Search results for "A1"
showing 10 items of 6089 documents
WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer
2019
Triple-negative breast cancers (TNBCs) are characterized by a poor prognosis and lack of targeted treatments, and thus, new therapeutic strategies are urgently needed. Inhibitors against programmed death-1 (PD-1)/PD-1 ligand (PD-L1) have shown significant efficacy in various solid cancers, but their activity against TNBCs remains limited. Here, we report that human TNBCs molecularly stratified for high levels of PD-L1 (PD-L1High) showed significantly enriched expression of immune and cancer stemness pathways compared with those with low PD-L1 expression (PD-L1Low). In addition, the PD-L1High cases were significantly associated with a high stemness score (SSHigh) signature. TNBC cell lines g…
Human Dental Pulp Stem Cells Exhibit Different Biological Behaviours in Response to Commercial Bleaching Products
2018
The purpose of this study was to evaluate the diffusion capacity and the biological effects of different bleaching products on human dental pulp stem cells (hDPSCs). The bleaching gel was applied for 90, 30 or 15 min to enamel/dentine discs that adapted in an artificial chamber. The diffusion of hydrogen peroxide (HP) was analysed by fluorometry and the diffusion products were applied to hDPSCs. Cell viability, cell migration and cell morphology assays were performed using the eluates of diffusion products. Finally, cell apoptosis and the expression of mesenchymal stem cell markers were analysed by flow cytometry. Statistical analysis was performed using analysis of variance and Kruskal&nda…
Identification of the integrin-binding site on coagulation factor VIIa required for proangiogenic PAR2 signaling.
2018
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease-activated receptor 2 (PAR2) that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor VIIa (FVIIa) elicits TF cytoplasmic domain-dependent proangiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin-binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1. A po…
Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell…
2020
AbstractIn human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhib…
The Influence of Hydrogen Bonding on Sphingomyelin/Colipid Interactions in Bilayer Membranes
2016
The phospholipid acyl chain composition and order, the hydrogen bonding, and properties of the phospholipid headgroup all influence cholesterol/phospholipid interactions in hydrated bilayers. In this study, we examined the influence of hydrogen bonding on sphingomyelin (SM) colipid interactions in fluid uni- and multilamellar vesicles. We have compared the properties of oleoyl or palmitoyl SM with comparable dihydro-SMs, because the hydrogen bonding properties of SM and dihydro-SM differ. The association of cholestatrienol, a fluorescent cholesterol analog, with oleoyl sphingomyelin (OSM) was significantly stronger than its association with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, …
Dual proteotoxic stress accelerates liver injury via activation of p62‐Nrf2
2021
Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and H…
On the continuous and discontinuous maximal operators
2018
Abstract In the first part of this paper we study the regularity properties of a wide class of maximal operators. These results are used to show that the spherical maximal operator is continuous W 1 , p ( R n ) ↦ W 1 , p ( R n ) , when p > n n − 1 . Other given applications include fractional maximal operators and maximal singular integrals. On the other hand, we show that the restricted Hardy–Littlewood maximal operator M λ , where the supremum is taken over the cubes with radii greater than λ > 0 , is bounded from L p ( R n ) to W 1 , p ( R n ) but discontinuous.
Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…
2019
Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…
Enrichment, isolation and biodegradation potential of psychrotolerant polychlorinated-biphenyl degrading bacteria from the Kongsfjorden (Svalbard Isl…
2016
Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), have been detected in abiotic Arctic matrices: surface sediments and seawater from coastal areas in the Kongsfjorden were collected and analyzed. Levels of PCBs varied depending on the sampling site. Total PCB concentrations were between 11.63 (site C2W) and 27.69 pg l-1 (site AW). These levels were comparable to those reported previously in lake sediments from the northern Svalbard. The occurrence and biodegradation potential of cold-adapted PCB-oxidizing bacteria in seawater and sediment along the fjord was also evaluated. After enrichment with biphenyl, 246 isolates were obtained with 45 of them that were abl…
DEBATE: Do interventions based on behavioral theory work in the real world?
2019
Abstract Background Behavioral scientists suggest that for behavior change interventions to work effectively, and deliver population-level health outcomes, they must be underpinned by behavioral theory. However, despite implementation of such interventions, population levels of both health outcomes and linked behaviors have remained relatively static. We debate the extent to which interventions based on behavioral theory work in the real world to address population health outcomes. Discussion Hagger argues there is substantive evidence supporting the efficacy and effectiveness of interventions based on behavioral theory in promoting population-level health behavior change in the ‘real world…