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| 1 | Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals显示文摘AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR. | Mazen Noureddin Micaela M Wong Tsuyoshi Todo Shelly C Lu Arun J Sanyal Edward A Mena | 2018 | World Journal of Gastroenterology2018，24，11： | 6 |
| 2 | 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 |
| 3 | The fusarium wilt resistance locus Fom-2 of melon contains a single resistance gene with complex features显示文摘 | TAREK J JOSEPH J K SHELLY J N CLAUDE E T RALPH A D | 2004 | The Plant Journal2004，39，： | 1 |
| 4 | The relationship between quality of life and functioning for children with cerebral palsy显示文摘 | Shelly A Davis E Waters E | 2008 | Developmental Medicine & Child Neurology2008，50，： | 1 |
| 5 | An elemen- tary school outbreak of varicella attributed to vaccine failure: policy implications显示文摘 | Brian R lee Shelly L Fearer Claudia A Miller | 2004 | J Infect Dis2004，190，： | 1 |
| 6 | 查看详情显示文摘 | Ng B K Shellie R A Dicinoski G W | | 0，，32： | 1 |
| 7 | The α1- and α2-isoforms of Na-K-ATPase play different roles in skeletal muscle contractility 显示文摘 | Suiwen He Daniel A Shelly | 2001 | Am J Physiol Regul Integr Comp Physiol2001，281，3： | 1 |
| 8 | Fast Quantum Logic Gates with Trapped Ions Interacting with External Laser and Quantized Cavity Field Beyond the Lamb-Dick Regime显示文摘 | SHELLY SHARMA S VIDIELLA-BARRANCO A | 2003 | Phys Lett A2003，309，： | 1 |
| 9 | Na-pump 2-isoform specificallycouples to contractility in vascular smooth muscle:evidence fromgenetargeted neonatal mice显示文摘 | Shelly DA He S Moseley A | 2004 | Am J Physiol Cell Physiol2004，286，4： | 1 |
| 10 | Using the implicit associationtest to measure self--esteem and self--concept显示文摘 | Greenwald A G Shelly D Farnham | 2000 | Journal of Personality and Social Psychology2000，79，6： | 1 |
| 11 | Differential expression of cytokeratins in follicular variant of papillary carcinoma: An immunohistochemical study and its diagnostic utility显示文摘 | Zubair W Baloch Susan Abraham Shelly Roberts Virginia A LiVolsi | 1999 | Human Pathology1999，，10： | 1 |
| 12 | Aspirin dose and six-month outcome after an acute coronary syndrome显示文摘 | Martin J Quinn Herbert D Aronow Robert M Califf Deepak L Bhatt Shelly Sapp Neal S Kleiman Robert A Harrington David F Kong David E Kandzari Eric J Topol | 2004 | Journal of the American College of Cardiology2004，，6： | 1 |
| 13 | Mismatch negativity: an index of a preattentive processing deficit in schizophrenia显示文摘 | Shelly A M Ward P B Catts S V | 1991 | Biol Psychiatry1991，30，： | 1 |
| 14 | Tickborne flaviviruses antagonize both iRF-1and type IFN signaling to inhibit dendritic cell function显示文摘 | Shelly J Robertson Kirk J Lubick Brett A | 2014 | Journal of Immunology2014，192，6： | 1 |
| 15 | Profile and prevalence of aspirin resistance in patients with cardiovascular disease显示文摘 | Patricia A Gum Kandice Kottke-Marchant Emilio D Poggio Hitinder Gurm Patricia A Welsh Linda Brooks Shelly K Sapp Eric J Topol | 2001 | The American Journal of Cardiology2001，，3： | 1 |
| 16 | The impnat of earing for a child with cerebral palsy: quality of life for mothers and fathers 显示文摘 | Davis E Shelly A Waters E | 2010 | Child Care Health Dev2010，36，1： | 1 |
| 17 | Genomie organiza- tion of human MXI1, a putative tumor suppressor gene 显示文摘 | WECHSLER D S SHELLY C A DANG C V | 1996 | Ge- nomic1996，32，3： | 1 |
| 18 | A doubleblind,placebo controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome显示文摘 | Shelly MA Feigin A | 2004 | Am J Kidney Dis2004，43，4： | 1 |
| 19 | MXI1, a putative tumor suppressor gene, suppresses growth of human g|io- blastoma cells显示文摘 | WECHSLER D S SHELLY C A PETROFF C A | 1997 | Cancer Res1997，57，21： | 1 |
| 20 | Expression of ErbB- 2/HER2 in epithelia:bimodal regulation by Lin-7显示文摘 | Shelly M Mosesson Y Citri A | 2003 | Dev Cell2003，5，3： | 1 |
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