Search results for "I3"

Guanosine Protects Glial Cells Against 6-Hydroxydopamine Toxicity

2014

Increasing body of evidence indicates that neuron-neuroglia interaction may play a key role in determining the progression of neurodegenerative diseases including Parkinson’s disease (PD), a chronic pathological condition characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra. We have previously reported that guanosine (GUO) antagonizes MPP+-induced cytotoxicity in neuroblastoma cells and exerts neuroprotective effects against 6-hydroxydopamine (6-OHDA) and beta-amyloid-induced apoptosis of SH-SY5Y cells. In the present study we demonstrate that GUO protected C6 glioma cells, taken as a model system for astrocytes, from 6-OHDA-induced neurotoxicity. We show tha…

PD-1-induced T cell exhaustion is controlled by a Drp1-dependent mechanism

2020

AbstractPD-1 signalling downregulates the T cell response, promoting an exhausted state in tumor-infiltrating T cells, through mostly unveiled molecular mechanisms. Drp1-dependent mitochondrial fission plays a crucial role to sustain T cell motility, proliferation, survival and glycolytic engagement and, interestingly, such processes are exactly those inhibited by PD-1 in tumor-infiltrating T cells. Here we show that the signature of PD-1pos CD8+ T cells infiltrating MC38-derived murine tumor mass is having downregulated Drp1 activity and more fused mitochondria, compared to PD-1neg counterparts. Also, PD-1pos lymphocytic elements infiltrating human colon cancer rarely express active Drp1. …

Impaired Th1 responses in mice deficient in Epstein-Barr virus-induced gene 3 and challenged with physiological doses of Leishmania major.

2005

Protection against Leishmania major is dependent on IL-12 release from L. major-infected dendritic cells (DC) that induce IFN-gamma-producing Th1/Tc1 cells. IL-27, a novel member of the IL-12 family, is a heterodimer composed of p28 and IL-12p40-related Epstein-Barr virus-induced gene 3 (EBI3), and was shown to be produced by DC. In this study, we utilized EBI3-deficient mice to investigate the role of IL-27 in leishmaniasis using physiological low-dose infections that mimic natural transmissions. Lesions in EBI3(-/-) mice were significantly larger between weeks 3 and 10 post infection, reaching up to approximately threefold increased lesion volumes compared to wild types. In parallel, derm…

XPO1 (Exportin-1) Is a Major Regulator of Human Erythroid Differentiation. Potential Clinical Applications to Decrease Ineffective Erythropoiesis of …

2015

Abstract Background We and others have shown that normal human erythroid cell maturation requires a transient activation of caspase-3 at late stages of maturation (Zermati et al, J Exp Med 2001). We further documented that, in human erythroblasts, the chaperone HSP70 is constitutively expressed and, at late stages of maturation, translocates into the nucleus and protects GATA-1, the master transcriptional factor critical for erythropoiesis, from caspase-3 cleavage (Ribeil et al, Nature 2007). During the maturation of human β-TM erythroblasts, HSP70 is sequestrated by excess of α-globin chains in the cytoplasm and as a consequence, GATA-1 is no longer protected from caspase-3 cleavage result…

Le paradoxe du seuil de pauvreté endogène dans les indices de pauvreté

2007

Justice et inégalités: un amendement à la théorie de John Rawls

1992

National audience; On se demande si les principes de justice de Rawls ne sont pas exagérément inégalitaires, malgré leur côté "juste". On examine donc ce qu'il advient de l'optimum de Rawls, le maximin, quand de l'aversion pour l'inégalité" apparaît. Le maximin consiste à se placer sur un certain point de la courbe d'efficience, en admettant une certaine dose d'inégalité, pourvu que l'on donne le maximum possible aux plus défavorisés. On tient compte d'externalités en reprenant la notion d'envie sous la forme d'une aversion pour l'inégalité, essentiellement de la part des plus défavorisés. On ne peut plus raisonner sur la courbe frontière des rémunérations possibles et on démontre la validi…

Maternal Employment and Happiness: The Effect of Non-Participation and Part-Time Employment on Mothers' Life Satisfaction

2009

"In contrast to unemployment, the effect of non-participation and parttime employment on subjective well-being has much less frequently been the subject of economists' investigations. In Germany, many women with dependent children are involuntarily out of the labor force or in part-time employment because of family constraints (e.g., due to lack of available and appropriate childcare). Using data from the German Socio-Economic Panel (SOEP) Study, this paper analyzes the impact of involuntary familyrelated non-participation and part-time employment on mothers' life satisfaction. Controlling for unobserved individual fixed effects, I find that both the pecuniary effects (foregone earnings) an…

Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells.

2009

Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT-29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT-29 cells were treated with an inhibitor of the phosphoinositide…

Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in vitro studies

2013

Background: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is caused by germ line mutations in the PTEN gene. Symptoms include cancer pre- disposition, immune deviations, and lipomas/lipomatosis. No causal standard therapy is available. We describe a therapeutic attempt with the mammalian target of rapamycin (mTOR) inhibitor sirolimus for a PHTS patient suffering from thymus hyperplasia and lipomatosis. We furthermore assessed the in vitro effects of sirolimus and other inhibitors on lipoma cells of the patient. Methods: The patient underwent clinical and blood examinations and whole-body magnetic resonance imaging to assess tumor sizes. Lipoma cells of the patient we…

New agents and approaches for targeting the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR cell survival pathways.

2012

The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have…