Search results for "BLAST"
showing 10 items of 2136 documents
Quaking and miR-155 interactions in inflammation and leukemogenesis.
2015
Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas …
Evolving therapies for liver fibrosis
2013
Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for li…
Targeted therapy of liver fibrosis/cirrhosis and its complications.
2011
Department of Pharmacokinetics, Toxicology, and Targeting, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA; Division of Molecular and Translational Medicine, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany
Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice
2006
Background/Aims In hepatic fibrogenesis, stellate cells are activated leading to production and deposition of extracellular matrix. To clarify the role of PDGF-B in liver fibrogenesis, we overexpressed PDGF-B in the liver of transgenic mice. Methods Transgenic mice for the conditional overexpression of PDGF-B in the liver under control of an albumin promoter were generated utilising the Cre/loxP system. Constitutive PDGF-B expression was achieved after breeding with mice expressing Cre-recombinase under actin promoter control. Tamoxifen inducible expression was achieved after breeding with mice expressing Cre under transthyretin receptor promoter control. Levels of fibrosis were assessed an…
Fibroblast Growth Factor 21 Limits Lipotoxicity by Promoting Hepatic Fatty Acid Activation in Mice on Methionine and Choline-Deficient Diets
2014
Background & Aims Nonalcoholic fatty liver disease is a common consequence of human and rodent obesity. Disruptions in lipid metabolism lead to accumulation of triglycerides and fatty acids, which can promote inflammation and fibrosis and lead to nonalcoholic steatohepatitis. Circulating levels of fibroblast growth factor (FGF)21 increase in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis; therefore, we assessed the role of FGF21 in the progression of murine fatty liver disease, independent of obesity, caused by methionine and choline deficiency. Methods C57BL/6 wild-type and FGF21-knockout (FGF21-KO) mice were placed on methionine- and choline-deficient (MCD)…
NR1H4 rs35724 G>C variant modulates liver damage in nonalcoholic fatty liver disease
2021
Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G>C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n = 124). Results: The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic conf…
Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.
2012
A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC…
Physico-chemical evolution of low-pH cements : influence of the temperature and the retention mechanisme of alkalins
2010
Because of their high alkalinity, Portland cement (OPC)-based materials may have deleterious effects in an underground waste repository. A solution would be to use low-alkalinity cements (also referred as low-pH cements) generating interstitial solutions with a reduced pH (11 instead of 13.5 for OPC), and thus showing an improved chemical compatibility with the repository environment. In this work, the investigated formulations were based on binary (OPC / silica fume) or ternary (OPC / silica fume / slag or fly ash) blends, with high substitution levels of CEM I (from 30% to 80%). This research project met two main objectives: (i) study the chemical evolution of low-pH cements at 50°C or 80…
DPP-4 is overexpressed in lung tissue from idiopathic pulmonary patients and activates lung fibroblasts
2020
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible form of fibrotic interstitial lung disease, characterized by uncontrolled fibroblast invasion. Dipeptidyl peptidase-4 (DPP-4)/ glucagon-like peptide 1 (GLP-1) system is involved in multiple effects, including cardiac, liver or kidney fibrosis. However, its implication in IPF has not been described. Objective: To analyse the implication of DPP4/GLP1 system in IPF. Methods: Protein expression of DPP4, GLP-1 and GLP-1 receptor was analyzed in lung tissues from 7 IPF patients. TGFβ1-induced fibroblast to myofibroblast transition (FMT), epithelial to mesenchymal transition (EMT) and mesothelial to mesenchymal trans…