Activation of TLR4 signaling promotes gastric cancer progression by inducing mitochondrial ROS production

Chronic infection, such as Helicobacter pylori infection, has been associated with the development of gastric cancer (GC). Pathogen-associated molecular patterns can trigger inflammatory responses via Toll-like receptors (TLRs) in GC. Here we showed that Toll-like receptor 4 (TLR4) was highly expressed in GC cells and was associated with the aggressiveness of GC. The binding of lipopolysaccharide (LPS) to TLR4 on GC cells enhanced proliferation without affecting apoptosis. Higher level of reactive oxygen species (ROS) was induced after activation of TLR4 signaling in GC. Using oxidase inhibitors and antioxidants, we found that mitochondrial ROS (mROS) was major source of TLR4-stimulated ROS generation. This elevated mROS production can be inhibited by diphenylene iodonium (DPI), and the blocking of the mROS production rather than ROS neutralization resulted in cell cycle arrest and the loss of mitochondrial potential, which were plausible reason for decreased cell viability. Furthermore, the increased mROS owing to TLR4 signaling resulted in the activation of Akt phosphorylation and NF-κB p65 nuclear translocation. Altogether, these results reveal a novel pathway linking innate immune signaling to GC cell proliferation, implicate mROS as an important component of cell survival signals and further establish mitochondria as hubs for GC therapies.     

Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells.     

RhoGAPs Attenuate Cell Proliferation by Direct Interaction with p53 Tetramerization Domain

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Numerical Modelling of Electroosmotic Driven Flow in Nanoporous Media by Lattice Boltzmann Method

The lattice Boltzmann method was employed to simulate electroosmotic driven flow and Debye layer screening in conducting electrolyte around a porous structure with average size of 40 nm. The charge screening around the nanopores was investigated by solving the vector-superpositioned potential equilibrium distribution function and adding electro-kinetic force term to the evolution equation. In this intermediate case of moderate Debye length, the electrophoresis problem becomes complicated. The motion of the particles distorts the screening cloud, which becomes asymmetric, resulting in very complex interactions between the electrolyte, the screening cloud and the particle; but the Electroosmotic Flow (EOF) behaviour was still considered based on the Helmoholtz-Smoluchowski model with adaptation to fit nanoporous flow in the porous structure. In the present approach, the flow in the nanopores is directly modelled; the detailed flow information can be obtained by simplifying the repeated macrostructure. Due to the symmetry of the domain, the size of computational domain can be largely reduced by less repeated spherical nanoparticles. Each pore of the medium contains several lattice nodes on the simplified curved edges and potential gradients are produced by adjusting the zeta potential value. The velocity results for pressure-driven and EOF flows agree well with the analytical solutions and recent experimental results. In particular, the interface between solid particles and fluids, the influences of porosity, solid particle diameter, yield stress and electric parameters in EOF were investigated. The anti-adhesion effect of electroosmotic pumping effect was evaluated, and the pulsed DC was applied in order to enhance the performance of the electroosmotic pumping. The results demonstrate that the present lattice Boltzmann model is capable of modelling flow through nanoporous media at certain restrictions while some results deviate from the predictions based on the macroscopic theories.     

Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas

Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.     

Estimation of Endocarpon pusillum Hedwig carbon budget in the Tengger Desert based on its photosynthetic rate

This study investigated the photosynthetic rate of the lichen Endocarpon pusillum at the Chinese Academy of Sciences Shapotou Desert Research Station and estimated its annual contribution to the carbon budget in the ecosystem. The software SigmaPlot 10.0 with “Macro-Area below curves” was used to calculate the carbon fixation capacity of the lichen. The total carbon budget (ΣC) of the lichen was obtained by subtracting the respiratory carbon loss (ΣDR) from the photosynthetic carbon gain (ΣNP). Because water from precipitation plays an important role in photosynthesis in this ecosystem, the annual carbon budget of E. pusillum at the station was estimated based on the three-year average precipitation data from 2009 to 2011. Our results indicate that the lichen fixes 14.6 g C m^?2 annually. The results suggest that artificial inoculation of the crust lichen in the Tengger Desert could not only help reduce the sand and dust storms but also offer a significant carbon sink, fixing a total of 438000 t of carbon over the 30000 km² of the Tengger Desert. The carbon sink could potentially help mitigate the atmospheric greenhouse effect. Our study suggests that the carpet-like lichen E. pusillum is an excellent candidate for “Bio-carpet Engineering” of arid and semi-arid regions.     

Newly discovered insect RNA viruses in China

Insects are a group of arthropods and the largest group of animals on Earth,with over one million species described to date.Like other life forms,insects suffer from viruses that cause disease and death.Viruses that are pathogenic to beneficial insects cause dramatic economic losses on agriculture.In contrast,viruses that are pathogenic to insect pests can be exploited as attractive biological control agents.All of these factors have led to an explosion in the amount of research into insect viruses in recent years,generating impressive quantities of information on the molecular and cellular biology of these viruses.Due to the wide variety of insect viruses,a better understanding of these viruses will expand our overall knowledge of their virology.Here,we review studies of several newly discovered RNA insect viruses in China.