A randomized, double-blind, phase 2b study to investigate the efficacy, safety, tolerability and pharmacokinetics of a single-dose regimen of ferroquine with artefenomel in adults and children with uncomplicated Plasmodium falciparum malaria.

Background: For uncomplicated Plasmodium falciparum malaria, highly efficacious single-dose treatments are expected to increase compliance and improve treatment outcomes, and thereby may slow the development of resistance. The efficacy and safety of a single-dose combination of artefenomel (800 mg) plus ferroquine (400/600/900/1200 mg doses) for the treatment of uncomplicated P. falciparum malaria were evaluated in Africa (focusing on children ≤ 5 years) and Asia.

Immunomodulation of human intestinal T cells by the synthetic CD80 antagonist RhuDex®.

Deregulated activation of mucosal lamina propria T cells plays a central role in the pathogenesis of intestinal inflammation. One of the means to attenuate T cell activation is by blocking the CD28/CD80 co-stimulatory pathway. Here we investigate RhuDex®, a small molecule that binds to human CD80, for its effects on the activation of lamina propria T cells employing a gut-culture model of inflammation.

Secretion of a pneumococcal type II secretion system pilus correlates with DNA uptake during transformation.

Streptococcus pneumoniae is a major human pathogen that successfully adapts to the host environment via an efficient uptake system for free DNA liberated from other organisms in the upper respiratory tract, facilitating immune evasion and drug resistance. Although the initial signaling events leading to pneumococcal competence for DNA transformation and the fate of DNA when it has been taken up have been extensively studied, the actual mechanism by which DNA in the environment may traverse the thick capsular and cell wall layers remains unknown. Here we visualize that induction of competence results in the formation of a native morphologically distinct pilus structure on the bacterial surface.

ETosis: a novel cell death pathway.

The formation of extracellular traps (ETs) by neutrophils and mast cells is an important mechanism in the innate immune response. These structures consist of a chromatin-DNA backbone with attached antimicrobial peptides and enzymes that trap and kill microbes. After stimulation of neutrophils and mast cells with phorbol esters, chemoattractant peptides, or chemokines, the generation of reactive oxygen species (ROS), such as hydrogen peroxide, by NAPDH [nicotinamide adenine dinucleotide phosphate (reduced form)] oxidase initiates a signaling cascade that leads to the disintegration of the nuclear and cellular membranes and the formation of ETs.

The capsule sensitizes Streptococcus pneumoniae to alpha-defensins human neutrophil proteins 1 to 3.

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Its polysaccharide capsule causes resistance to phagocytosis and interferes with the innate immune system's ability to clear infections at an early stage. Nevertheless, we found that encapsulated pneumococci are sensitive to killing by a human neutrophil granule extract.