiologia Galinhas/classificação Galinhas/microbiologia Cor Ácidos Graxos/análise Ácidos Graxos/metabolismo Aditivos Alimentares/farmacologia Contaminação de Alimentos/prevenção & controle Microbiologia de Alimentos Qualidade dos Alimentos Interações Hospedeiro-Patógeno/efeitos dos fármacos Concentração de Íons de Hidrogênio Ácidos Láuricos/farmacologia Carne/microbiologia Carne/normas Músculos Peitorais/metabolismo Músculos Peitorais/microbiologia Especificidade da Espécie [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Fatty Acids); 0 (Food Additives); 0 (Lauric Acids); 1160N9NU9U (lauric acid) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170522 [Lr] Data última revisão: 170522 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170419 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0175693

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[PMID]: 28237592 [Au] Autor: Klop G; Dijkstra J; Dieho K; Hendriks WH; Bannink A [Ad] Endereço: Animal Nutrition Group, Wageningen Livestock Research, Wageningen University and Research, PO Box 338, 6700 AH Wageningen, the Netherlands. [Ti] Título: Enteric methane production in lactating dairy cows with continuous feeding of essential oils or rotational feeding of essential oils and lauric acid. [So] Source: J Dairy Sci;100(5):3563-3575, 2017 May. [Is] ISSN: 1525-3198 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Rumen microbes can adapt to feed additives, which may make the decrease in enteric CH production upon feeding an additive a transient response only. This study investigated alternate feeding of 2 CH mitigating feed additives with a different mode of action on persistency of lowering CH production compared with feeding a single additive over a period of 10 wk. Four pairs of cows were selected, and within pairs, cows were randomly assigned to either the control (AR-AR) or the alternating (AR-LA) concentrate treatment. The AR concentrate contained a blend of essential oils (Agolin Ruminant, Agolin SA, Bière, Switzerland; 0.17 g/kg of dry matter) and the LA concentrate contained lauric acid (C12:0; 65 g/kg of dry matter). A basal concentrate without Agolin Ruminant and lauric acid was fed during the pretreatment period (2 wk). Thereafter, the cows assigned to the AR-AR treatment received the AR concentrate during all 10 treatment weeks (5 periods of 2 wk each), whereas cows assigned to the AR-LA treatment received AR and LA concentrates rotated on a weekly basis. Methane emission was measured in climate respiration chambers during periods 1, 3, and 5. From period 3 onward, dry matter intake and milk protein concentration were reduced with the AR-LA treatment. Milk fat concentration was not affected, but the proportion of C12:0 in milk fat increased upon feeding C12:0. Molar proportions of acetate and propionate in rumen fluid were lower and higher, respectively, with the AR-LA than with the AR-AR treatment. Methane yield (g/kg of dry matter intake) and intensity (g/kg of fat- and protein-corrected milk yield) were not affected by treatment. Methane yield and intensity were significantly lower (12 and 11%, respectively) in period 1 compared with the pretreatment period, but no significant difference relative to pretreatment period was observed in period 3 (numerically 9 and 7% lower, respectively) and in period 5 (numerically 8 and 4% lower, respectively). Results indicate a transient decrease in CH yield and intensity in time, but no improvement in extent or persistency of the decline in CH due to rotational feeding of essential oils and C12:0 in lactating dairy cows. [Mh] Termos MeSH primário: Lactação Óleos Voláteis/metabolismo [Mh] Termos MeSH secundário: Ração Animal Animais Bovinos Dieta/veterinária Feminino Ácidos Láuricos Metano/biossíntese Leite/metabolismo Rúmen/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Lauric Acids); 0 (Oils, Volatile); OP0UW79H66 (Methane) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170522 [Lr] Data última revisão: 170522 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170227 [St] Status: MEDLINE

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[PMID]: 28111388 [Au] Autor: Saarani NN; Jamuna-Thevi K; Shahab N; Hermawan H; Saidin S [Ad] Endereço: Faculty of Biosciences & Medical Engineering, Universiti Teknologi Malaysia. [Ti] Título: Antibacterial efficacy of triple-layered poly(lactic-co-glycolic acid)/nanoapatite/lauric acid guided bone regeneration membrane on periodontal bacteria. [So] Source: Dent Mater J;36(3):260-265, 2017 May 31. [Is] ISSN: 1881-1361 [Cp] País de publicação: Japan [La] Idioma: eng [Ab] Resumo: A guided bone regeneration (GBR) membrane has been extensively used in the repair and regeneration of damaged periodontal tissues. One of the main challenges of GBR restoration is bacterial colonization on the membrane, constitutes to premature membrane degradation. Therefore, the purpose of this study was to investigate the antibacterial efficacy of triple-layered GBR membrane composed of poly(lactic-co-glycolic acid) (PLGA), nanoapatite (NAp) and lauric acid (LA) with two types of Gram-negative periodontal bacteria, Fusobacterium nucleatum and Porphyromonas gingivalis through a disc diffusion and bacterial count tests. The membranes exhibited a pattern of growth inhibition and killing effect against both bacteria. The increase in LA concentration tended to increase the bactericidal activities which indicated by higher diameter of inhibition zone and higher antibacterial percentage. It is shown that the incorporation of LA into the GBR membrane has retarded the growth and proliferation of Gram-negative periodontal bacteria for the treatment of periodontal disease. [Mh] Termos MeSH primário: Antibacterianos Regeneração Óssea Ácidos Láuricos [Mh] Termos MeSH secundário: Apatitas Bactérias Ácido Láctico Membranas Artificiais Periodontia Polímeros [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Bacterial Agents); 0 (Apatites); 0 (Lauric Acids); 0 (Membranes, Artificial); 0 (Polymers); 33X04XA5AT (Lactic Acid) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170823 [Lr] Data última revisão: 170823 [Sb] Subgrupo de revista: D [Da] Data de entrada para processamento: 170124 [St] Status: MEDLINE [do] DOI: 10.4012/dmj.2016-177

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[PMID]: 28054477 [Au] Autor: Alves NF; de Queiroz TM; de Almeida Travassos R; Magnani M; de Andrade Braga V [Ad] Endereço: Biotechnology Center, Federal University of Paraiba, João Pessoa, PB, Brazil. [Ti] Título: Acute Treatment with Lauric Acid Reduces Blood Pressure and Oxidative Stress in Spontaneously Hypertensive Rats. [So] Source: Basic Clin Pharmacol Toxicol;120(4):348-353, 2017 Apr. [Is] ISSN: 1742-7843 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The effects of acute administration of lauric acid (LA), the most abundant medium-chain fatty acid of coconut oil, on blood pressure, heart rate and oxidative stress were investigated in spontaneously hypertensive rats (SHR). Intravenous doses of LA reduced blood pressure in a dose-dependent fashion (1, 3, 4, 8 and 10 mg/kg) in both SHR and Wistar Kyoto rats. LA (10 to 3 × 10 M) induced vasorelaxation in isolated superior mesenteric artery rings of SHR in the presence (n = 7) or absence (n = 8) of functional endothelium [maximum effect (ME) = 104 ± 3 versus 103 ± 4%]. After exposure to KCl (60 mM), LA also induced concentration-dependent vasorelaxation (n = 7) compared to that under Phe-induced contraction (ME = 113.5 + 5.1 versus 104.5 + 4.0%). Furthermore, LA-induced vasorelaxation in vessels contracted with S(-)-BayK8644 (200 nM), a L-type Ca channel agonist (ME = 91.4 + 4.3 versus 104.5 + 4.0%, n = 7). Lastly, LA (10 M) reduced NADPH-dependent superoxide accumulation in the heart (18 ± 1 versus 25 ± 1 MLU/min/µg protein, n = 4, p < 0.05) and kidney (82 ± 3 versus 99 ± 4 MLU/min/µg protein, n = 4, p < 0.05). Our data show that LA reduces blood pressure in normotensive and hypertensive rats. In SHR, this effect might involve Ca channels in the resistance vessels and by its capability of reducing oxidative stress in heart and kidneys. [Mh] Termos MeSH primário: Antioxidantes/uso terapêutico Pressão Sanguínea/efeitos dos fármacos Hipertensão/tratamento farmacológico Ácidos Láuricos/uso terapêutico Estresse Oxidativo/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Antioxidantes/administração & dosagem Relação Dose-Resposta a Droga Endotélio Vascular/efeitos dos fármacos Endotélio Vascular/metabolismo Frequência Cardíaca/efeitos dos fármacos Hipertensão/metabolismo Técnicas In Vitro Injeções Intravenosas Ácidos Láuricos/administração & dosagem Artéria Mesentérica Superior/efeitos dos fármacos Ratos Endogâmicos SHR Ratos Endogâmicos WKY Superóxidos/metabolismo Vasoconstritores/farmacologia Vasodilatação/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antioxidants); 0 (Lauric Acids); 0 (Vasoconstrictor Agents); 11062-77-4 (Superoxides); 1160N9NU9U (lauric acid) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170324 [Lr] Data última revisão: 170324 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170106 [St] Status: MEDLINE [do] DOI: 10.1111/bcpt.12700

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[PMID]: 27978622 [Au] Autor: Meng Y; Zhang J; Zhang F; Ai W; Zhu X; Shu G; Wang L; Gao P; Xi Q; Zhang Y; Liang X; Jiang Q; Wang S [Ad] Endereço: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University , Guangzhou 510642, P. R. China. [Ti] Título: Lauric Acid Stimulates Mammary Gland Development of Pubertal Mice through Activation of GPR84 and PI3K/Akt Signaling Pathway. [So] Source: J Agric Food Chem;65(1):95-103, 2017 Jan 11. [Is] ISSN: 1520-5118 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: It has been demonstrated that dietary fat affects pubertal mammary gland development. However, the role of lauric acid (LA) in this process remains unclear. Thus, this study aimed to investigate the effects of LA on mammary gland development in pubertal mice and to explore the underlying mechanism. In vitro, 100 µM LA significantly promoted proliferation of mouse mammary epithelial cell line HC11 by regulating expression of proliferative markers (cyclin D1/3, p21, PCNA). Meanwhile, LA activated the G protein-coupled receptor 84 (GPR84) and PI3K/Akt signaling pathway. In agreement, dietary 1% LA enhanced mammary duct development, increased the expression of GPR84 and cyclin D1, and activated PI3K/Akt in mammary gland of pubertal mice. Furthermore, knockdown of GPR84 or inhibition of PI3K/Akt totally abolished the promotion of HC11 proliferation induced by LA. These results showed that LA stimulated mammary gland development of pubertal mice through activation of GPR84 and PI3K/Akt signaling pathway. [Mh] Termos MeSH primário: Ácidos Láuricos/farmacologia Glândulas Mamárias Animais/efeitos dos fármacos Glândulas Mamárias Animais/crescimento & desenvolvimento Fosfatidilinositol 3-Quinases/metabolismo Proteínas Proto-Oncogênicas c-akt/metabolismo Puberdade/efeitos dos fármacos Receptores Acoplados a Proteínas-G/metabolismo [Mh] Termos MeSH secundário: Animais Proliferação Celular/efeitos dos fármacos Ciclina D1/genética Ciclina D1/metabolismo Feminino Glândulas Mamárias Animais/metabolismo Camundongos Camundongos Endogâmicos C57BL Fosfatidilinositol 3-Quinases/genética Proteínas Proto-Oncogênicas c-akt/genética Puberdade/genética Puberdade/metabolismo Receptores Acoplados a Proteínas-G/genética Transdução de Sinais/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Gpr84 protein, mouse); 0 (Lauric Acids); 0 (Receptors, G-Protein-Coupled); 136601-57-5 (Cyclin D1); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170421 [Lr] Data última revisão: 170421 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161217 [St] Status: MEDLINE [do] DOI: 10.1021/acs.jafc.6b04878

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[PMID]: 27900443 [Au] Autor: Beyer N; Kulig JK; Bartsch A; Hayes MA; Janssen DB; Fraaije MW [Ad] Endereço: Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands. [Ti] Título: P450 fused to phosphite dehydrogenase allows phosphite-driven selective oxidations. [So] Source: Appl Microbiol Biotechnol;101(6):2319-2331, 2017 Mar. [Is] ISSN: 1432-0614 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: To facilitate the wider application of the NADPH-dependent P450 we fused the monooxygenase with a phosphite dehydrogenase (PTDH). The resulting monooxygenase-dehydrogenase fusion enzyme acts as a self-sufficient bifunctional catalyst, accepting phosphite as a cheap electron donor for the regeneration of NADPH.The well-expressed fusion enzyme was purified and analyzed in comparison to the parent enzymes. Using lauric acid as substrate for P450 , it was found that the fusion enzyme had similar substrate affinity and hydroxylation selectivity while it displayed a significantly higher activity than the non-fused monooxygenase. Phosphite-driven conversions of lauric acid at restricted NADPH concentrations confirmed multiple turnovers of the cofactor. Interestingly, both the fusion enzyme and the native P450 displayed enzyme concentration dependent activity and the fused enzyme reached optimal activity at a lower enzyme concentration. This suggests that the fusion enzyme has an improved tendency to form functional oligomers.To explore the constructed phosphite-driven P450 as a biocatalyst, conversions of the drug compounds omeprazole and rosiglitazone were performed. PTDH-P450 driven by phosphite was found to be more efficient in terms of total turnover when compared with P450 driven by NADPH. The results suggest that PTDH-P450 is an attractive system for use in biocatalytic and drug metabolism studies. [Mh] Termos MeSH primário: Bacillus megaterium/química Proteínas de Bactérias/química Sistema Enzimático do Citocromo P-450/química NADH NADPH Oxirredutases/química NADPH-Ferri-Hemoproteína Redutase/química NADP/química Fosfitos/química Proteínas Recombinantes de Fusão/química [Mh] Termos MeSH secundário: Bacillus megaterium/enzimologia Proteínas de Bactérias/genética Proteínas de Bactérias/metabolismo Biocatálise Clonagem Molecular Sistema Enzimático do Citocromo P-450/genética Sistema Enzimático do Citocromo P-450/metabolismo Escherichia coli/genética Escherichia coli/metabolismo Expressão Gênica Cinética Ácidos Láuricos/química Ácidos Láuricos/metabolismo NADH NADPH Oxirredutases/genética NADH NADPH Oxirredutases/metabolismo NADP/metabolismo NADPH-Ferri-Hemoproteína Redutase/genética NADPH-Ferri-Hemoproteína Redutase/metabolismo Omeprazol/química Omeprazol/metabolismo Oxirredução Fosfitos/metabolismo Proteínas Recombinantes de Fusão/genética Proteínas Recombinantes de Fusão/metabolismo Especificidade por Substrato Tiazolidinedionas/química Tiazolidinedionas/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (Lauric Acids); 0 (Phosphites); 0 (Recombinant Fusion Proteins); 0 (Thiazolidinediones); 05V02F2KDG (rosiglitazone); 1160N9NU9U (lauric acid); 53-59-8 (NADP); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.6.- (NADH, NADPH Oxidoreductases); EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase); EC 1.6.2.4 (flavocytochrome P450 BM3 monoxygenases); EC 1.6.99.- (NAD phosphite oxidoreductase); KG60484QX9 (Omeprazole) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170307 [Lr] Data última revisão: 170307 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161201 [St] Status: MEDLINE [do] DOI: 10.1007/s00253-016-7993-7

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MEDLINE

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[PMID]: 27894987 [Au] Autor: Albertini B; Bertoni S; Melegari C; Dolci LS; Passerini N [Ad] Endereço: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy. Electronic address: beatrice.albertini@unibo.it. [Ti] Título: A novel approach for dry powder coating of pellets with Ethylcellulose. Part I: Evaluation of film formulation and process set up. [So] Source: Int J Pharm;516(1-2):380-391, 2017 Jan 10. [Is] ISSN: 1873-3476 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: An innovative dry powder coating technology was developed in a high-shear granulator using ethylcellulose (E10) as polymer. Several solid plasticizers were investigated with the aim of decreasing the polymer Tg at least to the highest possible working temperature (80°C). DSC analysis of physical mixtures of E10 and plasticizers evidenced that lauric acid (LA) was the most effective plasticizer. In order to reach the target temperature a liquid plasticizer, oleic acid (OA), was introduced in the coating formulation. Free films were then prepared and the target minimum film forming temperature (MFFT) was established in the range 70-80°C. Depending on the LA:OA weight ratio, Kollidon VA64 was included to decrease the LA recrystallization, while talc served as anti-sticking agent. Curing at the MFFT ensured the formation of homogeneous and stable films with good stability on storage. The dry powder coating process of placebo pellets was then developed, consisting of a combination of liquid assisted and thermal adhesion methods. The best coating formulations in terms of yields, coating efficiency (expressed as Relative Standard Deviation of the weight applied) and low pellets aggregation were based on E10:LA:OA in a weight ratio of 65:20:15 and 60:20:20. Moreover pellets remained stable after 1year of storage (25°C/60% R.H.). [Mh] Termos MeSH primário: Celulose/análogos & derivados Excipientes/química Plastificantes/química Polímeros/química [Mh] Termos MeSH secundário: Varredura Diferencial de Calorimetria Celulose/química Química Farmacêutica/métodos Cristalização Estabilidade de Medicamentos Armazenamento de Medicamentos Ácidos Láuricos/química Ácido Oleico/química Pós Temperatura Ambiente Fatores de Tempo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Excipients); 0 (Lauric Acids); 0 (Plasticizers); 0 (Polymers); 0 (Powders); 1160N9NU9U (lauric acid); 2UMI9U37CP (Oleic Acid); 7Z8S9VYZ4B (ethyl cellulose); 9004-34-6 (Cellulose) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170509 [Lr] Data última revisão: 170509 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161130 [St] Status: MEDLINE

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