Aspisol inhibits tumor growth and induces apoptosis in breast cancer

Nonsteroidal anti-inflammatory drugs inhibit cell proliferation and induce apoptosis in various cancer cell lines, which is considered to be an important mechanism for their anti-tumor activity and cancer prevention. However, the molecular mechanisms through which these compounds induce apoptosis are not well understood. Aim: to determine the effects of nonselective cyclooxygenase-2 (COX-2) inhibitor, aspisol on breast cancer cells in vitro and in vivo. Methods: The cytotoxic activity of aspisol was evaluated by MTT assay. The apoptosis index of cells was measured by flow cytometry. Immunohistochemical staining was used to detect expressions of COX-2 and caspase-3 in MDA-MB-231 cells. The expression of bcl-2 and bax was analyzed by Western blot analysis. The content of prostaglandin E2 (PGE2) in MDA-MB-231 cells was estimated by ELISA. In vivo apoptosis of the tumor cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Results: Our results showed that aspisol reduced viability of MDA-MB-231 cells in time- and dose- dependent fashions and induced apoptosis by increase of caspase-3 and bax expressions while decrease of COX-2 and bcl-2 expression in vitro. In addition, exposure to aspisol decreased the basal release of PGE2. In vivo, aspisol also inhibited the proliferation of breast cancer cells and induced their apoptosis. Conclusions: Our in vitro and in vivo data indicated that the antitumor effects of aspisol on breast cancer cells was probably mediated by the induction of apoptosis, and it could be linked to the downregulation of the COX-2 or bcl-2 expression and up-regulation of caspase-3 or bax expression.Нестероидные противовоспалительные препараты ингибируют пролиферацию клеток и вызывают апоптоз во многих опухолевых клеточных линиях, что считается важным механизмом их противоопухолевой активности и профилактики развития рака. Тем не менее молекулярные механизмы апоптотического действия этих препаратов изучены недостаточно. Цель: изучить действие неспецифического ингибитора циклогексиназы-2 (COX-2) — аспизола — на злокачественные клетки рака молочной железы in vitro и in vivo. Методы: выживаемоть клеток MDA-MB-231 определяли с помощью MTT-теста. Апоптотический индекс измеряли с помощью проточной цитометрии и иммуногистохимическим окрашиванием с антителами против COX-2 и каспазы-3. Экспрессию bcl-2 и bax изучали с помощью Вестерн-блот-анализа. Содержание простагландина E2 (PGE2 ) в клетках MDA-MB-231 оценивали методом ELISA. In vivo апоптоз опухолевых клеток определяли путем выявления разрывов ДНК с помощью концевой дезоксинуклеот-идилтранферазы (метод TUNEL). Результаты: показано, что в зависимости от времени инкубации и дозы аспизол угнетал рост клеток MDA-MB-231 in vitro и вызывал их апоптоз на фоне повышения экспрессии каспазы-3 и bax, а также снижения экспрессии COX-2 и bcl-2. В условиях in vivo аспизол также ингибировал пролиферацию злокачественных клеток рака молочной железы и вызывал их апоптоз. Выводы: данные, полученные in vitro и in vivo, свидетельствуют о противоопухолевом эффекте аспизола на клетки рака молочной железы, что скорее всего опосредовано его проапоптотическим действием и может быть связано со снижением экспрессии COX-2 и bcl-2, а также повышением экспрессии каспазы-3 и bax

Magnetic resonance imaging of glutamate in neuroinflammation

AbstractInflammation in central nervous system (CNS) is one of the most severe diseases, and also plays an impellent role in some neurodegenerative diseases. Glutamate (Glu) has been considered relevant to the pathogenesis of neuroinflammation. In order to diagnose neuroinflammation incipiently and precisely, we review the pathobiological events in the early stages of neuroinflammation, the interactions between Glu and neuroinflammation, and two kinds of magnetic resonance techniques of imaging Glu (chemical exchange saturation transfer and magnetic resonance spectroscopy)

Kaonic hydrogen and deuterium in Hamiltonian effective field theory

The anti-kaon nucleon scattering lengths resulting from a Hamiltonian effective field theory analysis of experimental data and lattice QCD studies are presented. The same Hamiltonian is then used to compute the scattering length for the system, taking careful account of the effects of recoil on the energy at which the KNT-matrices are evaluated. These results are then used to estimate the shift and width of the 1S levels of anti-kaonic hydrogen and deuterium. The K¯p result is in excellent agreement with the SIDDHARTA measurement. In the K¯d case the imaginary part of the scattering length and consequently the width of the 1S state are considerably larger than found in earlier work. This is a consequence of the effect of recoil on the energy of the KN energy, which enhances the role of the Λ (1405) resonance.Zhan-Wei Liu, Jia-Jun Wu, Derek B. Leinweber, Anthony W. Thoma

Spinor Fields and Symmetries of the Spacetime

In the background of a stationary black hole, the "conserved current" of a particular spinor field always approaches the null Killing vector on the horizon. What's more, when the black hole is asymptotically flat and when the coordinate system is asymptotically static, then the same current also approaches the time Killing vector at the spatial infinity. We test these results against various black hole solutions and no exception is found. The spinor field only needs to satisfy a very general and simple constraint.Comment: 19 page

Changes in impacts of climate extremes: human systems and ecosystems

In this chapter, two different types of impacts on human and ecological systems are examined: (i) impacts of extreme weather and climate events; and (ii) extreme impacts triggered by less-than-extreme weather or climate events (in combination with non-climatic factors, such as high exposure and/or vulnerability). Where data are available, impacts are examined from sectoral and regional perspectives.Peer Reviewe

Heterogeneous microstructure and mechanical behaviour of Al-8.3Fe-1.3V-1.8Si alloy produced by laser powder bed fusion

The relationship between processing parameters, microstructure, and mechanical properties of Al-8.3Fe-1.3V-1.8Si alloy processed by laser powder bed fusion is seldom studied. Therefore, fully dense alloys with two parameters were selected to investigate this key issue. The results show that the alloy with low power and scanning speed (S200) shows fan-shell-shaped melt pools and laser tracks while another (S350) shows a deeper and wider melt pool. Both alloys obtain a heterogeneous microstructure without a secondary phase in melt pool (MP) and a nano-sized phase in melt pool boundary (MPB). The difference between solid-solution strengthening and Orowan strengthening in MP and MPB contributes to the difference in compressive yield strength (S200: 380 ± 14 MPa and S350: 705 ± 16 MPa), and heterogeneous nano-hardness results in different crack behaviours and failure strains. This work indicates that adjusting processing parameters is an effective method to control microstructure and mechanical properties of this alloy

Electronic Structure of the Complex Hydride NaAlH4

Density functional calculations of the electronic structure of the complex hydride NaAlH4 and the reference systems NaH and AlH3 are reported. We find a substantially ionic electronic structure for NaAlH4, which emphasizes the importance of solid state effects in this material. The relaxed hydrogen positions in NaAlH4 are in good agreement with recent experiment. The electronic structure of AlH3 is also ionic. Implications for the binding of complex hydrides are discussed.Comment: 4 pages, 5 figure

Contributions to the cross shock electric field at supercritical perpendicular shocks: Impact of the pickup ions

A particle-in-cell code is used to examine contributions of the pickup ions (PIs) and the solar wind ions (SWs) to the cross shock electric field at the supercritical, perpendicular shocks. The code treats the pickup ions self-consistently as a third component. Herein, two different runs with relative pickup ion density of 25% and 55% are presented in this paper. Present preliminary results show that: (1) in the low percentage (25%) pickup ion case, the shock front is nonstationary. During the evolution of this perpendicular shock, a nonstationary foot resulting from the reflected solar wind ions is formed in front of the old ramp, and its amplitude becomes larger and larger. At last, the nonstationary foot grows up into a new ramp and exceeds the old one. Such a nonstationary process can be formed periodically. hen the new ramp begins to be formed in front of the old ramp, the Hall term mainly contributed by the solar wind ions becomes more and more important. The electric field Ex is dominated by the Hall term when the new ramp exceeds the old one. Furthermore, an extended and stationary foot in pickup ion gyro-scale is located upstream of the nonstationary/self-reforming region within the shock front, and is always dominated by the Lorentz term contributed by the pickup ions; (2) in the high percentage (55%) pickup ion case, the amplitude of the stationary foot is increased as expected. One striking point is that the nonstationary region of the shock front evidenced by the self-reformation disappears. Instead, a stationary extended foot dominated by Lorentz term contributed by the pickup ions, and a tationary ramp dominated by Hall term contributed by the solar wind ions are clearly evidenced. The significance of the cross electric field on ion dynamics is also discussed.Comment: 11 pages, 6 figs and 1 table. This paper will be published in the journal: Astrophysics and Space Scienc

Spin-Polarized Transport Across an La0.7_{0.7}Sr0.3_{0.3}MnO3_{3}/YBa2_{2}Cu3_{3}O7_{7} Interface: Role of Andreev Bound States

Transport across an La$_{0.7}$Sr$_{0.3}MnO$_{3}/YBa$_{2}Cu$_{3}$O$_{7}$(LSMO/YBCO), interface is studied as a function of temperature and surface morphology. For comparison, control measurements are performed in non-magnetic heterostructures of LaNiO$_{3}$/YBCO and Ag/YBCO. In all cases, YBCO is used as bottom layer to eliminate the channel resistance and to minimize thermal effects. The observed differential conductance re ects the role of Andreev bound states in a-b planes, and brings out for the first time the suppression of such states by the spin-polarized transport across the interface. The theoretical analysis of the measured data reveals decay of the spin polarization near the LSMO surface with temperature, consistent with the reported photoemission data.Comment: 5 pages LaTeX, 3 eps figures included, accepted by Physical Review

A Real Space Description of Field Induced Melting in the Charge Ordered Manganites: II. the Disordered Case

We study the effect of A site disorder on magnetic field induced melting of charge order (CO) in half doped manganites using a Monte-Carlo technique. Strong A-site disorder destroys CO even without an applied field. At moderate disorder, the zero field CO state survives but has several intriguing features in its field response. Our spatially resolved results track the broadening of the field melting transition due to disorder and explain the unusual dependence of the melting scales on bandwidth and disorder. In combination with our companion paper on field melting of charge order in clean systems we provide an unified understanding of CO melting across all half doped manganites.Comment: 9 pages, pdflatex, 10 embedded png fig