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| 1 | Soluble ST2:A new and promising activity marker in ulcerative colitis显示文摘AIM:To correlate circulating soluble ST2(sST2) levels with the severity of ulcerative colitis(UC) and serum levels of pro-inflammatory cytokines,and to demonstrate the predictive power of sST2 levels for differentiation between active and inactive UC.METHODS:We recruited 153 patients:82 with UC,26 with Crohn's disease(CD) and 43 disease controls [non-inflammatory bowel disease(IBD)].Subjects were excluded if they had diagnosis of asthma,autoimmune diseases or hypertension.The serum levels of sST2 and pro-inflammatory cytokines [pg/mL;median(25th-75th)] as well as clinical features,endoscopic and histological features,were subjected to analyses.The sST2 performance for discrimination between active and inactive UC,non-IBD and healthy controls(HC) was determined with regard to sensitivity and specificity,and Spearman's rank correlation coefficient(r).To validate the method,the area under the curve(AUC) of receiver-operator characteristic(ROC) was determined(AUC,95% CI) and the total ST2 content of the colonic mucosa in UC patients was correlated with circulating levels of sST2.RESULTS:The serum sST2 value was significantly higher in patients with active [235.80(90.65-367.90) pg/mL] rather than inactive UC [33.19(20.04-65.32) pg/mL],based on clinical,endoscopic and histopathological characteristics,as well as compared with non-IBD and HC(P < 0.001).The median level of sST2 in CD patients was 54.17(35.02-122.0) pg/mL,significantly higher than that of the HC group only(P < 0.01).The cutoff was set at 74.87 pg/mL to compare active with inactive UC in a multicenter cohort of patients.Values of sensitivity,specificity,and ability to correctly classify UC,according to activity,were 83.33%,83.33% and 83.33%,respectively.The AUC of the ROC curve to assess the ability of this molecule to discriminate between active vs inactive UC was 0.92(0.86-0.97,P < 0.0001).The serum levels of sST2 in patients with UC significantly correlated with endoscopic and histo-pathological scores(r = 0.76 and r = 0.67,P < 0.0001,respectively),and with the pro-inflammatory cytokine,tumor necrosis factor-α(r = 0.69 and r = 0.61,respectively,P < 0.0001).Interestingly,we found a direct correlation between total intestinal ST2 content and serum levels of sST2,adjusted to endoscopic activity score in patients with mild(r = 0.44,P = 0.004),moderate(r = 0.59,P = 0.002) and severe disease(r = 0.82,P = 0.002).Only patients with inactive UC showed no significant correlation(r = 0.45,P = 0.267).CONCLUSION:sST2 levels correlated with disease severity and inflammatory cytokines,are able to differentiate active from inactive UC and might have a role as a biomarker. | David Díaz-Jiménez Lucía E Núez Caroll J Beltrán Enzo Candia Cristóbal Suazo Manuel varez-Lobos María-Julieta González Marcela A Hermoso Rodrigo Quera | 2011 | World Journal of Gastroenterology2011，17，17： | 8 |
| 2 | 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 |
| 3 | 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 |
| 4 | 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 |
| 5 | Patents and innovation counts as measures of regional production of new knowledge显示文摘 | Zoltan J Acs Luc Anselin Attila Varga | 2002 | Research Policy2002，，7： | 4 |
| 6 | Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study显示文摘 | LUC G BARD J M ARVEILER D | 2001 | Atherosclerosis2001，163，2： | 2 |
| 7 | Patents and innovation counts as measures of regional production of new knowledge显示文摘 | Zoltan J Acs Luc Anselin Attila Varga | 2002 | Research Policy2002，，7： | 2 |
| 8 | Patents and innovation counts as measures of regional production of new knowledge显示文摘 | Zoltan J Acs Luc Anselin Attila Varga | 2002 | Research Policy2002，，7： | 1 |
| 9 | Plasma cystatipment of cornary heart disease:The PRIME Study显示文摘 | Luc G Bard J M Lesuer C | | 0，，2： | 1 |
| 10 | Credit scoring using the hybrid neural discriminant technique显示文摘 | Leea T S Chiub C C Luc C J | 2002 | Expert Systems with Applications2002，，23： | 1 |
| 11 | Plant parasitic nematodes in sub-tropical and tropical agriculture 显示文摘 | Luc M Sikora R A Bridge J | 1990 | CAB International1990，，： | 1 |
| 12 | Plant parasitic nematodes in subtropical and tropical agriculture显示文摘 | Luc M Sikoro R A Bridge J | 1990 | UK: CAB International1990，，： | 1 |
| 13 | C-reactive protein, interleukin-6 and fibrinogen as predictors of coronary heart disease:the PRIME study 显示文摘 | Luc G Bard J M Juhan-Vague I | 2003 | Arterioscler Thromb Vasc Biol2003，23，7： | 1 |
| 14 | Effects of in- stdin-like growth factor 1 in preventing acute coronary syn- dromes: The PRIME study显示文摘 | J B RUIDAVVEIS G LUC E MACH | 2011 | Athemaclero6is2011，218，2： | 1 |
| 15 | Poly ( I : C) in- duces controlled release of IL-363, from keratinocytes inthe absence of cell death显示文摘 | Rana AA Lucs AV DeVoti J | 2015 | Immunol Res2015，63，13： | 1 |
| 16 | Contribution of novel biomarkers to incident stable angina and acute coronary syndrome:the PRIME Study显示文摘 | Empana J P Canoui-Poitrine F Luc G | 2008 | Eur Heart J2008，29，16： | 1 |
| 17 | Interleukin-1 g and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction(PRIME)显示文摘 | Blankenberg S Luc G Ducimetiere P Arveiler D Ferrieres J Amouyel P | 2003 | Circulation2003，108，： | 1 |
| 18 | Contributions of depressivemood and circulating inflammatory markers to coronary heartdisease in healthy European:The prospective epidemiological studyof myocardial infarction(PRIME)显示文摘 | Empana J P Sykes D H Luc G | 2005 | Circulation2005，111，7： | 1 |
| 19 | Bread, beer and wine: Saccharomyces cerevisiae Diversity reflects human history显示文摘 | Legras J luc Merdinoglu D Cornuet J marie | 2007 | Molecular Ecology2007，16，10： | 1 |
| 20 | Plasma cystatin-C and development of coronary heart disease: the PRIME Study显示文摘 | Luc G Bard J Lesueur C | 2006 | Atherosclerosis2006，185，2： | 1 |
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