Aszonapyrone A Isolated from Neosartorya spinosa IFM 47025 Inhibits the NF-κB Signaling Pathway Activated by Expression of the Ependymoma-Causing Fusion Protein ZFTA-RELA

Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.

Detection of Adhesion Molecules on Inflamed Macrophages at Early-Stage Using SERS Probe Gold Nanorods

In recent years, it has been shown that inflammatory biomarkers can be used as an effective signal for disease diagnoses. The early detection of these signals provides useful information that could prevent the occurrence of severe diseases. Here, we employed surface-enhanced Raman scattering(SERS) probe gold nanorods(GNRs) as a tool for the early detection of inflammatory molecules in inflamed cells. A murine macrophage cell line(Raw264.7) stimulated with lipopolysaccharide(LPS) was used as a model in this study. The prepared SERS probe GNRs containing 4-mercaptobenzoic acid as a Raman reporter to generate SERS signals were used for detection of intracellular adhesion molecule-1(ICAM-1) in macrophages after treatment with LPS for varying lengths of time. Our results show that SERS probe GNRs could detect significant differences in the expression of ICAM-1 molecules in LPS-treated macrophages compared to those in untreated macrophages after only 1 h of LPS treatment. In contrast, when using fluorescent labeling or enzyme-linked immunosorbent assays(ELISA) to detect ICAM-1, significant differences between inflamed and un-inflamed macrophages were not seen until the cells had been treated with LPS for 5 h. These results indicate that our SERS probe GNRs provide a higher sensitivity for detecting biomarker molecules in inflamed macrophages than the conventional fluorescence and ELISA techniques, and could therefore be useful as a potential diagnostic tool for managing disease risk.

Effects of selenium-containing compounds on Cu^(2+)/Zn^(2+)-induced neuronal cell death and potential application as therapeutic agents for neurological diseases

In many tissues, trace metals such as iron(Fe), zinc(Zn), and copper(Cu) are important for various physiological functions such as immune function, cell division, and enzyme function. However, it has been shown in humans and experimental animal models that excessive amounts of these trace metals in the body can induce various diseases in the central nervous system, liver.

Aged Garlic Extract Reduces ROS Production and Cell Death Induced by 6-Hydroxydopamine through Activation of the Nrf2-ARE Pathway in SH-SY5Y Cells

Many degenerative or pathological processes, such as aging, cancer and coronary heart disease, are related to reactive oxygen species (ROS) and radical-mediated reactions. We examined the effectiveness of aged garlic extract (AGE), a garlic preparation rich in water-soluble cysteinyl moieties, for protection of cells from ROS produced by 6-hydroxy-dopamine (6-OHDA) using human neuroblastoma SH-SY5Y cells. Concomitant treatment of cells with AGE (2 and 4 mg/ml) showed the dose-dependent protective effect on the cell death induced by 6-OHDA. In addition, the AGE treatment significantly suppressed the increase of ROS generation by 6-OHDA. Furthermore, the protective effect of AGE was accompanied by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the increase of mRNAs of heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. These two enzymes are important in the cellular antioxidant system. These results indicated that AGE protected cells from ROS damage by not only capturing ROS directly but also activating the cellular antioxidant system by stimulating antioxidant gene expression via the Nrf2-ARE pathway. The present study suggested that AGE may be useful for prevention and treatment of cell damage caused by ROS.

Role of Self-Loop in Cell-Cycle Network of Budding Yeast

Study of network dynamics is very active area in biological and social sciences. However, the relationship between the network structure and the attractors of the dynamics has not been fully understood yet. In this study, we numerically investigated the role of degenerate self-loops on the attractors and its basin size using the budding yeast cell-cycle network model. In the network, all self-loops negatively suppress the node (self-inhibition loops) and the attractors are only fixed points, i.e. point attractors. It is found that there is a simple division rule of the state space by removing the self-loops when the attractors consist only of point attractors. The point attractor with largest basin size is robust against the change of the self-inhibition loop. Furthermore, some limit cycles of period 2 appear as new attractor when a self-activation loop is added to the original network. It is also shown that even in that case, the point attractor with largest basin size is robust.

Computational Creation of Hollow Mask Type Illusionary Solids with Shading Effect

＂Hollow mask illusion＂ is an optical illusion and appears due to an error in the process of reconstructing the three-dimensional objects from our two-dimensional retinal image. In this paper, we present a computational method to create ＂Hollow mask＂ type new illusionary solid by calculating the hollow structure and its shading. The straight line Voronoi diagram for a given shape obtains the three-dimensional vertices of the hollow structure and the shading effect on each surface is calculated under the assumption that each surface has diffusely reflecting surface（Lambertian reflectance）. We also show two examples of our new illusionary solid works.