SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum

Background

In healthy lungs, epithelial sodium channel (ENaC) is regulated by short, palate, lung, and nasal clone 1 (SPLUNC1). In cystic fibrosis (CF), ENaC is hyperactivated in part due to a loss of SPLUNC1 function. We have developed SPX-101 to replace the lost function of SPLUNC1 in the CF lung.

Human serum albumin-coated lipid nanoparticles for delivery of siRNA to breast cancer

Human serum albumin (HSA)-coated lipid nanoparticles (HSA-LNPs) loaded with phrGFP-targeted siRNA (HSA-LNPs-siRNA) were prepared and evaluated for gene downregulation effect in phrGFP-transfected breast cancer cells and the corresponding xenograft tumor model. HSA-LNPs-siRNA were successfully prepared with a particle size of 79.5±5.5 nm. In phrGFP-transfected MCF-7 cells, HSA-LNPs-siRNA significantly decreased cell fluorescence even in the presence of fetal bovine serum (FBS). Moreover, cell fluorescence and phrGFP mRNA expression were significantly downregulated by HSA-LNPs-siRNA in phrGFP-transfected MCF-7, MDA-MB-231, and SK-BR-3 cells in comparison with control or HSA-LNPs-siRNA (scrambled). In phrGFP-transfected MCF-7 xenograft tumor model, tumor fluorescence was significantly decreased after three IV administrations of HSA-LNPs-siRNA at a dose of 3 mg/kg in comparison with siRNA alone. HSA-LNPs-siRNA demonstrated a superior pharmacokinetic profile in comparison with siRNA at a dose of 1mg/kg. These results show that the novel nonviral carrier, HSA-LNPs, may be used for the delivery of siRNA to breast cancer cells.From the Clinical EditorTargeted delivery of siRNA to cancer cells may be a viable anti-cancer strategy with low toxicity. In this study the novel nonviral carrier, human serum albumin-coated lipid nanoparticles (HSA-LNP) were demonstrated as an efficient delivery agent of siRNA to breast cancer cells.     

From the Cover: Forest contraction in north equatorial Southeast Asia during the Last Glacial Period

Today, insular Southeast Asia is important for both its remarkably rich biodiversity and globally significant roles in atmospheric and oceanic circulation. Despite the fundamental importance of environmental history for diversity and conservation, there is little primary evidence concerning the nature of vegetation in north equatorial Southeast Asia during the Last Glacial Period (LGP). As a result, even the general distribution of vegetation during the Last Glacial Maximum is debated. Here we show, using the stable carbon isotope composition of ancient cave guano profiles, that there was a substantial forest contraction during the LGP on both peninsular Malaysia and Palawan, while rainforest was maintained in northern Borneo. These results directly support rainforest “refugia” hypotheses and provide evidence that environmental barriers likely reduced genetic mixing between Borneo and Sumatra flora and fauna. Moreover, it sheds light on possible early human dispersal events.