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| 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 | Analysis of orthopedic surgical procedures in children with cerebral palsy显示文摘BACKGROUND Orthopedic surgery in children with cerebral palsy(CP)aims to improve function and prevent deformities.Each child’s condition in CP is unique and many covariables influence surgical decision-making including a patient's age and their functional level.Little is known about the frequency of different types of orthopedic surgery in children with CP who have varied functional levels,particularly in countries from Latin America.AIM To assess the type of orthopedic surgical procedures in relation to age and gross motor function in children with CP.METHODS This retrospective study included all children with CP(n=245)treated with elective orthopedic surgery at a Uruguayan university hospital between October 2010 and May 2016 identified from a surgical database.Eighteen children(7%)were lost to follow-up due to missing medical charts.Demographics,gross motor function classification(GMFCS),and orthopedic surgeries were obtained from the medical records of 227 children.Chi-squared tests and analysis of variance were used to assess the frequency of surgery,accounting for GMFCS levels.Mean age for soft tissue vs bone surgery was compared with the independent samples t-test.RESULTS A total of 711 surgical procedures were performed between 1998 and 2016.On average,children had 3.1 surgical procedures and the mean age at first surgery was 8.0 years.There were no significant differences in age at first surgery among GMFCS levels(P=0.47).The most common procedures were lower leg soft tissue surgery(n=189,27%),hip tenotomy(n=135,19%),and hamstring tenotomy(n=104,14%).For children with GMFCS level Ⅰ,the mean number of surgeries per child[1.8(range 1-9)]differed significantly at P<0.05 in children with GMFCS levels Ⅱ[3.2(1-12)],Ⅲ[3.2(1-8)],Ⅳ[3.3(1-13)],and Ⅴ[3.6(1-11)].Within Ⅱ,Ⅲ,Ⅳ,and Ⅴ,there was no significant difference in mean number of surgeries per child when comparing across the groups.The proportion of soft tissue surgery vs bone surgery was higher in GMFCS levels Ⅰ-Ⅲ(80%-85%)compared to levels IV(68%)and V(55%)(P<0.05).CONCLUSION The frequency of surgical procedures per child did not increase with higher GMFCS level after level Ⅰ.However,the proportion of bone surgery was higher in GMFCS levels Ⅳ-Ⅴ compared to Ⅰ-Ⅲ. | Ignacio Rehbein Viviana Teske Ignacio Pagano Alejandro Cúneo María Elena Pérez Johan von Heideken | 2020 | World Journal of Orthopedics2020，11，4： | 2 |
| 3 | Competition between fusion-evaporation and multifragmentation in central collisions in ^(58)Ni+^(48)Ca at 25A MeV显示文摘The experimental data concerning the58Ni+48Ca reaction at Elab(Ni)=25A MeV,collected by using the CHIMERA 4π device,have been analyzed in order to investigate the competition among different reaction mechanisms for central collisions in the Fermi energy domain.As a main criterion for centrality selection we have chosen the flow angle(flow) method,making an event-by-event analysis that considers the shape of events,as it is determined by the eigenvectors of the experimental kinetic-energy tensor.For the selected central events(flow >60°) some global variables,good to characterize the pattern of central collisions have been constructed.The main features of the reaction products were explored by using different constraints on some of the relevant observables,like mass and velocity distributions and their correlations.Much emphasis was devoted,for central collisions,to the competition between fusion-evaporation processes with subsequent identification of a heavy residue and a possible multifragmentation mechanism of a well defined(if any) transient nuclear system.Dynamical evolution of the system and pre-equilibrium emission were taken into account by simulating the reactions in the framework of transport theories.Different approaches have been envisaged(dynamical stochastic BNV calculations + sequential SIMON code,QMD,CoMD,etc.).Preliminary comparison of the experimental data with BNV calculations shows reasonable agreement with the assumption of sequential multifragmentation emission in the mass region of IMFs close to the heavy residues.Possible deviations from sequential processes were found for those IMFs in the region of masses intermediate between the mass of heavy residues and the mass of light IMFs.Further simulations are in progress.The experimental analysis will be enriched also by information obtained inspecting the IMF-IMF correlation function,in order to elucidated the nature of space-time decay property of the emitting source associated with events having the largest IMF multiplicity. | FRANCALANZA L ABBONDANNO U AMORINI F BARLINI S BINI M BOUGAULT R BRUNO M CARDELLA G CASINI G AGOSTINO M D' De FILIPPO V De SANCTIS J GERACI E GIUSSANI A GRAMEGNA F GUIOT B KRAVCHUK V La GUIDARA E LANZALONE G Le NEINDRE N MAIOLINO C MARINI P MORELLI L OLMI A PAGANO A PAPA M PIANTELLI S PIRRONE S POLITI G POGGI G PORTO F RUSSOTTO P RIZZO F VANNINI G VANNUCCI L | 2013 | Nuclear Science and Techniques2013，24，5： | 2 |
| 4 | The choice of stock ownership structure: agency costs, monitoring, and the decision to go public 显示文摘 | Pagano M Roell A | 1998 | Quarterly Journal of Economics1998，113，1： | 1 |
| 5 | The epiderniology of fungal infections in patients with hematologic malignancies : the SE1FEM - 2004 study显示文摘 | Pagano L Caira M Candoni A | 2006 | Haematologica2006，91，8： | 1 |
| 6 | Differentiation of H9c2 cardiomyoblasts : the role of adenylate cyclase system 显示文摘 | Pagano M Naviglio S Spina A | 2004 | J Cell Physiol2004，198，3： | 1 |
| 7 | Upregulated expres- sion of rat heart interceUular adhesion mo|ecutar-1 in an- giotensin II -but not phenylephrine-induced hypertension 显示文摘 | Kiarash A Pagano PT Tayeh M | 2001 | Hypertens2001，37，1： | 1 |
| 8 | Bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria-dependent pathway显示文摘 | Métrailler-Ruchonnet I Pagano A Carnesecchi S | | 0，，： | 1 |
| 9 | The choice of stock ownership struc- ture: Agency costs,monitoring,and the decision to go pub- lic显示文摘 | Pagano M Roell A | 1998 | The Quarterly Journal of Economics1998，113，1： | 1 |
| 10 | Endogenous communication among lenders and entrepreneurial incentives显示文摘 | Padilla A | 1997 | Review of Financial Studies1997，10，： | 1 |
| 11 | bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mito- ehondria-dependent pathway 显示文摘 | Memailler-Ruchonnet l Pagano A Camesecchi S | 2007 | Free Radic Biol Med2007，42，7： | 1 |
| 12 | A review of advances in flash flood forecasting显示文摘 | Hapuarachchi H A P Wang Q J Pagano T C | 2011 | Hydrological Processes2011，25，18： | 1 |
| 13 | Moderate alcohol consamption, glucose metabolism and lipolysis: the effect on adiponectin and tumor necrosis factor alpha显示文摘 | Sambataro M Marangoni A Pianta A Vettor R Pagano C | 2003 | J Endocrinol Invest2003，26，12： | 1 |
| 14 | The Choice of Stock Ownership Structure:Agency Costs,Monitoring and the Decision to Go Public显示文摘 | Pagano and Roell A | 1998 | Quarterly Journal of Economics1998，，113： | 1 |
| 15 | The choice of stock ownership structure :agency costs, monitoring, and the decision to go public显示文摘 | Pagano M A Roel | 1998 | Quarterly Journal of Economics1998，，113： | 1 |
| 16 | Zygomycosis in Europe: Analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007 显示文摘 | Skiada A Pagano L Groll A | 2011 | Clin Microbiol infect2011，17，12： | 1 |
| 17 | Rituximab chimeric anti- CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenie purpura显示文摘 | Stasi R Pagano A Stipa E | 2001 | Blood2001，98，4： | 1 |
| 18 | Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the Eu- ropean Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007显示文摘 | SKIADA A PAGANO L GROLL A | 2011 | Clin Micro- biol Infect2011，7，12： | 1 |
| 19 | Regulation of neuronal differentiation in human CNS stem cell progeny by leukemia inhibitory factor显示文摘 | Galli R Pagano SF Gritti A | 2000 | Dev Neurosci2000，22，12： | 1 |
| 20 | Fentons pretreatment of mature landfill leachate显示文摘 | Lopez A Pagano M Volpe A | 2004 | Chemosphere2004，54，7： | 1 |
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