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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 | AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update: Endorsed by the National Heart, Lung, and Blood Institute显示文摘 | Sidney C. Smith Jerilyn Allen Steven N. Blair Robert O. Bonow Lawrence M. Brass Gregg C. Fonarow Scott M. Grundy Loren Hiratzka Daniel Jones Harlan M. Krumholz Lori Mosca Richard C. Pasternak Thomas Pearson Marc A. Pfeffer Kathryn A. Taubert | 2006 | Circulation2006，，19： | 4 |
| 3 | Characteristics of Trays Using Inertial Separation Technology显示文摘Though they look very different,UOP SimulFlowTM,Koch-Glitsch Ultra-FracTM,Jaeger CoFloTM and Shell ConSepTM trays fall into the same category of trays using inertial separation technology. However,flooding mechanisms and the trends of entrainment and efficiency are different due to their different working principles. This paper provides a detailed analysis of these trays using available information from literature and U.S. Patents. Efforts are also made to interpret the observations reported. In terms of tray efficiency,it is found that SimulFlow,Ultra-Frac and CoFlo trays are typical point efficiency devices due to a completely mixed liquid pool on the tray deck,while ConSep trays can take advantage of liquid concentration gradient on the tray deck,which makes this tray at-tractive among all ultra high capacity trays. | YANG Quan Giuseppe Mosca Mario Roza | 2010 | Chinese Journal of Chemical Engineering2010，18，6： | 4 |
| 4 | Intranasal rapamycin ameliorates Alzheimerlike cognitive decline in a mouse model of Down syndrome显示文摘Background:Down syndrome(DS)individuals,by the age of 40s,are at increased risk to develop Alzheimer-like dementia,with deposition in brain of senile plaques and neurofibrillary tangles.Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain,prior and after the development of Alzheimer Disease(AD).The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways,including insulin signaling and autophagy,involved in pathology onset and progression.Within this context,the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena.By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol(InRapa)that maximizes brain delivery and reduce systemic side effects.Methods:Ts65Dn mice were administered with InRapa for 12 weeks,starting at 6 months of age demonstrating,at the end of the treatment by radial arms maze and novel object recognition testing,rescued cognition.Results:The analysis of mTOR signalling,after InRapa,demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR(reduced to physiological levels),which led,through the rescue of autophagy and insulin signalling,to reduced APP levels,APP processing and APP metabolites production,as well as,to reduced tau hyperphosphorylation.In addition,a reduction of oxidative stress markers was also observed.Discussion:These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis,thus ultimately resulting in improved cognition.Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals. | Antonella Tramutola Chiara Lanzillotta Eugenio Barone Andrea Arena Ilaria Zuliani Luciana Mosca Carla Blarzino D.Allan Butterfield Marzia Perluigi Fabio Di Domenico | 2018 | Translational Neurodegeneration2018，7，1： | 3 |
| 5 | Feasibility of robotic pancreaticoduodenectomy显示文摘 | U. Boggi S. Signori N. De Lio V. G. Perrone F. Vistoli M. Belluomini C. Cappelli G. Amorese F. Mosca | 2013 | Br J Surg2013，，7： | 3 |
| 6 | A comparison of root characteristics in relation to nutrient and water stress in two maize hybrids显示文摘 | T. Vamerali M. Saccomani S. Bona G. Mosca M. Guarise A. Ganis | 2003 | Plant and Soil2003，，1： | 2 |
| 7 | Comparison of reversed-phase enantioselective HPLC methods for determining the enantiomeric purity of (S)-omeprazole in the presence of its related substances显示文摘A simple analytical high-performance liquid chromatography(HPLC) method was applied for the enantiomeric excess determination of esomeprazole((S)-OME), the enantiopure active ingredient contained in drug products, in the presence of its potential organic impurities A-E. The enantioselective separation was accomplished on the immobilized-type Chiralpak ID-3 chiral stationary phase(CSP)under reversed-phase conditions. The results were evaluated and compared with those obtained by the of fi cial enantioselective method of European Pharmacopoeia used as the reference for checking the enantiomeric excess of(S)-OME. It has been established that the use of the Chiralpak ID-3 CSP allows the determination of the enantiomeric purity of(S)-OME without any interference coming from its chiral and achiral related substances. The analytical procedure of the drug regulatory agencies based on the AGP CSP suffered instead from poor speci fi city due to overlap of the peaks pertinent to the achiral impurity A and the chiral impurity(R)-OME(impurity F). | Bruno Gallinella Rosella Ferretti Leo Zanitti Isabella Sestili Antonina Mosca Roberto Cirilli | 2016 | Journal of Pharmaceutical Analysis2016，6，2： | 2 |
| 8 | T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression显示文摘 | Elena Klyushnenkova Joseph D Mosca Valentina Zernetkina Manas K Majumdar Kirstin J Beggs Donald W Simonetti Robert J Deans Kevin R McIntosh | 2005 | Journal of Biomedical Science2005，，1： | 2 |
| 9 | Defining the Learning Curve for Team-Based Laparoscopic Pancreaticoduodenectomy显示文摘 | Paul J. Speicher Daniel P. Nussbaum Rebekah R. White Sabino Zani Paul J. Mosca Dan G. Blazer Bryan M. Clary Theodore N. Pappas Douglas S. Tyler Alexander Perez | 2014 | Annals of Surgical Oncology2014，，12： | 2 |
| 10 | Immunotherapy with Autologous, Human Dendritic Cells Transfected with Carcinoembryonic Antigen mRNA显示文摘 | Michael A. Morse Smita K. Nair Paul J. Mosca Amy C. Hobeika Timothy M. Clay Yuping Deng David Boczkowski Alan Proia Donna Neidzwiecki Pierre-A. Clavien# Herbert I. Hurwitz Jeffrey Schlom Eli Gilboa H. Kim Lyerly | 2003 | Cancer Investigation2003，，3： | 2 |
| 11 | Angel Estimation in Amplitude Comparison Monopulse Systems显示文摘 | Mosca E | 1969 | IEEE Transactions on Aerospace and Electronic Systems1969，5，2： | 1 |
| 12 | Effects of the somatostatin analog Lanreotide on the circulating level of chromogranin - A, prostate - specific antigen, and insulin like growth factor - 1 in advanced prostate cancer patients 显示文摘 | Berruti A Dogliotti L Mosca A | 2001 | Prostate2001，47，3： | 1 |
| 13 | Effect of somatostatin on mensenteric vascular resistance in normal dan portal hypertenstion rats显示文摘 | Sieber C Mosca P G Groszmann R J | 1992 | Am J Physiol1992，262，： | 1 |
| 14 | Scripta Mater显示文摘 | Gargano P Mosca H Bozzolo G | 2003 | 48:6952003，48，： | 1 |
| 15 | Cardiovascular disease in women: a statement for healt hcare professionals from the American Heart Association 显示文摘 | Mosca L Manson J E Sut herland S E | 1997 | Circulation1997，96，： | 1 |
| 16 | Growth of ZnO tetrapods for nanostructure-based gas sensors 显示文摘 | Calestani D Zha M Mosca R | 2010 | Sens Actuators B2010，144，2： | 1 |
| 17 | High dose, extended-in- terval colistin administration in critically ill patients: is this the right dosing strategy? a preliminary study 显示文摘 | Dalfino L Puntillo F Mosca A | 2012 | Clin Infect Dis2012，54，12： | 1 |
| 18 | Pushing structoral information into the yeast interactome by high-throughput protein docking experiments 显示文摘 | Mosca R Pons C Fernmdez-Recio J | 2009 | PLoS Comput Biol2009，5，10： | 1 |
| 19 | Site preference of ternary alloying additions to NiTi: Fe, Pt, Pd, Au, A1, Cu, Zr and Hl'显示文摘 | Guillenno Bozzolo Ronald D Noebe Hugo O Mosca | 2005 | Journal of Alloys and Compounds2005，389，： | 1 |
| 20 | Structured zeolite NaX coatings on ceramic cordierite monolith supports for PSA applications显示文摘 | Alessandra Mosca Jonas Hedlund Paul A Webley | 2010 | Microp Mesop Mater2010，130，： | 1 |
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