Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.

Our understanding of the cellular mechanisms by which animals regulate their response to starvation is limited, despite the strong relevance of the problem to major human health issues. The L1 diapause of Caenorhabditis elegans, where first-stage larvae arrest in response to a food-less environment, is an excellent system to study this mechanism. We found, through genetic manipulation and lipid analysis, that biosynthesis of ceramide, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic interaction analysis suggests that ceramide may act in both insulin-IGF-1 signaling (IIS)-dependent and IIS-independent pathways to affect starvation survival. Genetic and expression analyses indicate that ceramide is required for maintaining the proper expression of previously characterized starvation-responsive genes, genes that are regulated by the IIS pathway and tumor suppressor Rb, and genes responsive to pathogen. These findings provide an important insight into the roles of sphingolipid metabolism, not only in starvation response, but also in aging and food-response-related human health problems.

Hydrogel Nanoparticles with Thermally Controlled Drug Release.

Improving the therapeutic efficacy and reducing systemic side effects of drugs is an important aspect in chemotherapy. The strategy presented here is the use of cisplatin loaded, temperature-sensitive, hydrogel nanoparticles (CisPt-NPs) and their ability to deliver and release chemodrugs selectively, based on thermal stimuli. The specially synthesized CisPt-NPs show a temperature-dependent increase of cisplatin release, at neutral pH (as in blood and normal tissue), in both the presence and absence of common metallic ions, as well as at the low pH found in lysosomes, where endocytosed NPs often localize. These CisPt-NPs were uptaken by breast cancer MDA-MB-435 cells, via endocytosis, and then mostly localized in the lysosomes. The in vitro cytotoxicity tests show that these CisPt-NPs have a significantly better efficacy at the slightly elevated temperatures. Potential applications are discussed.