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| 1 | m TOR signaling in liver regeneration: Rapamycin combined with growth factor treatment显示文摘AIM: To investigate the effects of mammalian target of rapamycin(mT OR) inhibition on liver regeneration and autophagy in a surgical resection model.METHODS: C57BL/6 mice were subjected to a 70% partial hepatectomy(PH) and treated intraperitoneally every 24 h with a combination of the m TOR inhibitor rapamycin(2.5 mg/kg per day) and the steroid dexamethasone(2.0 mg/kg per day) in phosphate bufferedsaline(PBS) or with PBS alone as vehicle control. In the immunosuppressant group, part of the group was treated subcutaneously 4 h prior to and 24 h after PH with a combination of human recombinant interleukin 6(IL-6; 500 μg/kg per day) and hepatocyte growth factor(HGF; 100 μg/kg per day) in PBS. Animals were sacrificed 2, 3 or 5 d after PH and liver tissue and blood were collected for further analysis. Immunohistochemical staining for 5-Bromo-2'-deoxyuridine(Brd U) was used to quantify hepatocyte proliferation. Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3(LC3)-Ⅱ protein expression as a marker for autophagy. Hepatic gene expression levels of proliferation-, inflammation- and angiogenesisrelated genes were examined by real-time reverse transcription-polymerase chain reaction and serum bilirubin and transaminase levels were analyzed at the clinical chemical core facility of the Erasmus MC-University Medical Center.RESULTS: m TOR inhibition significantly suppressed regeneration, shown by decreased hepatocyte proliferation(2% vs 12% Brd U positive hepatocyte nuclei at day 2, P < 0.01; 0.8% vs 1.4% at day 5, P = 0.02) and liver weight reconstitution(63% vs 76% of initial total liver weight at day 3, P = 0.04), and furthermore increased serum transaminase levels(aspartate aminotransferase 641 U/L vs 185 U/L at day 2, P = 0.02). Expression of the autophagy marker LC3-Ⅱ, which was reduced during normal liver regeneration, increased after mT OR inhibition(46% increase at day 2, P = 0.04). Hepatic gene expression showed an increased inflammation-related response [tumor necrosis factor(TNF)-α 3.2-fold upregulation at day 2, P = 0.03; IL-1Ra 6.0-fold upregulation at day 2 and 42.3-fold upregulation at day 5, P < 0.01] and a reduced expression of cell cycle progression and angiogenesis-related factors(HGF 40% reduction at day 2; vascular endothelial growth factor receptor 2 50% reduction at days 2 and 5; angiopoietin 1 60% reduction at day 2, all P ≤ 0.01). Treatmentwith the regeneration stimulating cytokine IL-6 and growth factor HGF could overcome the inhibitory effect on liver weight(75% of initial total liver weight at day 3, P = 0.02 vs immunosuppression alone and P = 0.90 vs controls) and partially reversed gene expression changes caused by rapamycin(TNF-α and IL-1Ra levels at day 2 were restored to control levels). However, no significant changes in hepatocyte proliferation, serum injury markers or autophagy were found.CONCLUSION: mT OR inhibition severely impairs liver regeneration and increases autophagy after PH. These effects are partly reversed by stimulation of the IL-6 and HGF pathways. | Suomi MG Fouraschen Petra E de Ruiter Jaap Kwekkeboom Ron WF de Bruin Geert Kazemier Herold J Metselaar Hugo W Tilanus Luc JW van der Laan Jeroen de Jonge | 2013 | World Journal of Transplantation2013，3，3： | 6 |
| 2 | New therapeutic opportunities for Hepatitis C based on small RNA显示文摘Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, anti-sense oligonucleotides (ASO), or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA (miR-122) in viral replication and discuss its potential for HCV molecular therapy. | Qiu-wei Pan Scot D Henry Bob J Scholte Hugo W Tilanus Harry LA Janssen Luc JW van der Laan | 2007 | World Journal of Gastroenterology2007，13，33： | 4 |
| 3 | On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients显示文摘AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials. | Nanne KH de Boer Luc JJ Derijks Lennard PL Gilissen Daniel W Hommes Leopold GJB Engels Sybrand Y de Boer Gijsbertus den Hartog Piet M Hooymans Anja BU M(?)kelburg Barend D Westerveld Anton HJ Naber Chris JJ Mulder Dirk J de Jong | 2005 | World Journal of Gastroenterology2005，11，35： | 4 |
| 4 | Cre-mediated gene deletion in the mammary gland显示文摘 | KAY-UWE W WALL R J LUC S-O | 1997 | Nucleic Acids Res1997，25，： | 1 |
| 5 | Assessment of stroke volume variation for prediction of fluid responsiveness using the modified FloTrac and PiCCOplus system显示文摘 | Christoph K Alban S Luc W | 2008 | Critical Care2008，12，3： | 1 |
| 6 | Modeling of Quasistatic Magnetic Hysteresis with Feed-Forward Neural Networks显示文摘 | Dimitre M Luc D Marc D W | 2001 | Journal of Applied Physics2001，89，11： | 1 |
| 7 | Fetal trauma:brain imaging in four neonates显示文摘 | Luc Breysem V Cossey E Mussen P Demaerel W Van de Voorde M Smet | 2004 | European radiology2004，14，9： | 1 |
| 8 | Biological evaluation of proanthocyanidin dimers and related polyphenols 显示文摘 | Tess D B Luc P Myriam W | 1999 | J Nat Prod1999，62，7： | 1 |
| 9 | ROC analysis in ordi-nal regression learning显示文摘 | WILLEM W BERNARD D LUC B | 2008 | Pattern Recognition Letters2008，29，1： | 1 |
| 10 | On the scalability ofordered multi-class ROC analysis显示文摘 | WILLEM W BERNARD D LUC B | 2008 | Computational Statisticsamp Data Analysis2008，52，7： | 1 |
| 11 | Estimated creatinine clearance instead of plasma creatinine level as prognostic test for postoperative renal function in patients undergoing coronary artery bypass surgery显示文摘 | Luc Noyez Izabella Plesiewicz Freek W A Verheugt | | 0，，： | 1 |
| 12 | Estimated creatinine clearance instead of p lasma creatinine level as prognostic test for postoperative renal function in patients undergoing coronary artery bypasssurgery 显示文摘 | Luc N Izabella P Freek W | 2006 | Eur J of Cardio thorac Surg2006，29，4： | 1 |
| 13 | Toward an assessment of perceived HRM system strength: Scale develop- ment and validation显示文摘 | Jeroen D Sophie D W Luc S | 2012 | International Journal of Hu- man Resource Management2012，23，7： | 1 |
| 14 | Defective recovery of QT dispersion following transcatheter aortic valve implantation: frequency, predictors and prognosis显示文摘BackgroundCorrected QT 分散(cQTD ) 与不一致的室的 repolarisation 被相关并且增加了死亡。在有大动脉的狭窄的病人, cQTD 被显示出在大动脉的阀门培植(TAVI ) 是的 transcatheter 的外科的阀门代替,而是效果以后改善了未知。因此,在 222 个病人全部的 TAVI.MethodsA 与在 2005 年 11 月和 2012 年 1 月之间的 Medtronic-CoreValve 系统经历了 TAVI 以后,我们寻求了在 6 个月探索频率,预言者和有缺点的 cQTD 恢复的预示的效果。或谁在一级或 III antiarrhythmics 上或在长期的血液透析上的病人发达 atrial 纤维性颤动,新捆分支块或在 TAVI 被排除以后,成为了依赖的心律调整器。作为结果, pre- , up 以后和后续 ECG (中部:6 个月) 分析在 45 个合格病人是可得到的。有缺点的 cQTD 恢复在 6 months.ResultsIn 在基线 cQTD 以外被定义为任何前进 45 个病人,吝啬的 cQTD 是 47 ±在基线的 23 ms, 45 ±17 ms 立即在 TAVI 和 40 ± 以后;在 6 个月的 16 ms (15% 减小, P = 0.049 ) 。比作基线,而有缺点的 cQTD 恢复在 40% 是在场的,在 6 个月的 cQTD 在 60% 病人被改进。cQTD 增加立即在 TAVI 以后是在 6 个月的有缺点的 cQTD 恢复的一个独立预言者(每 10 ms 增加;或:1.89, 95% CI:1.15-3.12 ) 。由 univariable 分析,有缺点的 cQTD 恢复与迟了的死亡被联系(HR:1.52, 95% CI:1.05-2.17 ).ConclusionsDespite 在 TAVI 以后的 cQTD 的渐渐的减小, 40% 病人在与迟了的死亡被联系的 6 个月有有缺点的恢复。在 TAVI 以后的更多的详细 ECG 分析可以帮助避免迟了的死亡。 | Rutger-Jan Nuis Gokhan Turgut Robert M van der Boon Nicolas M van Mieghem Sjoerd T Nauta Patrick W Serruys Ron T van Domburg Giulio Zuchelli Luc Jordaens Peter P de Jaegere | 2015 | Journal of Geriatric Cardiology2015，12，5： | 1 |
| 15 | Tar in biomass producer gas,the energy research centre of the Netherlands (ECN) experience:An enduring challenge显示文摘 | Rabou Luc P L M Zwart Robin W R Vreugdenhil Berend J | 2009 | Energy and Fuels2009，23，12： | 1 |
| 16 | Versatile Formationof CdSe Nanoparticle - Single Walled Carbon NanotubeHybrid Structures显示文摘 | LUC G AKEY A WANG W | 2009 | Journal of American ChemistrySociety2009，131，： | 1 |
| 17 | penetrating radar data processing: Ground Clutter characterization and removal 显示文摘 | John W B Luc V K Hichem S | 1999 | Technical report IRIS - TR - 00591999，，： | 1 |
| 18 | Calcineurin Inhibitors Stimulate and Mycophenolic Acid Inhibits Replication of Hepatitis E Virus显示文摘 | Yijin Wang Xinying Zhou Yannick Debing Kan Chen Luc J W Van der laan Johan Neyts Harry L A Janssen Herold J. Metselaar Maikel P. Peppelenbosch Qiuwei Pan | 2014 | Gastroenterology2014，，： | 1 |
| 19 | Bispectral index (BIS) helps predicting bad neurological outcome in comatose survivors after cardiac arrest and induced therapeutic hypethermia 显示文摘 | Pascal S Christophe W Luc M | 2009 | Resuscitation2009，80，4： | 1 |
| 20 | Low surface energy polymeric films from partially fluorinated photocurable solventless liquid oligoesters 显示文摘 | Ming W H Luc V R Robert V D G | 2001 | Polymer Bulletin2001，47，34： | 1 |
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