Search results for "CASS"
showing 10 items of 433 documents
PI3K inhibition reduces murine and human liver fibrogenesis in precisioncut liver slices
2019
Background: Liver fibrosis results from continuous inflammation and injury. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Omipalisib is a selective inhibitor of the PI3K/mTOR pathway that controls nutrient metabolism, growth and proliferation. It has shown antifibrotic properties in vitro. While clinical trials for idiopathic pulmonary fibrosis have been initiated, an in-depth preclinical evaluation is lacking. We evaluated omipalisib's effects on fibrogenesis using the ex vivo model of murine and human precision-cut tissue slices (PCTS).Methods: Murine and human liver and jejunum PCTS were incubated with omipalisib up to 10 mu M for 48 h. PI3K pathway act…
The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM
2018
The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aβ through endothelial cells. Late-onset AD risk fact…
LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis
2016
International audience; Blastic plasmacytoid dendritic cell (PDC) neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from PDCs. No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared with those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDCs. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN …
Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses
2016
Article
Nonacidic Farnesoid X Receptor Modulators.
2017
As a cellular bile acid sensor, farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and glucose homeostasis, and liver protection. Clinical results have validated FXR as therapeutic target in hepatic and metabolic diseases. To date, potent FXR agonists share a negatively ionizable function that might compromise their pharmacokinetic distribution and behavior. Here we report the development and characterization of a high-affinity FXR modulator not comprising an acidic residue.
The Generalist Inside the Specialist: Gut Bacterial Communities of Two Insect Species Feeding on Toxic Plants Are Dominated by Enterococcus sp.
2016
Some specialist insects feed on plants rich in secondary compounds, which pose a major selective pressure on both the phytophagous and the gut microbiota. However, microbial communities of toxic plant feeders are still poorly characterized. Here, we show the bacterial communities of the gut of two specialized Lepidoptera, Hyles euphorbiae and Brithys crini, which exclusively feed on latex-rich Euphorbia sp. and alkaloid-rich Pancratium maritimum, respectively. A metagenomic analysis based on high-throughput sequencing of the 16S rRNA gene revealed that the gut microbiota of both insects is dominated by the phylum Firmicutes, and especially by the common gut inhabitant Enterococcus sp. Staph…
Diverse relations between ABC transporters and lipids: An overview.
2016
It was first discovered in 1992 that P-glycoprotein (Pgp, ABCB1), an ATP binding cassette (ABC) transporter, can transport phospholipids such as phosphatidylcholine, -ethanolamine and -serine as well as glucosylceramide and glycosphingolipids. Subsequently, many other ABC transporters were identified to act as lipid transporters. For substrate transport by ABC transporters, typically a classic, alternating access model with an ATP-dependent conformational switch between a high and a low affinity substrate binding site is evoked. Transport of small hydrophilic substrates can easily be imagined this way, as the molecule can in principle enter and exit the transporter in the same orientation. …
The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates
2017
16 páginas, 7 figuras, 2 tablas
Efficiency of Target Larvicides Is Conditioned by ABC-Mediated Transport in the Zoonotic Nematode Anisakis pegreffii
2018
Anisakiasis is among the most significant emerging foodborne parasitoses contracted through consumption of thermally unprocessed seafood harboring infective Anisakis species larvae. The efficacy of the currently applied anthelminthic therapy in humans and in model organisms has not proven sufficient, so alternative solutions employing natural compounds combined with chemical inhibitors should be explored. By testing toxicity of the natural monoterpenes nerolidol and farnesol and the conventional anthelminthics abamectin and levamisole in the presence/absence of MK-571 and Valspodar, which inhibit the ABC transporter proteins multidrug resistance protein (MRP-like) and P-glycoprotein (P-gp),…
Positive impact of ABCB1 polymorphisms in overall survival and complete remission in acute myeloid leukemia: a systematic review and meta-analysis
2015
Positive impact of ABCB1 polymorphisms in overall survival and complete remission in acute myeloid leukemia: a systematic review and meta-analysis