Search results for "script"

Loss of Nrf2 in bone marrow-derived macrophages impairs antigen-driven CD8+ T cell function by limiting GSH and Cys availability

2015

NF-E2-related factor 2 (Nrf2), known to protect against reactive oxygen species, has recently been reported to resolve acute inflammatory responses in activated macrophages. Consequently, disruption of Nrf2 promotes a proinflammatory macrophage phenotype. In the current study, we addressed the impact of this macrophage phenotype on CD8(+) T cell activation by using an antigen-driven coculture model consisting of Nrf2(-/-) and Nrf2(+/+) bone marrow-derived macrophages (BMDMΦ) and transgenic OT-1 CD8(+) T cells. OT-1 CD8(+) T cells encode a T cell receptor that specifically recognizes MHC class I-presented ovalbumin OVA(257-264) peptide, thereby causing a downstream T cell activation. Interes…

Increased immunosuppressive function of CD4(+)CD25(+)Foxp3(+)GITR+ T regulatory cells from NFATc2((-/-)) mice controls allergen-induced experimental …

2012

The expansion of effector T cells is tightly controlled by transcription factors like nuclear factor of activated T cells (NFAT) family members that mediate early intracellular responses to T cell receptor-mediated signals. In this study we show that, after allergen challenge, NFATc2((-/-)) mice had augmented number of functionally intact CD4(+)CD25(++)GITR(++) T regulatory (T regs) cells in the lung. Anti-GITR antibody treatment inhibited T regulatory cell function and enhanced the number of activated lung CD4(+) T cells associated with increased IL-2 and pSTAT-5 in the airways of NFATc2((-/-)) mice in experimental allergic asthma. This agonistic treatment led to increased inflammation in …

2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors.

2004

Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a substituted pyrimidin-2-yl ring at the N-3 were synthesised and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of human immunodeficiency virus type-1 (HIV-1) replication at 10–40 nM concentrations with minimal cytotoxicity. Structure–activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro anti-HIV activity of this class of potent antiretroviral agents. The compounds had significantly reduced activity against the characteristic N…

Synergistic targeting of FLT3 mutations in AML via combined menin-MLL and FLT3 inhibition

2020

Abstract The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. In this study, transcriptional profiling after pharmacological inhibition of the menin-MLL complex revealed specific changes in gene expression, with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being the most pronounced. Combining menin-MLL inhibition with specific small-molecule kinase inhibitors…

Sodium chloride is an ionic checkpoint for human Th2 cell responses and shapes the atopic skin microenvironment

2018

One sentence summarySodium is an ionic checkpoint for the induction and amplification of human Th2 cell responses and shapes the atopic skin microenvironment, where it could serve as a novel therapeutic target for Th2 mediated diseases.AbstractThere has been a strong increase in the incidence of allergic diseases over the last 50 years. Environmental factors most likely account for this phenomenon. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation, which is characteristic of atopic diseases, remains unclear. It has previously been reported that dietary sodium chloride promotes the polarization of Th17 cells with implications for aut…

Problematic discharge from hospital for patients prescribed opioids for cancer pain.

2005

A narratological approach to content selection in audio description: towards a strategy for the description of narratological time

2012

As more and more countries start to provide audio description services for a growing range of products and events, research into this new discipline is growing and diversifying as well. Two questions that seem to be at the heart of much of this research focus on what should be described and how this should be done, in other words on content selection and formulation of the description. The present article looks at the first of these two questions and approaches it from a narratological point of view. After a general discussion of the use of narratology for audio description, the focus will shift to one particular constituent of narrative, namely time. The different temporal aspects will be …

Extraction and fusion of spectral parameters for face recognition

2011

This is the copy of journal's version originally published in Proc. SPIE 7877: http://spie.org/x10.xml?WT.svl=tn7. Reprinted with permission of SPIE. Many methods have been developed in image processing for face recognition, especially in recent years with the increase of biometric technologies. However, most of these techniques are used on grayscale images acquired in the visible range of the electromagnetic spectrum. The aims of our study are to improve existing tools and to develop new methods for face recognition. The techniques used take advantage of the different spectral ranges, the visible, optical infrared and thermal infrared, by either combining them or analyzing them separately …

Redox signaling in acute pancreatitis

2015

Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On th…

The role of oxidative stress in pro-inflammatory activation of human endothelial cells on Ti6Al4V alloy

2013

Inflammation is an important step in the early phase of tissue regeneration around an implanted metallic orthopaedic device. However, prolonged inflammation, which can be induced by metallic corrosion products, can lead to aseptic loosening and implant failure. Cells in peri-implant tissue as well as metal corrosion can induce reactive oxygen species (ROS) formation, thus contributing to an oxidative microenvironment around an implant. Understanding cellular reactions to implant-induced oxidative stress and inflammatory activation is important to help prevent an adverse response to metallic materials. In an earlier study we have shown that endothelial cells grown on Ti6Al4V alloy are subjec…