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| 1 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 2 | Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study显示文摘BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS. | Sabrina Berens Yuanjun Dong Nikola Fritz Jutta Walstab Mauro D'Amato Tenghao Zheng Verena Wahl Felix Boekstegers Justo Lorenzo Bermejo Cristina Martinez Stefanie Schmitteckert Egbert Clevers Felicitas Engel Annika Gauss Wolfgang Herzog Robin Spiller Miriam Goebel-Stengel Hubert Mönnikes Viola Andresen Frieling Thomas Jutta Keller Christian Pehl Christoph Stein-Thöringer Gerard Clarke Timothy G Dinan Eamonn M Quigley Gregory Sayuk Magnus Simrén Jonas Tesarz Gudrun Rappold Lukas van Oudenhove Rainer Schaefert Beate Niesler | 2022 | World Journal of Gastroenterology2022，28，21： | 2 |
| 3 | Incidental congenital coronary artery vascular fistulas in adults:Evaluation with adenosine-13N-ammonia PET-CT显示文摘AIM To assess the functionality of congenital coronary artery fistulas(CAFs) using adenosine stress ^(13)N-ammonia positron emission tomography computed tomography(PET-CT).METHODS Congenital CAFs were incidentally detected during coronary angiography(CAG) procedures in 11 adult patients(six males and five females) with a mean age of 64.3 years(range 41-81). Patients were collected from three institutes in the Netherlands. The characteristics of the fistulas(origin, pathway and termination), multiplicity of the origins and pathways of the fistulous vessels were assessed by CAG. Five patients underwent adenosine pharmacologic stress ^(13)N-ammonia PET-CT to assess myocardial perfusion and the functional behavior of the fistula. RESULTS Eleven patients with 12 CAFs, 10 unilateral and one bilateral, originating from the left anterior descending coronary artery(n = 8), right coronary artery(n = 2) and circumflex(n = 2). All fistulas were of the vascular type, terminating into either the pulmonary artery(n = 11) or coronary sinus(n = 1). The CAG delineated the characteristics of the fistula(origin, pathway and termination). Multiplicity of the origins and pathways of the fistulous vessels were common in most fistulas(8/12, 67% and 9/12, 75%, respectively). Multiplicity was common among the different fistula components(23/36, 64%). Adenosine pharmacologic stress ^(13)N-ammonia PET-CT revealed normal myocardial perfusion and ejection fraction in all but one patient, who showed a reduced ejection fraction.CONCLUSION PET-CT may be helpful for assessing the functional status of congenital CAFs in selected patients regarding clinical decision-making. Studies with a larger patient series are warranted. | Salah AM Said Aly Agool Arno HM Moons Mounir WZ Basalus Nils RL Wagenaar Rogier LG Nijhuis Jutta M Schroeder-Tanka Riemer HJA Slart | 2018 | World Journal of Cardiology2018，10，10： | 2 |
| 4 | Emerging role of caldesmon in cancer:A potential biomarker for colorectal cancer and other cancers显示文摘Colorectal cancer(CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division. Caldesmon(CaD) is an actin-binding protein encoded by the CALD1 gene as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight CaD, expressed in smooth muscle, and low-molecular weight CaD(l-CaD), expressed in nonsmooth muscle cells. According to our comprehensive review of the literature, CaD, particularly l-CaD, plays a key role in the development, metastasis, and resistance to chemoradiotherapy in colorectal, breast, and urinary bladder cancers and gliomas, among other malignancies. CaD is involved in many aspects of the carcinogenic hallmarks, including epithelial mesenchymal transition via transforming growth factor-beta signaling, angiogenesis, resistance to hormonal therapy, and immune evasion. Recent data show that CaD is expressed in tumor cells as well as in stromal cells, such as cancerassociated fibroblasts, where it modulates the tumor microenvironment to favor the tumor. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues, making these transcripts ideal targets for drug design. In this review, we will analyze these features of CaD with a focus on CRC and show how the currently available data qualify CaD as a potential candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer. | Alya R Alnuaimi Vidhya A Nair Lara J Bou Malhab Eman Abu-Gharbieh Anu Vinod Ranade Gianfranco Pintus Mohamad Hamad Hauke Busch Jutta Kirfel Rifat Hamoudi Wael M Abdel-Rahman | 2022 | World Journal of Gastrointestinal Oncology2022，14，9： | 2 |
| 5 | Newmiero RNAs from mouse and human 显示文摘 | Mariana LQ Reinhard R Jutta M | 2003 | Rna2003，9，： | 1 |
| 6 | Nuclear factor-eythroid 2-related factor 2 prevents alcohol-induced fulmlnant liver injury 显示文摘 | Jutta L Silke M JUrgen B | 2008 | Gastroenterology2008，134，4： | 1 |
| 7 | Porcine mannan-binding lectin A binds to actinobacillus snis and Hatmophilus parasuu显示文摘 | Brandon N L Jutta D H Janet I M | 2006 | Developmental and Comparative Immunology2006，30，： | 1 |
| 8 | Risk factors for functional status decline in community-living elderly people:a systematic literature review显示文摘 | Andreas E Stuck N Jutta M | | 0，，： | 1 |
| 9 | Long-term repeatability of induced sputum cells and inflammatory markersin stable, moderately severe COPD显示文摘 | Kai M Beeh M D Jutta Beier | 2003 | Chest2003，123，： | 1 |
| 10 | A development shell for cooperative problem-solving environments显示文摘 | Francois C Francois J M | | Mathematics and Compute rs in0，，： | 1 |
| 11 | Porcine mannan-binding lectin A bind to Actinobacillus suis and Haemophilus parasuis显示文摘 | Brandon N L Jutta D H Janet I M | 2006 | Developmental and comparative immunology2006，30，10： | 1 |
| 12 | Does health information matter for modifying consumption?a field experi-ment measuring the impact of risk information on fish con-sumption显示文摘 | JuTTA R STEPHAN M SANDRINE B et aL | 2009 | Review of Agricultural Economics2009，31，1： | 1 |
| 13 | The use of formaldehyde in RNA-protein cross-linking studies with ribosomal subunits from Escherichia coli显示文摘 | Klaus M(o)ller Jutta Rinke Alexander Ross | 1977 | European Journal of Biochemistry1977，76，1： | 1 |
| 14 | Method development for the determination of selected pesticides on tobacco by high-performance liquid chromatography–electrospray ionisation-tandem mass spectrometry显示文摘 | Bernhard Mayer-Helm Ludwig Hofbauer Jutta Müller | 2007 | Talanta2007，，5： | 1 |
| 15 | Catalytic Properties of 26 S and 20 S Proteasomes and Radiolabeling of MB1,LMP7,and C7 Subunits Associated with Trypsin-like and Chymotrypsin-like Activities显示文摘 | Jutta Reidlinger Angela M | 1997 | Biochemistry and Molecular Biology1997，272，40： | 1 |
| 16 | Plasma Resistin Levels and Risk of Myocardial Infarction and Ischemic Stroke显示文摘 | Cornelia Weikert Sabine Westphal Klaus Berger Jutta Dierkes Matthias M?hlig Joachim Spranger Eric B. Rimm Stefan N. Willich Heiner Boeing Tobias Pischon | 2008 | The Journal of Clinical Endocrinology & Metabolism2008，，7： | 1 |
| 17 | Synergistic killing of Streptococcus pneumoniae with the bacteriophage lytic enzyme Cpl-1 and penicillin or gentamicin depends on the level of penicillin resistance显示文摘 | Djurkovic S Loeffler Jutta M Fischetti VA | 2005 | Antimicrob Agents Chemother2005，49，： | 1 |
| 18 | Directed evolution of a bacterial α- amylase: Toward enhanced pH- performance and higher specific activity 显示文摘 | Cornelius B Jutta S Karl-Heinz M | 2003 | Protein Sci2003，，12： | 1 |
| 19 | Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase显示文摘 | Sophia P Pavlova Jutta Veits Günther M Keil | 2009 | Vaccine2009，27，： | 1 |
| 20 | Protection of chickens against H5N1 highly pathogenic avian influenza virus in- fection by live vaccination with infectious laryngotracheitis virus re- combinants expressing H5 hemagglutinin and N1 neuraminidase 显示文摘 | SOPHIA P P JUTTA V GUNTHER M K | 2009 | Vaccine2009，27，： | 1 |
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