Sharper image: A newly developed polysaccharide/drug conjugate (see picture) responds to changes in pH value and was shown to penetrate HeLa tumors in mice as determined by fluorescence imaging. It has the potential to be used in photodynamic therapy, thereby targeting the tumor while having no detrimental effects on the surrounding tissue.

Recently, we have shown that the microtubule-associated protein tau is essential for ␤-amyloid (A␤)-induced neurotoxicity in hippocampal neurons. However, the mechanisms by which tau mediates A␤-induced neurite degeneration remain poorly understood. In the present study, we analyzed whether tau cleavage played a role in these events. Our results showed that pre-aggregated A␤ induced the generation of a 17 kDa tau fragment in cultured hippocampal neurons. The generation of this fragment was preceded by the activation of calpain-1. Conversely, inhibitors of this protease, but not of caspases, completely prevented tau proteolysis leading to the generation of the 17 kDa fragment and significantly reduced A␤-induced neuronal death. Furthermore, the expression of this fragment in cultured hippocampal neurons induced the formation of numerous varicosity-bearing tortuous processes, as well as the complete degeneration of some of those neurite processes. These results suggest that A␤-induced neurotoxicity may be mediated, at least in part, through the calpain-mediated generation of a toxic 17 kDa tau fragment. Collectively, these results provide insight into a novel mechanism by which tau could mediate A␤-induced neurotoxicity.

Type 2 diabetes is a heterogeneous disease characterized by insulin resistance and altered glucose and lipid metabolism in multiple organs. To understand the complex series of events that occur during the development of obesityassociated diabetes, we examined the temporal pattern of changes in insulin action and glucose metabolism in individual organs during chronic high-fat feeding in C57BL/6 mice. Insulin-stimulated cardiac glucose metabolism was significantly reduced after 1.5 weeks of high-fat feeding, and cardiac insulin resistance was associated with blunted Akt-mediated insulin signaling and GLUT4 levels. Insulin resistance in skeletal muscle, adipose tissue, and liver developed in parallel after 3 weeks of high-fat feeding. Diet-induced whole-body insulin resistance was associated with increased circulating levels of resistin and leptin but unaltered adiponectin levels. High-fat feeding caused insulin resistance in skeletal muscle that was associated with significantly elevated intramuscular fat content. In contrast, diet-induced hepatic insulin resistance developed before a marked increase in intrahepatic triglyceride levels. Cardiac function gradually declined over the course of high-fat feeding, and after 20 weeks of high-fat diet, cardiac dysfunction was associated with mild hyperglycemia, hyperleptinemia, and reduced circulating adiponectin levels. Our findings demonstrate that cardiac insulin resistance is an early adaptive event in response to obesity and develops before changes in whole-body glucose homeostasis. This suggests that obesity-associated defects in cardiac function may not be due to insulin resistance per se but may be attributable to chronic alteration in cardiac glucose and lipid metabolism and circulating adipokines. Diabetes 54: 3530 -3540, 2005

We have developed a simple approach for the large-scale synthesis of water-soluble green carbon nanodots (G-dots) from many kinds of large food waste-derived sources. About 120 g of G-dots per 100 kg of food waste can be synthesized using our simple and environmentally friendly synthesis approach. The G-dots exhibit a high degree of solubility in water because of the abundant oxygen-containing functional groups around their surface. The narrow band of photoluminescence emission (400-470 nm) confirms that the size of the G-dots (∼4 nm) is small because of a similar quantum effects and emission traps on the surfaces. The G-dots have excellent photostability; their photoluminescence intensity decreases slowly (∼8%) under continuous excitation with a Xe lamp for 10 days. We carried out cell viability assay to assess the effect of cytotoxicity by introducing G-dots in cells such as Chinese hamster ovary cells (CHO-K1), mouse muscle cells (C2C12), and African green monkey kidney cells (COS-7), up to a concentration of 2 mg mL(-1) for 24 h. Due to their high photostability and low cytotoxicity, these G-dots are excellent probes for in vitro bioimaging. Moreover, the byproducts (not including G-dots) of G-dot synthesis from large food-waste derived sources promoted the growth and development of seedlings germinated on 3DW-supplemented gauze. Because of the combined advantages of green synthesis, high aqueous stability, high photostability, and low cytotoxicity, the G-dots show considerable promise in various areas, including biomedical imaging, solution state optoelectronics, and plant seed germination and/or growth.

BackgroundFucoidan is a sulfated polysaccharide found in brown algae; it has been shown to exhibit a number of biological effects, including anti-tumor effects. In this study, we evaluated the effects of fucoidan on apoptosis in HT-29 and HCT116 human colon cancer cells.MethodsHT-29 and HCT116 cells were cultured with various concentrations of fucoidan (0 - 20 μg/mL). Apoptosis was assayed via Hoechst staining and Annexin V staining followed by flow cytometric analysis. Western blot analyses and JC-1 staining were conducted to determine the levels of apoptosis-regulating proteins and mitochondrial membrane permeability, respectively.ResultsFucoidan induced substantial reductions in viable cell numbers and apoptosis of HT-29 and HCT116 cells in a dose-dependent manner. In HT-29 cells, fucoidan also increased the levels of cleaved caspases-8, -9, -7, and -3, and cleaved poly (ADP-ribose) polymerase (PARP) levels. The levels of the X-linked inhibitor of apoptosis protein and survivin were attenuated in the fucoidan-treated cells. Fucoidan was also shown to enhance mitochondrial membrane permeability, as well as the cytochrome c and Smac/Diablo release from the mitochondria. Fucoidan increased the levels of the Bak and truncated Bid proteins, but reduced the levels of Mcl-1. Additionally, fucoidan increased the levels of the tumor necrosis factor-related apoptosis-inducing ligand, Fas and death receptor 5 proteins. The caspase-8 and -9 inhibitors Z-IETD-FMK and Z-LEHD-FMK induced a reduction in fucoidan-mediated apoptosis. Caspase-8 inhibitor inhibited the fucoidan-induced cleavage of Bid, caspases-9 and -3, and PARP.ConclusionThe findings of this study indicate that fucoidan induces apoptosis in HT-29 and HCT116 human colon cancer cells, and that this phenomenon is mediated via both the death receptor-mediated and mitochondria-mediated apoptotic pathways. These results suggest that fucoidan may prove useful in the development of a colon cancer-preventive protocol.