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| 1 | Protective action of glutamine in rats with severe acute liver failure显示文摘BACKGROUND Severe acute liver failure(SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function.Thioacetamide(TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2(Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress.AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκBmediated inflammation in rats with TAA-induced IHAG.METHODS Male Wistar rats(n = 28) were divided into four groups: control,control+glutamine, TAA, and TAA + glutamine. Two TAA doses(400 mg/kg)were administered intraperitoneally, 8 h apart. Glutamine(25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances(TBARS), catalase(CAT), glutathione peroxidase(GPx), glutathione S-transferase(GST), glutathione(GSH), Nrf2, Kelch-like ECH-associated protein 1(Keap1),NADPH quinone oxidoreductase1(NQO1), superoxide dismutase(SOD)] and inflammatory process.RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatoryinfiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS(P < 0.001), GSH(P < 0.01), IL-1β, IL6, and TNFα levels(P <0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP(P <0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group(P<0.01, P <0.01, and P <0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2(P < 0.05), NQO1, and SOD(P < 0.01), as well as levels of IL-10(P <0.001), while decreasing expression of Keap1, TLR4, NFκB(P < 0.001), COX-2 and iNOS,(P < 0.01), and reducing NO_2 and NO_3 levels(P < 0.05).CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway,thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation. | Elizangela G Schemitt Renata M Hartmann Josieli R Colares Francielli Licks Jéferson O Salvi Cláudio A Marroni Norma P Marroni | 2019 | World Journal of Hepatology2019，11，3： | 5 |
| 2 | Wnt signaling and Loxl2 promote aggressive osteosarcoma显示文摘Osteosarcoma(OS)is the most frequent primary malignant bone tumor in urgent need of better therapies.Using genetically modified mouse models(GEMMs),we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2.c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding,and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2.Concordantly,inhibition of Wnt ligand secretion by inactivating the Wnt-less(Wls)gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS.Wls-deficient osteosarcomas proliferate less,are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers.Importantly,Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models.Finally,OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies.Congruently,a strong correlation between c-FOS,LOXL2 and WNT7B/WNT9A expression is observed in human OS samples,and c-FOS/LOXL2 co-expression correlates with OS aggressiveness and decreased patient survival.Therefore,therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric,recurrent,and metastatic OS. | Kazuhiko Matsuoka Latifa Bakiri Lena I.Wolff Markus Linder Amanda Mikels-Vigdal Ana Patiño-García Fernando Lecanda Christine Hartmann Maria Sibilia Erwin F.Wagner | 2020 | Cell Research2020，30，10： | 5 |
| 3 | Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection显示文摘AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159)polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD)and chronic hepatitis C virus (HCV) infection.METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls.Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined.RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci,serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However,no association was found between CD14 genotypes and histological staging or grading.CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease. | C Meiler M Mühlbauer M Johann A Hartmann B Schnabl N Wodarz G Schmitz J Schlmerich C Hellerbrand | 2005 | World Journal of Gastroenterology2005，11，38： | 3 |
| 4 | A comparative investigation of DNA adducts, DNA strand breaks and gene mutations induced by benzopyrene and (+/-)-anti-benzopyrene-7,8-diol 9,10-oxide in cultured human cells显示文摘 | Hanelt S Helbig R Hartmann A | 1997 | Mutat Res1997，390，12： | 2 |
| 5 | The incidence end risk factors for hypotension after spinal enesthesia induction:an analysis with automated data collection显示文摘 | Hartmann B Junger A Klasen J | 2002 | Anesth Analg2002，94，6： | 1 |
| 6 | Glutl expression is increased in hepatocellular and promotes tumorigenesis 显示文摘 | AMANN T MAEGDEFRAU U HARTMANN A | 2009 | Am J Pathol2009，174，4： | 1 |
| 7 | Use of the alkaline in vivo Comet assay for mechanistic genotoxicity investigations显示文摘 | HARTMANN A SCHUMACHER M | 2004 | Mutagenesis2004，19，1： | 1 |
| 8 | Caspase-3:A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease显示文摘 | Hartmann A Hunot S Michel PP | 2000 | PNAS2000，27，： | 1 |
| 9 | Identification d fluoroquinolone antibiotics as the main source of human genotoxieity in native hospital waatewater显示文摘 | HARTMANN A ALDER A C KOLLER T | 1998 | Environmental Toxicololgy and Chemistry1998，17，： | 1 |
| 10 | Production of auxin and other indolic and phenolic compounds by Paenibacillus polymyxa strains isolated from different proximity to plant roots显示文摘 | Lebuhn M Heulin T Hartmann A | 1997 | FEMS Microbiol Ecology1997，22，： | 1 |
| 11 | Identification of fluoroquinolone antibiotics as the main source of genotoxicity in native hospital wastewater 显示文摘 | Hartmann A Alder A Koller T | 1998 | Environmental Toxicology and Chemistry1998，17，3： | 1 |
| 12 | Recommendations for conducting the in vivo alkaline Comet assay显示文摘 | A Hartmann E Agurll C Beevers | 2003 | Mutagenesis2003，18，1： | 1 |
| 13 | Intermittent saline flushes during haemodialysis do not alleviate coagulation and clot formation in stable patients receivingreduced doses of dalteparin显示文摘 | Sagedal S Hartmann A Osnes K | 2006 | Nephrol Dial Transplant2006，21，2： | 1 |
| 14 | Rapid identi- fication of Staphylococcus aureus in blood cuhurgs by a combination of fluorescence in sitn hybridization using peptide nucleic acid probes and flow cytometry 显示文摘 | HARTMANN H STENDER H SCHAFER A | 2005 | J Clin Microbiol2005，43，9： | 1 |
| 15 | Electrophoretic and immu- noehemical study of collagens from sepia officinalis Cartilage 显示文摘 | Rigo C Hartmann D J Bairati A | 2002 | Biochimica et Biophysi Acta2002，1572，： | 1 |
| 16 | The inflammatory response in the Parkinson brain显示文摘 | Hunot S Hartmann A Hirsch EC | | 0，，： | 1 |
| 17 | A novel, self- expanding, nitinol stent in medically refractory intracranial atherosclerotic stenoses: the Wingspan study显示文摘 | Bose A Hartmann M Henkes H | 2007 | Stroke2007，38，5： | 1 |
| 18 | S3 Guideline: Sedation for gastrointestinal endoscopy 2008显示文摘 | A. Riphaus T. Wehrmann B. Weber J. Arnold U. Beilenhoff H. Bitter S. von Delius D. Domagk A. Ehlers S. Faiss D. Hartmann W. Heinrichs M.-L. Hermans C. Hofmann S. In der Smitten M. Jung G. K?hler M. Kraus J. Martin A. Meining J. Radke T. R?sch H. Seifert A | 2009 | Endoscopy2009，，09： | 1 |
| 19 | Caspase-3:A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson’s disease显示文摘 | Hartmann A Hunot S Michel PP | 2000 | Proc Natl Acad Sci U S A2000，97，6： | 1 |
| 20 | A Hydro-code Material Model for Concrete显示文摘 | Hartmann T Pietzsch A Gebbeken N | 2010 | International Journal of Protective Structures2010，1，4： | 1 |
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