Evaluation of in vitro and in vivo Cytotoxic Activities and Kinase Inhibition of Newly Synthesized Cyclo (Nα-Dinicotinoyl)-Bis-[(L-Valinyl)-L-Lysine Methyl Ester]

222-225Cancer is a major risk disease affecting human survival. The pharmaceutical companies are continuing searching for new drug candidates with promising anticancer activities, and reduced side effects. The current work aimed at synthesized a new tripeptide with potential pharmacological properties. L-Valine methyl ester was used to prepare cyclo (Nα-dinicotinoyl)-bis-[(L-valinyl)-L-lysine methyl ester. The new compound revealed promising in vitro cytotoxic activities against different neuroblastoma, cervical carcinoma, fibrosarcoma as well as hepatocellular carcinomas. Furthermore, we also found that the obtained IC50 of the compound decreased by about 50% during its in vivo anti-prostate cancer evaluation. Furthermore, the mechanism of action studies proposes that the new prepared derivative affects cancer cells trough the inhibition of VEGFR-2 kinase enzyme

Novel Li3ClO based glasses with superionic properties for lithium batteries

Three types of next generation batteries are currently being envisaged among the international community: metal-air batteries, multivalent cation batteries and all-solid-state batteries. These battery designs require high-performance, safe and cost effective electrolytes that are compatible with optimized electrode materials. Solid electrolytes have not yet been extensively employed in commercial batteries as they suffer from poor ionic conduction at acceptable temperatures and insufficient stability with respect to lithium-metal. Here we show a novel type of glasses, which evolve from an antiperovskite structure and that show the highest ionic conductivity ever reported for the Li-ion (25 mS cm-1 at 25 °C). These glassy electrolytes for lithium batteries are inexpensive, light, recyclable, non-flammable and non-toxic. Moreover, they present a wide electrochemical window (higher than 8 V) and thermal stability within the application range of temperatures

A probabilistic multi-objective approach for FACTS devices allocation with different levels of wind penetration under uncertainties and load correlation

This study presents a probabilistic multi-objective optimization approach to obtain the optimal locations and sizes of static var compensator (SVC) and thyristor-controlled series capacitor (TCSC) in a power transmission network with large level of wind generation. In this study, the uncertainties of the wind power generation and correlated load demand are considered. The uncertainties are modeled in this work using the points estimation method (PEM). The optimization problem is solved using the Multi-objective particle swarm optimization (MOPSO) algorithm to find the best position and rating of the flexible AC transmission system (FACTS) devices. The objective of the problem is to maximize the system loadability while minimizing the power losses and FACTS devices installation cost. Additionally, a technique based on fuzzy decision-making approach is employed to extract one of the Pareto optimal solutions as the best compromise one. The proposed approach is applied on the modified IEEE 30-bus system. The numerical results evince the effectiveness of the proposed approach and shows the economic benefits that can be achieved when considering the FACTS controller

RUTIN ATTENUATES IRON OVERLOAD-INDUCED HEPATIC OXIDATIVE STRESS IN RATS

Iron is an essential element that participates in several metabolic activities of the cell. However, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants, and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against iron overload (IOL)-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg/kg b.w.) as one dose every two days, by intraperitoneal injections (IP) and administerated rutin (50 mg/kg b.w.) as one daily oral dose until the sacrificed day. Blood samples and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profile [iron, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), transferrin (Tf) and transferrin saturation% (TS%)], ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels, as well as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), nitric oxide (NO) and total nucleic acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that IOL resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels as well as AST and ALT activities. Moreover, it increased liver iron, L-MDA, and NO levels. Meanwhile, it decreased serum UIBC, albumin, total protein, total cholesterol, triacylglycerols levels, as well as liver GSH, TNA levels, and Gpx, CAT and SOD activities when compared with the control rats. Rutin administration to IOL-rats resulted in significant decrease in serum iron, TIBC, Tf, TS%, ferritin levels, and AST and ALT activities as well as liver iron, L-MDA, and NO levels. Rutin also induced significant increases in serum UIBC, albumin, total protein and total cholesterol levels, as well as liver GSH, CAT and SOD activities compared with the IOL-rats. This study provides in vivo evidence that rutin administration can improve the antioxidant defence systems against IOL-induced hepatic oxidative stress in rats. This protective effect in liver of iron loaded rats may be due to both the antioxidant and metal chelation activities

Evaluation of in vitro and in vivo Cytotoxic Activities and Kinase Inhibition of Newly Synthesized Cyclo (Nα-Dinicotinoyl)-Bis-[(L-Valinyl)-L-Lysine Methyl Ester]

Cancer is a major risk disease affecting human survival. The pharmaceutical companies are continuing searching for new drug candidates with promising anticancer activities, and reduced side effects. The current work aimed at synthesized a new tripeptide with potential pharmacological properties. L-Valine methyl ester was used to prepare cyclo (Nα-dinicotinoyl)-bis-[(L-valinyl)-L-lysine methyl ester. The new compound revealed promising in vitro cytotoxic activities against different neuroblastoma, cervical carcinoma, fibrosarcoma as well as hepatocellular carcinomas. Furthermore, we also found that the obtained IC50 of the compound decreased by about 50% during its in vivo anti-prostate cancer evaluation. Furthermore, the mechanism of action studies proposes that the new prepared derivative affects cancer cells trough the inhibition of VEGFR-2 kinase enzyme

Dissociation constants and thermodynamic properties of amino acids used in CO2 absorption from (293 to 353) K

The second dissociation constants of the amino acids βalanine, taurine, sarcosine, 6-aminohexanoic acid, DL-methionine, glycine, L-phenylalanine, and L-proline and the third dissociation constants of L-glutamic acid and L-aspartic acid have been determined from electromotive force measurements at temperatures from (293 to 353) K. Experimental results are reported and compared to literature values. Values of the standard state thermodynamic properties are derived from the experimental results and compared to the values of commercially available amines used as absorbents for CO 2 capture.

The diacylglycerol kinase α/Atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells

Guardian: Hypervisor as Security Foothold for Personal Computers

Abstract. Personal computers lack of a security foothold to allow the end-users to protect their systems or to mitigate the damage. Existing candidates either rely on a large Trusted Computing Base (TCB) or are too costly to widely deploy for commodity use. To fill this gap, we propose a hypervisor-based security foothold, named as Guardian, for commodity personal computers. We innovate a bootup and shutdown mechanism to achieve both integrity and availability of Guardian. We also propose two security utilities based on Guardian. One is a device mon-itor which detects malicious manipulation on camera and network adaptors. The other is hyper-firewall whereby Guardian expects incoming and outgoing network packets based on policies specified by the user. We have implemented Guardian ( ≈ 25K SLOC) and the two utilities ( ≈ 2.1K SLOC) on a PC with an Intel pro-cessor. Our experiments show that Guardian is practical and incurs insignificant overhead to the system.

Europium as an inhibitor of Amyloid-β(1-42) induced membrane permeation

Soluble Amyloid-beta (Aβ) oligomers are a source of cytotoxicity in Alzheimer's disease (AD). The toxicity of Aβ oligomers may arise from their ability to interact with and disrupt cellular membranes mediated by GM1 ganglioside receptors within these membranes. Therefore, inhibition of Aβ–membrane interactions could provide a means of preventing the toxicity associated with Aβ. Here, using Surface Plasmon field-enhanced Fluorescence Spectroscopy, we determine that the lanthanide, Europium III chloride (Eu3+), strongly binds to GM1 ganglioside-containing membranes and prevents the interaction with Aβ42 leading to a loss of the peptides ability to cause membrane permeation. Here we discuss the molecular mechanism by which Eu3+ inhibits Aβ42-membrane interactions and this may lead to protection of membrane integrity against Aβ42 induced toxicity