Glycitin exerts anticancer effect on human lung cancer cells through induction of apoptosis, cell cycle arrest, and inhibition of PI3K/AKT signal pathway

Purpose: To determine the effect of glycitin on PI3K/AKT signaling, migration, invasion, apoptosis, and cell cycle in A549 lung cancer cells.Methods: 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays were used to determine the proliferation and colony generation potency of A549 cells, respectively, after treatment with glycitin (0 - 120 μM). Apoptosis in A549 cells was measured using DAPI and Annexin V/PI-FITC assays. Cell cycle arrest was assessed byflow cytometry, while the effect of glycitin on migration and invasion of A549 cells was determined by Transwell assay. The effect of glycitin on expressions of proteins associated with PI3K/AKT signaling in A549 cells was measured using western blotting.Results: Glycitin significantly inhibited the proliferation and colony generation potential of A549 cells (p < 0.05). The antiproliferative effects of glycitin on A549 cells were mediated through stimulation of apoptosis and cell cycle arrest at G0/G1-phase. The compound also distorted normal cellular morphology by causing membrane damage and nuclear fragmentation. The proportion of cells in the G0/G1-phase increased after glycitin treatment, when compared to the other two phases, demonstrating cell cycle arrest (p < 0.05). Glycitin suppressed the migration and invasion of A549 cells. However, Western blotting results showed that glycitin down-regulated the expressions of PI3K/AKT signaling proteins in A549 cells (p < 0.05).Conclusion: Glycitin produced significant anticancer effect on A549 cells via enhanced apoptosis, induction of cell cycle arrest, and inhibition of PI3K/AKT signalling. Moreover, it suppressed the migration and invasion of A549 cells. Therefore, glycitin is a potential lead molecule for the development of a therapeutic agent for invasive lung cancer

Innate immune modulation in atherosclerosis - with focus on ApoB100 derived danger associated signal 1 (ApoBDS-1)

Elevated level of LDL is the most important risk factor for atherosclerosis. ApoB100 is the only unexchangeable protein in LDL particle. Recent reports have shown that native peptides of ApoB100 trigger activation of adaptive immune responses. Whether ApoB100 can activate innate immune response is unknown. In this thesis, we identified a native ApoB100 peptide from human ApoB100, named ApoB100 danger associated signal-1 (ApoBDS-1), given its biological nature totrigger innate proinflammatory responses in monocytes and macrophages. Besides macrophages, ApoBDS-1 can also activate platelets and endothelial cells, eliciting proinflammatory mediators and promoting platelet-leukocyte aggregates through complex molecular mechanisms involving Ca2+ flux, ROS production, MAPKs activation, PI3K-Akt activation, and microRNA regulations. ApoBDS-1 contributes to the activation of inflammatory signaling in human atherosclerotic plaque. We showed that ApoBDS-1 exists in human carotid plaques by immunofluorescence staining. Size-exclusion chromatography and Western blot confirmed that some low molecular weight fractions isolated from plaque contain ApoBDS-1 epitopes and possess ApoBDS-1-like bioactivity for induction of IL-8. These findings suggest that active ApoBDS-1 presents in atherosclerotic lesions. Analysis of BiKE database indicates that inflammasome pathways are involved in atherosclerosis and associated with the disease severity. Our studies show that ApoBDS-1 is an endogenous activator of NLRP3 inflammasome, inducing IL-1β in monocytes and macrophagesvia NLRP3-dependent caspase-1 activation. We also found that ApoBDS-1 could induce NLRP3 inflammasome complex formation in vivo, and activate NLRP3 inflammasome by induction of K+ efflux. Lastly, we explored the receptor/interacting protein for ApoBDS-1 using far Western blot and 2-D electrophoresis and identified TNF receptor associated protein 1 (Trap1) as an ApoBDS-1 specific interacting protein. Trap1 and ApoBDS-1 are colocalised mainly in cytoplasm and also on cell surface membrane. Biacore SPR analysis suggests that ApoBDS-1 binds toTrap1 with a medium affinity depending on the last 5 amino acids in its C-terminal domain. Trap1 is indispensable for ApoBDS-1 function since ApoBDS-1 induced cytokine secretion and reactive oxygen species can be inhibited by Geldanamycin, an inhibitor of Trap1 or by knocking down of Trap1 using specific shRNA. Taken together, we have identified ApoBDS-1 as the innate immune activator in ApoB100. Blocking the interaction of ApoBDS-1 and Trap1, or inhibition of ApoBDS-1 induced signaling pathways may represent new therapeutic options for atherosclerosis treatment

Quantized passive filtering for switched delayed neural networks

The issue of quantized passive filtering for switched delayed neural networks with noise interference is studied in this paper. Both arbitrary and semi-Markov switching rules are taken into account. By choosing Lyapunov functionals and applying several inequality techniques, sufficient conditions are proposed to ensure the filter error system to be not only exponentially stable, but also exponentially passive from the noise interference to the output error. The gain matrix for the proposed quantized passive filter is able to be determined through the feasible solution of linear matrix inequalities, which are computationally tractable with the help of some popular convex optimization tools. Finally, two numerical examples are given to illustrate the usefulness of the quantized passive filter design methods

Electrochemical Synthesis of Rare Earth Ceramic Oxide Coatings

Rare earth ceramic oxides are used in several applications including, phosphors, gas sensors, fuel cells, catalytic converters, and corrosion protection. These materials exhibit attractive properties such as fracture toughness, stiffness, and high strength-to-weight ratios. Synthesis of rare earth oxides includes a long list of techniques, but electrodeposition is one that has not been used as extensively as other techniques. This chapter discusses in detail the electrochemical synthesis of lanthanum, cerium, and praseodymium oxides. The physical and chemical properties of the electrodeposited oxides are characterized by x-ray diffraction, scanning electron microscopy, x-ray photoelectron spectroscopy, and other techniques. The electrochemical synthesis and post-treatment of other rare earth oxides, such as gadolinium, terbium, samarium, neodymium, europium, and dysprosium oxides are also covered in this chapter. Two main mechanisms of electrodeposition for rare earth oxides are discussed in detail

PhysarumSpreader: a new bio-Inspired methodology for identifying influential spreaders in complex networks

Identifying influential spreaders in networks, which contributes to optimizing the use of available resources and efficient spreading of information, is of great theoretical significance and practical value. A random-walk-based algorithm LeaderRank has been shown as an effective and efficient method in recognizing leaders in social network, which even outperforms the well-known PageRank method. As LeaderRank is initially developed for binary directed networks, further extensions should be studied in weighted networks. In this paper, a generalized algorithm PhysarumSpreader is proposed by combining LeaderRank with a positive feedback mechanism inspired from an amoeboid organism called Physarum Polycephalum. By taking edge weights into consideration and adding the positive feedback mechanism, PhysarumSpreader is applicable in both directed and undirected networks with weights. By taking two real networks for examples, the effectiveness of the proposed method is demonstrated by comparing with other standard centrality measures