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[PMID]:29402262
[Au] Autor:Liu MW; Wei R; Su MX; Li H; Fang TW; Zhang W
[Ad] Endereço:Department of Emergency, the First Hospital Affiliated To Kunming Medical University, 295 Xichang Road, Wu Hua District, Kunming, 650032, China. Lmw2004210@163.com.
[Ti] Título:Effects of Panax notoginseng saponins on severe acute pancreatitis through the regulation of mTOR/Akt and caspase-3 signaling pathway by upregulating miR-181b expression in rats.
[So] Source:BMC Complement Altern Med;18(1):51, 2018 Feb 05.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In China, Panax notoginseng has been used to treat oxidative stress-related diseases for a long time. Panax notoginseng saponins is an extract from Panax notoginseng Ledeb. Its therapeutic potential is related to antioxidant activity, but related mechanisms are still unclear. The study aims to assess the protection effects of Panax notoginseng saponins in the taurocholate-induced rat model of acute pancreatitis (AP) and explore underlying mechanisms. METHODS: A rat model of severe acute pancreatitis (SAP) was established in rats induced with taurocholate. Panax notoginseng saponins was firstly administered in the treatment group via intravenous injection. After 2 h, taurocholate administration was performed. After 24 h, the expression levels of miR-181b, Beclin1, LC3-II, Akt and mTOR from pancreas tissues were measured by Western Blotting and RT-PCR. Then the expression levels of Caspase-3 and Blc-2 were determined by immunohistochemistry. Apoptosis was assessed by the TUNEL assay. Amylase and lipase in serum were determined by ELISA and pancreatic water contents in pancreatic tissue were measured. After eosin and hematoxylin staining, the histologic analysis was performed. RESULTS: After SAP induction by taurocholate and the treatment with Panax notoginseng saponins for 24 h, we detected the up-regulated miR-181b, the reduced Bcl-2 expression, the increased activity of mTOR/Akt, the blocked Beclin1 and LC3-II expressions, and the enhanced Caspase-3 expression. Serum lipase and amylase levels were significantly decreased in the treatment group of Panax notoginseng saponins compared to the control group. Histological analysis results verified the attenuation effects of Panax notoginseng saponins on taurocholate-induced pancreas injury, apoptosis, and autophagy. CONCLUSION: By up-regulating the miR-181b expression level, Panax notoginseng saponins significantly reduced taurocholate-induced pancreas injury and autophagy and increased apoptosis. The significant protection effects of Panax notoginseng saponins suggested its potential in treating taurocholate induced-acute pancreatitis.
[Mh] Termos MeSH primário: Caspase 3/metabolismo
MicroRNAs/metabolismo
Panax notoginseng
Pancreatite/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Saponinas/farmacologia
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Modelos Animais de Doenças
Masculino
MicroRNAs/genética
Pâncreas/efeitos dos fármacos
Pâncreas/patologia
Pancreatite/patologia
Extratos Vegetais
Ratos
Ratos Sprague-Dawley
Transdução de Sinais/efeitos dos fármacos
Ácido Taurocólico/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN181 microRNA, rat); 0 (MicroRNAs); 0 (Plant Extracts); 0 (Saponins); 5E090O0G3Z (Taurocholic Acid); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.1.1 (mTOR protein, rat); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-018-2118-8


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[PMID]:28926819
[Au] Autor:Heerema JL; Helbing CC; Pyle GG
[Ad] Endereço:Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada T1K 6T5. Electronic address: jody.heerema@gmail.com.
[Ti] Título:Use of electro-olfactography to measure olfactory acuity in the North American bullfrog (Lithobates (Rana) catesbeiana) tadpole.
[So] Source:Ecotoxicol Environ Saf;147:643-647, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Olfaction is an important sense for aquatic organisms because it provides information about their surroundings, including nearby food, mates, and predators. Electro-olfactography (EOG) is an electrophysiological technique that measures the response of olfactory tissue to olfactory stimuli, and responses are indicative of olfactory acuity. Previous studies have used this technique on a variety of species including frogs, salamanders, daphniids and, most extensively, fish. In the present study, we introduce a novel modified EOG method for use on Lithobates (Rana) catesbeiana tadpoles. Responses to a number of olfactory stimuli including amino acids, an algal extract (Spirulina), and taurocholic acid were tested, as measured by EOG. Tadpoles exhibited consistent and reliable responses to L-alanine and Spirulina extract. Tadpoles also exhibited concentration-dependent responses to Spirulina extract. These findings indicate that tadpole EOG is a viable electrophysiology technique that can be used in future research to study olfactory physiology and impairment in tadpoles.
[Mh] Termos MeSH primário: Fenômenos Eletrofisiológicos
Larva/fisiologia
Percepção Olfatória/fisiologia
Olfato/fisiologia
[Mh] Termos MeSH secundário: Alanina/química
Animais
Técnicas Eletroquímicas
Microeletrodos
Rana catesbeiana
Spirulina/química
Ácido Taurocólico/química
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5E090O0G3Z (Taurocholic Acid); OF5P57N2ZX (Alanine)
[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:170920
[St] Status:MEDLINE


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[PMID]:28455390
[Au] Autor:Christian WV; Hinkle PM
[Ad] Endereço:Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, U.S.A.
[Ti] Título:Global functions of extracellular, transmembrane and cytoplasmic domains of organic solute transporter ß-subunit.
[So] Source:Biochem J;474(12):1981-1992, 2017 05 25.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Transport of bile acids across the basolateral membrane of the intestinal enterocyte is carried out by the organic solute transporter (Ost) composed of a seven-transmembrane domain (TMD) subunit (Ostα) and an ancillary single TMD subunit (Ostß). Although previous investigations have demonstrated the importance of the TMD of Ostß for its activity, further studies were conducted to assess the contributions of other regions of the Ostß subunit. Transport activity was retained when Ostß was truncated to contain only the TMD with 15 additional residues on each side and co-expressed with Ostα, whereas shorter fragments were inactive. To probe the broader functions of Ostß segments, chimeric proteins were constructed in which N-terminal, TMD or C-terminal regions of Ostß were fused to corresponding regions of receptor activity-modifying protein (RAMP1), a single TMD protein required by several seven-TMD G-protein-coupled receptors including the calcitonin receptor-like receptor (CLR). Ostß/RAMP1 chimeras were expressed with Ostα and CLR. As expected, replacing the Ostß TMD abolished transport activity; however, replacing either the entire N-terminal or entire C-terminal domain of Ostß with RAMP1 sequences did not prevent plasma membrane localization or the ability to support [ H]taurocholate uptake. Co-immunoprecipitation experiments revealed that the C-terminus of Ostß is a previously unrecognized site of interaction with Ostα. All chimeras containing N-terminal RAMP1 segments allowed co-expressed CLR to respond to agonists with strong increases in cyclic AMP. These results provide new insights into the structure and function of the heteromeric Ost transporter complex.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
[Mh] Termos MeSH secundário: Absorção Fisiológica/efeitos dos fármacos
Animais
Transporte Biológico/efeitos dos fármacos
Peptídeo Relacionado com Gene de Calcitonina/genética
Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Proteína Semelhante a Receptor de Calcitonina/agonistas
Proteína Semelhante a Receptor de Calcitonina/genética
Proteína Semelhante a Receptor de Calcitonina/metabolismo
AMP Cíclico/metabolismo
Células HEK293
Seres Humanos
Imunoprecipitação
Proteínas de Membrana Transportadoras/química
Proteínas de Membrana Transportadoras/genética
Camundongos
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Domínios e Motivos de Interação entre Proteínas
Transporte Proteico
Proteína 1 Modificadora da Atividade de Receptores/química
Proteína 1 Modificadora da Atividade de Receptores/genética
Proteína 1 Modificadora da Atividade de Receptores/metabolismo
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Sistemas do Segundo Mensageiro/efeitos dos fármacos
Homologia Estrutural de Proteína
Ácido Taurocólico/metabolismo
Trítio
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (CALCA protein, human); 0 (CALCRL protein, human); 0 (Calcitonin Receptor-Like Protein); 0 (Membrane Transport Proteins); 0 (Peptide Fragments); 0 (Ramp1 protein, mouse); 0 (Receptor Activity-Modifying Protein 1); 0 (Recombinant Fusion Proteins); 0 (organic solute transporter alpha, mouse); 0 (organic solute transporter beta, mouse); 10028-17-8 (Tritium); 5E090O0G3Z (Taurocholic Acid); 83652-28-2 (Calcitonin Gene-Related Peptide); E0399OZS9N (Cyclic AMP)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171217
[Lr] Data última revisão:
171217
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20161093


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[PMID]:28934223
[Au] Autor:Adeyemi O; Alvarez-Laviada A; Schultz F; Ibrahim E; Trauner M; Williamson C; Glukhov AV; Gorelik J
[Ad] Endereço:Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
[Ti] Título:Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis.
[So] Source:PLoS One;12(9):e0183167, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated. METHODS: High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400µM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes. RESULTS: TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1µM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1µM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30µM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L. CONCLUSION: Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.
[Mh] Termos MeSH primário: Canais de Cálcio Tipo T/metabolismo
Colestase/prevenção & controle
Fenômenos Eletrofisiológicos/efeitos dos fármacos
Coração Fetal/efeitos dos fármacos
Ventrículos do Coração/efeitos dos fármacos
Ventrículos do Coração/fisiopatologia
Ácido Ursodesoxicólico/farmacologia
[Mh] Termos MeSH secundário: Animais
Cálcio/farmacologia
Colestase/metabolismo
Colestase/fisiopatologia
Feminino
Coração Fetal/metabolismo
Coração Fetal/fisiopatologia
Seres Humanos
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/metabolismo
Gravidez
Ratos
Ácido Taurocólico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels, T-Type); 5E090O0G3Z (Taurocholic Acid); 724L30Y2QR (Ursodeoxycholic Acid); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183167


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[PMID]:28910295
[Au] Autor:DiMarzio M; Rusconi B; Yennawar NH; Eppinger M; Patterson AD; Dudley EG
[Ad] Endereço:Department of Food Science, The Pennsylvania State University, University Park, PA, United States of America.
[Ti] Título:Identification of a mouse Lactobacillus johnsonii strain with deconjugase activity against the FXR antagonist T-ß-MCA.
[So] Source:PLoS One;12(9):e0183564, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bile salt hydrolase (BSH) activity against the bile acid tauro-beta-muricholic acid (T-ß-MCA) was recently reported to mediate host bile acid, glucose, and lipid homeostasis via the farnesoid X receptor (FXR) signaling pathway. An earlier study correlated decreased Lactobacillus abundance in the cecum with increased concentrations of intestinal T-ß-MCA, an FXR antagonist. While several studies have characterized BSHs in lactobacilli, deconjugation of T-ß-MCA remains poorly characterized among members of this genus, and therefore it was unclear what strain(s) were responsible for this activity. Here, a strain of L. johnsonii with robust BSH activity against T-ß-MCA in vitro was isolated from the cecum of a C57BL/6J mouse. A screening assay performed on a collection of 14 Lactobacillus strains from nine different species identified BSH substrate specificity for T-ß-MCA only in two of three L. johnsonii strains. Genomic analysis of the two strains with this BSH activity revealed the presence of three bsh genes that are homologous to bsh genes in the previously sequenced human-associated strain L. johnsonii NCC533. Heterologous expression of several bsh genes in E. coli followed by enzymatic assays revealed broad differences in substrate specificity even among closely related bsh homologs, and suggests that the phylogeny of these enzymes does not closely correlate with substrate specificity. Predictive modeling allowed us to propose a potential mechanism driving differences in BSH activity for T-ß-MCA in these homologs. Our data suggests that L. johnsonii regulates T-ß-MCA levels in the mouse intestinal environment, and that this species may play a central role in FXR signaling in the mouse.
[Mh] Termos MeSH primário: Amidoidrolases/genética
Amidoidrolases/metabolismo
Lactobacillus johnsonii/isolamento & purificação
Análise de Sequência de DNA/métodos
Ácido Taurocólico/análogos & derivados
[Mh] Termos MeSH secundário: Amidoidrolases/química
Animais
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Ceco/microbiologia
Clonagem Molecular
DNA Bacteriano/genética
Lactobacillus johnsonii/enzimologia
Lactobacillus johnsonii/genética
Camundongos
Camundongos Endogâmicos C57BL
Modelos Moleculares
Filogenia
Especificidade por Substrato
Ácido Taurocólico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (DNA, Bacterial); 25696-60-0 (tauromuricholic acid); 5E090O0G3Z (Taurocholic Acid); EC 3.5.- (Amidohydrolases); EC 3.5.1.24 (choloylglycine hydrolase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183564


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[PMID]:28784620
[Au] Autor:Sohail MI; Schmid D; Wlcek K; Spork M; Szakács G; Trauner M; Stockner T; Chiba P
[Ad] Endereço:Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics (M.I.S., M.S., P.C.), Institute of Physiology, Center for Physiology and Pharmacology (D.S.), Institute of Cancer Research (G.S.), Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, De
[Ti] Título:Molecular Mechanism of Taurocholate Transport by the Bile Salt Export Pump, an ABC Transporter Associated with Intrahepatic Cholestasis.
[So] Source:Mol Pharmacol;92(4):401-413, 2017 Oct.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The bile salt export pump (BSEP/ABCB11) transports bile salts from hepatocytes into bile canaliculi. Its malfunction is associated with severe liver disease. One reason for functional impairment of BSEP is systemic administration of drugs, which as a side effect inhibit the transporter. Therefore, drug candidates are routinely screened for potential interaction with this transporter. Hence, understanding the functional biology of BSEP is of key importance. In this study, we engineered the transporter to dissect interdomain communication paths. We introduced mutations in noncanonical and in conserved residues of either of the two nucleotide binding domains and determined the effect on BSEP basal and substrate-stimulated ATPase activity as well as on taurocholate transport. Replacement of the noncanonical methionine residue M584 (Walker B sequence of nucleotide binding site 1) by glutamate imparted hydrolysis competency to this site. Importantly, this mutation was able to sustain 15% of wild-type transport activity, when the catalytic glutamate of the canonical nucleotide binding site 2 was mutated to glutamine. Kinetic modeling of experimental results for the ensuing M584E/E1244Q mutant suggests that a transfer of hydrolytic capacity from the canonical to the noncanonical nucleotide binding site results in loss of active and adoption of facilitative characteristics. This facilitative transport is ATP-gated. To the best of our knowledge, this result is unprecedented in ATP-binding cassette proteins with one noncanonical nucleotide binding site. Our study promotes an understanding of the domain interplay in BSEP as a basis for exploration of drug interactions with this transporter.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Ácidos e Sais Biliares/metabolismo
Colestase Intra-Hepática/metabolismo
Ácido Taurocólico/metabolismo
[Mh] Termos MeSH secundário: Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
Transportadores de Cassetes de Ligação de ATP/química
Sítios de Ligação/fisiologia
Transporte Biológico/fisiologia
Células HEK293
Seres Humanos
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB11 protein, human); 0 (ATP Binding Cassette Subfamily B Member 11); 0 (Bile Acids and Salts); 5E090O0G3Z (Taurocholic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1124/mol.117.108688


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[PMID]:28717103
[Au] Autor:Toyoda Y; Kashikura K; Soga T; Tagawa YI
[Ad] Endereço:Department of Pharmacy, The University of Tokyo Hospital.
[Ti] Título:Metabolomics of an in vitro liver model containing primary hepatocytes assembling around an endothelial cell network: comparative study on the metabolic stability and the effect of acetaminophen treatment.
[So] Source:J Toxicol Sci;42(4):445-454, 2017.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Recently, a novel culture system consisting of primary hepatocytes structured over a network of endothelial cells on the Engelbreth-Holm-Swarm (EHS) gel has been reported. This in vitro liver model on the EHS gel (IVL ) has been shown to maintain the expression of hepatic genes and their functional activity. Moreover, the IVL was more sensitive to xenobiotics than hepatocyte monocultures, suggesting the potential utility of this culture system for compound hepatotoxicity screening. However, the effect of this three-dimensional structure formation on the cellular metabolic profile of hepatocytes in the IVL is not well understood. To address this concern, we performed metabolome analysis using capillary electrophoresis-time of flight mass spectrometry. Between the IVL and mono-cultured hepatocytes on the EHS gel, there was no significant difference in the levels of metabolites of the urea cycle and the tricarboxylic acid cycle, essential amino acids, and adenylate energy charge (AEC) which is an important indicator of cellular energy status. On the other hand, acetaminophen-dependent decrease of the AEC in the IVL was greater than that in the monoculture, suggesting the higher sensitivity of IVL to acetaminophen-induced hepatotoxicity which is caused by metabolic activation of this drug. Further analysis showed that the levels of taurocholate, one of the major conjugated bile acids, were higher in the IVL than in the monoculture. Considering that the construction of the IVL did not seem to disturb the major cellular metabolism, our findings would strengthen the concept that IVL would have beneficial effects on the maintenance of hepatic functions.
[Mh] Termos MeSH primário: Acetaminofen/toxicidade
Hepatócitos
Células Endoteliais da Veia Umbilical Humana
Fígado
Metabolômica
Modelos Anatômicos
Testes de Toxicidade/métodos
[Mh] Termos MeSH secundário: Animais
Eletroforese Capilar
Metabolismo Energético/efeitos dos fármacos
Géis
Hepatócitos/efeitos dos fármacos
Hepatócitos/metabolismo
Seres Humanos
Técnicas In Vitro
Fígado/efeitos dos fármacos
Fígado/metabolismo
Espectrometria de Massas
Metabolômica/métodos
Camundongos Endogâmicos BALB C
Ácido Taurocólico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gels); 362O9ITL9D (Acetaminophen); 5E090O0G3Z (Taurocholic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.2131/jts.42.445


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[PMID]:28441432
[Au] Autor:Chen J; Huang C; Wang J; Zhou H; Lu Y; Lou L; Zheng J; Tian L; Wang X; Cao Z; Zeng Y
[Ad] Endereço:Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
[Ti] Título:Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial peptide level during acute necrotizing pancreatitis in rats.
[So] Source:PLoS One;12(4):e0176583, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Intestinal barrier dysfunction plays an important role in acute necrotizing pancreatitis (ANP) and intestinal microbiota dysbiosis was involved in intestinal barrier failure. Paneth cells protect intestinal barrier and are associated with intestinal microbiota. Here, we investigated changes in intestinal microbiota and antimicrobial peptides of Paneth cells in ileum during ANP. METHODS: Rats with ANP were established by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct and sacrificed at 24h and 48h, respectively. Injuries of pancreas and distal ileum were evaluated by histopathological score. Intestinal barrier function was assessed by plasma diamine oxidase activity (DAO) and D-lactate. Systemic and intestinal inflammation was evaluated by TNFα, IL-1ß and IL-17A concentration by ELISA, respectively. 16S rRNA high throughput sequencing on fecal samples was used to investigate the changes in intestinal microbiota in the ANP group at 48h. Lysozyme and α-defensin5 were measured by real-time PCR, western blot and immunofluoresence. RESULTS: ANP rats had more severe histopathological injuries in pancreas and distal ileum, injured intestinal barrier and increased expression of TNFα, IL-1ß and IL-17A in plasma and distal ileum compared with those of the sham-operated (SO) group. Principal component analysis (PCA) showed structural segregation between the SO and ANP groups. Operational taxonomic unit (OTU) number and ACE index revealed decreased microbiota diversity in the ANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. At phyla level, Saccharibacteria and Tenericutes decreased significantly. At genus level, Escherichia-Shigella and Phascolarctobacterium increased significantly, while Candidatus_Saccharimonas, Prevotellaceae_UCG-001, Lachnospiraceae_UCG-001, Ruminiclostridium_5 and Ruminococcaceae_UCG-008 decreased significantly. Lysozyme and α-defensin5 mRNA expression levels decreased significantly in ANP group at 48h. Protein expression of lysozyme decreased in ANP groups at 24h and 48h. Meanwhile, the relative abundance of Escherichia-Shigella correlated inversely with the decrease in lysozyme. CONCLUSION: The disorder in intestinal microbiota and decreases of Paneth cell antimicrobial peptides might participate in the pathogenesis of intestinal barrier dysfunction during ANP.
[Mh] Termos MeSH primário: Disbiose/microbiologia
Microbioma Gastrointestinal
Íleo/microbiologia
Pancreatite Necrosante Aguda/microbiologia
Celulas de Paneth/microbiologia
[Mh] Termos MeSH secundário: Animais
Disbiose/metabolismo
Disbiose/patologia
Íleo/metabolismo
Íleo/patologia
Interleucina-17/metabolismo
Masculino
Pancreatite Necrosante Aguda/induzido quimicamente
Pancreatite Necrosante Aguda/metabolismo
Celulas de Paneth/metabolismo
Celulas de Paneth/patologia
Ratos
Ratos Sprague-Dawley
Ácido Taurocólico
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-17); 0 (Tumor Necrosis Factor-alpha); 5E090O0G3Z (Taurocholic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176583


  9 / 3442 MEDLINE  
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[PMID]:28370901
[Au] Autor:Xu W; Okayama N; Iwasawa A; Yayota M
[Ad] Endereço:The United Graduate School of Agriculture Science, Gifu University, Gifu, Japan.
[Ti] Título:Temporal changes in liver tissue metabolome of lambs fed low-quality roughage.
[So] Source:Anim Sci J;88(9):1352-1363, 2017 Sep.
[Is] ISSN:1740-0929
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Early experience with low-quality roughage may induce adaptations in ruminants' metabolism. This study was conducted to explore the variation in the hepatic metabolomes of lambs fed low-quality roughage beginning early in life. Five lambs were fed Sudan grass hay (crude protein (CP): 4.6% of the dry matter (DM), neutral detergent fiber, 68.5% of DM) for 6 months during time periods P1, P2 and P3, which consisted of 2 months each. The metabolizable energy (ME) and CP intake satisfied lambs' maintenance requirements in P1 and P2, but the ME intake was 78.5% of the maintenance ME requirement in P3. Liver metabolomics was carried out in P2 and P3 by the capillary electrophoresis and time-of-flight mass spectrometry system. Eight amino acids and six amino acid metabolism-related metabolites were altered between P2 and P3. Several intermediates of glycolysis/gluconeogenesis decreased, while nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate increased in P3. Taurocholic acid and taurine increased, while glycocholic acid decreased in P3. The results suggested that amino acid utilization and the efficiency of glycolysis/gluconeogenesis might be adjusted to accommodate the low-quality roughage fed to the lambs during early stages of life. The composition of bile acids might also be optimized to promote the efficiency of lipid absorption.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Ração Animal
Dieta/veterinária
Fibras na Dieta/administração & dosagem
Qualidade dos Alimentos
Fígado/metabolismo
Metaboloma
Ovinos/metabolismo
[Mh] Termos MeSH secundário: Animais
Ácidos e Sais Biliares/metabolismo
Proteínas na Dieta
Ingestão de Energia
Gluconeogênese
Glicólise
NAD/metabolismo
NADP/metabolismo
Rúmen/metabolismo
Taurina/metabolismo
Ácido Taurocólico/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Bile Acids and Salts); 0 (Dietary Fiber); 0 (Dietary Proteins); 0U46U6E8UK (NAD); 1EQV5MLY3D (Taurine); 53-59-8 (NADP); 5E090O0G3Z (Taurocholic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1111/asj.12792


  10 / 3442 MEDLINE  
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[PMID]:28318878
[Au] Autor:Kobayashi T; Koizumi T; Kobayashi M; Ogura J; Horiuchi Y; Kimura Y; Kondo A; Furugen A; Narumi K; Takahashi N; Iseki K
[Ad] Endereço:Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
[Ti] Título:Insulin stimulates transport of organic anion compounds mediated by organic anion transporting polypeptide 2B1 in the human intestinal cell line Caco-2.
[So] Source:Drug Metab Pharmacokinet;32(2):157-163, 2017 Apr.
[Is] ISSN:1880-0920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells). However, the effect of insulin on OATP2B1 in the small intestine has not been fully investigated. We found that Rab8A was associated with OATP2B1-mediated estrone-3-sulfate (E3S) uptake. Insulin stimulated the uptake of E3S by Caco-2 cells and the enhancement was sustained for 120 min. The Vmax value of E3S uptake significantly increased upon insulin exposure. Caco-2 cells treated with insulin showed increased OATP2B1 expression at the cell surface. The apical-to-basal transport of E3S was also increased by insulin. The increase of E3S transport was inhibited by the cold condition (4 °C) or the OATP2B1 inhibitor, taurocholate. These results indicate that insulin acts on the small intestine to increase OATP2B1-mediated absorption.
[Mh] Termos MeSH primário: Insulina/farmacologia
Transportadores de Ânions Orgânicos/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico/efeitos dos fármacos
Células Cultivadas
Seres Humanos
Intestino Delgado/efeitos dos fármacos
Intestino Delgado/metabolismo
Transportadores de Ânions Orgânicos/antagonistas & inibidores
Transportadores de Ânions Orgânicos/genética
Ácido Taurocólico/farmacologia
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (Organic Anion Transporters); 0 (SLCO2B1 protein, human); 5E090O0G3Z (Taurocholic Acid)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170321
[St] Status:MEDLINE



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