Dual Functioned Hexapeptide-Coated Lipid-Core Nanomicelles Suppress Toll-Like Receptor-Mediated Inflammatory Responses through Endotoxin Scavenging and Endosomal pH Modulation.

Excessive activation of Toll-like receptor (TLR) signaling pathways and the circulating endotoxin are key players in the pathogenesis of many acute and chronic inflammatory diseases. Regulation of TLR-mediated inflammatory responses by bioactive nanodevices represents a promising strategy for treating these diseases. In searching for novel, clinically applicable nanodevices with potent TLR inhibitory activities, three types of hexapeptide-modified nano-hybrids with different cores of phospholipid nanomicelles, liposomes, and poly(lactic-co-glycolic acid) nanoparticles are constructed. Interestingly, only the peptide-modified lipid-core nanomicelles (M-P12) display potent TLR inhibitory activities. Further mechanistic studies disclose that lipid-core nanomicelles have a generic property to bind to and scavenge lipophilic TLR ligands including lipopolysaccharide to block the ligand-receptor interaction and down-regulate the TLR signaling extracellularly. In addition, the peptide modification enables M-P12 a unique capability to modulate endosomal acidification upon being endocytosed into macrophages, which subsequently regulates the endosomal TLR signal transduction. In an acute lung injury mouse model, intratracheal administration of M-P12 can effectively target lung macrophages and reduce lung inflammation and injuries. This work defines a dual mechanism of action of the peptide-modified lipid-core nanomicelles in regulating TLR signaling, and provides new strategies for the development of therapeutic nanodevices for treating inflammatory diseases.

Morphology, morphogenesis and molecular phylogeny of a novel saline soil ciliate, Urosoma quadrinucleatum n. sp. (Ciliophora, Hypotrichia).

The morphology and morphogenesis of a new saline soil hypotrichous ciliate, Urosoma quadrinucleatum n. sp., collected from northwestern China, were studied based on live observations and protargol stained specimens. The new species is characterized as follows: size in vivo 90-130 × 20-30 µm; body outline elongate-elliptical with both ends broadly rounded; four macronuclear nodules; cortical granules present; paroral in front of endoral; usually 16 frontal-ventral-transverse cirri. Urosoma quadrinucleatum n. sp. has almost the same morphogenetic characteristics as its congeners U. gigantea and U. salmastra, and differs from other three congeners whose morphogenesis is known in the formation of the frontal-ventral-transverse cirral anlagen as well as the development of marginal and dorsal kineties anlagen. The sequence differences among U. quadrinucleatum n. sp. and other Urosoma species further support the validity of the present organism as novel species. Further, U. quadrinucleatum n. sp. clusters with U. salmastra in the phylogenetic analyses based on small subunit ribosomal RNA gene (SSU rDNA) sequence data.