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| 1 | Biomarkers and subtypes of deranged lipid metabolism in nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)with varying degrees of fibrosis,to cirrhosis,which is a major risk factor for hepatocellular carcinoma.Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia,with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA)and triglycerides(TG)from circulation and de novo lipogenesis saturate the rate of FAβ-oxidation and verylow density lipoprotein(VLDL)-TG export.Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH,and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression.This review focuses on the importance of the classification of NAFLD patients into different subtypes,corresponding to the main alteration(s)in the major pathways that regulate FA homeostasis leading,in each case,to the initiation and progression of NASH.This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments. | José M Mato Cristina Alonso Mazen Noureddin Shelly C Lu | 2019 | World Journal of Gastroenterology2019，25，24： | 19 |
| 2 | Methionine adenosyltransferases in liver cancer显示文摘Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy. | Ben Murray Lucia Barbier-Torres Wei Fan JoséM Mato Shelly C Lu | 2019 | World Journal of Gastroenterology2019，25，31： | 10 |
| 3 | 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 |
| 4 | 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 |
| 5 | 新一代渴望导管: 在肺的栓塞的处理的可行性显示文摘 AIM: To report our preliminary experience with a new generation aspiration catheter in the treatment of symptomatic pulmonary embolism(PE). METHODS: A retrospective database search for pulmonary artery embolectomy since introduction of the Pronto.035' and XL extraction catheter(Vascular Solutions, Minneapolis, MN) at our institution in 10/2009 was performed. Ten consecutive patients were identified in which the Pronto.035' or XL catheter was used between 01/2010 and 03/2013. All patients were referred for catheter based embolectomy due to contraindications to systemic lysis, or for being in such a critical clinical condition that immediate percutaneous treatment deemed warranted. The computed tomography(CT) right to left heart ratio as predictor for the severity of the PE was retrospectively evaluated on standard axial views. The difference between pre- and post-procedure pulmonary pressure measures was taken to assess the procedural effect.RESULTS: Extensive PE was confirmed angiographically in all patients. Measured right- to left ventricle(RV/LV) ratios were elevated beyond one in seven of the eight available CTs. Acute procedural success defined as clinical removal of visible thrombus and improvement in mean pulmonary artery pressure was seen in all recorded patients(n = 8), the mean pulmonary pressures declined from a median(range) of 35.5(19-46) to 23(10-37, P = 0.008) mmHg. Neither death nor other complications occurred intra- or immediately periprocedural, yet short term mortality within 30 d was found in 6 out of 9 patients, one patient was lost in follow up. The cause of death within 30 d in the 6 patients was identified as: Circulatory failure in direct connection with the PE(n = 2), stroke, sepsis, or succumbing to malignancy in a hospice setting(n = 2). CONCLUSION: Success in thrombus removal with improved pulmonary hypertension and systemic hypotension suggests this aspiration technique to be effective. Aspiration catheters should be part of further trials. | Wolf E Heberlein Mollie E Meek Omar Saleh James C Meek Shelly Y Lensing William C Culp | 2013 | World Journal of Radiology2013，5，11： | 2 |
| 6 | S-adenosylmethionine显示文摘 | Shelly C Lu | 2000 | Int J Biochem Cell Biol2000，32，： | 2 |
| 7 | Glutathione synthesis 显示文摘 | Shelly C L | 2012 | Biochimica et Biophysica Acta2012，111，： | 1 |
| 8 | Molecular dynamics investigation of a Newtonian black film 显示文摘 | GAMBA Z HAUTMAN J SHELLY J C | 1992 | Langmuir1992，8，12： | 1 |
| 9 | Postharvest quality of 'Valencia' orange after exposure to hot,moist forced air for fruit fly disinfestations显示文摘 | Shellie K C | 1994 | HortScience1994，29，3： | 1 |
| 10 | S-Adenosylmethionine显示文摘 | SHELLY C L | 2000 | Int J Biochem Cell Biol2000，32，4： | 1 |
| 11 | Sensory Properties of Ginseng Solutions Modified by Masking Agents 显示文摘 | Lauren C Tamamoto Shelly J Schmidt Soo-Yeun Lee | 2010 | Journal of Food Science2010，75，7： | 1 |
| 12 | Alcohol, DNA Methylation, and Cancer显示文摘 | Varela-Rey Marta Woodhoo Ashwin Martinez-Chantar Maria-Luz Mato José M Lu Shelly C | 2013 | Alcohol Research2013，，1： | 1 |
| 13 | Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type la 显示文摘 | Lei KJ Shelly LL Pan C J | 1993 | Science1993，262，： | 1 |
| 14 | Role of methionine adenosyltransferase and S-adenosyl-methionine in alcohol-associated liver cancer显示文摘 | SHELLY C L MATO J M | 2005 | Alcohol2005，35，3： | 1 |
| 15 | Gas chromatographic technologies for the analysis of essential oils 显示文摘 | MARRIOTT P J SHELLIE R CORNWELL C | 2001 | Journal of Chromatography A2001，936，12： | 1 |
| 16 | Activation of SGKI by HGF, Racl and integrin- mediated cell adhesion in MDCK cells: PI-3K-dependent and-inde- pendent pathways 显示文摘 | Shelly C Herrera R | 2002 | J CellSci2002，115，19： | 1 |
| 17 | Sexual selection in relation to pest-management strategies显示文摘 | Boake C R B Shelly T E Kaneshiro K Y | 1996 | Annual Review of Entomology1996，41，： | 1 |
| 18 | Direct polymer intercalation in single crystal vermiculites显示文摘 | Shelly D B Hsien C W Emmanuel P G | 2000 | Polymer2000，41，： | 1 |
| 19 | Nontuberculous Myeobacteria Infections and Anti-Tumor Necrosis Factor-α Ther- apy显示文摘 | KEVIN L W ERIC C SHELLIE Y | 2009 | Emerging Infectious Diseases2009，15，10： | 1 |
| 20 | Role of S-adenosyl-L-methionine in liver health and injury显示文摘 | Mato J M Shelly C | 2007 | HepatoIogy2007，45，5： | 1 |
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