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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 | 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 |
| 3 | Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial显示文摘 | Craig S Anderson Yining Huang Ji Guang Wang Hisatomi Arima Bruce Neal Bin Peng Emma Heeley Christian Skulina Mark W Parsons Jong Sung Kim Qing Ling Tao Yue Chun Li Jian Dong Jiang Li Wen Tai Jin Li Zhang En Xu Yan Cheng Stephane Heritier Lewis B Morgenste | 2008 | Lancet Neurology2008，，5： | 4 |
| 4 | Replacement value for DL-methionine in male broiler chicks 显示文摘 | Schutte J B Jong J Smink W | 1997 | Poult Sci1997，76，： | 1 |
| 5 | Reconstruction for renal artery aneurysm: Operative techniques and long-term results显示文摘 | Jong A H Young K W | 2003 | J Vas Surg2003，37，2： | 1 |
| 6 | Monitoring cerebral oxygenation:experimental syudies and preliminary clinical results of continuous monitoring of cerebral fluid and brain tissue oxygen tension显示文摘 | Mass A Fleckenstein W Jong A | 1993 | Acta Neurochir1993，59，： | 1 |
| 7 | Catalytic growth of macroscopic carbon nanofiber bodies with high bulk density and high mechanical strength显示文摘 | Lee M K van der Dillen A J van Geus J W Jong K P de Bitter J H | 2006 | Carbon2006，44，： | 1 |
| 8 | Controlled release of platelet-derived growth factor using ethylene vinyl acetate copolymer(EVAc)coated on stainless-steel wires显示文摘 | Walsh W R Kim H D Jong Y S | 1995 | Biomaterials1995，16，17： | 1 |
| 9 | XPS studies on the electronic structure of bonding between solid and solutes:Adsorption of arsenate,chromate,phosphate,Pb2+,and Zn2+ ions on amorphous black ferric oxyhydroxide显示文摘 | DING M JONG B H W S DE ROOSENDAAL S J | 2000 | Geochimica et Cosmochimica Acta2000，64，6： | 1 |
| 10 | Using genetic algorithms for concept learning显示文摘 | DE JONG K A SPEARS W M GORDON F D | 1993 | Machine Learning1993，13，： | 1 |
| 11 | Study on macrophage ac- tivation and structural characteristics of purified polysaccharide from the liquid culture broth of Cordyceps militaris显示文摘 | JONG S L JEONG S K DONG P W | 2010 | Carbohydrate Pol- ymers2010，，82： | 1 |
| 12 | Electric-field and temperature dependence of the hole mobility in poly (p-phenylene vinylene)显示文摘 | Blom P W M De Jong M J M Van Munster M G | 1997 | Physical Review B1997，55，2： | 1 |
| 13 | Dynamic mold surface temperature control using induction heating and its effects on the surface appearance of weld line 显示文摘 | CHEN S C JONG W R CHANG J A | 2006 | Journal of Applied Polymer Science2006，101，2： | 1 |
| 14 | Enterovirus protein 2B po(u)res out the calcium:a viral strategy to survive?显示文摘 | van Kuppeveld F J M de Jong A S Melchers W J G | 2005 | Trends in Microbiology2005，13，2： | 1 |
| 15 | Colloids and colloid-facilitated transport of contaminants in soils 显示文摘 | De Jonge L W Kjaegaard C Moldrup P | 2004 | Vadose Zone Journal2004，3，2： | 1 |
| 16 | Trapdoor security in a search- able public-key encryption scheme with a designated tester显示文摘 | Hyun S R Jong H P Susilo W | 2010 | Jour- nal of Systems and Software2010，83，5： | 1 |
| 17 | Biomass combustion in fluidized bed boilers:potential problems and remedies显示文摘 | Khan A A Jong W Jansens P J | 2009 | Fuel Processing Technology2009，90，1： | 1 |
| 18 | Dynamic mold surface temperature control using induction and heater heating combined with coolant cooling显示文摘 | CHEN S C JONG W R CHANG J A CHANG Y J | 2006 | International Polymer Processing2006，21，5： | 1 |
| 19 | Peptide transport by the multidrug resistance protein MRP1 显示文摘 | de Jong M C Slootstra J W Scheffer G L | 2001 | Cancer Res2001，61，6： | 1 |
| 20 | Modeling gamma radiation dose in dwellings due to building materials显示文摘 | De Jong P Van Dijk W | 2008 | Health Phys2008，94，1： | 1 |
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