25 research outputs found
INVESTIGATION OF SOME MOLECULAR MECHANISMS OF CYTOTOXIC 1,5-DIARYL-3-OXO-1,4-PENTADIENES
No full textGlutathione S-transferase GSTð has been one of the significant targets for cancer treatment in the
past several years. The reason behind that is 1) its overexpression in some cancer cells compared
to normal ones 2) its ability to cause resistance against cancer chemotherapeutics and 3) its
protective role against reactive oxygen species (ROS). We have synthesized a large number of
compounds which have strong potency against different cancer cell lines. These compounds
possess a 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore. In the present study some
investigations as to the way in which cytotoxicity is mediated was undertaken. Our results have
demonstrated that the analogs NC 2067 and NC 2081 behaved as substrates for GSTð and
reduced the level of GSH. This was apparent by the decrease in the concentrations of both
compounds after the addition of GSTð and GSH. In addition, both agents caused about 3-7 folds
increase in ROS levels. The dichlorodihydrofluorescein dye was used for this purpose due to its
fluorescence characteristic after being oxidized by ROS. High levels of these species cause a
drop in the mitochondrial membrane potential. This phenomenon was detected when the
monomeric form of JC-1 levels were increased after treatment. The reduction of 2-3 folds was
seen when the cells were treated with the IC50 values of both compounds. In addition, both
agents inhibited oxygen consumption implicating their ability to inhibit oxidative
phosphorylation. We also evaluated the effect of both agents on mitochondrial swelling. NC
2081 caused swelling using concentrations of 10 ìM and 50 ìM. This was apparent when the
absorption of an isolated rat liver mitochondrial solution decreased after the addition of the
compound. The addition of the higher concentration caused about 2 fold greater effect than the
lower one. On the other hand, compound NC 2067 produced minimal swelling only at a
concentration of 50 ìM
IN VITRO STUDIES ON CYANIDIN PROTECTION AGAINST DOXORUBICIN CARDIOMYOCYTE CYTOTOXICITY AND ANTICANCER ACTIVITY
No full textMitochondrial reactive oxygen species (ROS) are recognized for their role in several health related problems when produced at excessively high concentrations. Due to their potent antioxidant activity and potential mitochondriotropic behavior, the anthocyanidins may have the potential to lower mitochondrial ROS levels. Nevertheless, the effect of anthocyanidins remains overlooked due to their presumed low stability and bioavailability. In addition, this instability has lead to a general belief that the phenolic degradation products, protocatechuic acid (PCA) and phloroglucinaldehye (PGA), exert the bioactivity rather than the parent compound.
In this work, doxorubicin-induced cytotoxicity in differentiated H9c2 cardiomyocytes was initially established as a model in which the mitochondrial antioxidant activity of the selected flavonoids would be examined. First, we delineated the mechanisms by which doxorubicin affected H9c2 cell survival and mitochondrial function. The results showed that the early effects of doxorubicin on mitochondrial superoxide generation led to a delayed effect on cell survival. Using this model, we then revealed the protective ability of cyanidin against doxorubicin-induced cytological damage, showing protection to mitochondria. While cyanidin co-incubation with doxorubicin did not show protection when cell survival was assessed after 24 h, it gave delayed protection after a further 24 h drug-free period. Using the delayed protection model, we also showed that cyanidin had greater bioactivity over other flavonoids tested (quercetin, catechin and cyanidin-3-glucoside (C3G)). The protection by cyanidin also exceeded that of its degradation products (PCA and PGA), suggesting that the parent compound has additional bioactivity. The cytoprotective ability of the flavonoids was related to their ability to lower mitochondrial superoxide at early time points, with cyanidin being the most effective. Experiments on doxorubicin cytotoxicity to HepG2 (liver cancer) and K562 (erythroleukemia) cells showed no protective effect with cyanidin. These results suggest cyanidin protects cardiomyocytes but does not interfere with the cytotoxic activity of doxorubicin in the cancer cell lines.
Investigations on the degradation of cyanidin in physiological media, UV-vis, HPLC and MS analytical techniques provided evidence that cyanidin does not degrade immediately to PCA and PGA. Instead, intermediate compounds (hemiketal and chalcone) survived for sufficient periods to exert putative bioactivity. Studies on the influence of different media on the degradation of cyanidin showed that the stability in human serum was significantly higher (t½ 43.2 min at room temperature, 22 ¬± 1°C) compared to phosphate buffered saline and Dulbecco’s Modified Eagle’s Medium with and without 10% fetal bovine serum (t½ 10.2-32.6 min).
In conclusion, using differentiated H9c2 cells, our results show an ability of cyanidin to survive long enough in cell culture media, and presumably intracellularly, to exert cytoprotection against doxorubicin which exceeded that of other flavonoids (quercetin, catechin, C3G) and its degradation products (PCA and PGA). The results present cyanidin as a possible antioxidant choice to use in clinical practice to protect the heart from the mitochondrial toxicity of doxorubicin and warrants investigation into this possible therapeutic application
Leon Trostsky And His Political Role in the Bolshevik Revolution 1917-1924.
No full textThe Russian revolution is not a revolution against the rule and the overthrow of the tsarist state in Russia, but rather a radical change of new political, social and cultural concepts, which had an impact on the world. Trotsky is considered the father and architect of the October Revolution of 1917, and he is credited with its success, while Lenin and Stalin were far from the events because of their persecution by the state, so Trotsky bore the burden of the revolution, preparing for it and coordinating between all its parties in all Russian lands, until its success through his intelligence in managing Things and his enthusiastic speeches, but this devotion of Trotsky to the revolution was met with hatred from Stalin and enemies for him. Trotsky did not seek power and governmental positions, but Lenin assigned him to manage several positions, including the Ministry of Defense. After Lenin's death, Trotsky did not seek to replace him, but handed over power to Stalin, who worked to banish Trotsky and work to banish him from the Soviet Union, because he believed that Trotsky and his revolutionary ideas were the enemy. The most dangerous to his rule and one of the rare personalities opposed to his rule, and worked to exile him from the Soviet Union and then work to assassinate him later in 1939 AD. Despite the deliberate absence of the role of Trotsky by Stalin and after him and his attempt to show a picture contrar
Circuit Design for Memristor based In-Memory Computing
No full textModern computing systems suffer due to inability of CMOS-device technology and conventional Von-Neumann architectures to support today's ever-increasing demand of high performance, reliability, cost and energy-efficiency. While CMOS device suffers from high static leakage, reduced reliability and manufacturing complexity; conventional computing architecture suffers from high power consumption with memory access and performance bottlenecks. Non-volatile and CMOS-compatible emerging memristive device technology with extremely compact memory structures offers in-memory computing solutions. However, research lacks quantitative benchmarking of memristor-based primitive logic designs. Moreover, the arithmetic and functional circuit design solutions are inefficient and hence incompetent to replace the state-of-the-art.The thesis first covers device level physics of different memristive devices, elaborating their basic structures, working principles and behavioural analyses using Verilog-A models. Building on single device behavioural analyses, a comprehensive exploration and quantitative benchmarking of all existing primitive gates is provided, thereby concluding that scouting logic design technique is the optimal logic gate to perform in-memory computing. Going forward, using scouting logic as the building block, the work presents efficient arithmetic and functional circuit designs that outperform previously proposed in-memory computing solutions and attempts to make a strong case to challenge the current CMOS-based state-of-the-art computing paradigm.Different flavours of a novel circuit design are proposed to tackle limitations common to circuits implementing primitive arithmetic operations and complex multiply-accumulate (dot-product) operations supporting data-intensive applications. The proposed circuit deploys in-built sample-and-hold and two bit-wise weighting techniques to enable pipelining and self-timing-path to improve accuracy against variations. As compared to 4-bit adder utilising integrate and fire circuit (IFC) that is optimised for area/power, the proposed design improves the speed, area, and energy consumption by 4X, 2.5X, and 11X, respectively. Incorporating additional components such as high-gain differential amplifier and modified IFC provides a highly accurate, linear, power efficient dot product engine with significant improvement in memristor endurance. To perform 64_4 dot 64_1, the proposed dot product engine improves the speed, area and energy consumption by 2X, 3.5X and 54X, respectively, as compared to area-efficient IFC-based engine, while also extending the range of operands operated in parallel by >3X. Compared to highly accurate SAR-ADC(current sense amplifier) based dot product engine, the proposed design improves the speed, area and energy by a factor of 0.4X(1.2X), 200X(6X) and 260X(108X), respectively, with comparable accuracy. Read endurance is significantly improved as < 0.1V is maintained across the memristors during the dot-product operation, as opposed to > 1V endured using prior proposed designs. To showcase the scalability and versatility of the proposed circuit designs, design prepositions of multi-operand 4-bit adder, 4x4 multiplier and 4-bit comparator are also presented. Supporting equations, graphs, figures and tables have been included to justify the choices made as part of this work and to enhance the understanding of novel non-volatile memristor based in-memory computing.MNEMOSENEElectrical Engineering | Microelectronic
Optimizing photo-mineralization of aqueous methyl orange by nano-ZnO catalyst under simulated natural conditions.
No full textInternational audiencePhoto-degradation of organic contaminants into non-hazardous mineral compounds is emerging as a strategy to purify water and environment. Tremendous research is being done using direct solar light for these purposes. In this paper we report on optimum conditions for complete mineralization of aqueous methyl orange using lab-prepared ZnO nanopowder catalyst under simulated solar light. Nano-scale ZnO powder was prepared in the lab by standard methods, and then characterized using electronic absorption spectra, photolumenscence emission (PL) spectra, XRD, and SEM. The powder involved a wurtzite structure with ~19 nm particles living in agglomerates. Photo-degradation progressed faster under neutral or slightly acidic conditions which resemble natural waters. Increasing catalyst concentration increased photodegradation rate to a certain limit. Values of catalyst turn over number and degradation percentage increased under higher light intensity, whereas the quantum yield values decreased. The photocatalytic efficiency of nano-ZnO powders in methyl orange photodegradation in water with solar light has been affected by changing the working conditions. More importantly, the process may be used under natural water conditions with pH normally less than 7, with no need to use high concentrations of catalyst or contaminant. The results also highlight the negative impact of possible high concentrations of CO2 on water purification processes. Effects of other added gaseous flows to the reaction mixture are also discussed. ZnO nano-particles are useful catalyst for complete mineralization of organic contaminants in water. Photo-degradation of organic contaminants with ZnO nano-particles, methyl orange being an example, should be considered for future large scale water purification processes under natural conditions
Photocatalytic degradation of phenazopyridine contaminant in soil with direct solar light
No full textAnthocyanin-Sensitized TiO<sub>2</sub> Nanoparticles for Phenazopyridine Photodegradation under Solar Simulated Light
No full textPharmaceutical wastes are emerging as water contaminants. Like other organic contaminants, it is necessary to find safe and economic methods to remove them from the water. In this work, anthocyanin was used as a natural dye sensitizer for the wide band gap nanosize rutile TiO2. The TiO2/Anthocyanin particles were supported on activated carbon particle surfaces. The resulting composite, which was prepared and characterized by different methods, was then used as a catalyst in the photodegradation of phenazopyridine (a model pharmaceutical contaminant) under a solar simulated light. Depending on experimental conditions, up to 90% of the contaminant was mineralized leaving no new organic products in the reaction mixture. The results show the feasibility of using the activated carbon-supported TiO2/Anthocyanin photocatalyst for pharmaceutical contaminant removal in water. The natural dye anthocyanin readily sensitized the TiO2 to visible light. The unsupported TiO2, with its nanosize particles, was not easy to recover by simple separation methods, while the activated carbon-supported catalyst was easily isolated by decantation after reaction cessation. Moreover, the recovered AC/TiO2 catalyst could also be regenerated by adding fresh anthocyanin sensitizer after recovery for further reuse. Keeping the contaminant molecules closer to the catalytic sites by adsorption, the support also enhanced the efficiency of photocatalyst.</jats:p
Alternative natural dyes in water purification: Anthocyanin as TiO2-sensitizer in methyl orange photo-degradation
No full textNatural molecular dye, anthocyanin, is described here as safe sensitizer for TiO2 particles in photo-degradation of organic contaminants in water. The dye is a promising replacement for the more costly and hazardous heavy metal based systems, such as CdS particles and Ru-compounds. TiO2/anthocyanin effectively catalyzed the photo-degradation of methyl orange contaminant under solar simulator radiation. The new TiO2/anthocyanin catalyst showed comparable efficiency to earlier systems, while avoiding their hazardous nature. When supported onto activated carbon (AC) particles, the resulting AC/TiO2/anthocyanin system showed enhanced efficiency and ease of recovery from the catalytic reaction mixture. The natural dye molecules showed the tendency to degrade under photo-degradation conditions, just like earlier hazardous sensitizers. However, complete mineralization of anthocyanin occurred leaving no traces of organic species in solution. Sensitizer degradation caused deactivation of the supported catalyst on recovery. Such a shortcoming was overcome by re-treatment of the recovered catalysts with fresh dye. Effects of different reaction parameters on the catalyst efficiency were studied. A mechanism, similar to earlier CdS-sensitized catalyst systems, is proposed for the TiO2/anthocyanin catalyst
Diaminobenzene Schiff Base Induces Caspase 9-dependent Apoptosis In U937 Leukemia Cells Diaminobenzene Schiff Base Induces Caspase 9-dependent Apoptosis In U937 Leukemia Cells
No full textAbstract Metal complex Schiff base compounds have been shown to be cytotoxic in vitro. However little is known concerning anticancer activity of Schiff bases that lack metal cations. The antineoplastic properties of two isomeric derivatives of diaminobenzene bis-Schiff base compounds, namely: N,N '-Bis(2-hydroxy-3-methoxybenzylidene)-1,2-diaminobe nzene (2MJ) and N,N '-Bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminobe nzene (2MH) towards U937 and K562 leukemia cell lines were investigated in this study. Both compounds were more cytotoxic towards U937 lymphoma cell with little effect on K562 cells when analysed using Sodium 3′-[1-(phenylamino-carbonyl)-3,4-Tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) cell proliferation assay technique . The IC 50 value for 2MJ was almost half of 2MH . Both compounds were also found to induce apoptosis in U937 leukemia cells as evidenced by the induction of caspase 3 and 7. The level of caspase 3/7 induction was more pronounced in cells treated with 2MJ compared to 2MH. Caspase-9 was identifiedas the regulatory upstream caspase activated in U937 cells treatedwith 2MH and 2MJ, implicating the mitochondrial apoptoticpathway in diaminobenzene Schiff base-induced leukemia cell death. Both agents caused negligible effect on caspase-8 indicating a non Fas ligand receptor involvement in the apoptosis cascade. Neither compounds showed significant mutagenic outcome in the AMES mutagenicity assay. The result of this study highlights the potential of diaminobenzene bis-Schiff base compounds as a prospective agent to target cancer cells via the mitochondria
Photocatalytic degradation of phenazopyridine contaminant in soil with direct solar light
No full textPhotocatalytic degradation of waste pharmaceutics, with solar radiation, is described here as a feasible method to purify pre-contaminated soils. Phenazopyridine has been used as a model soil contaminant. Two different nano-size powders have been first examined as catalysts, namely commercial TiO2 (anatase) and commercial ZnO. As the ZnO showed higher catalytic efficiency, the study was then focused on it. The commercial ZnO powder was then compared with lab-prepared ZnO powder, and the latter shows relatively higher efficiency. The ZnO was used in two different ways. In one way, dry ZnO catalyst powder was spread onto the soil, while in the other way the ZnO was sprayed onto the soil surface by a wet spray method. The spray technique shows slightly higher efficiency, in addition to being easier to apply at future large scale. Depending on conditions and type of photocatalyst used, up to 90% contaminant removal can be achieved in 30 min. In case of photocatalysis experiments, the reacted contaminant molecules undergo complete degradation with no detectable side reaction organic products. Possible evaporation or escape of organic contaminant, or other possibly resulting organics, is ruled out by a series of control experiments. Photodegradation process takes place only at the catalytic sites on the soil surface, where contaminant molecules that diffuse from the soil bulk are completely degraded. Other useful organisms inside the soil are not affected as they are kept away from catalyst sites. A plausible mechanism is proposed for the degradation process.</p
