12 research outputs found
Automatic versus manual forwarding in web surveys - A cognitive load perspective on satisficing responding.
Focal structures analysis: identifying influential sets of individuals in a social network
Knowledge and attitudes toward thirdhand smoke among parents with children under 3 years in Spain
Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release
DaGO-Fun: tool for Gene Ontology-based functional analysis using term information content measures
Efeito in vitro da triiodotironina sob o potencial osteogênico reduzido de células-tronco mesenquimais do tecido adiposo de ratas ovariectomizadas e com osteoporose
The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery
International audienceThe state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival