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The modern treatment strategy for keratoconus (KC) involves sequential application of medical technologies aimed at stabilizing pathological changes in the cornea and restoring visual acuity., Purpose: This study compares the effect of implantation of intrastromal corneal ring segment (ICRS) and fitting of individual scleral rigid contact lenses (RCLs) on visual functions in patients with stage II-III KC after previously performed corneal collagen cross-linking., Material and Methods: The Helmholtz National Medical Research Center of Eye Diseases examined and treated 34 patients (69 eyes) aged 18 to 33 years with stage II-III KC. The study included patients who had previously undergone standard corneal collagen cross-linking. Depending on the type of optical correction, the patients were divided into two groups: patients in group 1 underwent ICRS implantation using a femtosecond laser; patients in group 2 were fitted with individual scleral RCLs., Results: Improvement in clinical and functional parameters was observed in both groups. A higher clinical and functional result was achieved in group 2., Conclusion: For patients with stable stage II-III KC, it is advisable to recommend fitting of individual scleral RCLs for visual rehabilitation.

Background: We investigated the role of A2B-adenosine receptor in regulating immunosuppressive metabolic stress in the tumor microenvironment. Novel A2B-adenosine receptor antagonist PBF-1129 was tested for antitumor activity in mice and evaluated for safety and immunologic efficacy in a phase I clinical trial of patients with non-small cell lung cancer., Methods: The antitumor efficacy of A2B-adenosine receptor antagonists and their impact on the metabolic and immune tumor microenvironment were evaluated in lung, melanoma, colon, breast, and epidermal growth factor receptor-inducible transgenic cancer models. Employing electron paramagnetic resonance, we assessed changes in tumor microenvironment metabolic parameters, including pO2, pH, and inorganic phosphate, during tumor growth and evaluated the immunologic effects of PBF-1129, including its pharmacokinetics, safety, and toxicity, in patients with non-small cell lung cancer., Results: Levels of metabolic stress correlated with tumor growth, metastasis, and immunosuppression. Tumor interstitial inorganic phosphate emerged as a correlative and cumulative measure of tumor microenvironment stress and immunosuppression. A2B-adenosine receptor inhibition alleviated metabolic stress, downregulated expression of adenosine-generating ectonucleotidases, increased expression of adenosine deaminase, decreased tumor growth and metastasis, increased interferon γ production, and enhanced the efficacy of antitumor therapies following combination regimens in animal models (anti-programmed cell death 1 protein vs anti-programmed cell death 1 protein plus PBF-1129 treatment hazard ratio = 11.74 [95% confidence interval = 3.35 to 41.13], n = 10, P < .001, 2-sided F test). In patients with non-small cell lung cancer, PBF-1129 was well tolerated, with no dose-limiting toxicities; demonstrated pharmacologic efficacy; modulated the adenosine generation system; and improved antitumor immunity., Conclusions: Data identify A2B-adenosine receptor as a valuable therapeutic target to modify metabolic and immune tumor microenvironment to reduce immunosuppression, enhance the efficacy of immunotherapies, and support clinical application of PBF-1129 in combination therapies., (© The Author(s) 2023. Published by Oxford University Press.)

For the first time, a prototype of a portable device for the potentiometric determination of antioxidant capacity based on a new measurement principle is proposed. A feature of the approach is the use of an electrochemical microcell with separated spaces and two identical electrodes with immobilized reagents. An antioxidant solution is introduced into one half-cell, and the antioxidants interact with the reagents. The other half-cell contains only reagents. The potential difference between the electrodes is due to the change in the ratio of the oxidized and reduced form of the reagents, which occurs as a result of the reaction with the antioxidants in one of the half-cells and is related to their concentration. The range of linearity of the microcell with immobilized reagents is 40-4000 μM-eq, and the limit of detection is 20 μM-eq. The device was successfully tested in the analysis of standard antioxidant solutions. The recoveries were (92-113)%, and the relative standard deviation did not exceed 15%. A good correlation was found between the data obtained by the approach and the potentiometric method in a macrocell for fruit juice analysis. Pearson's coefficient for the obtained experimental data was 0.9955. The proposed portable device is promising and can be used in field conditions.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1/Tusc2 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, and altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether the pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1/Tusc2-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed the dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and the cochlear hypothalamic-pituitary-adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins and calcium-linked transporters and voltage-gated channels. These findings suggest that the pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss.

A hypoxic-hyperoxic preconditioning (HHP) may be associated with cardioprotection by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Patients ( n = 120) were randomly assigned to an HHP and a control group. A safe, inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 min) was determined by measuring the anaerobic threshold. At the hyperoxic phase, a 75-80% oxygen fraction was used for 30 min. The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs. 23 (41.1%), p = 0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low for more than 24 h in the control group. The endothelial damage markers appeared to be predictors of postoperative complications. The HHP with individual parameters based on the anaerobic threshold is a safe procedure, and it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

Nowadays, magnetoelectric nanomaterials are on their way to finding wide applications in biomedicine for various cancer and neurological disease treatment, which is mainly restricted by their relatively high toxicity and complex synthesis. This study for the first time reports novel magnetoelectric nanocomposites of Co x Fe 3-x O 4 -BaTiO 3 series with tuned magnetic phase structures, which were synthesized via a two-step chemical approach in polyol media. The magnetic Co x Fe 3-x O 4 phases with x = 0.0, 0.5, and 1.0 were obtained by thermal decomposition in triethylene glycol media. The magnetoelectric nanocomposites were synthesized by the decomposition of barium titanate precursors in the presence of a magnetic phase under solvothermal conditions and subsequent annealing at 700 °C. X-ray diffraction revealed the presence of both spinel and perovskite phases after annealing with average crystallite sizes in the range of 9.0-14.5 nm. Transmission electron microscopy data showed two-phase composite nanostructures consisting of ferrites and barium titanate. The presence of interfacial connections between magnetic and ferroelectric phases was confirmed by high-resolution transmission electron microscopy. Magnetization data showed expected ferrimagnetic behavior and σ s decrease after the nanocomposite formation. Magnetoelectric coefficient measurements after the annealing showed non-linear change with a maximum of 89 mV/cm*Oe with x = 0.5, 74 mV/cm*Oe with x = 0, and a minimum of 50 mV/cm*Oe with x = 0.0 core composition, that corresponds with the coercive force of the nanocomposites: 240 Oe, 89 Oe and 36 Oe, respectively. The obtained nanocomposites show low toxicity in the whole studied concentration range of 25-400 μg/mL on CT-26 cancer cells. The synthesized nanocomposites show low cytotoxicity and high magnetoelectric effects, therefore they can find wide applications in biomedicine.

Pterygium is among the most frequent indications for extraocular ophthalmic surgery. The main method of pterygium treatment - its excision - is often combined with transplantation, non-transplantation, medication and other methods. However, the frequency of pterygium recurrence can exceed 35%, and the cosmetic and refraction outcomes satisfy neither the patient, nor the surgeon., Purpose: The study analyses the technical capability and feasibility for transplantation of the Bowman's layer in the treatment of recurrent pterygium., Material and Methods: The transplantation of the Bowmen's layer was performed according to the developed technique on 7 eyes with recurrent pterygium (7 patients aged 34 to 63 years). The combined surgery technique consisted of pterygium resection, laser ablation, autoconjunctival plasty, exposure to a cytostatic drug, non-suture transplantation of the Bowman's layer. Maximum length of the follow-up was 36 months. Analysis involved data from refractometry, visometry (without correction and with spectacle correction), and optical coherence tomography of the retina., Results: There were no complications in any of the studied cases. The cornea and the transplant retained transparency throughout the entire follow-up duration. 36 months after surgery mean spectacle-corrected visual acuity amounted to 0.86±0.2, topographic astigmatism - 1.48±1.4 diopters. Recurrence of pterygium was not observed. All patients were satisfied with the cosmetic outcomes of the treatment., Conclusion: Non-suture transplantation of the Bowmen's layer recovers normal anatomy, physiology and transparency of the cornea after repeat surgical intervention for pterygium. No pterygium recurrences were observed throughout the entire follow-up after treatment with the proposed combined technique.

Redox-responsive and magnetic nanomaterials are widely used in tumor treatment separately, and while the application of their combined functionalities is perspective, exactly how such synergistic effects can be implemented is still unclear. This report investigates the internalization dynamics of magnetic redox-responsive nanoparticles (MNP-SS) and their cytotoxicity toward PC-3 and 4T1 cell lines. It is shown that MNP-SS synthesized by covalent grafting of polyethylene glycol (PEG) on the magnetic nanoparticle (MNP) surface via SS-bonds lose their colloidal stability and aggregate fully in a solution containing DTT, and partially in conditioned media, whereas the PEGylated MNP (MNP-PEG) without S-S linker control remains stable under the same conditions. Internalized MNP-SS lose the PEG shell more quickly, causing enhanced magnetic core dissolution and thus increased toxicity. This was confirmed by fluorescence microscopy using MNP-SS dual-labeled by Cy3 via labile disulfide, and Cy5 via a rigid linker. The dyes demonstrated a significant difference in fluorescence dynamics and intensity. Additionally, MNP-SS demonstrate quicker cellular uptake compared to MNP-PEG, as confirmed by TEM analysis. The combination of disulfide bonds, leading to faster dissolution of the iron oxide core, and the high-oxidative potential Fe 3+ ions can synergically enhance oxidative stress in comparison with more stable coating without SS-bonds in the case of MNP-PEG. It decreases the cancer cell viability, especially for the 4T1, which is known for being sensitive to ferroptosis-triggering factors. In this work, we have shown the effect of redox-responsive grafting of the MNP surface as a key factor affecting MNP-internalization rate and dissolution with the release of iron ions inside cancer cells. This kind of synergistic effect is described for the first time and can be used not only in combination with drug delivery, but also in treatment of tumors responsive to ferroptosis.

FUS1/TUSC2 (FUSion1/TUmor Suppressor Candidate 2) is a tumor suppressor gene (TSG) originally described as a member of the TSG cluster from human 3p21.3 chromosomal region frequently deleted in lung cancer. Its role as a TSG in lung, breast, bone, and other cancers was demonstrated by several groups, but molecular mechanisms of its activities are starting to unveil lately. They suggest that Fus1-dependent mechanisms are relevant in etiologies of diseases beyond cancer, such as chronic inflammation, bacterial and viral infections, premature aging, and geriatric diseases. Here, we revisit the discovery of FUS1 gene in the context of tumor initiation and progression, and review 20 years of research into FUS1 functions and its molecular, structural, and biological aspects that have led to its use in clinical trials and gene therapy. We present a data-driven view on how interactions of Fus1 with the mitochondrial Ca 2+ (mitoCa 2+ ) transport machinery maintain cellular Ca 2+ homeostasis and control cell apoptosis and senescence. This Fus1-mediated cellular homeostasis is at the crux of tumor suppressor, anti-inflammatory and anti-aging activities., (© 2022. The Author(s).)

The magneto-mechanical approach is a powerful technique used in many different applications in biomedicine, including remote control enzyme activity, cell receptors, cancer-selective treatments, mechanically-activated drug releases, etc. This approach is based on the use of a combination of magnetic nanoparticles and external magnetic fields that have led to the movement of such nanoparticles with torques and forces (enough to change the conformation of biomolecules or even break weak chemical bonds). However, despite many theoretical and experimental works on this topic, it is difficult to predict the magneto-mechanical effects in each particular case, while the important results are scattered and often cannot be translated to other experiments. The main reason is that the magneto-mechanical effect is extremely sensitive to changes in any parameter of magnetic nanoparticles and the environment and changes in the parameters of the applied magnetic field. Thus, in this review, we (1) summarize and propose a simplified theoretical explanation of the main factors affecting the efficiency of the magneto-mechanical approach; (2) discuss the nature of the MNP-mediated mechanical forces and their order of magnitude; (3) show some of the main applications of the magneto-mechanical approach in the control over the properties of biological systems.

Acute and chronic kidney injuries induce increased cell cycle progression in renal tubules. While increased cell cycle progression promotes repair after acute injury, the role of ongoing tubular cell cycle progression in chronic kidney disease is unknown. Two weeks after initiation of chronic kidney disease, we blocked cell cycle progression at G1/S phase by using an FDA-approved, selective inhibitor of CDK4/6. Blocking CDK4/6 improved renal function and reduced tubular injury and fibrosis in 2 murine models of chronic kidney disease. However, selective deletion of cyclin D1, which complexes with CDK4/6 to promote cell cycle progression, paradoxically increased tubular injury. Expression quantitative trait loci (eQTLs) for CCND1 (cyclin D1) and the CDK4/6 inhibitor CDKN2B were associated with eGFR in genome-wide association studies. Consistent with the preclinical studies, reduced expression of CDKN2B correlated with lower eGFR values, and higher levels of CCND1 correlated with higher eGFR values. CDK4/6 inhibition promoted tubular cell survival, in part, through a STAT3/IL-1β pathway and was dependent upon on its effects on the cell cycle. Our data challenge the paradigm that tubular cell cycle progression is beneficial in the context of chronic kidney injury. Unlike the reparative role of cell cycle progression following acute kidney injury, these data suggest that blocking cell cycle progression by inhibiting CDK4/6, but not cyclin D1, protects against chronic kidney injury.

According to the World Health Organization, breast cancer is the most common oncological disease worldwide. There are multiple animal models for different types of breast carcinoma, allowing the research of tumor growth, metastasis, and angiogenesis. When studying these processes, it is crucial to visualize cancer cells for a prolonged time via a non-invasive method, for example, magnetic resonance imaging (MRI). In this study, we establish a new genetically encoded material based on Quasibacillus thermotolerans ( Q.thermotolerans, Qt ) encapsulin, stably expressed in mouse 4T1 breast carcinoma cells. The label consists of a protein shell containing an enzyme called ferroxidase. When adding Fe 2+ , a ferroxidase oxidizes Fe 2+ to Fe 3+ , followed by iron oxide nanoparticles formation. Additionally, genes encoding mZip14 metal transporter, enhancing the iron transport, were inserted into the cells via lentiviral transduction. The expression of transgenic sequences does not affect cell viability, and the presence of magnetic nanoparticles formed inside encapsulins results in an increase in T2 relaxivity.

The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2 H -imidazole-derived phenolic compounds affording the bifunctional 2 H -imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2 H -imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2 H -imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship "structure-antioxidant properties" was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2 H -imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2 H -imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (10 4 mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.

One of the main factors associated with worse prognosis in oncology is metastasis, which is based on the ability of tumor cells to migrate from the primary source and to form secondary tumors. The search for new strategies to control migration of metastatic cells is one of the urgent issues in biomedicine. One of the strategies to stop spread of cancer cells could be regulation of the nuclear elasticity. Nucleus, as the biggest and stiffest cellular compartment, determines mechanical properties of the cell as a whole, and, hence, could prevent cell migration through the three-dimensional extracellular matrix. Nuclear rigidity is maintained by the nuclear lamina, two-dimensional network of intermediate filaments in the inner nuclear membrane (INM). Here we present the most significant factors defining nucleus rigidity, discuss the role of nuclear envelope composition in the cell migration, as well consider possible approaches to control lamina composition in order to change plasticity of the cell nucleus and ability of the tumor cells to metastasize.

This article presents the results of a study of electrochemical transformations in aqueous and aprotic media of 5-methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidinide l-arginine monohydrate ( 1a , Triazid) obtained by electrochemical methods and ESR spectroscopy. The effect of pH on the current and the reduction potential of 1a in an aqueous Britton-Robinson buffer solution was studied. It was found that 1a is irreversibly reduced in aqueous acidic media on a glassy carbon electrode in one stage with the participation of six electrons and the formation of 5-methyl-6-amino-7-oxo-1,2,4-triazolo[1,5-a]pyrimidin. The electroreduction of 1a in DMF on a background of tetrabutylammonium salts proceeds in two stages, controlled by the kinetics of second-order reactions. In the first stage, the reduction of 1a is accompanied by protonation by the initial compound of the basic intermediate products formed in the electrode reaction (self-protonation mechanism). The second quasi-reversible stage of the electroreduction 1a corresponds to the formation of a dianion radical upon the reduction of the heterocyclic anion 5-methyl-6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidin, which is formed upon the potentials of the first peak. The ESR spectrum of the radical dianion was recorded upon electroreduction of Triazid in the presence of Bu 4 NOH. The effect of the formation of ion pairs on the reversibility of the second peak of the 1a transformation is shown. A change in the rate and regioselectivity of the protonation of the dianion radical in the presence of Na + and Li + ions is assumed. The results of studying the electroreduction of 1a by ESR spectroscopy with a TEMPO trap make it possible to assume the simultaneous formation of both a nitroxyl radical and a radical with the spin density localized on the nitrogen at the 4 position of the six-membered ring.

A clinical case of myocardial infarction in a patient with single ventricle heart defect is described.

The preparation and study of the biological properties of the pVAKS-GPVM DNA immunogen containing a gene encoding Marburgvirus glycoprotein are described. The specificity of blood serum antibodies of guinea pigs immunized with DNA immunogen was analyzed by ELISA. Inactivated viral preparation, recombinant glycoprotein (GP) obtained in the prokaryotic system and virus-like particles based on the recombinant vesicular stomatitis virus exhibiting Marburgvirus GP were used as the antigens. The neutralizing activity of antibodies of immunized animals was tested in vitro using a pseudovirus system. It was demonstrated that the developed immunogen administered to guinea pigs induced the production of specific antibodies that neutralize virus-like particles and Marburgvirus in cultured Vero cells.

Water content in the cornea may affect the outcome of its excimer laser ablation, especially in presbyopic patients with myopic refraction. This hypothesis can be tested by scanning the cornea in the terahertz (THz) range to determine its hydration level., Purpose: To study the effect of hydration of the cornea determined by non-contact THz scanning and its biomechanical parameters on the results of photorefractive keratectomy (PRK) in an experiment., Material and Methods: PRK was performed using the Nidek EC-5000 QUEST excimer laser on 8 rabbit eyes. Corneal hydration was evaluated by determining the reflection coefficient (RC) in the THz electromagnetic radiation range before PRK, after 3-5 days, and after 1, 2, 3, and 4 months. Clinical examination included autorefractometry, assessment of corneal thickness and other anatomical and optical parameters of the anterior eye segment (Galilei G6, Ziemer Ophthalmic Systems AG 6.0.2, Switzerland), measurement of corneal hysteresis (CH) and corneal resistance factor (CRF) using the Ocular Response Analyzer (ORA; Reichert, USA), as well as tear production (Schirmer test)., Results: The initial water content in the cornea has a significant effect on the thickness of the removed layer, i.e. on the PRK effect, with correlation coefficient of R s = -0.976 ( p <0.01). The correlation between CH and the ablation depth is less pronounced (R s =0.643), and CRF had no correlation with it (R s = -0.089). Biomechanical indicators of the cornea depend on its hydration: changes in CH and CRF after excimer laser ablation qualitatively coincide with changes in RC, the correlation coefficient between RC and the initial value of CH is R= -0.619 (moderate negative correlation)., Conclusion: THz scanning is an effective non-contact technology for monitoring corneal hydration level. The mismatch of the hypoeffect of keratorefractive excimer laser intervention planned for patients with presbyopia with the actual outcome can be caused by individual decrease in the initial water content in the cornea.

Background: To evaluate the effectiveness of neuromuscular electrical stimulation (NMES) in early rehabilitation of patients with postoperative complications after cardiovascular surgery., Methods: 37 patients (25 men and 12 women) aged 45 to 70 years with postoperative complications after cardiovascular surgery were included in the study. Eighteen patients underwent NMES daily since postoperative day 3 until discharge in addition to standard rehabilitation program (NMES group), and 19 patients underwent standard rehabilitation program only (non-NMES group). The primary outcome was the knee extensors strength at discharge in NMES group and in control. Secondary outcomes were the handgrip strength, knee flexor strength, and cross-sectional area (CSA) of the quadriceps femoris in groups at discharge., Results: Baseline characteristics were not different between the groups. Knee extensors strength at discharge was significantly higher in the NMES group (28.1 [23.8; 36.2] kg on the right and 27.45 [22.3; 33.1] kg on the left) than in the non-NMES group (22.3 [20.1; 27.1] and 22.5 [20.1; 25.9] kg, respectively; P < .001). Handgrip strength, knee flexor strength, quadriceps CSA, and 6 minute walk distance at discharge in the groups had no significant difference., Conclusions: This pilot study shows a beneficial effect of NMES on muscle strength in patients with complications after cardiovascular surgery. The use of NMES showed no effect on strength of non-stimulated muscle, quadriceps CSA, and distance of 6-minute walk test at discharge.Further blind randomized controlled trials should be performed with emphasis on the effectiveness of NEMS in increasing muscle strength and structure in these patients.

Aim      To study possible correlations between echocardiography (EchoCG) indexes and markers of myocardial fibrosis, procollagen I C-terminal propeptide (PICP) and procollagen III N-terminal propeptide (PIIINP) during one year following ST-segment elevation myocardial infarction (STEMI).Material and methods  120 patients with STEMI were evaluated. EchoCG was used to assess dimensions and volumes of heart chambers, left ventricular (LV) systolic function, mean pulmonary arterial pressure (mPAP), and indexes of LV diastolic function (Em, early diastolic lateral mitral annular velocity; e', peak early diastolic septal mitral annular velocity; E / e', ratio of peak early diastolic transmitral inflow velocity and mitral annular velocity  -, Е / А, ratio of peak early and late transmitral inflow velocities; DT, deceleration time of LV early diastolic filling). EchoCG indexes and serum concentrations of PICP and PIIINP were determined at 1 (point 1) and 12 (point 2) days of disease and one year after STEMI (point 3). The sample was divided into two groups: group 1 (n=86; 71.7 %) included patients with a LV ejection fraction (EF) ≥50 % and group 2 (n=34; 28.3 %) consisted of patients with LV EF ≤49 %.Results At one year, the number of patients with signs of diastolic dysfunction increased by 10% in group 1 whereas myocardial systolic dysfunction worsened in both groups. LV EF decreased in 15 (17.4%) patients of group 1 and in 4 (11.8%) patients of group 2. Concentrations of PIIINP were correlated with Em, E / e', mPAP, PICP, e', and LV EF.Conclusion      Direct correlations between PIIINP concentrations and Em, E / e', and mPAP were found in the group with LV EF ≥50 %. In the group with LV EF &lt;50 %, correlations were observed between PICP concentrations, LV EF, and e'. Also, in this group, the increase in PIIINP was statistically more significant. These results indicate continuing formation of myocardial fibrosis in a year following MI, which may underlie progression of chronic heart failure.

Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An analytical methodology is proposed for a comprehensive study of antioxidant properties of various objects based on the implementation of various mechanisms of antioxidant action. In order to interpret results regarding the action of antioxidants in living organisms it is proposed to adhere to certain requirements for research methods of antioxidant properties, for oxidizing agents of a radical and non-radical nature. The developed integrated approach consists in using the potentiometry method and is based on the antioxidant capacity determination which is founded on the interaction of antioxidants with the К 3 [Fe(CN) 6 ] by the ET-mechanism and the conjugation mechanism and the antiradical capacity determination based on the interaction of antioxidants with peroxyl radicals by the HAT-mechanism. Individual antioxidants of natural origin, plant materials extracts as well as synthesized 6-nitro-1,2,4-triazoloazin containing polyphenols fragments, which are complex conjugated structures, have been investigated. It has been shown that in the antioxidants study it is advisable to use the integrated approach that will allow to evaluate antioxidant properties from the point of view of various antioxidants action mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sutureless implantation of the mitral valve bioprosthesis using the valve-in-valve method was performed on a large animal (sheep). According to the results of a two-stage implantation (primary implantation of a xenopericardial 26-mm framed bioprosthesis and reimplantation of the developed 23-mm bioprosthesis), minor changes in quantitative indicators were revealed: an increase in the transprosthetic gradient by 1.3 mm Hg and a decrease in the area of the mitral orifice by 21.6%. Considerable reduction in the intervention time by 18 min was achieved (by 40% in comparison with the primary prosthesis). The absence of adverse events in the animal and complications in the post-operative period, as well as physiological hemodynamic indicators indicate the safety of the developed medical device.

In chicken embryos, nitric oxide (NO) is accumulated in the pool of NO donors: S-nitrosothiols, nitrosyl-iron complexes, high-molecular-weight nitro-compounds. Oxidation of NO to nitrate occurs with different intensity in the embryos of different chicken breeds. In some embryos, NO donors accumulate almost without oxidation. Stable concentration of NO donors and nitrate in the blood of adult chicken is a result of dynamic equilibrium between NO synthesis and elimination (oxidation, consumption by other tissues, and excretion). As NO oxidation occurs mainly not in the blood, but in other tissues, decomposition of NO donors and NO oxidation are determined the properties of these tissues, in particular, the presence of physiological targets of NO, rather than spontaneous processes. Hence, evaluation of the intensity of NO metabolism is important for prediction of the efficiency of preparations containing NO donors and stimulators of its synthesis.

Introduction: Diagnosis of chronic hepatitis B virus (HBV) infection particularly its occult form requires monitoring and repeat serological and molecular studies. The aim of the study was to investigate the possible relation between the case of a family outbreak of hepatitis A and the finding that a member of this family was diagnosed with chronic hepatitis B., Methodology: A mother and her two sons, one previously diagnosed with chronic HBV infection, were hospitalized due to suspected acute hepatitis. Serological markers for hepatitis A, hepatitis B and hepatitis C were assessed. Additionally, HBV DNA was tested with a sensitive PCR. Hepatitis B vaccine was administered to the mother to differentiate resolved from occult HBV infection., Results: A family outbreak of hepatitis A was confirmed, alongside a focus of chronic HBV infection. The serological profile for two brothers was HBsAg(+), anti-HBcIgM(-), anti-HBc(+), HBcAg(-)/anti-HBe(+). The mother was negative for all HBV markers except anti-HBc. HBV DNA was detected at a level of 461 IU/mL in the elder brother, 3647 IU/mL in the younger brother and was negative in the mother on two occasions. Her anti-HBc alone, having two sons with chronic HBV infection, and her lack of antibody response to hepatitis B vaccine despite being negative for HBV DNA, led to the diagnosis of probable occult HBV infection., Conclusion: Our results confirmed that a vaccination approach could facilitate diagnosis of chronic HBV infection in the presence of isolated anti-HBc. If it were not for a family outbreak of hepatitis A, this unexpected family HBV focus would not have been revealed., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Radka T Komitova, Ani Kevorkyan, Maria Atanasova, Aneta Ivanova, Elica Golkocheva.)

For the first time, the dependence of a redox potential change during a reaction of peroxyl radical generation and their interaction with antioxidants was studied. A regular change of a potential is due to oxidation of an antioxidant by initiating peroxyl radicals accompanied by an electron transfer. An original direct method for determining induction periods, inhibition coefficients and an antiradical capacity using the potentiometric method is proposed. Using the proposed approach the induction periods and the inhibition coefficients of various OH, NH, SH containing antioxidants were determined. The antiradical capacity of a herbal extract was studied. A high degree of correlation with a DPPH assay was obtained. RSD results obtained using the proposed approach do not exceed 7%., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Toxicological research of novel nanomaterials is a major developmental step of their clinical approval. Since iron oxide magnetic nanoparticles have a great potential in cancer treatment and diagnostics, the investigation of their toxic properties is very topical. In this paper we synthesized bovine serum albumin-coated iron oxide nanoparticles with different sizes and their polyethylene glycol derivative. To prove high biocompatibility of obtained nanoparticles the number of in vitro toxicological tests on human fibroblasts and U251 glioblastoma cells was performed. It was shown that albumin nanoparticles' coating provides a stable and biocompatible shell and prevents cytotoxicity of magnetite core. On long exposure times (48 hours), cytotoxicity of iron oxide nanoparticles takes place due to free radical production, but this toxic effect may be neutralized by using polyethylene glycol modification., (© 2018 Wiley Periodicals, Inc.)

Aim: To study diagnostic possibilities for determining the content of nitrite and N-nitroso compounds (NO 2 - +RNNO) in blood plasma and cerebrospinal fluid (CSF) in patients with acute ischemic stroke (IS)., Material and Methods: Twenty-four patients with IS were examined. The content of NO oxidation products was determined in venous blood and CSF by using an enzyme sensor based on the unique property of nitrite (NO 2 - ), N-nitroso compounds (RNNO), S-nitrosothiols and dinitrosyl iron complexes to inhibit the enzyme catalase in the presence of halide ions. The study was conducted on the 1st day of IS., Results and Conclusion: CSF in patients with IS contained nitrite and N-nitroso compounds (NO 2 - +RNNO) in concentrations ranging from 0.4 to 2.0 µm. The relationship between the size of IS and the concentration of NO 2 - +RNNO in CSF was shown. It was 1.01±0.13 µm in patients with medium IS and 0.71±0.07 µm in patients with small IS (U-criterion 16.5; p<0.05). There was no correlation between the severity of neurological deficit at the time of hospitalization and discharge from the hospital and the content of NO 2 - +RNNO in CSF (r=0.134; p>0.5; r=0.155; p>0.5, respectively). Plasma NO 2 - +RNNO levels were not associated with the presence and size of IS though they were elevated in patients with inflammatory complications. In conclusion, NO 2 - +RNNO can be considered as a marker of inflammation in patients with IS. Their presence in CSF reflects the extent of brain damage, but not the presence of concomitant inflammatory diseases.

Aims: Acquired hearing loss is a worldwide epidemic that affects all ages. It is multifactorial in etiology with poorly characterized molecular mechanisms. Mitochondria are critical components in hearing. Here, we aimed to identify the mechanisms of mitochondria-dependent hearing loss using Fus1 KO mice, our novel model of mitochondrial dysfunction/oxidative stress., Results: Using auditory brainstem responses (ABRs), we characterized the Fus1 KO mouse as a novel, clinically relevant model of age-related hearing loss (ARHL) of metabolic etiology. We demonstrated early decline of the endocochlear potential (EP) that may occur due to severe mitochondrial and vascular pathologies in the Fus1 KO cochlear stria vascularis. We showed that pathological alterations in antioxidant (AO) and nutrient and energy sensing pathways (mTOR and PTEN/AKT) occur in cochleae of young Fus1 KO mice before major hearing loss. Importantly, short-term AO treatment corrected pathological molecular changes, while longer AO treatment restored EP, improved ABR parameters, restored mitochondrial structure, and delayed the development of hearing loss in the aging mouse., Innovation: Currently, no molecular mechanisms linked to metabolic ARHL have been identified. We established pathological and molecular mechanisms that link the disease to mitochondrial dysfunction and oxidative stress., Conclusion: Since chronic mitochondrial dysfunction is common in many patients, it could lead to developing hearing loss that can be alleviated/rescued by AO treatment. Our study creates a framework for clinical trials and introduces the Fus1 KO model as a powerful platform for developing novel therapeutic strategies to prevent/delay hearing loss associated with mitochondrial dysfunction. Antioxid. Redox Signal. 27, 489-509.

Decreased energy production and increased oxidative stress are considered to be major contributors to aging and aging-associated pathologies. The role of mitochondrial calcium homeostasis has also been highlighted as an important factor affecting different pathological conditions. Here, we present evidence that loss of a small mitochondrial protein Fus1 that maintains mitochondrial homeostasis results in premature aging, aging-associated pathologies, and decreased survival. We showed that Fus1KO mice develop multiple early aging signs including lordokyphosis, lack of vigor, inability to accumulate fat, reduced ability to tolerate stress, and premature death. Other prominent pathological changes included low sperm counts, compromised ability of adult stem cells to repopulate tissues, and chronic inflammation. At the molecular level, we demonstrated that mitochondria of Fus1 KO cells have low reserve respiratory capacity (the ability to produce extra energy during sudden energy demanding situations), and show significantly altered dynamics of cellular calcium response.Our recent studies on early hearing and memory loss in Fus1 KO mice combined with the new data presented here suggest that calcium and energy homeostasis controlled by Fus1 may be at the core of its aging-regulating activities. Thus, Fus1 protein and Fus1-dependent pathways and processes may represent new tools and targets for anti-aging strategies.

Aim: Analyze HFRS morbidity in Russian Federation during the last 25 years (1990 - 2015)., Materials and Methods: Official statistics of Federal Service for Surveillance on Consumers' Rights Protection and Human Weillbeing (CPS), including Federal Centre of Hygiene and Epidemiology, were used for the analysis, as well as materials from regional departments of CPS and centers of hygiene and epidemiology. Epidemiologic analysis was the main method. Statistical treatment of the results obtained was carried out using gener- ally accepted methods of variation statistics with elements of system analysis. Results; For the studied period (1990 - 2015) 194 116 cases of HFRS were registered. Morbidity was registered in 8 federal districts of the Russian Federation in 58 subjects. The most intense epidemiologic situation was noted in Privolzhsky Federal District, that accounted for 86.4% of total HFRS morbidity during the -studied period. Analysis of morbidity was carried out in every federal district, most epidemically unfavorable territories are shown., Conclusion: The data presented on HFRS morbidity reflect -unfavorable situation for this disease in Russian Federation. Measures to prevent the emergence of diseases to reduce the general level of morbidity in Russian Federation are presented.

Background: Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in dialysis patients. The diagnosis of HCV infection in these patients is predominantly based on laboratory tests because of the specificity of the clinical course of the disease., Aim: The present prospective study aimed at determining very accurately the prevalence rate of HCV infection in patients on dialysis by simultaneously testing them for anti-HCV and for HCV RNA levels., Materials and Methods: For the present cross-sectional longitudinal study we recruited and followed up 93 patients from St George University Hospital Hemodialysis Unit between July 2013 and December 2014. All patients were tested for anti-HCV and HCV RNA. The anti-HCV negative patients were tested for anti-HCV and HCV RNA at least twice at intervals of 6 months or more (up to 12 months). Anti-HCV antibodies were identified using a third generation ELISA assay. Commercial kits for real-time polymerase chain reaction (RT-PCR) were used to detect HCV RNA in the plasma and mononuclear cells. Aminotransferase and gammaglutamyl transpeptidase levels were studied to find if liver inflammation was present., Results: The total seroprevalence in 68 patients was 20.6% (14). Of these, 10 patients were viremic (HCV RNA+/anti-HCV+), and 4 patients (5.9%) had discordant results (anti-HCV+/HCV RNA-). Acute hepatitis was detected in one patient. Duration of dialysis in HCV viremic patients was longer than that in aviremic patients (p=0.005)., Conclusions: The present study suggests that HCV infection in dialysis patients can be diagnosed more accurately if these patients are tested using two diagnostic methods - a serological test and a biomolecular assay. Further studies with larger sample size may prove the feasibility of such approach for all dialysis patients in this country.

Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus), in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term), olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie), spatial memory (learning impairments on finding the platform in the Morris water maze) and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation), association memory (passive avoidance) or in species-typical behavior (nest building) and no increased anxiety (open field, light-dark box) or depression/anhedonia (sucrose preference) at this relatively young age. These neurobehavioral deficits of the Fus1 KO mice at this relatively young age are highly relevant to sAD, making them suitable for effective research on pharmacological targets in the context of early intervention of sAD.

Thirty two years old man had history of atrioventricular re-entry tachycardia (AVRT) with concealed left-lateral accessory pathway (AP), 3-5episodes per year, 30-40 minutes duration without hemodynamic compromise. Two years ago patient underwent ablation of concealed left lateral AP. After that tachycardia became malignant (high-frequent 150 beats-min, incessant (lasting up to 18 h/day), resistant to AAD, and led to development of tachycardia-induced cardiomyopathy (EF was 16%, and 2 episodes of pulmonary oedema). During redo EPS we verified AVRT with conduction via decremental retrograde left lateral AP which corresponded to the criteria of permanent junctional reciprocating tachycardia (PJRT). Ablation effectively ceased the arrhythmia. After 18 months of follow up there are no symptoms of heart failure and recurrence of arrhythmia., Conclusions: We present a case of effective treatment of severe heart failure in a patient with arhythtmogenic cardiomyopathy due to malignant course of incessant tachycardia AVRT with retrograde decremental conduction via left lateral AP. Ablation of AP eliminated of arrhythmia. After 18 months of follow up patient had signs of left ventricle reverse remodeling and had not heart failure symptoms.

The habituation/cross-habituation test (HaXha) is a spontaneous odor discrimination task that has been used for many decades to evaluate olfactory function in animals. Animals are presented repeatedly with the same odorant after which a new odorant is introduced. The time the animal explores the odor object is measured. An animal is considered to cross-habituate during the novel stimulus trial when the exploration time is higher than the prior trial and indicates the degree of olfactory patency. On the other hand, habituation across the repeated trials involves decreased exploration time and is related to memory patency, especially at long intervals. Classically exploration is timed using a stopwatch when the animal is within 2 cm of the object and aimed toward it. These criteria are intuitive, but it is unclear how they relate to olfactory exploration, that is, sniffing. We used video tracking combined with plethysmography to improve accuracy, avoid observer bias, and propose more robust criteria for exploratory scoring when sniff measures are not available. We also demonstrate that sniff rate combined with proximity is the most direct measure of odorant exploration and provide a robust and sensitive criterion.

Hallmark of neuroblastoma is an ability of this malignant tumor to undergo spontaneous regression or differentiation into benign tumor during any stage of the disease, but it is little known about mechanisms of these phenomena. We studied effect of receptor tyrosine kinase receptor KIT on expression of genes, which may be involved in tumor spontaneous regression. Downregulation of KIT expression by RNA interference in SH-SY5Y cells causes suppression of neurotrophin receptor NGFR expression that may promote the loss of sensibility of cells to nerve growth factors, also it causes upregulation of TrkA receptor expression which can stimulate cell differentiation or apoptosis in NGF dependent manner. Furthermore there is an upregulation of genes which stimulate malignant cell detection by immune system, such as genes of major histocompatibility complex HLA class I HLA-B and HLA-C, and interferon-γ receptors IFNGR1 and IFNGR2 genes. Thus KIT can mediate neuroblastoma cell sensibility to neurotrophins and immune system components--two factors directly contributing to spontaneous regression of neuroblastoma.

Pelvic organ prolapse (POP) represents a urologic and gynecological disease, the development of which is governed both by environmental and genetic factors. We describe the results of our association study of polymorphic variants of genes involved in the assembly of elastic fibrils, namely, the lysyl oxidase protein 1 (LOXL1) and fibulin-3 (FBLN3) genes. We revealed an association of the rs2304719-T allele and rs2165241 (C)-rs2304719(T)-rs893821(T) haplotype of the LOXL1 gene with an increased risk of POP development, as well as a weak association with the disease of the rs3791660-C allele and the rs3791679(T)- rs1367228(A)-rs3791660(C)-rs2033316(A) haplotype of the FBLN3 gene.

The exposure to green light, which serves as a well-known activating factor for myogenesis during incubation of chicken eggs, contributes to intensification of embryonic metabolism of NO. A metabolic product, nitrate, is mainly accumulated in the muscles. These data suggest that light induces a NO-dependent activation of the factor, which intensifies muscle tissue development.

Mitochondria present a unique set of key intracellular functions such as ATP synthesis, production of reactive oxygen species (ROS) and Ca2+ buffering. Mitochondria both encode and decode Ca2+ signals and these interrelated functions have a direct impact on cell signaling and metabolism. High proliferative potential is a key energy-demanding feature shared by cancer cells and activated T lymphocytes. Switch of a metabolic state mediated by alterations in mitochondrial homeostasis plays a fundamental role in maintenance of the proliferative state. Recent studies show that tumor suppressors have the ability to affect mitochondrial homeostasis controlling both cancer and autoimmunity. Herein, we discuss established and putative mechanisms of calcium-dependent regulation of both T cell and tumor cell activities. We use the mitochondrial protein Fus1 as a case of tumor suppressor that controls immune response and tumor growth via maintenance of mitochondrial homeostasis. We focus on the regulation of mitochondrial Ca2+ handling as a key function of Fus1 and highlight the mechanisms of a crosstalk between Ca2+ accumulation and mitochondrial homeostasis. Given the important role of Ca2+ signaling, mitochondrial Ca2+ transport and ROS production in the activation of NFAT and NF-κB transcription factors, we outline the importance of Fus1 activities in this context.

Unlabelled: Current diagnosis of acute kidney injury (AKI) is one of the most pressing problems in the newborn in critical condition., Objective: To determine the diagnostic value of indicators of renal blood flow as a marker of acute kidney injury in critically ill newborns., Materials and Methods: The study included 40 infants in critical condition. A clinical assessment of severity of the condition during admission was carried out with Neonatal Multiple Organ Dysfunction Score (NEOMOD) and Neonatal Therapeutic Intervention Scoring System (NTISS). All patients underwent evaluation of clinical and instrumental parameters, including ultrasound of the renal vessels, renal vascular resistance index and speed performance., Conclusions: 1) biochemical markers used in routine clinical practice were not sufficiently informative for the diagnosis of AKI. 2) For a more accurate assessment of the risk of AKI using serum creatinine, GFR calculation and evaluation on a scale RIFLE it is should be focused on performance standards, appropriate for gestational age and birth weight. 3) Evaluation of blood flow at a particular index in the resistance of the main renal arteries had the greatest predictive value and had a relatively high sensitivity and specificity for the diagnosis of AKI.

Mechanism of radiosensitivity of normal tissues, a key factor in determining the toxic side effects of cancer radiotherapy, is not fully understood. We recently demonstrated that deficiency of mitochondrial tumor suppressor, Fus1, increases radiosensitivity at the organismal, tissue and cellular levels. Since Fus1-deficient mice and cells exhibit high levels of oxidative stress, we hypothesized that dysregulation of cellular antioxidant defenses may contribute to the increased radiosensitivity. To address this potential mechanism, we treated the Fus1 KO mice with an inhibitor of pathogenic oxidative reactions, pyridoxamine (PM). Treatment with PM ameliorated IR-induced damage to GI epithelium of Fus1 KO mice and significantly increased the survival of irradiated mice. In cultured Fus1 KO epithelial cells, IR-induced oxidative stress was enhanced because of inadequate cellular antioxidant defenses, such as low levels and/or activities of cytochrome C, Sod 2 and STAT3. This resulted in dysregulation of IR-induced DNA-damage response and DNA synthesis. Treatment of Fus1 KO cells with PM or Sod 2 mimetic Tempol normalized the oxidative stress response, thus compensating to a significant degree for inadequate antioxidant response. Our findings using Fus1 KO radiosensitive mice suggest that radiosensitivity is mediated via dysregulation of antioxidant response and defective redox homeostasis.

NO plays a specific role in avian embryogenesis stimulating the development of muscle tissue. The main consumer of NO synthesized at the initial stage of avian embryogenesis is presumably a factor stimulating myogenesis.

The increasing interest in the study of the antioxidant activity of different objects is caused by an unbalance between the formation of reactive oxygen species (ROS) and the performance of the antioxidant system in humans under certain conditions, which leads to oxidative stress and pathological states of the organism. This article presents a brief critical review of the methods that are used to measure integrated antioxidant activity (AOA). It is shown that the most promising methods for measuring AOA are electrochemical ones, particularly potentiometry, as it best fits the nature of the processes causing oxidative stress. The article gives the theoretical rational for requirements that an oxidizer of antioxidants (AO) should meet. The work presents the thermodynamic grounds for the use of an earlier proposed mediator system, kinetics of chemical reactions between AO and the mediator system. In order to confirm reliability and accuracy of the results, numerous correlation studies were conducted, aiming to compare the data obtained with the use the proposed method and independent analytical methods. The article presents the results of the potentiometric study of AOA for a variety of objects, including individual antioxidant → nutritional supplements → food → blood and blood fractions.