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| 1 | Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice显示文摘BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments. AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD. METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD)(14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice. CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients. | Kandy T Velázquez Reilly T Enos Jackie E Bader Alexander T Sougiannis Meredith S Carson Ioulia Chatzistamou James A Carson Prakash S Nagarkatti Mitzi Nagarkatti E Angela Murphy | 2019 | World Journal of Hepatology2019,11,8: | 6 |
| 2 | 睾酮缺乏症的诊断和治疗显示文摘近些年来,随着睾酮缺乏症(TD)发病率的上升、新药的不断开发、以及商业推广的深入,睾酮替代疗法(TST)的临床应用显著增多。然而,关于睾酮缺乏症的诊断标准以及TST的应用和监测,仍然不是很明确。此种现象主要源于睾酮的多重作用靶点。在人体内,睾酮参与了很多生理过程的调节,同时睾酮的表达水平也受很多疾病及药物的影响。因此,睾酮缺乏症的临床症状和体征具有多样性和非特异性,也就增加了睾酮缺乏症的诊断难度,尤其在老年人群中。临床上,关于血清睾酮水平的检测也存在争议,不同实验室之间存在一定的差异,因此也很难界定睾酮水平的诊断标准。很多医学专业组织试图制定睾酮缺乏症的诊断指南,但彼此间很难达成统一。另外,临床使用的睾酮制剂也层出不穷,相应的TST治疗方案也像TD的诊断标准一样不断更新和变化。临床上,随着TST的不断推进,专科医师必须不断更新对于TD和HTST的了解和治疗及应用。本文旨在阐述TD的最新概念及其诊断和治疗的新进展。 | James A McBride Culley C Carson Robert M Coward | 2015 | Asian Journal of Andrology2015,17,2: | 5 |
| 3 | Ron receptor-dependent gene regulation in a mouse model of endotoxin-induced acute liver failure显示文摘BACKGROUND:Prior experimentation has shown that loss of the tyrosine kinase(TK) signaling domain of the Ron receptor leads to marked hepatocyte protection in a model of lipopolysaccharideinduced acute liver failure(ALF) in D-galactosamine(GalN)sensitized mice.The aim of this study was to identify the role of Ron in the regulation of hepatic gene expression.METHODS:Microarray analyses were performed on liver RNA isolated sequentially from wild-type(WT) and TK-/mice during the progression of ALF.Gene array data were validated using Western and immunohistochemistry analyses as well as with ex vivo culture systems.RESULTS:At baseline,101 genes were differentially expressed between WT and TK-/-livers,which regulate processes involved in hypoxia,proliferation,apoptosis and metabolism.One hour after ALF induction,WT livers exhibited increased cytokine expression compared to TK-/-livers,and after 4 hours,an induction of suppressor of cytokine signaling(SOCS) genes as well as JAK-STAT pathway activation were prominent in TK-/livers compared to controls.CONCLUSION:Our studies suggest a novel hepato-protective mechanism in Ron TK-/-mice wherein increased and sustained SOCS production and JAK-STAT activation in the hepatocyte may inhibit the destructive proinflammatory milieu and promote survival factors which blunt hepatic death and the ensuing development of ALF. | Rishikesh M Kulkarni Louis W Kutcher William D Stuart Daniel J Carson Mike A Leonis Susan E Waltz | 2012 | Hepatobiliary & Pancreatic Diseases International2012,11,4: | 3 |
| 4 | Evaluation of in situ graft forces of a 2 - bundle tibial inlay posterior cruciate ligament reconstruction at various flexion angles 显示文摘 | Carson EW Deng XH Allen A | 2007 | Arthroscopy2007,23,5: | 1 |
| 5 | Particle sizing using passive ultrasonic measurement of particle-wall impact vibrations显示文摘 | Carson G Mulholland A J Nordon A | 2008 | Journal of Sound and Vibration2008,317,12: | 1 |
| 6 | Uncertainty,Opportunism and Governance:The Effects of Volatility and Ambiguity on Formal and Relational Contracting显示文摘 | CARSON S J MADHOK A WU T | 2006 | Academy of Management Journal2006,49,5: | 1 |
| 7 | The evidence for dietary prevention and treatment of cardiovascular disease 显示文摘 | van Horn L McCoin M Kris-Etherton P M Burke F Carson J A S Champagne C M | 2008 | Journal of the American Dietetic Association2008,108,: | 1 |
| 8 | Structural variation in the human genome显示文摘 | FEUK L CARSON A R Scherer S W | 2006 | Nat Rev Genet2006,7,2: | 1 |
| 9 | A multilevel investigation of antecedents and consequences of team member boundary-spanning behavior显示文摘 | Marrone J A Tesluk P E Carson J B | 2007 | Academy of Management Journal2007,50,6: | 1 |
| 10 | A Multilevel Investigation of Antecedents and Conse- quences of Team Member Boundary-Spanning Behav- ior显示文摘 | MARRONE J A TESLUK P E CARSON J B | 2007 | Academy of Management Journal2007,50,6: | 1 |
| 11 | MUC1:A multifunctional cell surface component of reproductive tissue epithelia显示文摘 | Brayman M Thathiah A Carson DD | 2004 | Repro Biol & Endocrin2004,2,: | 1 |
| 12 | Pulmonary embolism and mortality in patients with COPD显示文摘 | Carson JL Terrin ML Duff A | 1996 | Chest1996,110,5: | 1 |
| 13 | Bin loads-Part 2: concepts 显示文摘 | A W Jenike J R Johanson and J W Carson | 1973 | Journal of Engineering for Industry1973,,: | 1 |
| 14 | 'Unexplained' somatic symptoms, functional syndromes, and somatization: do we need a paradigm shift?显示文摘 | Sharp M Carson A | 2001 | Ann Intern Med2001,134,2: | 1 |
| 15 | Late-onset chronic inflammatory encephalopathy in immune competent and severe combined-immune deficient (SCID) mice with astrocyte-targeted expression of tumor necrosis factor显示文摘 | Stalder AK Carson M J Pagenstecher A at el | 1998 | AmJ Pathol1998,153,3: | 1 |
| 16 | ARB can decrease heart failure combined with AF显示文摘 | Maggloni A P Latini R Carson P E | 2005 | Am Heart J2005,149,: | 1 |
| 17 | Shared leadership in teams= An investigation of anteeedent conditions and per- formance显示文摘 | Carson J B Tesluk P E and Marrone J A | 2007 | Academy of Management Journal2007,50,5: | 1 |
| 18 | Depression in medical patients显示文摘 | Peveler R Carson A Rodin G | 2002 | BMJ2002,325,7356: | 1 |
| 19 | Is maximum conservative management an equivalent treatment option to dialysis for elderly patients with significant comorbid disease? 显示文摘 | Carson RC Juszczak M Davenport A | 2009 | Clin J Am Soc Nephrol2009,4,10: | 1 |
| 20 | Sustaining four wheel drive tourism in desert Australia: Exploring the evi- deuce from a demand perspective显示文摘 | Carson D Taylor A | 2008 | Tbe Rangeland Journal2008,30,1: | 1 |