48 research outputs found
Glutathione-dependent activities of Trypanosoma cruzi p52 makes it a new member of the thiol:disulphide oxidoreductase family
The First α Helix of Interleukin (Il)-2 Folds as a Homotetramer, Acts as an Agonist of the IL-2 Receptor ÎČ Chain, and Induces Lymphokine-Activated Killer Cells
Interleukin (IL)-2 interacts with two types of functional receptors (IL-2RαÎČÎł and IL-2RÎČÎł) and acts on a broad range of target cells involved in inflammatory reactions and immune responses. For the first time, we show that a chemically synthesized fragment of the IL-2 sequence can fold into a molecule mimicking the quaternary structure of a hemopoietin. Indeed, peptide p1â30 (containing amino acids 1â30, covering the entire α helix A of IL-2) spontaneously folds into an α-helical homotetramer and stimulates the growth of T cell lines expressing human IL-2RÎČ, whereas shorter versions of the peptide lack helical structure and are inactive. We also demonstrate that this neocytokine interacts with a previously undescribed dimeric form of IL-2RÎČ. In agreement with its binding to IL-2RÎČ, p1â30 activates Shc and p56lck but unlike IL-2, fails to activate Janus kinase (Jak)1, Jak3, and signal transducer and activator of transcription 5 (STAT5). Unexpectedly, we also show that p1â30 activates Tyk2, thus suggesting that IL-2RÎČ may bind to different Jaks depending on its oligomerization. At the cellular level, p1â30 induces lymphokine-activated killer (LAK) cells and preferentially activates CD8low lymphocytes and natural killer cells, which constitutively express IL-2RÎČ. A significant interferon Îł production is also detected after p1â30 stimulation. A mutant form of p1â30 (Asp20âLys), which is likely unable to induce vascular leak syndrome, remains capable of generating LAK cells, like the original p1â30 peptide. Altogether, our data suggest that p1â30 has therapeutic potential
Immunogenicity and antigenicity of the N-term repeat amino acid sequence of the Plasmodium falciparum P126 antigen
The P126 protein, a parasitosphorus vacuole antigen of Plasmodium falciparum has beenshoen to induce protective immunity in Saimiri and Aotus monkeys. In the present work we investigated its immunogenicity. Our results suggest that the N-term of P126 is poorly immunogenic and antibody response against the P126 could be under a MHC restricted control in C57BL/6(H-2b) mice, which could be problematic in ternms of a use of the P126 in a vaccine program. However, we observed that a synthetic peptide, copying the 6 octapeptide repeat corresponding to the N-term of the P126, induces an antibody response to the native molecule in C57BL/6 non-responder mice. Moreover, the vaccine-P126 recombinant induced anmtibodies against the N-term of the molecule in rabbits while the unprocessed P126 did not
The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM) paradigm : conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation
In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARM) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARM agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARM agonist safely reduces residual cardiovascular risk.Peer reviewe
Residual vascular risk in diabetes â will the SPPARM alpha concept hold the key?
No abstract available
Comment les politiques de santé impactent-elles les missions du pharmacien d'officine ?
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
Plantes et fleurs toxiques en vente chez les fleuristes et dans les jardineries
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
La réglementation européenne et américaine des médicaments biosimilaires
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
Le concept du "Lean" dans l'industrie pharmaceutique (méthodes et outils appliqués aux ateliers de production)
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
La valorisation des projets pharmaceutiques dans les jeunes sociétés innovantes
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF