|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 2 | Sedated vs unsedated colonoscopy:A prospective study显示文摘AIM:To compare sedated to unsedated colonoscopy in terms of duration,pain and the patient’s willingness to repeat the procedure.METHODS:Consecutive patients who underwent colonoscopies over a 2-year period were invited to participate.All patients who were to undergo our endoscopy unit were offered sedation with standard intravenous sedatives and analgesics,or an unsedated colonoscopy was attempted.Demographic details were recorded.The patient anxiety level prior to the procedure,time to reach the cecum,total discharge time,patient and endoscopist pain assessments,satisfaction after the examination and the patient’s willingness to return for the same procedure in the future were recorded.RESULTS:Among the 403 observed patients,more males were observed in the unsedated group(66.2%vs 55.2%,P=0.04).Additionally,the unsedated group patients were less anxious prior to the procedure(5.1vs 6.0,P<0.01).The colonoscopy completion rates were comparable between the 2 groups(85.9%vs84.2%,P=0.66).The time to reach the cecum was also comparable(12.2 min vs 11.8 min);however,the total discharge times were shorter in the unsedated group(20.7 min vs 83.0 min,P<0.01).Moreover,the average patient pain score(3.4 vs 5.7,P<0.01)was lower in the sedated group,while the satisfaction score(8.8 vs 7.8,P<0.01)was significantly higher.There was no significant difference,however,between the groups in terms of willingness to repeat the procedure if another was required in the future(83.3%vs 77.3%,P=0.17).CONCLUSION:Unsedated colonoscopy is feasible in willing patients.The option saves the endoscopy units up to one hour per patient and does not affect the patient willingness to return to the same physician again for additional colonoscopies if a repeated procedure is needed. | Abdulrahman M Aljebreen Majid A Almadi Felix W Leung | 2014 | World Journal of Gastroenterology2014，20，17： | 3 |
| 3 | Long-term follow-up of quality of life in high-risk patients undergoing transcatheter aortic valve implantation for symptomatic aortic valve stenosis显示文摘BackgroundTranscatheter 大动脉的阀门培植(TAVI ) 与严重征兆的大动脉的狭窄为病人成为了标准治疗(作为) 为外科的大动脉的阀门代替在很高的风险考虑了。这亚学习的目的是评估长期的(> 4 年) 在 octogenarians 的生活(QoL ) 的健康相关的质量经历了 TAVI.MethodsA 单个中心在在 TAVI 以后经历了框架分析评价 4 年的二十个病人的观察登记。健康相关的 QoL 被评估,用短 Form-36 ( SF-36 ),吗 EuroQoL-5D ( EQ-5D )和 questionnaires.ResultsThe 平均数 SF-36 subscale 在后续获得的视觉类似物分数(EQ管)是物理的工作 40.8 ????????????????????????????搠?潮潶???吗?湡楧灯慬瑳?????????愠杮潩牧灡票?€ 敦潭潲潰汰瑩慥???????????????愠桴牥'啼蠹溃浚? | Marjo JAG De Ronde-Tillmans Tom AJ de Jager Jeannette A Goudzwaard Nahid El Faquir Nicolas M van Mieghem Felix Zijlstra Elisabeth MWJ. Utens Francesco US Mattace-Raso MaRie J Lenzen Peter PT de Jaegere | 2018 | Journal of Geriatric Cardiology2018，15，4： | 3 |
| 4 | Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption显示文摘 | Felix SB Staudt A Landsberger M | 2002 | J Am Coll Cardiol2002，39，4： | 1 |
| 5 | The antagonism of glueoeortieoid inhibition of wound healing in rats by growth hormone-releasing factor显示文摘 | Kelley S F Felix A M Ehrlieh H P | 1990 | Proe Soe Exp Biol Med1990，194，4： | 1 |
| 6 | Variant angina associated with bitter orange in a dietary supplement显示文摘 | Gange C A Madias C Felix Gretzik E M | 2006 | Mayo Clinic Proc2006，81，： | 1 |
| 7 | Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial显示文摘 | Benjamin M Scirica Marc P Bonaca Eugene Braunwald Gaetano M De Ferrari Daniel Isaza Basil S Lewis Felix Mehrhof Piera A Merlini Sabina A Murphy Marc S Sabatine Michal Tendera Frans Van de Werf Robert Wilcox David A Morrow | 2012 | The Lancet . 2012 (9850)2012，，9850： | 1 |
| 8 | Parallcl ization of the Scatter Search for the p median Problem 显示文摘 | FELIX G L BELEN M B JOSE A M P | 2003 | Parallel Computing2003，29，5： | 1 |
| 9 | Robustness and evolution:concepts, insights and challenges from a developmentalmodel system显示文摘 | FELIX M A WAGNER A | 2008 | Heredity2008，100，： | 1 |
| 10 | There was a factor increases growth hormone levels in the rat显示文摘 | Frantz A V Heimer E P Felix A M | 1964 | Proc Natl Acad Sei USA1964，91，78： | 1 |
| 11 | Peripheral osteoma of the mandibular condyle显示文摘 | J C M A Mancini M Woltmann V B Felix | 2005 | Journal of the Chinese Medical Association2005，34，1： | 1 |
| 12 | The Contribution of Internal Audit as A Determinant of External Audit Fees and Factors Influencing this Con- tribution 显示文摘 | Felix W L Gramling A A Maletta M J | 2001 | Journal of Accounting Research2001，39，3： | 1 |
| 13 | Preparation of explant and organ culture and single cells from airway epithelium显示文摘 | Dirksen E R Felix J A Sanderson M J | 1995 | Methods Cell Biol1995，47，： | 1 |
| 14 | Simvastain decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats 显示文摘 | Giusti--Paiva A Martinez M R Felix J V | 2004 | Shock2004，21，3： | 1 |
| 15 | CFD calculation of a mixed flow pump characteristic from shutoff to maximum flow显示文摘 | Felix A M Peter H Philippe D | 2002 | Journal of Fluids Engineering ASME2002，124，3： | 1 |
| 16 | Solid-phase peptide synthesis of somatostatin using mild base cleavage of N alpha-9-fluorenylrnethyloxy- carbonyl amino acids显示文摘 | CHANG C D FELIX A M JIMENEZ M H | 1980 | Pept Protein Res1980，15，5： | 1 |
| 17 | Sphingolipids and cell death显示文摘 | Morales A Lee H Felix M | 2007 | Apoptosis2007，12，： | 1 |
| 18 | Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats显示文摘 | Simonides Warner S Mulcahey Michelle A Redout Everaldo M Muller Alice Zuidwijk Marian J Visser Theo J Wassen Frank W J S Crescenzi Alessandra da-Silva Wagner S Harney John Engel Felix B Obregon Maria-Jesús Larsen P Reed Bianco Antonio C Huan | 2008 | Journal of Clinical Investigation2008，，3： | 1 |
| 19 | Rational design,synthesis and biological evaluation of novel growth hormone releasing factor analogues显示文摘 | Compbell R M Bongers J Felix A M | 1995 | Biopolimers1995，31，2： | 1 |
| 20 | Patients with mild to moderate body dysmorphic disorder may benefit from rhinoplasty 显示文摘 | Felix G A A de Brito M J A Nahas F X | 2014 | Journal of Plastic Reconstructive & Aesthetic Surgery2014，67，5： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员