Ellagic acid controls cell proliferation and induces apoptosis in breast cancer cells via inhibition of cyclin-dependent kinase 6

Cyclin-Dependent Kinase 6 (CDK6) plays an important role in cancer progression, and thus, it is considered as an attractive drug target in anticancer therapeutics. This study presents an evaluation of dietary phytochemicals, capsaicin, tocopherol, rosmarinic acid, ursolic acid, ellagic acid (EA), limonene, caffeic acid, and ferulic acid for their potential to inhibit the activity of CDK6. Molecular docking and fluorescence binding studies revealed appreciable binding affinities of these compounds to the CDK6. Among them, EA shows the highest binding affinity for CDK6, and thus a molecular dynamics simulation study of 200 ns was performed to get deeper insights into the binding mechanism and stability of the CDK6-EA comple

The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome

<p>Abstract</p> <p>Background</p> <p>Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A) plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s) responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood.</p> <p>Methods</p> <p>We employed 2-dimensional difference gel electrophoresis (2D-DIGE), a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL) proteomes in wild type (WT) and SP-A knockout (KO) mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups.</p> <p>Results</p> <p>We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours) there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice.</p> <p>Conclusion</p> <p>We postulate that SP-A plays a role in reactive oxidant scavenging in WT mice and that its absence in the KO mice in the presence or absence of ozone exposure results in more pronounced, and presumably chronic, oxidative stress.</p

Nuclear magnetic resonance studies of some electrolyte solutions.

The equilibrium constant for the dissociation of the BeF₄˭ ion in aqueous solutions of the ammonium salt has been computed by using the intensities of the fluorine nuclear magnetic resonance signals to indicate the concentrations of the three species at equilibrium. The simple dissociation may be represented as; BeF₄˭⇢ BeF₃¯+ F¯ (i) KE = 8.0 ± 0.9 x 10¯²moles (Kg)¯¹at 33°C. The equilibrium was measured over the temperature range 0-50°C but no appreciable temperature coefficient was observed. Variation of the concentration of BeF₂ solution allows the identification of further resonances, which have been associated with the unionized BeF₂ and a possible existence of a BeBeF₄ species. Chemical shift changes in the ⁹Be nuclear resonance positions are minimal. Some suggestions are made regarding the kinetics of fluorine exchange in reaction (i). The large changes in ¹¹B-¹⁹F coupling constant and ¹⁹F chemical shift of BF₄¯ ion at different concentration in aqueous and mixed solvents (acetone/water, dioxane/ water and D.M.S.O./water) have been interpreted in terms of changes in the hydrogen bonding of water to the BF₄¯ ion. The unique behavior of chemical shift and coupling constant in D.M.S.O./water has been explained by preferential solvation of BF₄¯ ion by the protolysis product of D.M.S.O. in water. The concentration dependence of the fluorine chemical shift of diamagnetic salts of fluoroanions of the type F¯, BF₄¯ and SiF₆˭ have been studies and the molal chemical shift has been correlated with the size and the charge of the cation. A displacement of the fluorine chemical shift to low field was observed for F¯, BF₄¯, BeF₄˭, PF₆¯ and SiF₆˭ aqueous solutions with paramagnetic cations Cu⁺⁺, Ni⁺⁺, Co⁺⁺, Fe⁺⁺, Fe⁺⁺⁺, Cr⁺⁺⁺ and Mn⁺⁺. These shifts are explained on the basis of ion-pair formation between cation and fluoroanion. The molar shifts have been interpreted in terms of a contact interaction between unpared electron and ¹⁹F nucleus. The contribution due to Pseudo contact shift, which arises due to anisotropy in g-factor is probably small. The changes in ¹⁹F line width with the concentration of paramagnetic ion have been discussed in the light of exchange between freee and ion-paired fluoro-anion. Further evidence regarding the ion-pair formation in f luoro-borates has been obtained from ¹¹B chemical shift and line width measurements. ¹⁹F N.M.R. spectra of HF₂¯ ion of Na⁺, K⁺ and NH₄⁺ cations have been studied, and the equilibrium constant for the reaction HF₂ ⇢ HF + F¯ (ii) have been measured for the potassium salt. Preliminary investigations of different gallium fluoride complex in mixtures of AgF and Ga(ClO₄)₃ have been madeScience, Faculty ofChemistry, Department ofGraduat