489 research outputs found
The effects of quercetin and kaempferol on multidrug resistance and the expression of related genes in human erythroleukemic K562/A cells
Leukemia chemotherapy is believed to be impeded by multidrug resistance (MDR). Some compounds of flavonoid molecules were previously shown to inhibit drug transporter Pgp or induce apoptosis to sensitize MDR tumors. In this study, we attempted to investigate the possibility and mechanism of quercetin and kaempferol, flavonoid molecules, in reversing MDR. K562/A cells were cultured in vitro with the flavonoids as single and in combination respectively. Cell growth inhibition and adriamycin (ADR) sensitivity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 -diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was examined by Annexin V/PI staining method. Moreover, the expression of related genes for drug transporters and apoptosis was also tested after incubation with resveratrol for the first time. Results show a dose dependent manner and synergistic effect of the two compounds on K562/A. Furthermore, some of the genes in drug transporter families such as ATP-binding cassette (ABC) and solute carrier (SLC) and apoptosis related genes such as Bcl-2、tumor necrosis factor (TNF) and tumor necrosis factor receptor (TNFR) families were regulated. The experiment indicates that quercetin and kaempferol may be used as reveratrol in leukemia chemotherapy, but their interaction and difference should be noticed.Key words: Flavonoids, leukemia, multidrug resistance, polymerase chain reaction (PCR) array
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Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair.
Contrary to the long-held belief that DNA methylation of terminally differentiated cells is permanent and essentially immutable, post-mitotic neurons exhibit extensive DNA demethylation. The cellular function of active DNA demethylation in neurons, however, remains largely unknown. Tet family proteins oxidize 5-methylcytosine to initiate active DNA demethylation through the base-excision repair (BER) pathway. We found that synaptic activity bi-directionally regulates neuronal Tet3 expression. Functionally, knockdown of Tet or inhibition of BER in hippocampal neurons elevated excitatory glutamatergic synaptic transmission, whereas overexpressing Tet3 or Tet1 catalytic domain decreased it. Furthermore, dysregulation of Tet3 signaling prevented homeostatic synaptic plasticity. Mechanistically, Tet3 dictated neuronal surface GluR1 levels. RNA-seq analyses further revealed a pivotal role of Tet3 in regulating gene expression in response to global synaptic activity changes. Thus, Tet3 serves as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation
Neuronal Circuitry Mechanisms Regulating Adult Mammalian Neurogenesis
The adult mammalian brain is a dynamic structure, capable of remodeling in response to various physiological and pathological stimuli. One dramatic example of brain plasticity is the birth and subsequent integration of newborn neurons into the existing circuitry. This process, termed adult neurogenesis, recapitulates neural developmental events in two specialized adult brain regions: the lateral ventricles of the forebrain. Recent studies have begun to delineate how the existing neuronal circuits influence the dynamic process of adult neurogenesis, from activation of quiescent neural stem cells (NSCs) to the integration and survival of newborn neurons. Here, we review recent progress toward understanding the circuit-based regulation of adult neurogenesis in the hippocampus and olfactory bulb
Multi-authority attribute-based keyword search over encrypted cloud data
National Research Foundation (NRF) Singapore; AXA Research Fun
Towards Domain-Oriented Semi-Automated Model Matching for Supporting Data Exchange
The process of matching data represented in two different data models is a longstanding issue in the exchange of data between different software systems. While the traditional manual matching approach cannot meet today’s demands on data exchange, research shows that a fully automated generic approach for model matching is not likely, and generic semi-automated approaches are not easy to implement. In this paper, we present an approach that focuses on matching data models in a specific domain. The approach combines a basic model matching approach and a version matching approach to deduce new matching rules to enable data transfer between two evolving data models
Si3AlP: A new promising material for solar cell absorber
First-principles calculations are performed to study the structural and
optoelectronic properties of the newly synthesized nonisovalent and
lattice-matched (Si2)0.6(AlP)0.4 alloy [T. Watkins et al., J. Am. Chem. Soc.
2011, 133, 16212.] We find that the ordered CC-Si3AlP with a basic unit of one
P atom surrounded by three Si atoms and one Al atom is the most stable one
within the experimentally observed unit cell.1 Si3AlP has a larger fundamental
band gap and a smaller direct band gap than Si, thus it has much higher
absorption in the visible light region. The calculated properties of Si3AlP
suggest that it is a promising candidate for improving the performance of the
existing Si-based solar cells. The understanding on the stability and band
structure engineering obtained in this study is general and can be applied for
future study of other nonisovalent and lattice-matched semiconductor alloys
Magnetic structure and ferroelectric polarization of MnWO4 investigated by density functional calculations and classical spin analysis
The ordered magnetic states of MnWO4 at low temperatures were examined by
evaluating the spin exchange interactions between the Mn2+ ions of MnWO4 on the
basis of first principles density functional calculations and by performing
classical spin analysis with the resulting spin exchange parameters. Our work
shows that the spin exchange interactions are frustrated within each zigzag
chain of Mn2+ ions along the c-direction and between such chains of Mn2+ ions
along the a-direction. This explains the occurrence of a spiral-spin order
along the c- and a-directions in the incommensurate magnetic state AF2, and
that of a uudd spin order along the c- and a-directions in the commensurate
magnetic state AF1. The ferroelectric polarization of MnWO4 in the spiral-spin
state AF2 was examined by performing Berry phase calculations for a model
superstructure to find that the ferroelectric polarization occurs along the
b-direction, in agreement with experiment.Comment: 30 pages, 10 figures, 4 figure
Finding multiple target optimal intervention in disease-related molecular network
Drugs against multiple targets may overcome the many limitations of single targets and achieve a more effective and safer control of the disease. Numerous high-throughput experiments have been performed in this emerging field. However, systematic identification of multiple drug targets and their best intervention requires knowledge of the underlying disease network and calls for innovative computational methods that exploit the network structure and dynamics. Here, we develop a robust computational algorithm for finding multiple target optimal intervention (MTOI) solutions in a disease network. MTOI identifies potential drug targets and suggests optimal combinations of the target intervention that best restore the network to a normal state, which can be customer designed. We applied MTOI to an inflammation-related network. The well-known side effects of the traditional non-steriodal anti-inflammatory drugs and the recently recalled Vioxx were correctly accounted for in our network model. A number of promising MTOI solutions were found to be both effective and safer
Chiral patterns arising from electrostatic growth models
Recently, unusual and strikingly beautiful seahorse-like growth patterns have
been observed under conditions of quasi-two-dimensional growth. These
`S'-shaped patterns strongly break two-dimensional inversion symmetry; however
such broken symmetry occurs only at the level of overall morphology, as the
clusters are formed from achiral molecules with an achiral unit cell. Here we
describe a mechanism which gives rise to chiral growth morphologies without
invoking microscopic chirality. This mechanism involves trapped electrostatic
charge on the growing cluster, and the enhancement of growth in regions of
large electric field. We illustrate the mechanism with a tree growth model,
with a continuum model for the motion of the one-dimensional boundary, and with
microscopic Monte Carlo simulations. Our most dramatic results are found using
the continuum model, which strongly exhibits spontaneous chiral symmetry
breaking, and in particular finned `S' shapes like those seen in the
experiments.Comment: RevTeX, 12 pages, 9 figure
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