Significant advance has been made towards understanding glioblastoma metabolism through global metabolomic profiling. However, hitherto little is known about the role by which altered metabolism plays in driving the aggressive glioma phenotype. We have previously identified hypotaurine as one of the top-ranked metabolites for differentiating low- and high-grade tumors, and that there is also a strong association between the levels of intratumoral hypotaurine and expression of its biosynthetic enzyme, cysteamine (2-aminoethanethiol) dioxygenase (ADO). Using transcription profiling, we further uncovered that the ADO/hypotaurine axis targets CCL20 secretion through activating the NF-κB pathway to drive the self-renewal and maintenance of glioma ‘cancer stem cells’ or glioma cancer stem-like cells. Conversely, abrogating the ADO/hypotaurine axis using CRISPR/Cas9-mediated gene editing limited glioblastoma cell proliferation and self-renewal in vitro and tumor growth in vivo in an orthotopical mouse model, indicating that this metabolic pathway is a potential key therapeutic target. Collectively, our results unveil a targetable metabolic pathway, which contributes to the growth and progression of aggressive high-grade gliomas, as well as a novel predictive marker for glioblastoma diagnosis and therapy.
Cardiovascular disease is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Despite recent advances in the management of cardiovascular diseases, pharmaceutical treatment remains suboptimal because of poor pharmacokinetics and high toxicity. However, since being harnessed in the cancer field for the delivery of safer and more effective chemotherapeutics, nanoparticle-based drug delivery systems have offered multiple significant therapeutic effects in treating cardiovascular diseases. Nanoparticle-based drug delivery systems alter the biodistribution of therapeutic agents through site-specific, target-oriented delivery and controlled drug release of precise medicines. Metal-, lipid-, and polymer-based nanoparticles represent ideal materials for use in cardiovascular therapeutics. New developments in the therapeutic potential of drug delivery using nanoparticles and the application of nanomedicine to cardiovascular diseases are described in this review. Furthermore, this review discusses our current understanding of the potential role of nanoparticles in metabolism and toxicity after therapeutic action, with a view to providing a safer and more effective strategy for the treatment of cardiovascular disease.
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