18 research outputs found
Cold plasma therapy applied to non-small cell lung cancer: deciphering the relevant plasma parameters to induce antitumor effects
International audienc
Cold plasma therapy applied to non-small cell lung cancer: deciphering the relevant plasma parameters to induce antitumor effects
International audienc
At the frontier of physics and biology: cold plasma, a new therapeutic approach in lung cancer?
International audienc
At the frontier of physics and biology: cold plasma, a new therapeutic approach in lung cancer?
International audienc
Etude comparative de sources de plasma froid pour le traitement des cancers des voies biliaires et du poumon
International audienc
Etude comparative de sources de plasma froid pour le traitement des cancers des voies biliaires et du poumon
International audienc
Novel role for carbohydrate responsive element binding protein in the control of ethanol metabolism and susceptibility to binge drinking
International audienc
Exposure to wild-type AAV drives distinct capsid immunity profiles in humans
International audienceRecombinant adeno-associated virus (AAV) vectors have been broadly adopted as a gene delivery tool in clinical trials, owing to their high efficiency of transduction of several host tissues and their low immunogenicity. However, a considerable proportion of the population is naturally exposed to the WT virus from which AAV vectors are derived, which leads to the acquisition of immunological memory that can directly determine the outcome of gene transfer. Here, we show that prior exposure to AAV drives distinct capsid immunity profiles in healthy subjects. In peripheral blood mononuclear cells (PBMCs) isolated from AAV-seropositive donors, recombinant AAV triggered TNF-α secretion in memory CD8+ T cells, B cell differentiation into antibody-secreting cells, and anti-capsid antibody production. Conversely, PBMCs isolated from AAV-seronegative individuals appeared to carry a population of NK cells reactive to AAV. Further, we demonstrated that the AAV capsid activates IL-1ÎČ and IL-6 cytokine secretion in monocyte-related dendritic cells (moDCs). IL-1ÎČ and IL-6 blockade inhibited the anti-capsid humoral response in vitro and in vivo. These results provide insights into immune responses to AAV in humans, define a possible role for moDCs and NK cells in capsid immunity, and open new avenues for the modulation of vector immunogenicity
Dual regulation of TxNIP by ChREBP and FoxO1 in liver
International audienceTxNIP (Thioredoxin-interacting protein) is considered as a potential drug target for type 2 diabetes. Although TxNIP expression is correlated with hyperglycemia and glucotoxicity in pancreatic ÎČ cells, its regulation in liver cells has been less investigated. In the current study, we aim at providing a better understanding of Txnip regulation in hepatocytes in response to physiological stimuli and in the context of hyperglycemia in db/db mice. We focused on regulatory pathways governed by ChREBP (Carbohydrate Responsive Element Binding Protein) and FoxO1 (Forkhead box protein O1), transcription factors that play central roles in mediating the effects of glucose and fasting on gene expression, respectively. Studies using genetically modified mice reveal that hepatic TxNIP is up-regulated by both ChREBP and FoxO1 in liver cells and that its expression strongly correlates with fasting, suggesting a major role for this protein in the physiological adaptation to nutrient restriction