Feed-Forward and Feed-Back Circuits of the NRF2/AP-1 Composite Pathway

Being the central regulator of oxidative status of the cell, NRF2 must be regulated so that its activity can be rapidly and strongly induced when needed and quickly suppressed when not. Moreover, for the cell, NRF2 means much more than just antioxidant defense. Numerous general functions rely on NRF2 and related factors. All this implies that the NRF2 pathway has peculiar and powerful mechanisms of control of its activity. To a great extent, these mechanisms are based on feed-forward and feed-back circuits. These circuits, more than a dozen, are in the focus of this chapter

Oxidative Status Pathways: Systemic Biomarkers

Systemic biomarkers (i.e. biomarkers of functioning of cellular pathways) offer a broad spectrum of diagnostic capabilities. There are several approaches to using systemic biomarkers that derive from exact needs of a researcher or a clinical specialist. First, analyzing a multifunctional and multi-systemic pathway in circulating cells (e.g. leukocytes) allows to gather generalized information on functioning of the organism. Second, there are numerous pathways that, even still in circulating cells, allow to assess risks of developing or stage of development of numerous diseases, including the leaders of non-infection diseases mortality—cardiovascular diseases. Third, biopsy specimens can readily be used to assess the exact signaling type of a disease (especially cancer) thus helping in selecting the best treatment option. Due to unique properties of the human oxidative status pathways that are discussed in the present chapter, diagnostics specialists are now acquiring an all-in-one toolbox for profiling and detecting almost any non-infectious and a broad range of infectious diseases. In addition to properties of the human oxidative status pathways opening these possibilities, this chapter considers exact systemic biomarkers deriving from this approach, reveals some examples of usage of the resulting diagnostic technology and provides instances of successful clinical application of the systemic biomarker approach

Innovation processes management and its efficiency for area development

Nowadays an industrial complex efficiency depends on many factors, but the essential condition here is an innovative activity of enterprises and regions. Only this innovative activity makes it possible to provide competitive advantages both at the national and at the world economy levels. To improve economic performance, it is necessary that economic entities operating in various spheres of industrial production intensify innovation activities to strengthen and develop their market positions. It should also be taken into account that this is a two-sided process, as, on the one hand, regional conditions influence realization of industry innovative potential, and, on the other hand, innovative processes influence effective area development. The paper aims to analyze the main innovative processes taking place in the region and to estimate the efficiency of clustering while using expert analysis and performance indicators of each cluster

Innovative development of the building complex on the basis of environmental and energy-efficient technologies

The objective of the current study was to determine the priorities of innovative development of the building complex on the basis of the analysis of the environmental and energy-efficient technologies that were applied. Analysis of energy efficiency and environmental technologies in the construction industry showed that residential housing consumes 23% of the total primary energy supply in Russia. The construction sector is responsible for 30% of CO2 emissions into the atmosphere. Russia annually spends approximately 170 million tons of fuel equivalents for heating, ventilation and air conditioning of residential housing. Comparing Russia with the countries of similar climatic conditions it should be noted that energy consumption value in Russia is significantly higher (the excess ranges from 24 to 47% depending upon the building). Having analyzed the housing the authors offer the ways of building complex innovative development that mean the following: reindustrialization of material and technical resources of construction companies and the introduction of managerial innovations; the development and application of new high-tech building structures, products and materials that are to ensure the economic and environmental efficiency of buildings’ construction and operation

Innovative development of the building complex on the basis of environmental and energy-efficient technologies

The objective of the current study was to determine the priorities of innovative development of the building complex on the basis of the analysis of the environmental and energy-efficient technologies that were applied. Analysis of energy efficiency and environmental technologies in the construction industry showed that residential housing consumes 23% of the total primary energy supply in Russia. The construction sector is responsible for 30% of CO2 emissions into the atmosphere. Russia annually spends approximately 170 million tons of fuel equivalents for heating, ventilation and air conditioning of residential housing. Comparing Russia with the countries of similar climatic conditions it should be noted that energy consumption value in Russia is significantly higher (the excess ranges from 24 to 47% depending upon the building). Having analyzed the housing the authors offer the ways of building complex innovative development that mean the following: reindustrialization of material and technical resources of construction companies and the introduction of managerial innovations; the development and application of new high-tech building structures, products and materials that are to ensure the economic and environmental efficiency of buildings’ construction and operation

BaGdF₅ Nanophosphors Doped with Different Concentrations of Eu³⁺ for Application in X-ray Photodynamic Therapy

X-ray photodynamic therapy (XPDT) has been recently considered as an efficient alternative to conventional radiotherapy of malignant tissues. Nanocomposites for XPDT typically consist of two components—a nanophosphor which re-emits X-rays into visible light that in turn is absorbed by the second component, a photosensitizer, for further generation of reactive oxygen species. In this study, BaGdF5 nanophosphors doped with different Eu:Gd ratios in the range from 0.01 to 0.50 were synthesized by the microwave route. According to transmission electron microscopy (TEM), the average size of nanophosphors was ~12 nm. Furthermore, different coatings with amorphous SiO2 and citrates were systematically studied. Micro-CT imaging demonstrated superior X-ray attenuation and sufficient contrast in the liver and the spleen after intravenous injection of citric acid-coated nanoparticles. In case of the SiO2 surface, post-treatment core–shell morphology was verified via TEM and the possibility of tunable shell size was reported. Nitrogen adsorption/desorption analysis revealed mesoporous SiO2 formation characterized by the slit-shaped type of pores that should be accessible for methylene blue photosensitizer molecules. It was shown that SiO2 coating subsequently facilitates methylene blue conjugation and results in the formation of the BaGdF5: 10% Eu3+@SiO2@MB nanocomposite as a promising candidate for application in XPDT

The Rare-Earth Elements Doping of BaGdF₅ Nanophosphors for X-ray Photodynamic Therapy

It is known that the initiation of photodynamic therapy (PDT) in deep-seated tumors requires the use of X-rays to activate the reactive oxygen species generation in deep tissues. The aim of this paper is to synthesize X-ray nanophosphors and analyze their structural and luminescence characteristics to push the PDT process deep into the body. The article deals with BaGdF5:Eu3+, BaGdF5:Sm3+, and BaGdF5:Tb3+ nanophosphors synthesized using microwave synthesis. It is found that the nanoparticles are biocompatible and have sizes 5–17 nm. However, according to the analysis of X-ray excited optical luminescence, BaGdF5:Sm3+ nanophosphors will not be effective for treating deep-seated tumors. Thus, BaGdF5:Eu3+ and BaGdF5:Tb3+ nanoparticles meet the requirements for the subsequent production of nanocomposites based on them that can be used in X-ray photodynamic therapy

Individual expression features of GPX2, NQO1 and SQSTM1 transcript variants induced by hydrogen peroxide treatment in HeLa cells

Abstract Pathway activity assessment-based approaches are becoming highly influential in various fields of biology and medicine. However, these approaches mostly rely on analysis of mRNA expression, and total mRNA from a given locus is measured in the majority of cases. Notably, a significant portion of protein-coding genes produces more than one transcript. This biological fact is responsible for significant noise when changes in total mRNA transcription of a single gene are analyzed. The NFE2L2/AP-1 pathway is an attractive target for biomedical applications. To date, there is a lack of data regarding the agreement in expression of even classical target genes of this pathway. In the present paper we analyzed whether transcript variants of GPX2, NQO1 and SQSTM1 were characterized by individual features of expression when HeLa cells were exposed to pro-oxidative stimulation with hydrogen peroxide. We found that all the transcripts (10 in total) appeared to be significantly individually regulated under the conditions tested. We conclude that individual transcripts, rather than total mRNA, are best markers of pathway activation. We also discuss here some biological roles of individual transcript regulation