Challenges of drug development during the COVID-19 pandemic: Key considerations for clinical trial designs.

There is an urgent need for targeted and effective COVID-19 treatments. Several medications, including hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, tocilizumab and others have been identified as potential treatments for COVID-19. Bringing these repurposed medications to the public for COVID-19 requires robust and high-quality clinical trials that must be conducted under extremely challenging pandemic conditions.

In vivo regulation of neutrophil apoptosis by C5a during sepsis.

Delayed neutrophil apoptosis is characteristic of sepsis and may accentuate organ injury. It has been shown that PI-3K and MAPK pathways provide survival signaling in neutrophils. In this study, we demonstrate that neutrophils isolated from septic rats are resistant to apoptosis in comparison with the cells from normal animals.

Divergent signaling pathways in phagocytic cells during sepsis.

Neutrophil accumulation in the lung plays a pivotal role in the pathogenesis of acute lung injury during sepsis. Directed movement of neutrophils is mediated by a group of chemoattractants, especially CXC chemokines. Local lung production of CXC chemokines is intensified during experimental sepsis induced by cecal ligation and puncture (CLP), as reflected by rising levels of MIP-2 and cytokine-induced neutrophil chemoattractant-1 in bronchoalveolar lavage fluids.