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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 | Selective dorsal rhizotomy in cerebral palsy to improve functional abilities:evaluation of criteria for selection显示文摘 | PETRA E M JEROEN V WILLEM J R | 2005 | Childs Nerv Syst2005，21，6： | 1 |
| 3 | Abnormal Cervical Appearance: What to Do, When to Worry?显示文摘 | Casey Petra M Long Margaret E Marnach Mary L | 2011 | Mayo Clinic Proceedings2011，，2： | 1 |
| 4 | Methylene blue selectively stains intestinal metaplasia in Barrett' s esophagus显示文摘 | Canto M I Setrakian S Petras R E | 1996 | Gastrointost Enclosc1996，44，1： | 1 |
| 5 | ReverseELISA for IgG and IgM antibodies to detect Lassa vi-rus infections in Africa显示文摘 | Petra E Corinna T B Drosten C | 2006 | J Clin Virol2006，37，： | 1 |
| 6 | Electron tomography for heterogeneous catalysts and related nanostructured materials 显示文摘 | HEINER F PETRA E ARIE J | 2009 | Chemical Reviews2009，109，5： | 1 |
| 7 | Gut-mi- crobiota-brain axis and Its effect on neuropsychiatric disorders with suspected immune dysregulation显示文摘 | Petra AI Panagiotidou S Hatziagelaki E | 2015 | Clin Ther2015，37，5： | 1 |
| 8 | Binding to the high-affinity M-type receptor for secreted phospholipases A 2 is not obligatory for the presynaptic neurotoxicity of ammodytoxin A显示文摘 | Petra Prijatelj Nina Vardjan Edward G. Rowan Igor Kri?aj Jo?e Punger?ar | 2006 | Biochimie2006，，10： | 1 |
| 9 | 显示文摘 | Maria H Petra E | 2001 | Clin Endocrinol2001，54，： | 1 |
| 10 | X-ray powder diffraction quantitative analysis performed in situ at high temperature: Application to the determination of NiO in ceramic pigments 显示文摘 | GUALTIERI A F MAZZUCATO E VENTURELLI P VIANI A ZANNINI P PETRAS L | 1999 | Journal of Applied Crystallography1999，32，： | 1 |
| 11 | The C-terminal and β-wing regions of ammodytoxin A, a neurotoxic phospholipase A 2 from Vipera ammodytes ammodytes , are critical for binding to factor Xa and for anticoagulant effect显示文摘 | Petra Prijatelj Marlène Charnay Gabriela Ivanovski Zala Jenko Jo?e Punger?ar Igor Kri?aj Grazyna Faure | 2005 | Biochimie2005，，1： | 1 |
| 12 | Zeolite Y crystals with trimodal porosity as ideal hydrocrac- king catalysts 显示文摘 | de Jong Krijn P Heiner Friedrich de Jongh Petra E | 2010 | Angewandte Chemie International Edition2010，49，10： | 1 |
| 13 | Overexpression of an endogenous thionin enhances resistance of Arabidopsis against Fusaritvn oxysporum 显示文摘 | PETRA E KLAUS A HOLGER B | 1997 | The Plant Cell1997，，9： | 1 |
| 14 | Electron tomography for heterogeneous catalysts and related nanostructuredmaterials 显示文摘 | Heiner Friedrich Petra E de Jongh Arie J Verkleij | 2009 | Chem Rev2009，109，5： | 1 |
| 15 | Periodic Mesoporous organosilicas consisting of 3D hexagonally ordered interconnected globular pores显示文摘 | Carl V Heiner F Petra E | 2009 | J Phys Chem2009，113，14： | 1 |
| 16 | Determination of Sulfonylurea Herbicides in Water and Food Samples Using Sol-gel Glass-based Immunoaffinity Extraction and Liquid Chromatography-ultraviolet/Diode Array Detection or Liquid Chromatography-tandem Mass Spectrometry显示文摘 | PETRA D SEBASTIAN E HEINRICH J | 2006 | Agric Food Chem2006，54，： | 1 |
| 17 | Sinking Peat Bogs: Environmental Change in Holland显示文摘 | Van Dam Petra J E M | 2001 | Environmental History2001，，： | 1 |
| 18 | Cardiac anomalies in individuals with the 18q deletion syndrome; report of a child with Ebstein anomaly and review of the literature显示文摘 | Dorothée C. van Trier Ilse Feenstra Petra Bot Nicole de Leeuw Jos M.Th. Draaisma | 2013 | European Journal of Medical Genetics2013，，： | 1 |
| 19 | Serum hepcidin levels are associated with serum trigly-cerides and interleukin-6 concentrationsin patients with end- stage renal disease 显示文摘 | Samouilidou E Pantelias K Petras D | 2014 | Ther Apher Dial2014，18，3： | 1 |
| 20 | Medical image matching-A review with classification显示文摘 | PETRA A VAN D E EVERT-JAN D VIERGEVER M A | 1993 | IEEE Eng Med Biol1993，1，： | 1 |
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