254 research outputs found
Method for Identifying Regulators of Protein-Advanced Glycation End Product (Protein-Age) Formation
The invention relates to methods for identifying compounds which affect cellular stress. In particular, the method relates to identifying compounds which inhibit protein advanced glycation end product formation, where the compounds are carbonyl scavengers which inhibit the formation. The assay involves combing the substance of interest with histone H1 and ADP-ribose, and then measuring fluorescence and protein cross linking. Various inhibitors of protein AGE glycation have been identified, using this assay
Integral equations in MHD: theory and application
The induction equation of kinematic magnetohydrodynamics is mathematically
equivalent to a system of integral equations for the magnetic field in the bulk
of the fluid and for the electric potential at its boundary. We summarize the
recent developments concerning the numerical implementation of this scheme and
its applications to various forward and inverse problems in dynamo theory and
applied MHD.Comment: 17 pages, 4 figure
Method and Use of α-Amino-β-Mercapto-Ethane Derivatives as Dicarbonyl Scavengers for Treatment of Conditions Resulting from Protein, Lipid, and DNA Damage
Methods of inhibiting damage to proteins, lipids, and DNA by the use of penicillamines and other α-amino-β,β-mercapto-β,β-dimethyl-ethane compounds as dicarbonyl scavengers is disclosed
Current Tomography -- Localization of void fractions in conducting liquids by measuring the induced magnetic flux density
A novel concept of a measurement technology for the localization and
determination of the size of gas bubbles is presented, which is intended to
contribute to a further understanding of the dynamics of efficiency-reducing
gas bubbles in electrolyzers. A simplified proof-of-concept (POC) model is used
to numerically simulate the electric current flow through materials with
significant differences in electrical conductivity. Through an automated
approach, an extensive data set of electric current density and conductivity
distributions is generated, complemented with determined magnetic flux
densities in the surroundings of the POC cell at virtual sensor positions. The
generated data set serves as testing data for various reconstruction
approaches. Based on the measurable magnetic flux density, solving Biot-Savarts
law inversely is demonstrated and discussed with a model-based solution of an
optimization problem, of which the gas bubble locations are derived
Ceramic Substrates for High-temperature Electronic Integration
One of the most attractive ways to increase power handling capacity in power modules is to increase the operating temperature using wide-band-gap semiconductors. Ceramics are ideal candidates for use as substrates in high-power high-temperature electronic devices. The present article aims to determine the most suitable ceramic material for this application
Repurposing the Electron Transfer Reactant Phenazine Methosulfate (PMS) for the Apoptotic Elimination of Malignant Melanoma Cells through Induction of Lethal Oxidative and Mitochondriotoxic Stress
Redox-directed pharmacophores have shown potential for the apoptotic elimination of cancer cells through chemotherapeutic induction of oxidative stress. Phenazine methosulfate (PMS), a N-alkylphenazinium cation-based redox cycler, is used widely as an electron transfer reactant coupling NAD(P)H generation to the reduction of tetrazolium salts in biochemical cell viability assays. Here, we have explored feasibility of repurposing the redox cycler PMS as a superoxide generating chemotherapeutic for the pro-oxidant induction of cancer cell apoptosis. In a panel of malignant human melanoma cells (A375, G361, LOX), low micromolar concentrations of PMS (1-10 μM, 24 h) displayed pronounced apoptogenicity as detected by annexin V-ITC/propidium iodide flow cytometry, and PMS-induced cell death was suppressed by antioxidant (NAC) or pan-caspase inhibitor (zVAD-fmk) cotreatment. Gene expression array analysis in A375 melanoma cells (PMS, 10 µM; 6 h) revealed transcriptional upregulation of heat shock (HSPA6, HSPA1A), oxidative (HMOX1) and genotoxic (EGR1, GADD45A) stress responses, confirmed by immunoblot detection demonstrating upregulation of redox regulators (NRF2, HO-1, HSP70) and modulation of pro- (BAX, PUMA) and anti-apoptotic factors (Bcl-2, Mcl-1). PMS-induced oxidative stress and glutathione depletion preceded induction of apoptotic cell death. Furthermore, the mitochondrial origin of PMS-induced superoxide production was substantiated by MitoSOX-Red live cell fluorescence imaging, and PMS-induced mitochondriotoxicity (as evidenced by diminished transmembrane potential and oxygen consumption rate) was observable at early time points. After demonstrating NADPH-driven (SOD-suppressible) superoxide radical anion generation by PMS employing a chemical NBT reduction assay, PMS-induction of oxidative genotoxic stress was substantiated by quantitative Comet analysis that confirmed the introduction of formamido-pyrimidine DNA glycosylase (Fpg)-sensitive oxidative DNA lesions in A375 melanoma cells. Taken together, these data suggest feasibility of repurposing the biochemical reactant PMS as an experimental pro-oxidant targeting mitochondrial integrity and redox homeostasis for the apoptotic elimination of malignant melanoma cells.National Institutes of Health [1R01CA229418, 1R03CA230949, ES007091, ES006694]; National Institutes of Health (Arizona Cancer Center Support Grant) [CA023074]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling
In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo
- …