Ginger, the rhizome of Zingiber officinale, is a traditional medicine with carminative effect, antinausea, anti-inflammatory, and anticarcinogenic properties. In this study, we investigated the inhibitory effects of 6-shogaol and a related compound, 6-gingerol, on the induction of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with LPS. Western blotting and reverse transcription-PCR analyses demonstrated that 6-shogaol significantly blocked protein and mRNA expression of inducible NOS (iNOS) and COX-2 in LPS-induced macrophages. The in vivo anti-inflammatory activity was evaluated by a topical 12-O-tetradecanoylphorbol 13-acetate (TPA) application to mouse skin. When applied topically onto the shaven backs of mice prior to TPA, 6-shogaol markedly inhibited the expression of iNOS and COX-2 proteins. Treatment with 6-shogaol resulted in the reduction of LPS-induced nuclear translocation of nuclear factor-kappaB (NF kappaB) subunit and the dependent transcriptional activity of NF kappaB by blocking phosphorylation of inhibitor kappaB (I kappaB)alpha and p65 and subsequent degradation of I kappaB alpha. Transient transfection experiments using NF kappaB reporter constructs indicated that 6-shogaol inhibits the transcriptional activity of NF kappaB in LPS-stimulated mouse macrophages. We found that 6-shogaol also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2, but not p38 mitogen-activated protein kinase (MAPK). Taken together, these results show that 6-shogaol downregulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NF kappaB by interfering with the activation PI3K/Akt/I kappaB kinases IKK and MAPK.
The spin field effect transistor envisioned by Datta and Das[1] opens a gateway to spin information processing [2,3]. Although the coherent manipulation of electron spins in semiconductors is now possible [4][5][6][7], the realization of a functional spin field effect transistor for information processing has yet to be achieved, owing to several fundamental challenges such as the low spin-injection efficiency due to resistance mismatch [9], spin relaxation, and the spread of spin precession angles. Alternative spin transistor designs have therefore been proposed [10,11], but these differ from the field effect transistor concept and require the use of optical or magnetic elements, which pose difficulties for the incorporation into integrated circuits. Here, we present an all-electric and all-semiconductor spin field effect transistor, in which these obstacles are overcome by employing two quantum point contacts as spin injectors and detectors. Distinct engineering architectures of spin-orbit coupling are exploited for the quantum point contacts and the central semiconductor channel to achieve complete control of the electron spins-spin injection, manipulation, and detection-in a purely electrical manner. Such a device is compatible with large-scale integration and hold promise for future spintronic devices for information processing.Spin-orbit (SO) coupling-the interaction between a particle's spin and its motion-can be appreciated in the framework of an effective magnetic field B SO , which acts on charged particles when they move in an electric field E and is described by, where is Planck's constant divided by 2π, c is the speed of light, k is the particle's wavevector, and m is its mass. In semiconductor heterostructures, the electric field which gives rise to B SO can be created by breaking the structural inversion symmetry in the material, namely, the Rashba SO coupling [12,13]. Moreover, this electric field can easily be varied using metallic gates [14,15], thus controlling B SO . Such an effective magnetic field creates a link between the magnetic moment of the particle (spin) and the electric field acting upon it, offering a route for fast and coherent electrical control of spin states. While the SO coupling has been utilized for spin manipulation, approaches to spin injection and detection still rely on ferromagnetic and/or optical components, and the demonstration of an all-electric spin transistor device has remained elusive.Figure 1 illustrates our proposed spin field effect transistor (FET) and its operating principle. An InGaAs heterostructure (see Methods Summary), one of the strong contenders to replace Si in future generations of largescale integrated circuits (see International Technology Roadmap for Semiconductors; http://public.itrs.net), is used to provide a two-dimensional electron gas (2DEG) channel for ballistic electron transport under a metallic middle gate and between two gate-defined quantum point contacts (QPCs). The QPCs are narrow and short onedimensional (1D) constrictions, usually...
Malignant gliomas are resistant to many kinds of treatments including chemotherapy, radiotherapy and other adjuvant therapies. Autophagy is a novel response of cancer cells to ionizing radiation (IR) or chemotherapy, but its significance and underlying mechanism remains largely elusive. Induction of autophagy in glioma cells using irradiation and arsenic trioxide (ATO) has been reported separately. However, the combined effects of ATO and IR on the cell death processes of malignant glioma cells have not been thoroughly studied, especially in U118-MG cells. In the present study, we investigated the anticancer effect of IR combined with ATO and the underlying mechanisms on U118-MG human malignant glioma cells in vitro. We found that the enhanced cytotoxic effect of IR combined with ATO was through induction of more autophagy in U118-MG cells, which were characterized by the presence of acidic vascular organelle formation, determined by electron microscopic observation and immunoblotting of LC3. Combined treatment could induce more mitotic arrest compared to ATO or IR alone. In addition, we also found that the combined treatmentinduced autophagy occurred through inhibition of PI3K/Akt and activation of ERK1/2 signaling pathways. These findings suggest a potential therapeutic strategy for malignant gliomas, which are resistant to various proapoptotic therapies.
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