1,265 research outputs found
Tetrandrine, an activator of autophagy, induces autophagic cell death via PKC-α inhibition and mTOR-dependent mechanisms.
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes. In addition, tetrandrine induces cell death in a panel of apoptosis-resistant cell lines that are deficient for caspase 3, caspase 7, caspase 3 and 7, or Bax-Bak respectively. We also showed that tetrandrine-induced cell death is independent of necrotic cell death. Mechanistically, tetrandrine induces autophagy that depends on mTOR inactivation. Furthermore, tetrandrine induces autophagy in a calcium/calmodulin-dependent protein kinase kinase-β (CaMKK-β), 5′ AMP-activated protein kinase (AMPK) independent manner. Finally, by kinase profiling against 300 WT kinases and computational molecular docking analysis, we showed that tetrandrine is a novel PKC-α inhibitor, which lead to autophagic induction through PKC-α inactivation. This study provides detailed insights into the novel cytotoxic mechanism of an anti-tumor compound originated from the herbal plant, which may be useful in promoting autophagy mediated- cell death in cancer cell that is resistant to apoptosis.published_or_final_versio
Generalized Painleve-Gullstrand descriptions of Kerr-Newman black holes
Generalized Painleve-Gullstrand metrics are explicitly constructed for the
Kerr-Newman family of charged rotating black holes. These descriptions are free
of all coordinate singularities; moreover, unlike the Doran and other proposed
metrics, an extra tunable function is introduced to ensure all variables in the
metrics remain real for all values of the mass M, charge Q, angular momentum
aM, and cosmological constant \Lambda > - 3/(a^2). To describe fermions in
Kerr-Newman spacetimes, the stronger requirement of non-singular vierbein
one-forms at the horizon(s) is imposed and coordinate singularities are
eliminated by local Lorentz boosts. Other known vierbein fields of Kerr-Newman
black holes are analysed and discussed; and it is revealed that some of these
descriptions are actually not related by physical Lorentz transformations to
the original Kerr-Newman expression in Boyer-Lindquist coordinates - which is
the reason complex components appear (for certain ranges of the radial
coordinate) in these metrics. As an application of our constructions the
correct effective Hawking temperature for Kerr black holes is derived with the
method of Parikh and Wilczek.Comment: 5 pages; extended to include application to derivation of Hawking
radiation for Kerr black holes with Parikh-Wilczek metho
Numerical Study of Hydrodynamic Process in Chaohu Lake
In this paper, the hydrodynamic characteristics of water flow in Chaohu Lake are studied by using the finite volume coastal ocean model (FVCOM), which is verified by the observed data. The typical flow field and the 3-D flow structure are obtained for the lake. The flow fields under extreme conditions are analyzed to provide a prospective knowledge of the water exchange and the transport process.The influence of the wind on the flow is determined by the cross spectrum method. The results show that the wind-driven flow dominates most area of the lake. Under prevailing winds in summer and winter, the water flows towards the downwind side at the upper layer while towards the upwind side at the lower layer in most area except that around the Chaohu Sluice. The extreme wind speed is not favorable for the water exchange while the sluice's releasing water accelerates the process. The water velocity in the lake is closely related with the wind speed
RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro
<p>Abstract</p> <p>Background</p> <p>CD147 is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. CD147 has been implicated in numerous physiological and pathological activities. Enriched on the surface of many tumor cells, CD147 promotes tumor growth, invasion, metastasis and angiogenesis and confers resistance to some chemotherapeutic drugs. In this study, we investigated the possible role of CD147 in the progression of gastric cancer.</p> <p>Methods</p> <p>Short hairpin RNA (shRNA) expressing vectors targeting CD147 were constructed and transfected into human gastric cancer cells SGC7901 and CD147 expression was monitored by quantitative realtime RT-PCR and Western blot. Cell proliferation, the activities of MMP-2 and MMP-9, the invasive potential and chemosensitivity to cisplatin of SGC7901 cells were determined by MTT, gelatin zymography, Transwell invasion assay and MTT, respectively.</p> <p>Results</p> <p>Down-regulation of CD147 by RNAi approach led to decreased cell proliferation, MMP-2 and MMP-9 activities and invasive potential of SGC7901 cells as well as increased chemosensitivity to cisplatin.</p> <p>Conclusion</p> <p>CD147 involves in proliferation, invasion and chemosensitivity of human gastric cancer cell line SGC7901, indicating that CD147 may be a promising therapeutic target for gastric cancer.</p
Observation of CR Anisotropy with ARGO-YBJ
The measurement of the anisotropies of cosmic ray arrival direction provides
important informations on the propagation mechanisms and on the identification
of their sources. In this paper we report the observation of anisotropy regions
at different angular scales. In particular, the observation of a possible
anisotropy on scales between 10 and 30
suggests the presence of unknown features of the magnetic fields the charged
cosmic rays propagate through, as well as potential contributions of nearby
sources to the total flux of cosmic rays. Evidence of new weaker few-degree
excesses throughout the sky region R.A. is
reported for the first time.Comment: Talk given at 12th TAUP Conference 2011, 5-9 September 2011, Munich,
German
Vegetable Oil-Based Hyperbranched Thermosetting Polyurethane/Clay Nanocomposites
The highly branched polyurethanes and vegetable oil-based polymer nanocomposites have been showing fruitful advantages across a spectrum of potential field of applications.Mesua ferreaL. seed oil-based hyperbranched polyurethane (HBPU)/clay nanocomposites were prepared at different dose levels by in situ polymerization technique. The performances of epoxy-cured thermosetting nanocomposites are reported for the first time. The partially exfoliated structure of clay layers was confirmed by XRD and TEM. FTIR spectra indicate the presence of H bonding between nanoclay and the polymer matrix. The present investigation outlines the significant improvement of tensile strength, scratch hardness, thermostability, water vapor permeability, and adhesive strength without much influencing impact resistance, bending, and elongation at break of the nanocomposites compared to pristine HBPU thermoset. An increment of two times the tensile strength, 6 °C of melting point, and 111 °C of thermo-stability were achieved by the formation of nanocomposites. An excellent shape recovery of about 96–99% was observed for the nanocomposites. Thus, the formation of partially exfoliated clay/vegetable oil-based hyperbranched polyurethane nanocomposites significantly improved the performance
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