Structures and cytotoxicities of three new sesquiterpenes from cultures of Armillaria sp.

[Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s13659-012-0077-1 and is accessible for authorized users

Aloin promotes cell apoptosis by targeting HMGB1-TLR4-ERK axis in human melanoma cells

Aloin (ALO) is the major anthraquinone glycoside purified from the Aloe species. It is well known for its anti-tumor effects. However, the protective effects of ALO in melanoma cancer and underlying molecular mechanism remain unclear. High-mobility group protein B1 (HMGB1) is an intracellular protein, which has closely association with cell survival, proliferation and metastasis in various cancers. In this study, we explored the effect of ALO on cell survival and apoptosis by targeting HMGB1 signal pathway. We confirmed that ALO exerts a strong effect on promoting cell apoptosis of melanoma cells in vitro. Furthermore, HMGB1 release was significantly inhibited in melanoma cancer cells treated with ALO. Knockdown of HMGB1 could enhance melanoma cell death that is induced by ALO treatment. Moreover, HMGB1 facilitated ALO mediated melanoma cell apoptosis by binding to its receptor, Toll-like receptor 4 and activating extracellular regulated protein kinases (ERK) signal pathway. Altogether, our study demonstrated that ALO plays an important role in promoting apoptosis of melanoma cells by inhibiting HMGB1 release and activation of downstream ERK signal pathway

Grey scale enhancement by a new self-made contrast agent in early cirrhotic stage of rabbit liver

<p>Abstract</p> <p>Background</p> <p>The development of new ultrasound contrast agents (UCAs) has become one of the most promising fields in ultrasound medicine. This paper evaluates a new self-made contrast agent enhancement effect developed to study the fibrotic stages of the liver in perfusion models <it>in vivo</it>.</p> <p>Methods</p> <p>We constructed experimental models of hepatic fibrosis involving five stages from F0 to F4 via administration of CCL₄(0.01 ml/kg BW) every 3 days for 3 months. The intrahepatic circulatory time of the contrast agent was analyzed via an image and Cine-loop display. Calculations of the perfusion-related parameters including the peak signal intensity (PSI) and peak signal intensity time (PIT) of the portal vein and parenchyma were obtained from an analysis of the time-acoustic intensity curve.</p> <p>Results</p> <p>Hepatic artery to vein transmit time (HA-HVTT) was significantly shorter at F4 stage (mean 5.1 seconds) compared with those in other stages (mean 8.3 s, 7.5 s, 6.9 s, 6.6 s, P < 0.01). The average PSI difference of PV-parenchyma was 13.62 dB in F4 stage, demonstrating significant differences between F4 stage and other early stages (P < 0.001).</p> <p>Conclusion</p> <p>These results indicate that the new self-made contrast agent is capable of indicating intrahepatic hemodynamic changes. HA-HVTT and the PSI difference of the microbubble perfusion in liver parenchyma and PV were considered to differentiate the degree of hepatic fibrosis between F4 and other early stages.</p

The ID1-CULLIN3 Axis Regulates Intracellular SHH and WNT Signaling in Glioblastoma Stem Cells

SummaryInhibitor of differentiation 1 (ID1) is highly expressed in glioblastoma stem cells (GSCs). However, the regulatory mechanism responsible for its role in GSCs is poorly understood. Here, we report that ID1 activates GSC proliferation, self-renewal, and tumorigenicity by suppressing CULLIN3 ubiquitin ligase. ID1 induces cell proliferation through increase of CYCLIN E, a target molecule of CULLIN3. ID1 overexpression or CULLIN3 knockdown confers GSC features and tumorigenicity to murine Ink4a/Arf-deficient astrocytes. Proteomics analysis revealed that CULLIN3 interacts with GLI2 and DVL2 and induces their degradation via ubiquitination. Consistent with ID1 knockdown or CULLIN3 overexpression in human GSCs, pharmacologically combined control of GLI2 and β-CATENIN effectively diminishes GSC properties. A ID1-high/CULLIN3-low expression signature correlates with a poor patient prognosis, supporting the clinical relevance of this signaling axis. Taken together, a loss of CULLIN3 represents a common signaling node for controlling the activity of intracellular WNT and SHH signaling pathways mediated by ID1