Selenium effectively inhibits ROS-mediated apoptotic neural precursor cell death in vitro and in vivo in traumatic brain injury

AbstractThis study was designed to investigate possible prevention of apoptotic cell death by selenium, an antioxidant, using cultured brain-derived neural progenitor cells (NPCs) and an experimental mouse brain trauma (BT) model. We tested some of the neuroprotective effects of sodium selenite in NPC cells by monitoring thioredoxin reductase (TR) expression, optimum H2O2 removal, and consequent inhibition of pro-apoptotic events including cytochrome c release and caspase 3 and 9 activation. Analysis of key apoptotic regulators during H2O2-induced apoptosis of NPCs showed that selenite blocks the activation of c-jun N-terminal protein kinase (JNK)/P38 mitogen-activated protein kinase (MAPK), and Akt survival protein. Moreover, selenite activates p44/42 MAPK and inhibits the downregulation of Bcl2 in selenite-treated NPC cells. For in vivo experiments, the effects of selenite on H2O2 neurotoxicity were tested using several biochemical and morphologic markers. Here we show that selenite potentially inhibits H2O2-induced apoptosis of NPCs and in traumatic brain injury. This in vivo protective function was also associated with inhibition of H2O2-induced reactive oxygen species (ROS) generation, cytochrome c release and caspase 3 and 9 activation. Our data show that the protective function of selenite through attenuation of secondary pathological events most likely results from its comprehensive effects that block apoptotic cell death, resulting in the maintenance of functional neurons and in inhibition of astrogliosis. The finding that selenite administration prevents secondary pathological events in an animal model of traumatic brain injury, as well as its efficacy, may provide novel drug targets for treating brain trauma

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Movimiento del Nuevo Teatro (신연극, Sinyeongeuk) en Corea

Las nuevas formas teatrales que aparecen a partir de los inicios del siglo XX sufrieron una transformación a lo largo del tiempo. Pasaron de los intentos iniciales de romper con el teatro tradicional de un modo radical, para luego redescubrir éste como elemento coreanizador de las nuevas expresiones de las artes escénicas. Esta investigación nos servirá para entender mejor los fundamentos históricos y artísticos sobre los que se asientan las nuevas tendencias en las artes escénicas coreanas que les han llevado a salir de sus fronteras para entablar un diálogo con otras expresiones teatrales del mundo y dar el salto hacia una visión más global de sus propias características artísticas. Han pasado más de 100 años desde la entrada del teatro occidental en Corea. Estos 100 años de acogida del teatro occidental han dejado una profunda huella en la historia moderna del teatro coreano. Las raíces que el teatro occidental ha implantado en su historia moderna dominan el mundo del teatro actual. Para poder entender apropiadamente este proceso de implantación del teatro occidental en la península y su influencia sobre las artes escénicas coreanas es necesario estudiar detenidamente una de las corrientes teatrales más influyentes en la primera mitad del siglo XX, el llamado “Movimiento del Nuevo Teatro” (신연극, Sinyeongeuk).Centro de Estudios Coreano

Mitochondrial Hsp90s suppress calcium-mediated stress signals propagating from mitochondria to the ER in cancer cells

Background: Resistance to cell death in the presence of stressful stimuli is one of the hallmarks of cancer cells acquired during multistep tumorigenesis, and knowledge of the molecular mechanism of stress adaptation can be exploited to develop cancer-selective therapeutics. Mitochondria and the endoplasmic reticulum (ER) are physically interconnected organelles that can sense and exchange various stress signals. Although there have been many studies on stress propagation from the ER to mitochondria, reverse stress signals originating from mitochondria have not been well reported.Methods: After inactivation of the proteins by pharmacologic and genetic methods, the signal pathways were analyzed by fluorescence microscopy, flow cytometry, MTT assay, and western blotting. A mouse xenograft model was used to examine synergistic anticancer activity and the action mechanism of drugs in vivo.Results: We show in this study that mitochondrial heat shock protein 90 (Hsp90) suppresses mitochondria-initiated calcium-mediated stress signals propagating into the ER in cancer cells. Mitochondrial Hsp90 inhibition triggers the calcium signal by opening the mitochondrial permeability transition pore and, in turn, the ER ryanodine receptor, via calcium-induced calcium release. Subsequent depletion of ER calcium activates unfolded protein responses in the ER lumen, thereby increasing the expression of a pro-apoptotic transcription factor, CEBP homologous protein (CHOP). Combined treatment with the ER stressor thapsigargin and the mitochondrial Hsp90 inhibitor gamitrinib augmented interorganelle stress signaling by elevating CHOP expression, and showed synergistic cytotoxic activity exclusively in cancer cells in vitro and in vivo.Conclusions: Collectively, mitochondrial Hsp90s confer cell death resistance to cancer cells by suppressing the mitochondria-initiated calcium-mediated interorganelle stress response.open0

Self-regulated mechanism of Plk1 localization to kinetochores: lessons from the Plk1-PBIP1 interaction

Mammalian polo-like kinase 1 (Plk1) has been studied extensively as a critical element in regulating various mitotic events during M-phase progression. Plk1 function is spatially regulated through the targeting activity of the conserved polo-box domain (PBD) present in the C-terminal non-catalytic region. Recent progress in our understanding of Plk1 localization to the centromeres shows that Plk1 self-regulates its initial recruitment by phosphorylating a centromeric component PBIP1 and generating its own PBD-binding site. Paradoxically, Plk1 also induces PBIP1 delocalization and degradation from the mitotic kinetochores late in the cell cycle, consequently permitting itself to bind to other kinetochore components. Thus, PBIP1-dependent self-recruitment of Plk1 to the interphase centromeres serves as a prelude to the efficient delivery of Plk1 itself to other kinetochore components whose interactions with Plk1 are vital for proper mitotic progression

Successful Salvage Unrelated Umbilical Cord Blood Transplantation with Two Units After Engraftment Failure with Single Unit in Severe Aplastic Anemia

Severe aplastic anemia (SAA) patients without an HLA-matched sibling donor need alternative treatment options. Umbilical cord blood transplantation (UCBT) has become an alternative means for treating various diseases, but it has not been proved to be a satisfactory method to treat SAA. Here, we report the case of a girl who underwent successful two-unit UCBT after engraftment failure with a single unit. Two-unit UCBT is proposed to have better engraftment potential and to offer a better chance of survival, according to some reports. Increased cell dose and graft-versus-graft reaction could contribute to these advantages. With this promising result, two-unit UCBT could be an alternative treatment option for patients with SAA without an HLA-matched donor

Quantum Optical Induced-Coherence Tomography by a Hybrid Interferometer

Quantum interferometry based on induced-coherence phenomena has demonstrated the possibility of undetected-photon measurements. Perturbation in the optical path of probe photons can be detected by interference signals generated by quantum mechanically correlated twin photons propagating through a different path, possibly at a different wavelength. To the best of our knowledge, this work demonstrates for the first time a hybrid-type induced-coherence interferometer that incorporates a Mach-Zehnder-type interferometer for visible photons and a Michelson-type interferometer for infrared photons, based on double-pass pumped spontaneous parametric down-conversion. This configuration enables infrared optical measurements via the detection of near-visible photons and provides methods for characterizing the quality of measurements by identifying photon pairs of different origins. The results verify that the induced-coherence interference visibility is approximately the same as the heralding efficiencies between twin photons along the relevant spatial modes. Applications to both time-domain and frequency-domain quantum-optical induced-coherence tomography for three-dimensional test structures are demonstrated. The results prove the feasibility of practical undetected-photon sensing and imaging techniques based on the presented structure

Measurement of the Background Activities of a 100Mo-enriched powder sample for AMoRE crystal material using a single high purity germanium detector

The Advanced Molybdenum-based Rare process Experiment (AMoRE) searches for neutrino-less double-beta (0{\nu}\b{eta}\b{eta}) decay of 100Mo in enriched molybdate crystals. The AMoRE crystals must have low levels of radioactive contamination to achieve low background signals with energies near the Q-value of the 100Mo 0{\nu}\b{eta}\b{eta} decay. To produce low-activity crystals, radioactive contaminants in the raw materials used to form the crystals must be controlled and quantified. 100EnrMoO3 powder, which is enriched in the 100Mo isotope, is of particular interest as it is the source of 100Mo in the crystals. A high-purity germanium detector having 100% relative efficiency, named CC1, is being operated in the Yangyang underground laboratory. Using CC1, we collected a gamma spectrum from a 1.6-kg 100EnrMoO3 powder sample enriched to 96.4% in 100Mo. Activities were analyzed for the isotopes 228Ac, 228Th, 226Ra, and 40K. They are long-lived naturally occurring isotopes that can produce background signals in the region of interest for AMoRE. Activities of both 228Ac and 228Th were < 1.0 mBq/kg at 90% confidence level (C.L.). The activity of 226Ra was measured to be 5.1 \pm 0.4 (stat) \pm 2.2 (syst) mBq/kg. The 40K activity was found as < 16.4 mBq/kg at 90% C.L.Comment: 20 pages, 6 figures, 5 table