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| 1 | Exogenous sphingomyelinase causes impaired intestinal epithelial barrier function显示文摘AIM: To test the hypothesis that hydrolysis of sphingomyelin to ceramide changes the composition of tight junctions (TJs) with increasing permeability of the intestinal epithelium. METHODS: Monolayers of Caco-2 cells were used as an in vitro model for the intestinal barrier. Permeability was determined by quantifi cation of transepithelialflux and transepithelial resistance. Sphingolipid-rich membrane microdomains were isolated by a discontinuous sucrose gradient and characterized by Western-blot. Lipid content of microdomains was analysed by tandem mass spectrometry. Ceramide was subcellularly localized by immunofluorescent staining.RESULTS: Exogenous sphingomyelinase increased transepithelial permeability and decreased transepithelial resistance at concentrations as low as 0.01 U/mL. Lipid analysis showed rapid accumulation of ceramide in the membrane fractions containing occludin and claudin-4, representing TJs. In these fractions we observed a concomitant decrease of sphingomyelin and cholesterol with increasing concentrations of ceramide. Immunofluorescent staining confirmed clustering of ceramide at the sites of cell-cell contacts. Neutralization of surface ceramide prevented the permeability-increase induced by platelet activating factor. CONCLUSION: Our findings indicate that changes in lipid composition of TJs impair epithelial barrier functions. Generation of ceramide by sphingomyelinases might contribute to disturbed barrier function seen in diseases such as inflammatory, infectious, toxic or radiogenic bowel disease. | Jürgen Bock Gerhard Liebisch Joachim Schweimer Gerd Schmitz Gerhard Rogler | 2007 | World Journal of Gastroenterology2007，13，39： | 11 |
| 2 | Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inlammatory bowel disease显示文摘AIM:To determine free and conjugated serum bile acid (BA) levels in in? ammatory bowel disease (IBD) subgroups with defi ned clinical manifestations.METHODS: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy controls by liquid chromatography coupled to electrospray ionization tandem mass spectrometry.RESULTS: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the secondary BA lithocholic acid (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis (UC), while most other serum BA species were decreased significantly. Total BA, total BA conjugate, and total BA glycoconjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as significantly increased as the secondary BAs LCA, ursodeoxycholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode-oxycholic acid, were increased significantly compared to controls and patients without surgical interventions.CONCLUSION: Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diagnostic characterization and differentiation of IBD subgroups with defined clinical manifestations. | Carsten Gnewuch Gerhard Liebisch Thomas Langmann Benjamin Dieplinger Thomas Mueller Meinhard Haltmayer Hans Dieplinger Alexandra Zahn Wolfgang Stremmel Gerhard Rogler Gerd Schmitz | 2009 | World Journal of Gastroenterology2009，15，25： | 4 |
| 3 | Lithocholic acid induction of the FGF19 promoter in intestinal cells is mediated by PXR显示文摘AIM: To study the effect of the toxic secondary bile acid lithocholic acid (LCA) on the expression of fibroblast growth factor 19 (FGF19) in intestinal cells and to characterize the pregnane-X-receptor (PXR) response of the FGF19 promoter region. METHODS: The intestinal cell line LS174T was stimulated with various concentrations of chenodeoxy-cholic acid and lithocholic acid for several time points. FGF19 mRNA levels were determined with quantitative realtime RT-PCR. FGF19 deletion promoter constructs were generated and the LCA response was analzyed in reporter assays. Co-transfections with PXR and RXR were carried out to study FGF19 regulation by these factors. RESULTS: LCA and CDCA strongly up-regulate FGF19 mRNA expression in LS174T cells in a time and dose dependent manner. Using reporter gene assays with several deletion constructs we found that the LCA responsive element in the human FGF19 promoter maps to the proximal regulatory region containing two poten-tial binding sites for PXR. Overexpression of PXR and its dimerization partner retinoid X receptor (RXR) and stimulation with LCA or the potent PXR ligand rifampicin leads to a signifi cant induction of FGF19 promoter activ-ity in intestinal cells. CONCLUSION: LCA induced feedback inhibition of bile acid synthesis in the liver is likely to be regulated by PXR inducing intestinal FGF19 expression. | Wolfgang Wistuba Carsten Gnewuch Gerhard Liebisch Gerd Schmitz Thomas Langmann | 2007 | World Journal of Gastroenterology2007，13，31： | 4 |
| 4 | Comprehensive evaluation of the metabolic effects of insect meal from Tenebrio molitor L.in growing pigs by transcriptomics, metabolomics and lipidomics显示文摘Background:The hypothesis was tested that insect meal(IM)as protein source influences intermediary metabolism of growing pigs.To test this,30 male,5-week-old crossbred pigs were randomly assigned to 3 groups of 10 pigs each with similar body weights(BW)and fed isonitrogenous diets either without(CON)or with 5%IM(IM5)or 10%IM(IM10)from Tenebrio molitor L.for 4 weeks and key metabolic tissues(liver,muscle,plasma)were analyzed using omics-techniques.Results:Most performance parameters did not differ across the groups,whereas ileal digestibilities of most amino acids were 6.7 to 15.6%-units lower in IM10 than in CON(P<0.05).Transcriptomics of liver and skeletal muscle revealed a total of 166 and 198,respectively,transcripts differentially expressed between IM10 and CON(P<0.05).Plasma metabolomics revealed higher concentrations of alanine,citrulline,glutamate,proline,serine,tyrosine and valine and a lower concentration of asparagine in IM10 than in CON(P<0.05).Only one out of fourteen quantifiable amino acid metabolites,namely methionine sulfoxide(MetS),in plasma was elevated by 45%and 71%in IM5 and IM10,respectively,compared to CON(P<0.05).Plasma concentrations of both,major carnitine/acylcarnitine species and bile acids were not different across groups.Lipidomics of liver and plasma demonstrated no differences in the concentrations of triacylglycerols,cholesterol and the main phospholipids,lysophospholipids and sphingolipids between groups.The percentages of all individual phosphatidylcholine(PC)and phosphatidylethanolamine(PE)species in the liver showed no differences between groups,except those with 6 double bonds(PC 38:6,PC 40:6,PE 38:6,PE 40:6),which were markedly lower in IM10 than in CON(P<0.05).In line with this,the percentage of C22:6n-3 in hepatic total lipids was lower in IM10 than in the other groups(P<0.05).Conclusions:Comprehensive analyzes of the transcriptome,lipidome and metabolome of key metabolic tissues indicate that partial or complete replacement of a conventional protein source by IM in the diet has only a weak impact on the intermediary metabolism of growing pigs.Thus,it is concluded that IM from Tenebrio molitor L.can be used as a dietary source of protein in pigs without causing adverse effects on metabolism. | Sandra Meyer Denise K.Gessner Maria S.Braune Theresa Friedhoff Erika Most Marcus Höring Gerhard Liebisch Holger Zorn Klaus Eder Robert Ringseis | 2020 | Journal of Animal Science and Biotechnology2020，11，2： | 4 |
| 5 | The VP1 unique region of parvovirus B19 and its constituent phospholipase A2- like activity显示文摘 | Dorsch S Liebisch G Kaufmann B | 2002 | J Virol2002，76，4： | 1 |
| 6 | Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma显示文摘 | KAISER M MIETH M LIEBISCH P | 2008 | Eur J Haematol2008，80，6： | 1 |
| 7 | High-throughput analysis of sphingosine1-phosphate,sphinganine1-phos-phate,and lysophosphatidic acid in plasma samples by liquid chromatography-tandem mass spectrometry显示文摘 | Scherer M Schmitz G Liebisch G | 2009 | Clin Chem2009，55，6： | 1 |
| 8 | Velcade,intravenous cyclophosphamide and dexamethasone induction for previously untreated multiple myeloma (German DSMM Xia trial)显示文摘 | Einsele H Liebisch P Langer C | 2009 | {H}Blood2009，，22： | 1 |
| 9 | Ursodeoxy- cholyl lysophosphatidyl- ethanolamide inhibits lipoapoptosis by shifting fatty acid pools toward monosaturated and polyun- saturated fatty acids in mouse hepatocytes显示文摘 | CHAMULITRAT W LIEBISCH G XU W | 2013 | Mol Pharma- col2013，84，5： | 1 |
| 10 | Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma显示文摘 | Kaiser M Mieth M Liebisch P | 2008 | Eur J Haematol2008，80，6： | 1 |
| 11 | Serum con-centrations of DKK-1 correlate with the extent ofbone disease in patients with multiple myeloma显示文摘 | Kaiser M Mieth M Liebisch P | 2008 | Eur J Haematol2008，80，6： | 1 |
| 12 | Light-chain escape-multiple myeloma-an escape phenomenon from plateau phase:report of the largest patient series using LC-monitoring显示文摘 | KUHNEMUND A LIEBISCH P BAUCHMULLER K | 2009 | J Cancer Res Clin Oncol2009，135，： | 1 |
| 13 | ' Light - chain escape - multiple myeloma' - an escape phenomenon from plateau phase: report of the largest patient series using LC - monitoring 显示文摘 | Ktihnemund A Liebisch P Bauchmtiller K | 2009 | J Cancer Res Clin Oncol2009，135，3： | 1 |
| 14 | Diagnostic utility of the B-cell lineage markers CD20,CD79α,PAX5,and CD19 in paraffin-embedded tissues from lymphoid neoplasms显示文摘 | Adams H Liebisch P Schmid P | 2009 | Appl Immunohistochem Mol Morphol2009，17，： | 1 |
| 15 | Molecular characterization of Salmonella enterica subsp, enterica serovar choleraesuis field isolates and differentiation from homologous live vaccine strains suisaloral and SC-54显示文摘 | Weide-Botjes M Liebisch B Schwarz S | 1996 | J Clin Microbiol1996，34，10： | 1 |
| 16 | Changes in HDL-associated apolipoproteins relate to mortality in human sepsis and correlate to monocyte and platelet activation显示文摘 | Barlage S Gnewuch C Liebisch G | 2009 | Intensive Care Med2009，35，11： | 1 |
| 17 | Changes in HDL-assoeiated apolipoproteins relate to mortality in human sepsis and correlate to monocyte and platelet activation 显示文摘 | Barlage S Gnewueh C Liebisch G | 2009 | Intensive Care Med2009，35，11： | 1 |
| 18 | High-throughput analysis of sphingosine 1-phosphate, sphinganine 1 -phosphate, arid lysophosphatidic acid in plasma samples by liquid chromatography-tandem mass spectrometry显示文摘 | Scherer M Sehmitz G Liebisch G | 2009 | Clin Chem2009，55，6： | 1 |
| 19 | The VP1 unique region of parvovirus B19 and its constituent phospholipase A2-like activity显示文摘 | DORSCH S LIEBISCH G KAUFMANN B | 2002 | Virol2002，76，： | 1 |
| 20 | Fatal neonatal respiratory failure in an infant with congenital hypothyroidism due to haploinsufficiency of the NKX2-1 gene: alteration of pulmonary surfactant homeostasis 显示文摘 | Kleinlein B Griese M Liebisch G | 2011 | Arch Dis Child Fetal Neonatal Ed2011，96，6： | 1 |
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