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| 1 | Magnet- ic and Structural Properties of M-type Barium Hexaferrite Prepared by Co-precipitation显示文摘 | Philip Shepherd Kajal K Mallick Roger J Green | 2007 | Journal of Magnetism and Magnetic Materials2007，311，： | 1 |
| 2 | Dielectric properties of M-type barium hexaferrite prepared by co-precipitation显示文摘 | Kajal K Mallick Philip Shepherd Roger J Green | 2007 | J Eur Ceram Soc2007，27，： | 1 |
| 3 | Dielectric properties of M-type barium hexaferrite prepared by co-precipitation 显示文摘 | Mallick K K Shepherd Philip Green R J | 2007 | J Eur Ceram Soc2007，，27： | 1 |
| 4 | glucocorticoid inhibit apical G1UT2-trafficking and intestinal glucose absorption in rat small intestine显示文摘 | Philip A Helliwell Oliver J Mace | 2004 | J Physiol2004，5601，： | 1 |
| 5 | Prediction of Cardiovascular Events in Statin-Treated Stable Coronary Patients by Lipid and Nonlipid Biomarkers显示文摘 | Benoit J. Arsenault Philip Barter David A. DeMicco Weihang Bao Gregory M. Preston John C. LaRosa Scott M. Grundy Prakash Deedwania Heiner Greten Nanette K. Wenger James Shepherd David D. Waters John J.P. Kastelein | 2011 | Journal of the American College of Cardiology2011，，1： | 1 |
| 6 | A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000显示文摘 | Benjamin L. Shneider Morton B. Brown Barbara Haber Peter F. Whitington Kathleen Schwarz Robert Squires Jorge Bezerra Ross Shepherd Philip Rosenthal Jay H. Hoofnagle Ronald J. Sokol | 2006 | The Journal of Pediatrics2006，，： | 1 |
| 7 | Magnetic and structural properties of M-type barium hexaferrite prepared by co-precipitation显示文摘 | Philip Shepherd Kajal K Mallick Roger J Green | 2007 | Journal of Magnetism and Magnetic Materials2007，311，： | 1 |
| 8 | Adverse drug reaction deaths reported in United States vital statistics, 1999 - 2006显示文摘 | Greene Shepherd Philip Mohom Kristina Yacoub | 2012 | Ann Pharmacother2012，46，： | 1 |
| 9 | Bilateral reflex fracture of the coronoid process of the mandible: A case report显示文摘 | Philip M Sivarajasingam V Shepherd J | 1999 | Oral Maxillofae Surg1999，28，3： | 1 |
| 10 | Inhibition of vascular adhesion protein-1 modifies hepatic steatosis in vitro and in vivo显示文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is associated with obesity,insulin resistance and dyslipidaemia and currently is estimated to affect up to a third of all individuals in developed countries.Current standard of care for patients varies according to disease stage,but includes lifestyle interventions common insulin sensitizers,antioxidants and lipid modifiers.However,to date specific therapies have shown little histological or fibrosis stage improvement in large clinical trials,and there is still no licensed therapy for NAFLD.Given the high prevalence,limited treatment options and significant screening costs for the general population,new treatments are urgently required.AIM To assess the potential for inhibition of the amine oxidase enzyme vascular adhesion protein-1(VAP-1)to modify hepatic lipid accumulation in NAFLD.METHODS We have used immunochemical and qPCR analysis to document expression of VAP-1 and key functional proteins and transporters across the NAFLD spectrum.We then utilised hepatocytes in culture and human precision cut liver slices in concert with selective enzyme activity inhibitors to test the effects of activating the semicarbazide-sensitive amine oxidase activity of VAP-1 on hepatic lipid uptake and triglyceride export.A murine model of NAFLD was also used to determine the consequences of VAP-1 knockout and gene expression arrays were used to quantify the effects of VAP-1 activity on key lipid modifying and proinflammatory gene expression.RESULTS We confirmed that increasing severity of NAFLD and progression to cirrhosis was associated with a significant increase in hepatocellular VAP-1 expression.Hepatocytes in vitro exposed to recombinant VAP-1 and its substrate methylamine showed increased lipid accumulation as determined by quantification of Oil Red O uptake.This was recapitulated using hydrogen peroxide,and lipid accumulation was accompanied by changes in expression of the lipid transporter molecules FABP3,FATP6,insulin receptor subunits and PPARα.Human liver tissue exposed to recombinant VAP-1 or substrates for endo/exogenous VAP-1 produced less triglyceride than untreated tissue and demonstrated an increase in steatosis.This response could be inhibited by using bromoethylamine to inhibit the SSAO activity of VAP-1,and mice deficient in VAP-1/AOC3 also demonstrated reduced steatosis on high fat diet.Exposure of human liver tissue to methylamine to activate VAP-1 resulted in increased expression of FABP2 and 4,FATP3-5,caveolin-1,VLDLR,PPARGC1 and genes associated with the inflammatory response.CONCLUSION Our data confirm that the elevations in hepatic VAP-1 expression reported in nonalcoholic steatohepatitis can contribute to steatosis,metabolic disturbance and inflammation.This suggests that targeting the semicarbazide sensitive amine oxidase capacity of VAP-1 may represent a useful adjunct to other therapeutic strategies in NAFLD. | Emma L Shepherd Sumera Karim Philip N Newsome Patricia F Lalor | 2020 | World Journal of Hepatology2020，12，11： | 0 |
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