Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Disease Progression Mediated by Egr-1 Associated Signaling in Response to Oxidative Stress

When cellular reducing enzymes fail to shield the cell from increased amounts of reactive oxygen species (ROS), oxidative stress arises. The redox state is misbalanced, DNA and proteins are damaged and cellular transcription networks are activated. This condition can lead to the initiation and/or to the progression of atherosclerosis, tumors or pulmonary hypertension; diseases that are decisively furthered by the presence of oxidizing agents. Redox sensitive genes, like the zinc finger transcription factor early growth response 1 (Egr-1), play a pivotal role in the pathophysiology of these diseases. Apart from inducing apoptosis, signaling partners like the MEK/ERK pathway or the protein kinase C (PKC) can activate salvage programs such as cell proliferation that do not ameliorate, but rather worsen their outcome. Here, we review the currently available data on Egr-1 related signal transduction cascades in response to oxidative stress in the progression of epidemiologically significant diseases. Knowing the molecular pathways behind the pathology will greatly enhance our ability to identify possible targets for the development of new therapeutic strategies

Modifikasi Metode Setengah Reaksi untuk Menyetarakan Reaksi pada Pembelajaran Konsep Reaksi Redoks dan Elektrokimia di SMA

Redox reaction is one of difficult concepts to be understood. It is caused mainly by existing reaction redox balancing methods that give students some difficultness. For that case, this paper was meant to discuss about modifying reaction redox balancing method so that it can be acquired more easily. Algebra method is too mathematical. The more complex the reaction is, the more difficult its solution is. The complexity of rules of half reaction method on balancing redox reaction brings difficult understanding on students also. Even, on a particular condition, balancing process lead to break the rules. Half reaction method modification can simplify the rule students have to rote. Simplifying the method will reduce student bourdon. By this modification method, students need just to remember that in every condition, OH– and H+ ion is used to balance O and H atom respectively. Key words: redox reaction, reaction balancing method, half reaction method modification, redox and electrochemistr

Mechanism of Exact Transition between Cationic and Anionic Redox Activities in Cathode Material Li2FeSiO4.

The discovery of anion redox activity is promising for boosting the capacity of lithium ion battery (LIB) cathodes. However, fundamental understanding of the mechanisms that trigger the anionic redox is still lacking. Here, using hybrid density functional study combined with experimental soft X-ray absorption spectroscopy (sXAS) measurements, we unambiguously proved that Li(2- x)FeSiO4 performs sequent cationic and anionic redox activity through delithiation. Specifically, Fe2+ is oxidized to Fe3+ during the first Li ion extraction per formula unit (f.u.), while the second Li ion extraction triggered the oxygen redox exclusively. Cationic and anionic redox result in electron and hole polaron states, respectively, explaining the poor conductivity of Li(2- x)FeSiO4 noted by previous experiments. In contrast, other cathode materials in this family exhibit diversity of the redox process. Li2MnSiO4 shows double cationic redox (Mn2+-Mn4+) during the whole delithiation, while Li2CoSiO4 shows simultaneous cationic and anionic redox. The present finding not only provides new insights into the oxygen redox activity in polyanionic compounds for rechargeable batteries but also sheds light on the future design of high-capacity rechargeable batteries

Developing vanadium redox flow technology on a 9-kW 26-kWh industrial scale test facility: Design review and early experiments

Redox Flow Batteries (RFBs) have a strong potential for future stationary storage, in view of the rapid expansion of renewable energy sources and smart grids. Their development and future success largely depend on the research on new materials, namely electrolytic solutions, membranes and electrodes, which is typically conduced on small single cells. A vast literature on these topics already exists. However, also the technological development plays a fundamental role in view of the successful application of RFBs in large plants. Despite that, very little research is reported in literature on the technology of large RFB systems. This paper presents the design, construction and early operation of a vanadium redox flow battery test facility of industrial size, dubbed IS-VRFB, where such technologies are developed and tested. In early experiments a peak power of 8.9 kW has been achieved with a stack specific power of 77Wkg−1. The maximum tested current density of 635 mA cm−2 has been reached with a cell voltage of 0.5 V, indicating that higher values can be obtained. The test facility is ready to be complemented with advanced diagnostic devices, including multichannel electrochemical impedance spectroscopy for studying aging and discrepancies in the cell behaviors