Reactive metabolites of desipramine and clomipramine: The kinetics of formation and reactivity with DNA

Tricyclic antidepressants (TCAs), along with phenothyazines and some industrial chemicals, are shown to react with enzymes that exhibit peroxidase activity. These reactions result in the formation of reactive intermediates having unpaired electrons. The peroxidase oxidation and reactivity of two TCAs, desipramine and clomipramine, were investigated. As a model of peroxidase, horseradish peroxidase (HRP) was employed. The products of the peroxidase catalyzed oxidation of desipramine and clomipramine were identified as N-dealkylated compounds iminodibenzyl and 3-chloroiminodibenzyl using the GC/MS technique. Both drugs formed broad UV/vis absorption spectra in the presence of HRP and H(2)O(2), indicating the formation of a radical cations-reactive intermediate of the oxidation reaction. The dynamics of the formation of the desipramine intermediate was studied using UV/vis spectroscopy. The extinction coefficient was measured for the reactive intermediate, 7.80×10(3)M(-1)cm(-1), as well as the apparent Michaelis-Menten and catalytic constants, 4.4mM and 2.3s(-1), respectively. Both desipramine and clomipramine degraded DNA in the presence of HRP/H(2)O(2), as was revealed by agarose gel electrophoresis and PCI extraction. Manipulating the kinetic parameters of drug's radical formation and determining the extent of degradation to biomolecules could be potentially used for designing effective agents exhibiting specific reactivity.     

Testing Safety of Genetically Modified Products of Rice: Case Study on Sprague Dawley Rats

Russian Journal of Genetics - Genetic engineering is considered as background for crop protection against pest damage by adding new genes inside the grains. Rice, like other cereals is included in...     

Creating cell and animal models of human disease by genome editing using CRISPR/Cas9

A set of unique sequences in bacterial genomes, responsible for protecting bacteria against bacteriophages, has recently been used for the genetic manipulation of specific points in the genome. These systems consist of one RNA component and one enzyme component, known as CRISPR (“clustered regularly interspaced short palindromic repeats”) and Cas9, respectively. The present review focuses on the applications of CRISPR/Cas9 technology in the development of cellular and animal models of human disease. Making a desired genetic alteration depends on the design of RNA molecules that guide endonucleases to a favorable genomic location. With the discovery of CRISPR/Cas9 technology, researchers are able to achieve higher levels of accuracy because of its advantages over alternative methods for editing genome, including a simple design, a high targeting efficiency and the ability to create simultaneous alterations in multiple sequences. These factors allow the researchers to apply this technology to creating cellular and animal models of human diseases by knock‐in, knock‐out and Indel mutation strategies, such as for Huntington's disease, cardiovascular disorders and cancers. Optimized CRISPR/Cas9 technology will facilitate access to valuable novel cellular and animal genetic models with respect to the development of innovative drug discovery and gene therapy.     

Necrotic,apoptotic and autophagic cell fates triggered by nanoparticles

Nanomaterials have gained a rapid increase in use in a variety of applications that pertain to many aspects of human life. The majority of these innovations are centered on medical applications and a range of industrial and environmental uses ranging from electronics to environmental remediation. Despite the advantages of NPs, the knowledge of their toxicological behavior and their interactions with the cellular machinery that determines cell fate is extremely limited. This review is an attempt to summarize and increase our understanding of the mechanistic basis of nanomaterial interactions with the cellular machinery that governs cell fate and activity. We review the mechanisms of NP-induced necrosis, apoptosis and autophagy and potential implications of these pathways in nanomaterial-induced outcomes.

Abbreviations: Ag, silver; CdTe, cadmium telluride; CNTs, carbon nanotubes; EC, endothelial cell; GFP, green fluorescent protein; GO, graphene oxide; GSH, glutathione; HUVECs, human umbilical vein endothelial cells; NP, nanoparticle; PEI, polyethylenimine; PVP, polyvinylpyrrolidone; QD, quantum dot; ROS, reactive oxygen species; SiO₂, silicon dioxide; SPIONs, superparamagnetic iron oxide nanoparticles; SWCNT, single-walled carbon nanotubes; TiO₂, titanium dioxide; USPION, ultra-small super paramagnetic iron oxide; ZnO, zinc oxide.     

Evaluating soil biochemical/microbial indices as ecological indicators of different land use/cover in northern Iran

The objective of the study was to examine changes in microbial parameters have been used to monitor changes in soil quality under different land uses in north of Iran. The microbial parameters included microbial respiration (MR), substrate induced respiration (SIR), carbon availability index (CAI), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), ratio of MBC/MBN, metabolic quotient (qCO₂) and microbial ratio were determined under different land use/cover, i.e. virgin natural forest (VNF), degraded natural forest (DNF), alder plantation (AP), sequoia plantation (SP), improved fallow (IF) and home garden (HG) areas in northern Iran. Five composed samples per land use/cover were taken from the top 10 cm of the soil. MR and SIR (0.45 and 1.66 mg CO₂-C g^?1 day^?1, respectively) were found to be significantly higher under AP land uses than in the other areas. CAI did not differ for the land uses; MBC (591 and 590 mg kg^?1, respectively) had higher significantly under SP and VNF land uses than in the other areas. MBN (64.25 and 62.33, respectively mg kg^?1) was significantly higher in AP and VNF land uses, ratio of MBC/MBN (17.02) was higher in SP land use than other areas, HG had significantly higher qCO₂ (0.0012 μg CO₂-C mg^?1 MBC day^?1) and finally microbial ratio was significantly higher under IF (599.16) in comparison with HG > AP ≈ DNF > VNF > SP areas. Overall, our results indicate that AP land use (Alnus subcordata C. A. Mey.) increase of soil quality and alder plantation is suitable for rehabilitation of degraded natural forests.     

Circulating levels of asprosin and its association with insulin resistance and renal function in patients with type 2 diabetes mellitus and diabetic nephropathy

Molecular Biology Reports - Adipokines play an important role in the development of type 2 diabetes mellitus (T2DM) and its complications like nephropathy. Asprosin is a newly discovered adipokine...     

A Novel Pharmacological Protective Role for Safranal in an Animal Model of Huntington’s Disease

Neurochemical Research - Huntington’s disease (HD) is a progressive, neurodegenerative and inherited disease and recent years have witnessed the understanding of the cellular and molecular...     

Combination of conserved recombinant proteins (NP & 3M2e) formulated with Alum protected BALB/c mice against influenza A/PR8/H1N1 virus challenge

Biotechnology Letters - Influenza is one of the most important agents of pandemic outbreak causing substantial morbidity and mortality. Vaccination strategies of influenza must be adapted annually...     

Higher Oxidative Stability of Alpha-linolenic Acid Than Linoleic Acid in Nanoemulsions: a Comparison Between Bulk Flaxseed Oil and its O/W Nanoemulsions

In this study, the effects of different dispersed phase volume fractions (Φ 0.025 and 0.1) and storage temperature (4 and 25 °C) were determined on lipid oxidation, fatty acids profile, β-carotene degradation, and other physicochemical properties of flaxseed oil-in-water nanoemulsions. Nanoemulsions containing small anionic droplets (≈ 100 nm) were fabricated using high-pressure homogenization. Although an increase in the viscosity and physical stability of nanoemulsions was observed with increasing Φ, but mean droplet diameter and chemical stability decreased. β-carotene degradation, free fatty acids formation, as well as thiobarbituric acid-reactive substances production, were all faster in the more concentrated emulsions. As the storage temperature raised, physical and chemical stability both decreased. Interestingly, while the ratio of α-linolenic acid to linoleic acid in bulk oil decreased over time, an opposite trend was observed in the nanoemulsions. This effect was due to differences in the location of different unsaturated fatty acids inside the oil nanodroplets.