Stem cells hold great promise for the treatment of multiple human diseases and disorders. Tracking and monitoring of stem cells in vivo after transplantation can supply important information for determining the efficacy of stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be the most effective and safest non-invasive technique for stem cell tracking in living bodies. Commercial superparamagnetic iron oxide nanoparticles (SPIONs) in the aid of transfection agents (TAs) have been applied to labeling stem cells. However, owing to the potential toxicity of TAs, more attentions have been paid to develop novel SPIONs with specific surface coating or functional moieties which facilitate effective cell internalization in the absence of TAs. This review aims to summarize the recent progress in the design and preparation of SPIONs as cellular MRI probes, to discuss their applications and current problems facing in stem cell labeling and tracking, and to offer perspectives and solutions for the future development of SPIONs in this field.

A prodrug forms nanocapsules responsive to tumor GSH/ROS heterogeneity releasing the parent drug SN38 via thiolysis in the presence of GSH (glutathione) or via enhanced hydrolysis due to ROS (reactive oxygen species)-oxidation of the linker, giving rise to high in vitro cytotoxicity and in vivo anticancer therapeutic activity. The nanocapsules are a suitable size for tumor targeting by means of the EPR effect and have a fixed SN38 loading content of 35 wt%, ideal for translational nanomedicine.

Sterol regulatory element binding proteins (SREBPs) are transcription factors that activate transcription of the genes involved in cholesterol and fatty acid biosynthesis. In the present study, we show that a small synthetic molecule we previously discovered to block adipogenesis is an inhibitor of the SREBP activation. The diarylthiazole derivative, now called fatostatin, impairs the activation process of SREBPs, thereby decreasing the transcription of lipogenic genes in cells. Our analysis suggests that fatostatin inhibits the ER-Golgi translocation of SREBPs through binding to their escort protein, the SREBP cleavage-activating protein (SCAP), at a distinct site from the sterol-binding domain. Fatostatin blocked increases in body weight, blood glucose, and hepatic fat accumulation in obese ob/ob mice, even under uncontrolled food intake. Fatostatin may serve as a tool for gaining further insights into the regulation of SREBP.

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In animals, liver and white adipose are the main sites for the de novo fatty acid synthesis. Deletion of fatty acid synthase or acetyl-CoA carboxylase (ACC) 1 in mice resulted in embryonic lethality, indicating that the de novo fatty acid synthesis is essential for embryonic development. To understand the importance of de novo fatty acid synthesis and the role of ACC1-produced malonyl-CoA in adult mouse tissues, we generated liver-specific ACC1 knockout (LACC1KO) mice. LACC1KO mice have no obvious health problem under normal feeding conditions. Total ACC activity and malonyl-CoA levels were Ϸ70 -75% lower in liver of LACC1KO mice compared with that of the WT mice. In addition, the livers of LACC1KO mice accumulated 40 -70% less triglycerides. Unexpectedly, when fed fat-free diet for 10 days, there was significant up-regulation of PPAR␥ and several enzymes in the lipogenic pathway in the liver of LACC1KO mice compared with the WT mice. Despite the significant up-regulation of the lipogenic enzymes, including a >2-fold increase in fatty acid synthase mRNA, protein, and activity, there was significant decrease in the de novo fatty acid synthesis and triglyceride accumulation in the liver. However, there were no significant changes in blood glucose and fasting ketone body levels. Hence, reducing cytosolic malonyl-CoA and, therefore, the de novo fatty acid synthesis in the liver, does not affect fatty acid oxidation and glucose homeostasis under lipogenic conditions.Cre-loxP ͉ fatty acid synthesis ͉ tissue-specific knockout I n eukaryotes, acetyl-CoA carboxylase (ACC) is a biotinylated enzyme that catalyzes the ATP-dependent carboxylation of acetyl-CoA to produce malonyl-CoA. Fatty acid synthase (FAS), the multifunctional enzyme, catalyzes the synthesis of long-chain fatty acid, palmitate, by using acetyl-CoA as a primer, malonylCoA as a two-carbon donor for chain elongation, and NADPH for the reduction reactions. The synthesis of malonyl-CoA is the committed step toward the synthesis of fatty acids (1-5). In addition, malonyl-CoA also plays an important role in the regulation of fatty acid oxidation in the mitochondria as an inhibitor of the carnitine palmitoyl transferase 1, which performs the first step in the transfer of long-chain fatty acyl CoA into mitochondria for their oxidation (6, 7). Hence, malonyl-CoA participates in two opposing pathways, a substrate for fatty acid synthesis and a regulator of fatty acid oxidation. Lately, there are also reports that malonyl-CoA regulates orexigenic responses in hypothalamus (8) and insulin secretion by pancreatic ␤-islets (9, 10). Malonyl-CoA is generated by two isoforms of acetyl-CoA carboxylases, ACC1 and ACC2 of molecular mass 265 kDa and 280 kDa, respectively (11-16). ACC1 is a cytosolic enzyme, and ACC2 is associated with mitochondria (17). Although both isoforms are expressed in various tissues, ACC1 is predominantly expressed in lipogenic tissues such as liver, adipose, and lactating mammary gland, and ACC2 is predominantly expressed in muscle tissues and heart ...