Activation of AMPK by simvastatin inhibited breast tumor angiogenesis via impeding HIF-1α-induced pro-angiogenic factor.

Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cell-conditioned medium-induced angiogenic promotion in vitro, and resulted in dose-dependent anti-angiogenesis in vivo. Further genetic silencing of hypoxia-inducible factor-1α (HIF-1α) reduced vascular endothelial growth factor and fibroblast growth factor-2 expressions in 4T1 cells and correspondingly ameliorated HUVEC proliferation facilitated by tumor cell-conditioned medium. Additionally, simvastatin induced angiogenic inhibition through a mechanism of post-transcriptional downregulation of HIF-1α by increasing the phosphorylation level of AMP kinase. These results were further validated by the fact that 5-aminoimidazole-4-carboxamide ribonucleotide reduced HIF-1α protein levels and ameliorated the angiogenic ability of endothelial cells in vitro and in vivo. Critically, inhibition of AMPK phosphorylation by compound C almost completely abrogated simvastatin-induced anti-angiogenesis, which was accompanied by the reduction of protein levels of HIF-1α and its downstream pro-angiogenic factors. These findings reveal the mechanism by which simvastatin induces tumor anti-angiogenesis, and therefore identifies the target that explains the beneficial effects of statins on malignant tumors.

A new species of the water mite genus Sperchon Kramer, 1877 from China, with identifying Sperchon rostratus Lundblad, 1969 through DNA barcoding (Acari, Hydrachnidia, Sperchontidae).

A new species of the water mite genus Sperchon Kramer, 1877 from China, Sperchon fuxiensis Zhang, sp. n., is described and illustrated in this article. DNA barcoding for the new species is documented for future use. Descriptions of both male and female of Sperchon rostratus Lundblad, 1969 are given in the present study, and DNA barcoding for identifying S. rostratus is also discussed.

Space-charge Effect on Electroresistance in Metal-Ferroelectric-Metal capacitors.

Resistive switching through electroresistance (ER) effect in metal-ferroelectric-metal (MFM) capacitors has attracted increasing interest due to its potential applications as memories and logic devices. However, the detailed electronic mechanisms resulting in large ER when polarisation switching occurs in the ferroelectric barrier are still not well understood. Here, ER effect up to 1000% at room temperature is demonstrated in C-MOS compatible MFM nanocapacitors with a 8.8 nm-thick poly(vinylidene fluoride) (PVDF) homopolymer ferroelectric, which is very promising for silicon industry integration. Most remarkably, using theory developed for metal-semiconductor rectifying contacts, we derive an analytical expression for the variation of interfacial barrier heights due to space-charge effect that can interpret the observed ER response. We extend this space-charge model, related to the release of trapped charges by defects, to MFM structures made of ferroelectric oxides. This space-charge model provides a simple and straightforward tool to understand recent unusual reports. Finally, this work suggests that defect-engineering could be an original and efficient route for tuning the space-charge effect and thus the ER performances in future electronic devices.