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| 1 | Nonalcoholic steatohepatitis severity is defined by a failure in compensatory antioxidant capacity in the setting of mitochondrial dysfunction显示文摘AIM To comprehensively evaluate mitochondrial(dys) function in preclinical models of nonalcoholic steatohepatitis(NASH).METHODS We utilized two readily available mouse models of nonalcoholic fatty liver disease(NAFLD) with or without progressive fibrosis: Lep^(ob)/Lep^(ob)(ob/ob) and FATZO mice on high trans-fat, high fructose and high cholesterol(AMLN) diet. Presence of NASH was assessed using immunohistochemical and pathological techniques, and gene expression profiling. Morphological features of mitochondria were assessed via transmission electron microscopy and immunofluorescence, and function was assessed by measuring oxidative capacity in primary hepatocytes, and respiratory control and proton leak in isolated mitochondria. Oxidative stress was measured by assessing activity and/or expression levels of Nrf1, Sod1, Sod2, catalase and 8-OHdG. RESULTS When challenged with AMLN diet for 12 wk, ob/ob and FATZO mice developed steatohepatitis in the presence of obesity and hyperinsulinemia. NASH development was associated with hepatic mitochondrial abnormalities, similar to those previously observed in humans, including mitochondrial accumulation and increased proton leak. AMLN diet also resulted in increased numbers of fragmented mitochondria in both strains of mice. Despite similar mitochondrial phenotypes, we found that ob/ob mice developed more advanced hepatic fibrosis. Activity of superoxide dismutase(SOD) was increased in ob/ob AMLN mice, whereas FATZO mice displayed increased catalase activity, irrespective of diet. Furthermore, 8-OHd G, a marker of oxidative DNA damage, was significantly increased in ob/ob AMLN mice compared to FATZO AMLN mice. Therefore, antioxidant capacity reflected as the ratio of catalase:SOD activity was similar between FATZO and C57 BL6 J control mice, but significantly perturbed in ob/ob mice. CONCLUSION Oxidative stress, and/or the capacity to compensate for increased oxidative stress, in the setting of mitochondrial dysfunction, is a key factor for development of hepatic injury and fibrosis in these mouse models. | Michelle L Boland Stephanie Oldham Brandon B Boland Sarah Will Jean-Martin Lapointe Silvia Guionaud Christopher J Rhodes James L Trevaskis | 2018 | World Journal of Gastroenterology2018，24，16： | 7 |
| 2 | Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors显示文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs. | Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder | 2015 | World Journal of Gastroenterology2015，21，8： | 2 |
| 3 | H eritability of head size in dutch and Australian twin families at ages 0-50 Years 显示文摘 | Dirk J AS Michelle L Meike B | 2010 | Twin Research And Human Genetics2010，13，4： | 1 |
| 4 | Cyclic testing of a Buckling RestrainedRaced Frame Unconstrained Gusset Connections显示文摘 | Berman J W Michel B | 2009 | Journal of Structural Engineering2009，135，12： | 1 |
| 5 | Prevalence and incidence rate of HIV, hepatitis B and hepatitis C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995显示文摘 | Barbara B Christian J Michel B | 1998 | AIDS1998，12，15： | 1 |
| 6 | Photosynthesis, transpiration, leaf temperature, and somatal ativity of cotton plants under varying water potentials 显示文摘 | Pallas J E Michel B E | 1967 | Plant Physiology1967，42，1： | 1 |
| 7 | Propolis effects on pro-inflammatory cytokine production and Toll-like receptor 2 and 4 expression in stressed mice显示文摘 | Ana Carolina Pagliarone Cláudio Lera Orsatti Michelle Cristiane Búfalo Fabiane Missima Tatiana Fernanda Bachiega Jo?o Pessoa Araújo Júnior José Maurício Sforcin | 2009 | International Immunopharmacology2009，，11： | 1 |
| 8 | Effect of surfactant addition on phenanthrene biodegradation in sediments显示文摘 | Harry J T Joseph B H Michelle T J | 1995 | Environ Toxicol Chem1995，14，6： | 1 |
| 9 | Apropos d une observation de pheochromocytome vesical malin Conduite diagnostique et thfrapeutique 显示文摘 | Michel F Gattegno B Sicard J F etal | 1990 | Ann Urol1990，24，： | 1 |
| 10 | Junc- tional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synovium 显示文摘 | RABQUER B J PAKOZDI A MICHEL J E | 2008 | Bradley J Rabquer2008，58，10： | 1 |
| 11 | Chronic stress impairs rat growth and jejunal epithelial barrier function:role of mast cells 显示文摘 | SANTOS J MICHELLE B YANG P C | 2000 | Am J Physiol Gastrointest Liver Physiol2000，278，6： | 1 |
| 12 | Stress concentration in steel bridge orthotropic decks显示文摘 | Michele S P Ronaldo C B Aluision J R | 2005 | Journal of Constructional Steel Research2005，61，8： | 1 |
| 13 | Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years 显示文摘 | Storms W Michele TM Knorr B Noonan G Shapiro G Zhang J Shingo S Reiss TF | 2001 | Clin Exp Allergy2001，31，1： | 1 |
| 14 | Oxiliplatin combined to 5-FU and folinic acid (5-FU/FA) as second-third-line treatment in patients with advanced colorectal cancer显示文摘 | Greread B Bleiberg H Michel J | 1997 | Proc Ann Meet Am Soc Clin Oncol1997，16，： | 1 |
| 15 | Decomposition of laser altimeter waveforms 显示文摘 | Michelle A H Jean B M Bryan J | 2000 | IEEE Transaction on Geoseienee and Remote Sensing2000，38，4： | 1 |
| 16 | Holistic processing is finely tuned for faces of one'sown race 显示文摘 | Michel C Rossion B Han J Chung C S Caldara R | 2006 | Psychological Science2006，17，7： | 1 |
| 17 | An introduction to compressive sampling 显示文摘 | EMMANUEL J MICHEL B | 2008 | IEEE Transaction on Signal Processing2008，25，2： | 1 |
| 18 | Power requirements of gas-liquid agitated systems显示文摘 | Michel B J Miller S A | 1962 | AIChE J1962，8，2： | 1 |
| 19 | The American College of Rheumatology in 1990 criteria for the classification of Henoch-Schonlein purpura显示文摘 | MILLS J A MICHEL B A BLOCH D A | 1990 | Arthritis Rheum1990，33，： | 1 |
| 20 | 查看详情显示文摘 | Landen O L Boehly T R Bradley D K Braun D G Callahan D A Celliers P M Collins G W Dewald E L Divol L Glenzer S H Hamza A Hicks D G Hoffman N Izumi N Jones O S Kirkwood R K Kyrala G A Michel P Milovich J Munro D H Nikroo A Olson R E Robey H F Spears B K Th | | 0，，： | 1 |
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