Cytoprotective Activity of Polyamines Is Associated with the Alternative Splicing of RAD51A Pre-mRNA in Normal Human CD4+ T Lymphocytes

Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA damage and promote cell survival. In the present study, we demonstrated that polyamines have cytoprotective effects on normal human CD4⁺ T lymphocytes but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan, leading to an increase in cell survival and viability. The induction of RAD51A expression was in response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A pre-mRNA in normal human CD4⁺ T lymphocytes. The difference in the sensitivity of normal and cancer cells to polyamines may become the basis for the use of these compounds to protect normal lymphocytes during lymphoblastic chemotherapy.     

Improving Management Efficiency at Aerospace Enterprises

Russian Engineering Research - The adoption of an integrated management system, based on a systemic approach to production and management problems, improves management efficiency at an enterprise....     

Bioactive Polylactide Fibrous Materials Prepared by Crazing Mechanism

Bioactive suture materials made of biodegradable polymers containing biologically active substances are increasingly demanded in contemporary surgical practice. Herein, the functional fibrous materials are produced by structural modification of polylactide (PLA) fibers according to the crazing mechanism in water–ethanol solutions. The threshold of ethanol concentration, at which the breaking elongation of the polymer substantially increases (up to 600–700%), is found to be 30 wt%. The crazing mechanism is employed to fill the porous structure of PLA fibers by different antiseptic substances (brilliant green, iodine, and fuchsin). PLA loaded by 0.8 wt% of brilliant green exhibits antimicrobial activity on Escherichia coli and Candida guilliermondii. The additive is released stepwise for a prolongated time period (2.5 months). The addition of 1–6 wt% iodine dramatically accelerates the polymer degradation in sodium‐phosphate buffer solution at 37 °C. The obtained filled fibers may possess great interest for producing suture materials with prolonged action of functional components and variable degradation times.     

Measuring binding and speciation of hydrophobic organic chemicals at controlled freely dissolved concentrations and without phase separation

The binding and speciation of hydrophobic organic chemicals (HOCs) in aqueous solutions were determined by controlling chemical activity and measuring total concentrations. Passive dosing was applied to control chemical activities of HOCs in aqueous solutions by equilibrium partitioning from a poly(dimethylsiloxane) polymer preloaded with the chemicals. The HOC concentrations in the equilibrated solutions [C(solution(eq))] and water [C(water(eq))] were then measured. Free fractions of the HOCs were determined as C(water(eq))/C(solution(eq)), whereas enhanced capacities (E) of the solutions for HOCs were determined as C(solution(eq))/C(water(eq)). A mixture of polycyclic aromatic hydrocarbons served as model analytes, while humic acid, sodium dodecyl sulfate, hydroxypropyl-β-cyclodextrin, and NaCl served as model medium constituents. The enhanced capacities were plotted versus the concentrations of medium constituents, and simple linear regression provided precise partition ratios, salting out constants, and critical micelle concentrations. These parameters were generally in good agreement with published values obtained by solid phase microextraction and fluorescence quenching. The very good precision was indicated by the low relative standard errors for the partition ratios of 0.5-8%, equivalent to 0.002-0.03 log unit. This passive dosing approach allows binding and speciation of HOCs to be studied without any phase separation steps or mass balance assumptions.     

Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis

Altered mitochondrial function is currently recognized as an important factor in atherosclerosis initiation and progression. Mitochondrial dysfunction can be caused by mitochondrial DNA (mtDNA) mutations, which can be inherited or spontaneously acquired in various organs and tissues, having more or less profound effects depending on the tissue energy status. Arterial wall cells are among the most vulnerable to mitochondrial dysfunction due to their barrier and metabolic functions. In atherosclerosis, mitochondria cause alteration of cellular metabolism and respiration and are known to produce excessive amounts of reactive oxygen species (ROS) resulting in oxidative stress. These processes are involved in vascular disease and chronic inflammation associated with atherosclerosis. Currently, the list of known mtDNA mutations associated with human pathologies is growing, and many of the identified mtDNA variants are being tested as disease markers. Alleviation of oxidative stress and inflammation appears to be promising for atherosclerosis treatment. In this review, we discuss the role of mitochondrial dysfunction in atherosclerosis development, focusing on the key cell types of the arterial wall involved in the pathological processes. Accumulation of mtDNA mutations in isolated arterial wall cells, such as endothelial cells, may contribute to the development of local inflammatory process that helps explaining the focal distribution of atherosclerotic plaques on the arterial wall surface. We also discuss antioxidant and anti-inflammatory approaches that can potentially reduce the impact of mitochondrial dysfunction.     

Effect of pulsed electric fields and high pressure on improved recovery of high-added-value compounds from olive pomace

Olive pomace is considered a solid by-product and a rich source of valuable compounds such as polyphenols, flavonoids with antioxidant properties, and proteins. Nonthermal technologies, which cause alterations to cell permeability, are being explored to assist conventional recovery techniques. The aim of this study was to assess the effect of pulsed electric fields (PEF) and high pressure (HP) on improved recovery yield of the high-added-value compounds or to shorten the extraction time of these compounds. Olive pomace (Tsounati cv) was pretreated with PEF (1.0 to 6.5 kV/cm, 0.9 to 51.1 kJ/kg, and 15 µs pulse width) or HP (200 to 600 MPa and 0 to 40 min). Evaluation of the intracellular compounds extracted via solid–liquid extraction (50% ethanol–water solution) was performed. More intense PEF and HP conditions resulted in a significant increase of the phenolic concentration up to 91.6% and 71.8%, respectively. The increased antioxidant capacity of each extract was correlated to phenolic compound concentration. The protein concentration that was achieved with PEF pretreatment was doubled; however, HP-pretreated extracts reached 88.1% higher yield than untreated for pressures up to 200 MPa. HP and PEF pretreatment decreased extraction completion time t₉₈ (needed time to recover the equal amount of phenolics and proteins of untreated after 60 min of conventional extraction) to 12 min and lower than 1 min, respectively. To conclude, both pretreatments are effective in improving the conventional extraction process for increased yield recovery of high-added-value compounds from olive pomace.     

Efficient PCA-driven EAs and metamodel-assisted EAs,with applications in turbomachinery

This article presents methods to enhance the efficiency of Evolutionary Algorithms (EAs), particularly those assisted by surrogate evaluation models or metamodels. The gain in efficiency becomes important in applications related to industrial optimization problems with a great number of design variables. The development is based on the principal components analysis of the elite members of the evolving EA population, the outcome of which is used to guide the application of evolution operators and/or train dependable metamodels/artificial neural networks by reducing the number of sensory units. Regarding the latter, the metamodels are trained with less computing cost and yield more relevant objective function predictions. The proposed methods are applied to constrained, single- and two-objective optimization of thermal and hydraulic turbomachines.     

Families of semipermeable curves in differential games with the homicidal chauffeur dynamics

Families of semipermeable curves in differential games with the homicidal chauffeur dynamics are studied both from theoretical and computational points of view. The knowledge of such families is very useful because semipermeable curves bound capture sets in games of kind. They can also appear as barrier lines on which value functions of time-optimal differential games are discontinuous. Two examples of differential games with the homicidal chauffeur dynamics are considered. Capture sets are constructed using semipermeable curves. The results are verified through computation of level sets of the value functions in the related time-optimal games.     

A comparative in-vitro study of the bactericidal efficacy of sodium hypochlorite and chlorhexidine gluconate plus cetrimide on root canal anaerobic bacterial flora

INTRODUCTION: The permanence of necrotic tissues and/or bacteria may be responsible for persistent root canal infection. Root canal irrigation plays an important role in the success of endodontic treatment given that, on the one hand, it encourages the progressive elimination of the smear layer and, on the other, it neutralises microbic flora within the canal. The aim of this study was to test root canal irrigants from a microbiological point of view: sodium hypochlorite 5% (Niclor Ogna, Milan) and a new generation irrigant based on chlorhexidine gluconate and cetrimide (Cetrexidine VEBAS S. Giuliano Milanese-MI). METHODS: The experiments were performed on a series of obligatory anaerobic bacteria which are most frequently found in the endodontium, all belonging to the international collection "American Type Culture Collection" (ATCC) and supplied by Dasit SpA, Cornaredo (MI). The following bacterial strains were used in the experiment: Actinimyces odontolyticus ATCC 17929, Fusobacterium nucleatum ATCC 25586, Prevotella melanginogenica ATCC 25845, Porphyromonas gingivalis ATCC 33277. The working concentration (CFU/ml) was defined as 0.5 McFarland which corresponds to a concentration of microorganisms equivalent to approx. 1.5 x 10(3) bacteria. Each irrigant was kept in contact with the bacterial species used for this experiment for 10', 20', 30'. RESULTS: The results obtained confirm the bactericidal efficacy of both irrigants used, even after a short contact time. CONCLUSIONS: This does not mean that all irrigants are the same and/or promise the same results. This was a microbiological study, but in practice it is important to bear in mind other variables, such as contact time. Moreover, in order to increase the probability of endodontic treatment, root canal irrigants are also required to satisfy other criteria: biocompatibility, scarce toxicity, high proteolytic power.