[Modern approaches to studying the molecular mechanisms of lung functioning in normal and pathological conditions]. / Sovremennye podkhody k izucheniyu molekulyarnykh mekhanizmov funktsionirovaniya legkikh v norme i pri patologii.

Problems with breathing and lung function are caused by the development of various lung diseases associated with lifestyle, harmful environmental factors and genetic predisposition. Knowledge of the molecular mechanisms of the development of the pathological process will allow on time identification of the disease or the development of targeted therapy. The article provides an overview of modern methods that make it possible to most accurately reproduce the structural, functional and mechanical properties of the lung (organ-on-a-chip), to perform non-invasive molecular studies of biomarkers of bronchopulmonary pathology using saliva diagnostics, as well as using DNA and RNA aptamers, verify tumor markers in biological samples of human tissue. Analysis of alterations in the pattern of protein glycosylation using glycodiagnostic methods makes it possible to detect lung cancer in the early stages.

[Caldesmon and tumor growth: prospects for optimizing diagnosis and targeted therapy]. / Kal'desmon i opukholevyi rost: perspektivy optimizatsii diagnostiki i targetnoi terapii.

Tumor invasion plays a key role in the progression of tumors. This process is regulated by the interactions of cells and tissues, in which physical, cellular and molecular determinants undergo changes throughout the entire period of progression of tumor growth. Tumor invasion is triggered and maintained by specialized signal cascades that control the dynamic state of the cytoskeleton in tumor cells, the processes of rearrangement of cell-matrix and intercellular connections, followed by cell migration to neighboring tissues. Studying the mechanisms of regulation of cell motor activity and determining its main regulators is an important task for understanding the pathophysiology of tumor growth. Caldesmon is an actin, myosin and calmodulin binding protein. It is involved in the regulation of smooth muscle contraction by inhibiting actin and myosin binding, in the formation of actin stress fibers, and in the transport of intracellular granules. Currently, caldesmon is considered as a potential biomarker of tumor cell invasion, migration, and metastasis. The study of signaling molecules involved in tumor progression, such as caldesmon, is necessary to predict response to chemotherapy and radiotherapy. This review highlights the main functions of caldesmon and analyzes its role in oncological pathology.

[Slowdown of replicative aging of fibroblasts by hyaluronan complexes with gold nanoparticles.]

Determination the activity of the genes of sirtuin-1, hyaluronidase, TGF-ß cytokine, calreticulin in the process of replicative aging of human fibroblasts in vitro and the effect of hyaluronan preparations with gold nanoparticles on the activity of replicative cell aging. Compared the expression of proteins of the studied genes using specific markers at 7 and 14 passages of cultivation of fibroblasts isolated from human skin, without drugs and in the presence of drugs in the growth medium. This work shows a decrease in the activity of the sirtuin 1 gene and an increase in the expression of hyaluronidase in the process of replicative aging of human fibroblasts. Found a means of slowing down replicative aging by activating the SIRT-1 gene and reducing the activity of hyaluronidase in action in the growth medium of hyaluronan preparations with gold nanoparticles. The discussed variants of cell transitions to the pathological state, caused by replicative aging and the mechanisms of slowing down the replicative aging of human fibroblasts.

[The role of the main risk factors and endocrine cells of the antrum of the stomach producing motilin in the occurrence of cholelithiasis].

AIM: To establish the role of the main risk factors and endocrine cells of the antrum of the stomach producing motilin (M-cells) in the occurrence of cholelithiasis. MATERIALS AND METHODS: The first group included 122 patients with cholelithiasis. The second group consisted of 30 healthy individuals who underwent medical examination. The groups were matched for gender and age. The work analyzed anamnestic, biochemical and anthropometric data. All patients underwent esophagogastroduodenoscopy with targeted biopsy of the mucous membrane from the antrum. Biopsies were subjected to cytological and immunohistochemical studies in order to verify Helicobacter pylori and estimate the number of M-cells. RESULTS: Patients with cholelithiasis more often belonged to the group of people of mental labor, had low physical activity, were committed to inappropriate nutrition and more often indicated the presence of aggravated heredity for cholelithiasis. Patients with gallstone disease had higher body mass index, waist volume, total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, lower high-density lipoprotein cholesterol, H. pylori infection was more often verified and M-cell hypoplasia in the mucous membrane was established. stomach in comparison with the representatives of the second group. CONCLUSION: Our results suggest that certain external factors, nutritional characteristics of the metabolic syndrome components, hypoplasia of M-cells in the gastric mucosa are important factors in the formation of calculi in the gallbladder.

[Neuroprotective effects of peptides.]

Neurodegenerative diseases are a heterogeneous group of nervous system pathologies. They are found mainly in people of an older age group. The incidence of neurodegenerative diseases is continuously growing due to an increase in the average life expectancy of the population. At the moment, there are no effective and safe treatments for neurodegenerative diseases, which are most often diagnosed at the stage of decompensation, when therapy is ineffective and does not bring positive outcomes. Most of the currently used drugs act only symptomatically. The review provides analyzed data and information about the prospects of using peptide bioregulators as neuroprotectors with high physiological activity and low immunogenicity.

[Vitamin D deficiency study in railway drivers.]

Heart rhythm disturbances are significant pathology and one of the reason of sudden cardiac arrest. Locomotive crew drivers are at high risk for cardiovascular diseases, including heart rhythm disturbances. Multiple factors as a professional stress, frequent night shifts, lack of insolation, diet disbalance, low physical activity, exposure to vibration and noise, and an unfavorable industrial climate. In this study it was found that railway-men are predisposed to vitamin D deficiency. This condition reduces resistance to stress and increases risk of unfavorable heart rhythm disturbances.

[Investigation of signal molecules in saliva: prospects of application for diagnostics of myocardial infarction and the aging rate of different age people.]

Among the diseases of the cardiovascular system in elderly people, ischemic heart disease and myocardial infarction (MI) occupy the first place in the structure of mortality. One of the main causes of disability and death from MI is late diagnosis. In this regard, the search for new, highly informative and non-invasive methods for diagnosing MI is an important task of molecular gerontology. An enzyme immunoassay showed that the concentration of TNF-α, IL-8 cytokines and p16 aging marker in saliva in elderly people without cardiovascular pathologies (CP) increases in 2,1-4,8 times as compared with middle-aged people. At the same time, in elderly people without CP the concentration in the saliva of the hormone irisin (FNDC5) decreases by 1,8 times as compared with middle-aged people. In middle-aged patients with MI the concentration of IL-8, TNF-α, MMP8, MMP9 in saliva increases 4,3-15,3 times, and FNDC5 decreases 1,8 times compared with those parameters without CP in this age group. In elderly people with MI the concentration of IL-8, TNF-α, MMP8 and MMP9 in saliva increases 4,3-7,1 times as compared with elderly people without CP. Thus, the study of the concentration of signaling molecules IL-8, TNF-α, MMP8, MMP9 in saliva can be used as a non-invasive method for diagnosing MI in people of middle and elderly age. To assess the rate of aging of the organism in middle-aged and elderly people without CP, a study of the concentration of p16 and FNDC5 molecules in saliva is recommended.

[Electrophysiological Cardiac Parameters and Results of Antiarrhythmic Treatment in Patients with Paroxysmal Atrial Fibrillation (Lone and Associated with Arterial Hypertension)].

PURPOSE: to assess cardiac electrophysiological parameters in patients with paroxysmal atrial fibrillation (AF), lone or with concomitant arterial hypertension (AH), and their prognostic significance relative to treatment effectiveness. MATERIALS AND METHODS: We included in this study 184 patients with paroxysmal AF (84 with concomitant AH and 100 with presumed lone AF). Cardiac electrophysiological study was performed in accordance with standardized protocol that included assessment of sinus node recovery time, sinoatrial, intraatrial and interatrial conduction time, and effective refractory periods (ERP) of right and left atria and atrioventricular node. Patients with inducible supraventricular reentrant arrhythmias that could potentially trigger AF underwent catheter radiofrequency ablation of those arrhythmias. Other patients received either antiarrhythmic drug therapy (AAD; n=79) or catheter cryo-ablation (CBA; n=81). Treatment was considered ineffective in case of any symptomatic or asymptomatic AF episode documented by ECG or Holter ECG within 12 months of follow-up. RESULTS: Patients with lone AF compared with those with AH had shorter ERP of the right atrium (219±21 ms vs. 253±44 ms, respectively, p<0.05) and more prominent dispersion of ERP of right and left atria (median 40 ms, interquartile range 10-50 ms vs. median 20 ms, interquartile range 10-22.5 ms, respectively, p<0.05). There was no statistically significant difference in other electrophysiology parameters between the groups. Sustained supraventricular reentrant arrhythmias were induced in 9% (9 of 100) patients with presumed lone AF and in 1.2% (1 of 84) patients with AH (p<0.05). All these arrhythmias were successfully ablated, and patients had no AF recurrence during 12-month follow-up. Among other patient treatment (CBA n=81, AAD n=79) was effective in 64% of those with lone AFib and in 34% - with AH (p<0.05). In multivariate multiple regression analysis, none of electrophysiological parameters could be assumed as a factor associated with the efficacy of CBA or AAD. CONCLUSION: Patients with lone AF had more prominent atrial electrophysiological inhomogeneity compared with patients with concomitant AH. Cardiac electrophysiological parameters had no influence on effectiveness of antiarrhythmic treatment.

Phenotype of obesity and gastroesophageal reflux disease in the context of comorbidity in patients with cardiovascular diseases.

The relevance of studying such problems as gastroesophageal reflux disease (GERD) and obesity is caused by their high prevalence in the developed countries of the world. Epidemiological data indicate that obesity is a significant risk factor for developing GERD due to increased intra-abdominal pressure and gastroesophageal gradient, slowing of gastric evacuation and formation of hiatal hernia. Abdominal obesity increases the likelihood of complications of GERD: erosive esophagitis, Barrett's esophagus and adenocarcinoma. This fact is connected with humoral influences: increased production of pro-inflammatory cytokines and leptin, and decreased secretion of adiponectin. Treatment of comorbid patients requires higher dosages and longer courses of antisecretory medicines, and an additional prescription of ursodeoxycholic acid.

Oral medical dissolution of gallstones in patients with gallstone disease

Being the main treatment for cholelithiasis, laparoscopic cholecystectomy does not always solve the problem. It often entails postcholecystectomy syndrome (PCS). Oral medication to dissolve gallstones with bile acids is alternative therapy for some patients. However, lack of efficacy and limited medical indications make it necessary to apply combination treatment tactics. This study was conducted to investigate the dissolution of gallstones during the combined effects of ursodeoxycholic acid (UDCA) and rosuvastatin as well as to assess the results of eradication therapy in the presence of H. pylory as a measure to prevent cholelithiasis in the course of treatment.

[Diseases of biliary tract in the context of association with oncological diseases of the digestive system].

Cancers of the gastrointestinal tract are widespread among the population and cause significant damage to the health care system. In order to improve the strategy of preventive measures and the detection of oncological diseases at the early stages, it is necessary to provide timely impact on possible risk factors contributing to the onset and progression of malignant neoplasms. This review demonstrates the association between the pathology of the biliary tract and oncological diseases of the digestive system, discusses the possible mechanisms of the influence of cholelithiasis and cholecystectomy on the development of malignant neoplasms of various parts of the gastrointestinal tract.

[Autoantibodies to M2-cholinoreceptors as a potential development factor of arrhythmia in patients with paroxysmal atrial fibrillation].

AIM: We aimed to assess autoantibodies to M2-cholinoceptors (M2-CR) in patients with paroxysmal lone atrial fibrillation (AF) and in patients with AF and arterial hypertension (AH). MATERIALS AND METHODS: 100 patients with lone AF and 84 patients with AF and AH were included. Patients underwent clinical blood and urinalysis, assessment of biochemistry blood panel, 12-lead ECG, 24-hour Holter monitoring, echocardiography and stress - testing (treadmill or stress - echocardiography). Assessment of IgM and IgG autoantibodies to M2-CR was performed by indirect immunoenzyme assay. The following peptide molecules were used as epitopes for detection of autoantibodies: M1 - amino acid sequence YTVIGYWPLGVVCDL (83-98) of the first extracellular loop of M2-CR; M2 - sequence VRTVEDGECYIQFFSNAAVTFGTAI (168-192) of the second extracellular loop of M2-CR; M3 - sequence NTFCAPCIPNTV (410-421) of the third extracellular loop of M2-CR; M4 - short sequence VEDGECYIQFFS (171-182) of the second extracellular loop of M2-CR; M1+M4 - chimeric molecule formed by sequences of the first and the second extracellular loops of M2-CR connected by disulfide bound YTVIGYWPLGVVCDL + VEDGECYIQFFS (83-98 + 171-182). RESULTS: Autoantibodies to M2-CR were found in 45% patients with lone AF and in 35% patients with AF and AH. In patients with lone AF prevalence of increased IgG to M2-CR were greater than in patients with AF and AH (32% vs 20%; p.

[Recent advances in diagnosis and management of atrial fibrillation].

Alterations of heart rhythm are a common clinical event. They can be caused by almost any kind of heart disorder. Atrial fibrillation (AF) is the most common type of abnormal heart rhythm. Prevalence of AF in the general population is 1-2%, and given that AF incidence rate continues to increase it can be predicted that the number of patients will be doubled within the next 50 years. This review provides the most recent diagnostic and treatment methods, including both unique domestic antiarrhythmic drugs and non - drug methods for AF treatment which were developed and implemented in clinical practice at NMRC of Cardiology of the Ministry of Health of the Russian Federation.

Freshwater mussels (Anodonta anatina) reduce transmission of a common fish trematode (eye fluke, Diplostomum pseudospathaceum).

Recent results suggest that bivalves can play an important role in restraining the spread of various aquatic infections. However, the ability of mussels to remove free-living stages of macroparasites and reduce their transmission is still understudied, especially for freshwater ecosystems. We investigated the influence of the common freshwater mussel (Anodonta anatina) on the transmission of a trematode (eye fluke, Diplostomum pseudospathaceum), which frequently infects fish in farms and natural habitats. In our experiments, mussels caused a significant decrease (P < 0·001) in the abundance of trematode free-living stages, from 6520 to 1770 cercariae L-1 on average (about 4-fold in 2 h). Individual clearance rates of mussels were 0·6‒3·7 L per hour (mean 1·9). These tests were followed by experimental infections of rainbow trout (Oncorhynchus mykiss) with different doses of D. pseudospathaceum cercariae in the presence or absence of mussels. Exposure of fish to cercariae in the presence of mussels significantly (P < 0·05) reduced the infection intensities in fish (by 30-40%) at all exposure doses. Our results indicate that freshwater bivalves can markedly reduce local cercariae densities and could be useful in mitigation of trematodoses harmful to fish farming.

[A study of the association between the kynurenine-3-monooxygenase gene and depression]. / Issledovanie svyazi gena kinurenin-3-monooksigenazy s depressiei.

AIM: To study the association between the kynurenine 3-monooxygenase (KMO) and depression. MATERIAL AND METHODS: КМО rs2275163 (C/T) and rs1053230 (A /G) polymorphisms were genotyped in patients diagnosed with depression (the main group) and age - and sex-matched healthy people. RESULTS: The rs2275163 polymorphism was not associated with depression. There was the association between the rs1053230 polymorphism and depression. The frequency of the low expression genotype GG was higher in the main group compared to controls (р=0.001, ОШ 2.8 (95% ДИ 1.73-4.24). This genotype was earlier reported to be associated with the increased levels of kynurenic acid in patients with bipolar disorders. CONCLUSION: The genotype GG can be considered as a risk factor of depression.

Core-shell-corona doxorubicin-loaded superparamagnetic Fe3O4 nanoparticles for cancer theranostics.

Superparamagnetic iron oxide magnetic nanoparticles (MNPs) are successfully used as contrast agents in magnetic-resonance imaging. They can be easily functionalized for drug delivery functions, demonstrating great potential for both imaging and therapeutic applications. Here we developed new pH-responsive theranostic core-shell-corona nanoparticles consisting of superparamagentic Fe3O4 core that displays high T2 relaxivity, bovine serum albumin (BSA) shell that binds anticancer drug, doxorubicin (Dox) and poly(ethylene glycol) (PEG) corona that increases stability and biocompatibility. The nanoparticles were produced by adsorption of the BSA shell onto the Fe3O4 core followed by crosslinking of the protein layer and subsequent grafting of the PEG corona using monoamino-terminated PEG via carbodiimide chemistry. The hydrodynamic diameter, zeta-potential, composition and T2 relaxivity of the resulting nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, thermogravimetric analysis and T2-relaxometry. Nanoparticles were shown to absorb Dox molecules, possibly through a combination of electrostatic and hydrophobic interactions. The loading capacity (LC) of the nanoparticles was 8 wt.%. The Dox loaded nanoparticles release the drug at a higher rate at pH 5.5 compared to pH 7.4 and display similar cytotoxicity against C6 and HEK293 cells as the free Dox.

[Comorbidity of depression and nonaffective - schizophrenia spectrum disorders: the clinical-epidemiological study EDIP]. / Komorbidnost' depressii i rasstroistv neaffektivnogo shizofrenicheskogo spektra: kliniko-epidemiologicheskoe issledovanie EDIP.

AIM: To explore the association between depression and heterogenic nonaffective symptom complexes in the study EDIP (Epidemiology of Depression and nonaffective Psychiatric disorders). MATERIAL AND METHODS: The study consisted of two stages. The first stage (91 patients) aimed to resolve organizational and methodological issues, the second stage was performed in the epidemiological sample of 705 patients. RESULTS AND CONCLUSION: The heterogeneity (inequivalence and bidirectionality) of associations between depression and heteronomous nonaffective disorders have been identified. The associations are distinguished in three types: 1) affinity (agonism); 2) repulsion (antagonism); 3) lack of selective interaction (inertness) between depression and nonaffective disorders. The results obtained are discussed in a context of two conceptually polar psychopathological models of comorbidity between depression and nonaffective disorders: 1) based on a nosological dichotomy «affective disease - schizophrenia¼ and 2) denying the abovementioned dichotomy. The first model places depression among disorders of a mild psychiatric register. The second model supposes the integration of depression with syndromes typical for schizophrenia in a common "affect-symptoms" space and considers the increase of depression frequency proportionally to duration and severity of schizophrenia. Our own results have shown that depression is observed not only among disorders of mild psychiatric registers, but also in schizophrenia, though with a significantly lower frequency (as a nonobligatory compound of a syndrome). Thus, depression influence in comorbid delusional, schizophrenic and other severe nonaffective disorders is greatly diminished.

[Medical and Dosimetric Register of the Siberian Group of Chemical Enterprises Personnel--the Basis for the Evaluation of Chronic, Radiation Exposure Effects].

The characteristic of medical and dosimetric register database of Siberian Group of Chemical Enterprises personnel is represented. This characteristic includes the description of the database structure, main sources of information, quantitative composition of the cohort under study, methods of evaluation of the external and internal irradiation doses, modern data on cancer incidence and reasons of death. The database is the basis for estimating the risk of the cancer and non-cancer effects after a long-term radiation exposure and dependence of "dose-response" at different levels: from population and group to cell and molecular. Now the database of register contains the information about more than 66,500 employees at the Siberian Group of Chemical Enterprises, about 22,000 of whom were exposed to external irradiation and more than 7500 employees--to internal irradiation. The register is the information resource of a large biological material bank. Using this bank, the research of chronic radiation exposure genetic effects and markers of individual radio sensitivity is performed.

Regulation of Na+ excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron: consequences and mechanisms.

Discretionary control of Na(+) excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine-tuned in the aldosterone-sensitive distal nephron by the activity of the epithelial Na(+) channel (ENaC). Here, ENaC functions as a final effector of the renin-angiotensin-aldosterone system (RAAS) during negative feedback control of blood pressure. Mutations affecting ENaC activity and abnormal regulation of this channel affect blood pressure through pathological changes to Na(+) excretion. Recent evidence demonstrates that powerful signalling pathways function in parallel with the RAAS to modulate ENaC activity and blood pressure. An inclusive paradigm is emerging with respect to regulation of blood pressure where ENaC serves as a critical point of convergence for several important signalling systems that affect renal Na(+) excretion. A robust inhibitory purinergic signalling system intrinsic to the distal nephron dynamically regulates ENaC through paracrine ATP signalling via the metabotropic P2Y2 purinergic receptor to properly match urinary Na(+) excretion to dietary Na(+) intake. This enables blood pressure to be maintained within a normal range despite broad changes in dietary Na(+) consumption. Loss of purinergic inhibition of ENaC increases blood pressure by causing inappropriate Na(+) excretion. In contrast, stimulation of the P2Y2 receptor promotes natriuresis and a decrease in blood pressure. Such observations identify purinergic signalling in the distal nephron as possibly causative, when dysfunctional, for certain forms of elevated blood pressure, and as a possible therapeutic target for the treatment of elevated blood pressure particularly that associated with salt sensitivity.

[Role of atrial structural and functional changes in the development and progression of atrial fibrillation].

Atrial fibrillation (AF) is one of the most common reasons for decreased life quality and increased mortality rates. Experimental and clinical data show that atrial structural and functional changes contribute to the development and progression of AF. The survey article considers the role of the systemic and local activities of the renin-angiotensin-aldosterone system and inflammatory mediators in the development of atrial structural remodeling, which may be a cause and a consequence of AF.