[Hyaluronan receptors: role in aging and age-associated processes.]

The review describes the involvement of various hyaluronic acid receptors, including CD44, RHAMM, HARE, TLR, LYVE-1, in maintaining normal homeostasis and aging, as well as in the development of age-associated inflammatory processes (inflamaging) and malignant tumors. The association of CD44 receptor activation with immune cells and the development of coronary heart disease has been shown. In addition, a link between the CD44 receptor and osteoarthritis has been shown, via TLR2 and TLR4. The oncogenic potential of RHAMM in relation to breast, prostate, leukemia, pancreas, lung and glioblastoma cancers has been described, with the strongest expression observed in metastatic tumors. In vivo and in vitro experiments, it was found that fragments of hyaluronic acid with a length of 4 to 25 disaccharides can contribute to the proliferation of lymphatic endothelial cells and lymphangiogenesis. Thus, hyaluronic acid receptors play an important role in the aging process through the regulation of inflamaging and in the development of malignant neoplasms.

[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.

[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.

[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.

[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.

[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.

[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.

[Optimization of the protein composition of an additive made from blood and milk]. / Optimizatsiia belkovogo sostava dobavki iz krovi i moloka.

A new protein composition from defibrinated blood and lactic acid paste, prepared from skim milk, has been recommended as a food product. Optimization of protein composition was conducted on the basis of amino acid components and the criterion of "minimal dispersity".

[Cholescintigraphy of gastroduodenal pathology in children]. / Kholestsintigrafiia pri gastroduodenal'noi patologii u detei.

The results of cholescintigraphy with 99mTc-HIDA in 245 children were analysed. The relationship of a latent time period with the state of the stomach-duodenum system was revealed. The specificity of this index was 82%, sensitivity 70%, accuracy 75% and pathology predictability 85%. The scintigraphic picture of a duodenobulbar reflux in the form of a RP "depot" in the ascending and upper horizontal part of the duodenum manifested itself with the specificity of 90% and predictability of pathology in 75%. Duodenogastric refluxes were revealed with the specificity of 94%, accuracy of 88% and pathology predictability of 90%. A low specificity of 34 and 43% was associated with a possibility of reflux detection in the lower horizontal part of the duodenum only.

[Scintigraphic semeiotics of gallbladder anomalies in children]. / Stsintigraficheskaia semiotika anomalii zhelchnogo puzyria u detei.

Altogether 103 children with different variants of gallbladder abnormalities (deformities, bends, contractions, septa, diverticula) were examined using radionuclide cholescintigraphy with 99mTc-HIDA. Scintigraphic signs of organic lesion were characterized by symptoms associated with the unevenness of the filling of the gallbladder, its shape and contours. Their frequency depended on anatomical defect site. Changes in the cervical part (70%) and in the body area (60%) were better diagnosed. Changes in the gallbladder fundus (12.5%) were practically undetectable. The calculation of quantitative indices of gallbladder filling and motor function made it possible to objectify the gravity of organic change of the organ, the nature and degree of its functional compensation.

[Hepatobiliary scintigraphy in the diagnosis of common bile duct cysts in children]. / Gepatobilistsintigrafiia v diagnostike kist obshchego zhelchnogo protoka u detei.

A cyst of the common bile duct, the most frequent variant of cystic dilatation of the extrahepatic biliary tract, presents a serious diagnostic problem. Using serial scintigraphy with 99mTc-HIDA 13 children with cysts of the common bile duct confirmed by the results of operative cholangiography, were examined. In 8 of them a radionuclide study was performed at varying times after operation (cyst extirpation with the establishing of hepatoenteroanastomosis--4 patients, and variants of internal drainage operations--4 patients). Typical scintigraphic signs were the following: sacculated or spheroidal dilatation of the common bile duct in combination with dilatation of the left (7), right (1) or both lobular bile ducts, absence of the gall bladder visualization. In the first 15 min of examination in large size cysts zones of the lowered accumulation of the radiopharmaceutical agent were revealed in the area of the portal fissure. Indicators of absorptive-excretory hepatic function changed mainly in children with spheroid-shaped cysts demonstrating alongside with the time of intestinal visualization the degree of disorder of permeability of the choledoch distal parts. The recovery of the anatomic-functional state of the biliferous system occurred earlier (up to 1.5 year) in children after cyst extirpation than after internal drainage operations. It manifested itself in returning the diameter of the bile ducts to normal and in the improvement of absorptive-excretory hepatic function.