Search results for "Press"
showing 10 items of 15058 documents
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. …
High-Pressure-Driven Reversible Dissociation of α-Synuclein Fibrils Reveals Structural Hierarchy
2017
The analysis of the α-synuclein (aS) aggregation process, which is involved in Parkinson's disease etiopathogenesis, and of the structural feature of the resulting amyloid fibrils may shed light on the relationship between the structure of aS aggregates and their toxicity. This may be considered a paradigm of the ground work needed to tackle the molecular basis of all the protein-aggregation-related diseases. With this aim, we used chemical and physical dissociation methods to explore the structural organization of wild-type aS fibrils. High pressure (in the kbar range) and alkaline pH were used to disassemble fibrils to collect information on the hierarchic pathway by which distinct β-sh…
Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer.
2016
Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcrip…
rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences
2018
Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle ce…
Bioactive triterpenes of protium heptaphyllum gum resin extract display cholesterol-lowering potential
2021
Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and…
Ursolic acid enhances stress resistance, reduces ROS accumulation and prolongs life span in C. elegans serotonin-deficient mutants.
2021
Introduction: Depression and anxiety disorders contribute to the global disease burden. Ursolic acid (UA), a natural compound present in many vegetables, fruits and medicinal plants, was tested in vivo for its effect on (1) enhancing resistance to stress and (2) its effect on life span. Methods: The compound was tested for its antioxidant activity in C. elegans. Stress resistance was tested in the heat and osmotic stress assay. Additionally, the influence on normal life span was examined. RT-PCR was used to assess possible serotonin targets. Results: UA prolonged the life span of C. elegans. Additionally, UA significantly lowered reactive oxygen species (ROS). Molecular docking studies, PCR…
Hemodynamic variations and anxiety during the surgical extraction of impacted lower third molars
2019
Background The surgical removal of an impacted third molar can cause patient anxiety. Such anxiety and the use of vasoconstrictor drugs and local anesthetics in turn can induce hemodynamic variations during the operation. A study is made of the variations in hemodynamic parameters (systolic and diastolic blood pressure and heart rate) and their correlation to patient gender and anxiety during surgical removal of an impacted lower third molar. Material and methods A prospective study was carried out in the Oral Surgery Unit of a university clinic, with the inclusion of 125 patients (mean age 24.9 years). Anesthesia was administered in the form of 4% articaine and adrenalin 1:200,000 for surg…
Exosomal Chaperones and miRNAs in Gliomagenesis: State-of-Art and Theranostics Perspectives
2018
Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their…
CitA (citrate) and DcuS (C4-dicarboxylate) sensor kinases in thermophilic Geobacillus kaustophilus and Geobacillus thermodenitrificans
2015
The thermophilic Geobacillus thermodenitrificans and Geobacillus kaustophilus are able to use citrate or C4-dicarboxylates like fumarate or succinate as the substrates for growth. The genomes of the sequenced Geobacillus strains (nine strains) each encoded a two-component system of the CitA family. The sensor kinase of G. thermodenitrificans (termed CitAGt) was able to replace CitA of Escherichia coli (CitAEc) in a heterologous complementation assay restoring expression of the CitAEc-dependent citC-lacZ reporter gene and anaerobic growth on citrate. Complementation was specific for citrate. The sensor kinase of G. kaustophilus (termed DcuSGk) was able to replace DcuSEc of E. coli. It respon…
Stem Cell-Derived, microRNA-Carrying Extracellular Vesicles: A Novel Approach to Interfering with Mesangial Cell Collagen Production in a Hyperglycae…
2016
Extracellular vesicles (EVs) that are derived from stem cells are proving to be promising therapeutic options. We herein investigate the therapeutic potential of EVs that have been derived from different stem cell sources, bone-marrow (MSC) and human liver (HLSC), on mesangial cells (MCs) exposed to hyperglycaemia. By expressing a dominant negative STAT5 construct (ΔNSTAT5) in HG-cultured MCs, we have demonstrated that miR-21 expression is under the control of STAT5, which translates into Transforming Growth Factor beta (TGFβ) expression and collagen production. A number of approaches have been used to show that both MSC- and HLSC-derived EVs protect MCs from HG-induced damage via the trans…