The antioxidant characteristics of medicinal plant extracts from Western Siberia

An antioxidant activity of the water-alcohol extracts of leaves of ten herbs from Western Siberia was studied. In vivo the capability of extracts to protect cells of Escherichia coli against the bacteriostatic action of H ₂O₂ and the influence of the extracts on the expression of the antioxidant gene katG coding catalase-hydroperoxidase I were investigated. In vitro the radical-binding activity with DPhPG^· (1,1-diphenyl-2-picrylhydrazyl radical), the chelating capability with ferrozine, and total composition of flavonoids and tannins were determined. The extracts of Filipendula stepposa and Limonium gmelinii were characterized by the highest antioxidant activity. According to data, the test extracts could have an antioxidant effect on bacteria in different ways at once including the direct inhibition of ROS (reactive oxygen species), iron ion chelation and antioxidant gene induction.     

The arsenolysis reaction in the biotechnological synthesis of ribavirin. The in vitro and in vivo inhibition of influenza A virus replication with a combination of ribavirin and ozeltamivir

The biotechnological method of synthesis of the antiviral drug ribavirin based on the transglycosylation reaction was improved due to the addition of catalytic amounts of sodium arsenate. This approach allows us to hydrolyze the excess natural nucleoside guanosine, a ribose donor, and, hence, made the composition of the reaction mixture less complicated, thus facilitating the process of ribavirin isolation. It was shown that in cell cultures the combination of ribavirin and oseltamivir carboxylate inhibited the replication of the influenza A virus more effectively than each of them alone. Similar results were obtained in experiments on laboratory animals (mouse Balb/c) infected with the influenza A virus H3N2/Aichi/68 strain.     

An Exposure to the Oxidized DNA Enhances Both Instability of Genome and Survival in Cancer Cells

Background

Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response.

Principal Findings

Here we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed.

Conclusions/Significance

Survival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted.     

Effect of Subpressor Dose of Angiotensin II on Pain-Related Behavior in Relation with Neuronal Injury and Activation of Satellite Glial Cells in the Rat Dorsal Root Ganglia

To clarify the role of angiotensin II (Ang II) in the regulation of sensory signaling, we studied the effect of subpressor dose (150 ng/kg/min) of Ang II on pain-related behavior in relation with neuronal injury and activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRGs) after chronic constriction injury (CCI). Systemic continuous delivery of Ang II induced the tactile, heat and cold hyperlagesia, when measured at 7 days ofpost-injury. Blockade of the AT₁ receptor with losartan (2.5 mg/kg/day) prevented tactile hyperalgesia and attenuated cold hyperalgesia, but did not affect the response to noxious heat stimulus. A marked increase of large-sized injured primary afferent neurons, detected by ATF3 immunolabeling, was seen in lower lumbar DRGs on ipsilateral side after Ang II treatment. Subpressor dose of Ang II induced an increase of activated SGCs (detected by GFAP immunolabeling) enveloping large-diameter neurons. Our results suggested that Ang II through the AT₁ receptor activation is an important regulatory factor in neuropathic pain perception and plays an important role in the injury of large-sized primary afferent neurons and activation of SGCs elicited by the CCI.     

DNAdigest and Repositive: Connecting the World of Genomic Data

There is no unified place where genomics researchers can search through all available raw genomic data in a way similar to OMIM for genes or Uniprot for proteins. With the recent increase in the amount of genomic data that is being produced and the ever-growing promises of precision medicine, this is becoming more and more of a problem. DNAdigest is a charity working to promote efficient sharing of human genomic data to improve the outcome of genomic research and diagnostics for the benefit of patients. Repositive, a social enterprise spin-out of DNAdigest, is building an online platform that indexes genomic data stored in repositories and thus enables researchers to search for and access a range of human genomic data sources through a single, easy-to-use interface, free of charge.     

Role of thiol redox systems in <Emphasis Type="Italic">Escherichia coli</Emphasis> response to thermal and antibiotic stresses

Isogenic knockout mutants of Escherichia coli deficient in components of the glutathione and thioredoxin redox systems and growing at various temperatures (20–46°C) exhibited considerable differences in growth rate and survival, as well as in expression of the antioxidant genes. In the parental strain E. coli BW25113 (wt) treated with ciprofloxacin, ampicillin, or streptomycin, dependence of survival on growth temperature was a V-shaped curve with the maximum sensitivity within the range corresponding to high growth rates (40–44°C). Significant inverse correlation was observed between log CFU at different temperatures and specific growth rate prior to antibiotic addition. This applied to most of the mutants, which exhibited higher resistance to the three antibiotics tested at nonoptimal temperatures (20 and 46°C) than at 37 and 40°C. No correlation was found between resistance to stress and antibiotics and expression of the antioxidant genes. The role of global regulators ppGpp and σ^s in E. coli resistance to antibiotics and nonoptimal temperatures was shown.     

Light waveguiding in bioinspired peptide nanostructures

Basic optical properties of bioinspired peptide nanostructures are deeply modified by thermally mediated refolding of peptide secondary structure from α‐helical to β‐sheet. This conformational transition is followed by the appearance in the β‐sheet structures of a wideband optical absorption and fluorescence in the visible region. We demonstrate that a new biophotonic effect of optical waveguiding recently observed in peptide/protein nanoensembles is a structure‐sensitive bimodal phenomenon. In the primary α‐helical structure input, light propagates via optical transmission window demonstrating conventional passive waveguiding, based on classical optics. In the β‐sheet structure, fluorescent (active) light waveguiding is revealed. The latter can be attributed to completely different physical mechanism of exciton‐polariton propagation, characterized by high effective refractive index, and can be observed in nanoscale fibers below diffraction limit. It has been shown that peptide material requirements for passive and active waveguiding are dissimilar. Original biocompatibility and biodegradability indicate high potential future applications of these bioinspired waveguiding materials in precise photobiomedicine towards advanced highly selective bioimaging, photon diagnostics, and optogenetics.     

Intracellular diffusion of adenosine phosphates is locally restricted in cardiac muscle

Recent studies have revealed the structural and functional interactions between mitochondria, myofibrils and sarcoplasmic reticulum in cardiac cells. Direct channeling of adenosine phosphates between organelles identified in the experiments indicates that diffusion of adenosine phosphates is limited in cardiac cells due to very specific intracellular structural organization. However, the mode of diffusion restrictions and nature of the intracellular structures in creating the diffusion barriers is still unclear, and, therefore, a subject of active research. The aim of this work is to analyze the possible role of two principally different modes of restriction distribution for adenosine phosphates (a) the uniform diffusion restriction and (b) the localized diffusion limitation in the vicinity of mitochondria, by fitting the experimental data with the mathematical model. The reaction-diffusion model of compartmentalized energy transfer was used to analyze the data obtained from the experiments with the skinned muscle fibers, which described the following processes: mitochondrial respiration rate dependency on exogenous ADP and ATP concentrations; inhibition of endogenous ADP-stimulated respiration by pyruvate kinase (PK) and phosphoenolpyruvate (PEP) system; kinetics of oxygen consumption stabilization after addition of 2 mM MgATP or MgADP; ATPase activity with inhibited mitochondrial respiration; and buildup of MgADP concentration in the medium after addition of MgATP. The analysis revealed that only the second mechanism considered--localization of diffusion restrictions--is able to account for the experimental data. In the case of uniform diffusion restrictions, the model solution was in agreement only with two measurements: the respiration rate as a function of ADP or ATP concentrations and inhibition of respiration by PK + PEP. It was concluded that intracellular diffusion restrictions for adenosine phosphates are not distributed uniformly, but rather are localized in certain compartments of the cardiac cells.     

AFM of biological material embedded in epoxy resin

We present a simple method to extract morphological details from the block face of epoxy embedded biopolymers by AFM. It is shown that topographical contrast and the identification of small structural details critically depend on the procedure of sample preparation before embedding (chemical fixation or high-pressure freezing and freeze-substitution) and on the hardness of the embedding epoxy resin. Ethanol treatment of the block face of the sample after microtomy elutes non-cross-linked polymer chains and makes the smallest details of the embedded biomaterial amenable to detection. AFM (height and phase contrast) examination of the block face of accordingly prepared cells of Caenorhabditis elegans provides data that are comparable to TEM.