Alexej Victorovich Sokolov

• PhD
• Head of laboratory at Research Institute of Influenza

As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was use...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to have a significant impact on global public health. Multiple mechanisms for SARS-CoV-2 cell entry have been described; however, the role of transferrin receptor 1 (TfR1) in SARS-CoV-2 infection has received little attention. We used ferristatin II to induce the degradation of...

The protective effects of recombinant human lactoferrin rhLF (branded “CAPRABEL™”) on the cognitive functions of rat offspring subjected to prenatal hypoxia (7% O2, 3 h, 14th day of gestation) have been analyzed. About 90% of rhLF in CAPRABEL was iron-free (apo-LF). Rat dams received several injections of 10 mg of CAPRABEL during either gestation (...

The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infe...

Hypochlorous acid (HOCl) derived from hydrogen peroxide and chloride anion by myeloperoxidase (MPO) plays a significant role in physiological and pathological processes. Herein we report a phenoxazine-based fluorescent probe Celestine Blue B (CB) that is applicable for HOCl detection in living cells and for assaying the chlorinating activity of MPO...

BACKGROUND: mTOR/S6K, ametabolicintracellularsignalingcascade, plays a keyroleinregulation of Th17 and Treg cell subsets activationanddifferentiation.Pathogenicmicrobes,using the arginine depletion as one of immune escape mechanisms,candisrupt the differentiationprogram of T-lymphocytesandreducetheeffectiveness of the immuneresponse. AIM: The aim o...

Objective: Phagocytes activation results in the production of reactive oxygen metabolites exerting antimicrobial and host-damaging activity. Although the main pool of papers shows their potentiating action on a key humoral nexus of innate immunity, complement system, the data are controversial. Combined action of reac­tive oxygen metabolites with a...

Hemostasis is a mechanism that stops bleeding from an injured vessel, involves multiple interlinked steps, culminating in the formation of a “clot” sealing the damaged area. Moreover, it has long been recognized that inflammation also provokes the activation of the coagulation system. However, there has been an increasing amount of evidence reveali...

BACKGROUND: Leukocyte myeloperoxidase catalyzes the formation of HOCl, which, by oxidizing and chlorinating biomolecules, contributes to the development of oxidative/halogenative stress. The latter in hyperglycemia may interfere with wound healing in patients with diabetes mellitus complications. AIM: Evaluation of the concentration of markers of o...

It is known that many tumors induce iron and zinc deficiency in the organism. We studied the content of these metals, as well as the specific activity of two antioxidant metal-dependent enzymes – catalase and superoxide dismutase of three distal organs (thymus, liver and spleen) in animals bearing transplantable hepatoma 22a. These alterations were...

Vaterite microparticles, metastable form of calcium carbonate, are promising forms of delivery of medicinal compounds. For more efficient delivery of target molecules (increased incorporation and retention), vaterite microparticles must be functionalized with biopolymers. In this article the effect of polysaccharides, mucin and vaterite micropartic...

Type 2 diabetes mellitus (T2DM) is accompanied by halogenative stress resulting from the excessive activation of neutrophils and neutrophilic myeloperoxidase (MPO) generating highly reactive hypochlorous acid (HOCl). HOCl in blood plasma modifies serum albumin (Cl-HSA). We studied the formation of neutrophil extracellular traps (NETs) in the whole...

Highly variable pandemic coronavirus SARS-CoV-2, which causes the hazardous COVID-19 infection, has been persistent in the human population since late 2019. A prompt assessment of individual and herd immunity against the infection can be accomplished by using rapid tests to determine antiviral antibody levels. The microneutralization assay (MN) is...

Reactive halogen species (RHS) are highly reactive compounds that are normally required for regulation of immune response, inflammatory reactions, enzyme function, etc. At the same time, hyperproduction of highly reactive compounds leads to the development of various socially significant diseases - asthma, pulmonary hypertension, oncological and ne...

Neutrophils are the primary cells of the innate immune system. They destroy pathogenic microorganisms carrying out the oxidative stress mechanism through phagocytosis and extracellular traps (NETs). There is no doubt about the need to study neutrophils’ functional activity, but there are some methodological problems with the nativity of conditions...

Our previous study showed that not only bovine lactoferrin (LF), the protein of milk and neutrophils, but also the human species forms complexes with oleic acid (OA) that inhibit tumor growth. Repeated injections of human LF in complex with OA (LF/8OA) to hepatoma-carrying mice decelerated tumor growth and increased animals’ longevity. However, whe...

The application of vaterite microparticles for mucosal delivery depends on their interaction with mucin and immune cells. As we have shown previously, the binding of mucin onto particles enhances the generation of reactive oxygen species by neutrophils. The attenuation of the pro-oxidant effect of the bound mucin through the modification of vaterit...

Pathogenic microbes use arginine-metabolizing enzymes as an immune evasion strategy. In this study, the impact of streptococcal arginine deiminase (ADI) on the human peripheral blood T lymphocytes function in vitro was studied. The comparison of the effects of parental strain (Streptococcus pyogenes M49-16) with wild type of ArcA gene and its isoge...

FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to cardiac surgery. Intraoperative venous blood is sampled for laboratory analysis immediately after shunt application; blood plasma lactoferrin concentration is determined; P is calculated by original formula. And if P is more than 36%, developing small cardiac output syndrome is pre...

Neutrophils are the leading cells of the innate immune system and the main population of leukocytes responsible for the primary reaction of the organism to various infectious agents. The latter are destroyed by neutrophils during the processes of phagocytosis and a cascade of reactions, including the respiratory burst. As a result of the respirator...

Endothelial cells (EC) are active participants in the inflammation process. During the infection, the change in endothelium properties provides the leukocyte infiltrate formation and restrains pathogen dissemination due to coagulation control. Pathogenic microbes are able to change the endothelium properties and functions in order to invade the blo...

The actin cytoskeleton is involved in the regulation of the barrier function of the endothelium. The bioavailability of arginine is an important factor determining of actin cytoskeleton dynamics. Pathogenic microorganisms can use arginine-hydrolyzing enzymes to disrupt the confluences of the vascular endothelium for subsequent dissemination. In thi...

COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control of the spread of new variants can be achieved through targeting of conserved viral epitopes. In this regard, the SARS-CoV-2 nucleocapsid (N) protein, which is much more conserved than the evolutionarily influenced spike protein...

Thrombosis is a venous or arterial vascular that can sometimes cause fatal outcomes. Development of effective pharmacological agents for antithrombotic therapy is still an urgent scientific and practical objective. Objective. To study the antithrombotic effects of blue mussel (Mytilus edulis) hydrolysate preparation. Material and methods. Biochemic...

Cationic antimicrobial peptides (CAMPs) have gained attention as promising antimicrobial therapeutics causing lower or no bacterial resistance. Considerable achievements have been made in designing new CAMPs that are highly active as antimicrobials. However, there is a lack of research on their interaction with biologically important proteins. This...

Hyperglycemia in diabetes mellitus induces modification of proteins by glucose and its derivative methylglyoxal (MG). Neutrophils perform their bactericidal activity mainly via reactive halogen (RHS) and oxygen (ROS) species generation catalyzed by myeloperoxidase (MPO) stored in neutrophil azurophilic granules (AGs) and membrane NADPH oxidase, res...

The work is devoted to the study of the structural characteristics of the myeloperoxidase–ceruloplasmin–thrombin complex using small-angle neutron scattering methods in combination with computer modeling, as well as surface plasmon resonance and solid-phase enzyme assay. We have previously shown that the functioning of active myeloperoxidase during...

Myeloperoxidase (MPO), an oxidant-producing enzyme of neutrophils, has been shown to prime platelet activity promoting immunothrombosis. Native MPO is a homodimer, consisting of two identical protomers (monomer) connected by a single disulfide bond. But in inflammatory foci, MPO can be found both in the form of a monomer and in the form of a dimer....

Left lung autotransplantation: 1. Left lung explantation. 2. Left lung ex-vivo perfusion with ABV-solution (1 L , t=21C, 5 mm Hg). 3. Left lung 1h storage with ice. 4. Left lung reimplantation

Step 1: Heparin infusion 25 000 U Lidocain infusion under ECG control Step 2: Sternotomy, pulmonary artery cannulation, left atrium vent, aortic+pulmonary artery cross-clamping. Step 3: Novel solution infusion (5-10 mm Hg) into pulmonary artery + lung preparation Step 4: Ex-vivo novel solution infusion into pulmonary artery/vein (ante/retrograd...

SAS code for calculation of correlation matrix.

Background The process of thrombus formation is thought to involve interactions between platelets and leukocytes. Leukocyte incorporation into growing thrombi has been well established in vivo, and a number of properties of platelet-leukocyte interactions critical for thrombus formation have been characterized in vitro in thromboinflammatory settin...

SAS code creates forest plot which shows complications between two groups

SAS code creates panelled boxplot. 1. First step: transpose data. 2. Second step: create panneled boxplots.

Allogenic heart transplantation in sheep.

BACKGROUND: Resistance of microorganisms caused dangerous to human health infections to traditional antibiotics is a serious problem for healthcare. In this regard, the development of new effective antimicrobial drugs and therapeutic approaches is an urgent task. Antimicrobial peptides (AMPs) are considered a promising alternative to traditional an...

Previously we have shown that lactoferrin (LTF), a protein of secondary neutrophilic granules, can be efficiently modified by hypohalous acids (HOCl and HOBr), which are produced at high concentrations during inflammation and oxidative/halogenative stress by myeloperoxidase, an enzyme of azurophilic neutrophilic granules. Here we compared the effec...

BACKGROUND: Myeloperoxidase (MPO), the enzyme of leukocytes, catalyzes the production of reactive halogen species, which can modify the structure of lipoproteins. Chlorination and nitration of tyrosine residues in apolipoprotein A-1 lead to the formation of dysfunctional high-density lipoproteins (HDL-p), thus blocking the reverse cholesterol trans...

Oligomerization of copper-containing ferroxidase of ceruloplasmin in the presence of protein-unbound copper in a solution has been investigated by small-angle X-ray scattering (SAXS). Ceruloplasmin is a monomer with a molecular weight of ~132 kDa. Copper chloride added in a concentration of 10 μM leads to dimerization of 60% of protein. According t...

Acute liver injury in its terminal phase trigger systemic inflammatory response syndrome with multiple organ failure. An uncontrolled inflammatory reaction is difficult to treat and contributes to high mortality. Therefore, to solve this problem a search for new therapeutic approaches remains urgent. This study aimed to explore the protective effec...

В 2017 году Европейское общество кардиологов обозначило важность проблемы диагностики ишемиче-ски-реперфузионного повреждения миокарда после операций коронарного шунтирования. Повреждение миокарда может сопровождаться критическим снижением сердечного индекса и повышением концен-трации кардиального тропонина I в крови. Прогностическое значение повыш...

High-performance autotolerant bioelectrodes should be ideally suited to design implantable bioelectronic devices. Because of its high redox potential and ability to reduce oxygen directly to water, human ceruloplasmin, HCp, the only blue multicopper oxidase present in human plasma, appears to be the ultimate biocatalyst for oxygen biosensors and al...

L-arginine is a key metabolite for nitric oxide production by endothelial cells, as well as signaling molecule of the mTOR signaling pathway. mTOR supports endothelial cells homeostasis and regulates activity of L-arginine-metabolizing enzymes, endothelial nitric oxide synthase, and arginase II. Disruption of the L-arginine metabolism in endothelia...

The homodimeric glycoprotein, anti-mullerian hormone (AMH), described over 70 years ago by A. Jost, is the least studied member of the transforming growth factor beta superfamily. Despite the antitumor activity of AMH discovered at the end of the last century, the creation of effective drugs based on AMH is hindered primarily by the lack of informa...

Introduction. Coronary artery bypass grafting is worldwide accepted method of treatment of ischemic heart disease. Nevertheless, intraoperative ischemic-reperfusion injury, especially when associated with graft dysfunction, could influence on surgical outcomes. There is no data about precise cut-off level of troponin I associated with graft failure...

Aggregation of human wild-type transthyretin (hTTR), a homo-tetrameric plasma protein, leads to acquired senile systemic amyloidosis (SSA), recently recognised as a major cause of cardiomyopathies in 1–3% older adults. Fragmented hTTR is the standard composition of amyloid deposits in SSA, but the protease(s) responsible for amyloidogenic fragments...

Treatment of complications of peptic ulcer disease is an urgent problem in abdominal surgery due to the high prevalence of bleeding (19-57) and perforations (3-14 cases per 100,000 population).The objective of the study was to assess the possibility of predicting the development of ulcerative disease complications determining the ratio of the level...

We investigated the effect of drugs (dapsone, paracetamol, and isoniazid) on the production of reactive oxygen and halogen species by neutrophils. The standard fluorescent method using scopoletin as well as recently developed fluorescent methods using oxazine dyes, celestine blue B, and gallocyanine were employed for this purpose. Celestine blue B...

invention refers to medicine, namely to cardiosurgery, and can be used for prediction of coronary artery bypass surgery (CABG) outcomes. Active myeloperoxidase concentration in the blood plasma is evaluated intraoperatively immediately after the shunt application. Value P is calculated by formula P=e-4.8498+0.0046×MPO×100 %, where MPO is concentrat...

Infiltration of growing thrombi by leukocytes, being the key part of the thromboinflammation, is well established in vivo. The study was aimed at the development of an ex vivo simulation of this phenomenon. Thrombus formation in anticoagulated whole blood from healthy volunteers and patients was visualized by fluorescent microscopy in parallel-plat...

Incidence of Parkinson disease progressively grows with increasing age and percentage of elderly people in the global population. Clear understanding of the causes of dopaminergic neurons death in Substantia nigra and Parkinson disease pathogenesis are currently absent, not speaking of an efficient therapy. However, an early diagnosis of dopaminerg...

Myeloperoxidase (MPO) is a unique heme-containing peroxidase that can catalyze the formation of hypochlorous acid (HOCl). The strong interaction of MPO with low-density lipoproteins (LDL) promotes proatherogenic modification of LDL by HOCl. The MPO-modified LDL (Mox-LDL) accumulate in macrophages, resulting in the formation of foam cells, which is...

Monoclonal antibodies (mAbs) against morphine are important in the development of immunotherapeutic and diagnostic methods for the treatment and prevention of drug addiction. By the surface plasmon resonance (SPR) and enzyme immunoassay techniques, we characterized two previously obtained mAbs 3K11 and 6G1 and showed their ability to recognize free...

This review discusses formation of reactive halogen species (RHS) catalyzed by myeloperoxidase (MPO), an enzyme mostly present in leukocytes. An imbalance between the RHS production and body’s ability to remove or neutralize them leads to the development of halogenative stress. RHS reactions with proteins, lipids, carbohydrates, and antioxi-dants i...

Objective. We aimed to analyze the alterations of concentration and activity of iron metabolism proteins in samples obtained from rats with hyperglycemia induced by streptozotocin (STZ). Methods. Concentration and activity of ceruloplasmin (Cp) and transferrin (Tf), concentration of glucose, fructosamine, hemoglobin, ferritin (Ft), and iron were me...

Reactive oxygen species (ROS) have a crucial role in human physiological and pathophysiological processes. Prolonged exposure to high ROS concentrations may lead to cardiovascular, neurodegenerative, etc. diseases. In this study, gallocyanine has been proposed to register the ROS production. The gallocyanine spectral properties changes under ROS (•...

Myeloperoxidase (MPO), an oxidant-producing enzyme, stored in azurophilic granules of neutrophils has been recently shown to influence red blood cell (RBC) deformability leading to abnormalities in blood microcirculation. Native MPO is a homodimer, consisting of two identical protomers (monomeric MPO) connected by a single disulfide bond but in inf...

Цель – определить тип коронарного шунтирования (КШ), ассоциированный с наименьшим ишемически-реперфузионным повреждением (ИРП) миокарда и воспалительным ответом.Задачи. Оценить степень ИРП, степень воспалительного ответа по уровню тропонина I (TnI), миелопероксидазы (MPO) и С-реактивного белка (СРБ) в плазме крови до и после разных типов операций К...

Bacteria colonizing human intestine adhere to the gut mucosa and avoid the innate immune system. We previously demonstrated that E. coli isolates can adsorb mucin from a diluted solution in vitro. Here, we evaluated the effect of mucin adsorption by E. coli cells on neutrophil activation in vitro. Activation was evaluated based on detection of reac...

The complement system and antimicrobial peptides (AMPs) are known to be vital humoral factors of innate immunity. Earlier we showed the double-sided influence of arenicin-1 (Ar-1), the AMP from a sea polychaeta Arenicola marina, on the complement activation. In this work we studied the binding of Ar-1 to C3b protein, the fragment of the central com...

The biodegradation of the fullerene molecule C60 under the action of the human myeloperoxidase enzyme accompanied by a complete loss of the topology of the fullerene core. Analysis of this reaction mixture using UV and FTIR spectroscopy, chromatographic and mass spectrometry methods showed that the degradation proceeds without the formation of sign...

This work focuses on the study of multimeric alpha-lactalbumin oleic acid and lactoferrin oleic acid complexes. The purpose of the research is to study possible mechanisms involved in their pro-apoptotic activities, as seen in some tumor cell cultures. Complexes featuring oleic acid (OA) with human alphalactalbumin (hAl) or with bovine alpha-lactal...

Objective — the study of hypochlorous acid (HOCl) and its derivatives production, which catalyzed by human neutrophil myeloperoxidase, using “turn-on” fluorescent sensor — celestine blue B. Materials and methods. Neutrophils were isolated from the venous blood of healthy donors. Phorbol 12-myristate 13-acetate, N-formyl-methionyl-leucyl-phenylalani...

Objective. We aimed to analyze the alterations of activity of iron metabolism members i.e. ceruloplasmin (Cp) and transferrin (Tf), in relation to the percentage of glycated hemoglobin. The latter is one of biochemical criteria of chronic hyperglycemia compensation in case of type 2 diabetes mellitus. Materials and methods. Concentration and activi...

Lactoferrin is a non-heme iron-binding glycoprotein with multiple health-beneficial functions including antimicrobial, antioxidant, anticarcinogenic, and immunomodulatory effects. There is emerging evidence that neutrophils may serve as targets of lactoferrin in vivo, and here we show how recombinant human lactoferrin (rhLf) can contribute to this...

A major obstacle in the development of next‐generation of thrombolytic drugs has been the fact that plasmin ‐ a serine protease that dissolves fibrin in blood clots ‐ despite being the only enzyme suitable for the clot cleavage, is still not used in practice due to its rapid inactivation. Here we point to a potential solution to this problem by dev...

Introduction: Lactoferrin (LF) is a cationic transferrin found in milk, some other exocrine secretions, and in neutrophils. LF has bactericidal, antianemic, immunomodulatory, antitumor, and antiphlogistic effects. Almost 90% of LF in human milk is iron-free (apo-LF) and has an extreme affinity toward Fe(III), which makes it an efficient iron chelat...

This work focuses on the study of multimeric alpha-lactalbumin oleic acid and lactoferrin oleic acid complexes. The purpose of the research is to study possible mechanisms involved in their pro-apoptotic activities, as seen in some tumor cell cultures. Complexes featuring oleic acid (OA) with human alpha-lactalbumin (hAl) or with bovine alpha-lacta...

Neutrophil myeloperoxidase (MPO) plays an important role in protecting the body against infections. MPO products–hypohalous acids and phenoxyl radicals–are strong oxidants that can damage not only foreign intruders but also host tissues, including blood plasma proteins. Here, we compared the MPO-induced oxidation of two plasma proteins with antioxi...

Lactoferrin (Lf) was discovered in the thirties of the twentieth century. Since that time a number of useful properties of Lf (antibacterial, antiviral, pro- and anti-inflammatory, etc.) have been found. That’s why Lf became a promising candidate for pharmaceuticals use. The concentration of Lf strikingly increases in inflammatory focuses due to ne...

Hypochlorous acid (HOCl), one of the major precursors of free radicals in body cells and tissues, is endowed with strong prooxidant activity. In living systems, dinitrosyl iron complexes (DNIC) with glutathione ligands play the role of nitric oxide donors and possess a broad range of biological activities. At micromolar concentrations, DNIC effecti...

Factor XIIIa (fXIIIa) is a transglutaminase that plays a crucial role in fibrin clot stabilization and regulation of fibrinolysis. It is known to bind to procoagulant platelets. In contrast, the zymogen fXIII interaction with platelets is not well characterized. We investigated the interaction of zymogen fXIII with activated platelet subpopulations...