Expression of AhR-regulated miRNAs in non-small cell lung cancer in smokers and never smokers.

Smoking is a risk factor for non-small cell lung cancer (NSCLC). The most common subtypes of NSCLC are lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC). The cigarette smoke contains aryl hydrocarbon receptor (AhR) ligands, such as benzo(a)pyrene (BaP). By activating the AhR, BaP can change the expression of many genes, including miRNA-encoding genes. In this study, we have evaluated the expression of few miRNAs potentially regulated by AhR (miR-21, -342, -93, -181a, -146a), as well as CYP1A1, a known AhR target gene, in lung tumor samples from smoking (n=40) and non-smoking (n=30) patients with LAC and from smoking patients with SCC (n=40). We have also collected macroscopically normal lung tissue >5 cm from the tumor margin. We compared the obtained data on the miRNA expression in tumors with data from The Cancer Genome Atlas (TCGA). We found that in 76.7% of non-smoking LAC patients, CYP1A1 mRNA was not detected in tumor and normal lung tissues, while in smoking patients, CYP1A1 expression was detected in tumors in almost half of the cases (47.5% for SCC and 42.5% for LAC). The expression profile of AhR-regulated miRNAs differed between LAC and SCC and depended on the smoking status. In LAC patients, the expression of oncogenic miRNA-21 and miRNA-93 in tumors was higher than in normal lung tissue from the same patients. However, in SCC patients from our sample, the levels of these miRNAs in tumor and non-transformed lung tissue did not differ significantly. The results of our studies and TCGA data indicate that the expression levels of miRNA-181a and miRNA-146a in LAC are associated with smoking: expression of these miRNAs was significantly lower in tumors of smokers. It is possible that their expression is regulated by AhR and AhRR (AhR repressor), and inhibition of AhR by AhRR leads to a decrease in miRNA expression in tumors of smoking patients. Overall, these results confirm that smoking has an effect on the miRNA expression profile. This should be taken into account when searching for new diagnostic and therapeutic targets for NSCLC.

[Adjuvant effect of dispersed fullerene C60 on the immune response to constructs harboring amino acid and nucleotide sequences of hepatitis C virus nonstructural NS5B protein].

INTRODUCTION: A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid. MATERIALS AND METHODS: An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated. RESULTS: Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60. CONCLUSIONS: Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.

In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 µM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

The Role of Modi-fiable and Non-Modifiable Factors in the Development of Right and Left Ventricular Myocardial Dysfunction in High-Risk Patients.

Aim      To study early manifestations of left ventricular (LV) and right ventricular (RV) myocardial remodeling in high-risk patients.Material and methods  Intracardiac hemodynamics was studied by equilibrium radionuclide ventriculography (ERVG) in 83 patients (mean age, 61.1±8.9 years) with preserved LV ejection fraction according to echocardiography data, a body weight index (BWI) >25 kg /m2, obesity, and type 2 diabetes mellitus (DM2). Parameters of intracardiac hemodynamics were compared in patients with different degrees of obesity and DM2 durations in age groups of younger and older than 60 years.Results All patients had both LV and RV diastolic dysfunction. The diastolic dysfunction progressed with age and DM2 duration, primarily by the restrictive type. The increase in BWI, in contrast, was associated with increases in ventricular volumetric parameters. It was noted that specifically modifiable risk factors (obesity and DM2), but not the age, mostly facilitated the impairment of RV relaxation.Conclusion      The strategy of normalizing the body weight and carbohydrate metabolism is priority in combatting the development and progression of chronic heart failure in high-risk group patients.

[Effect of vitamin D receptor activators on serum Klotho levels in 3b-4 stages chronic кidney disease patients: a prospective randomized study].

BACKGROUND: High risk of cardiovascular events is among leading problems in chronic kidney disease (CKD). Serum Klotho is supposed to be cardio- and nephroprotective; modification of its levels may be important in CKD. AIM: To evaluate the impact of vitamin D receptor activators (VDRA) on Klotho serum levels in CKD 3b4 stages patients. MATERIALS AND METHODS: Study included 90 CKD 3b4 stages patients who had elevated serum levels of parathyroid hormone (PTH). From them, 47 patients (group 1) started to treat with the selective VDRA (zemplar 1 mcg/day), and 43 patients (group 2) started to treat with non-selective VDRA (alfacalcidol 0.25 mcg/day). At baseline and after 12 months we conducted routine examination, serum Klotho measurement, and broad cardiovascular examination. RESULTS: The patients who managed to maintain a target serum PTH level, had higher Klotho serum level (p=0.037) at the end of the study. Patients who used selective VDRA significantly more often reached the target PTH level (p=0.032), had higher serum Klotho levels (p=0.037), and glomerular filtration rate (eGFR) level (p=0.048) than patients who used non-selective VDRA. In addition, patients treated with alfacalcidol more than 6 months, more often had hypercalcemia (p=0.047) and hyperphosphatemia (p=0.035). Group 2 showed higher: pulse wave velocity (p=0.051), left ventricular myocardial mass index (p=0.033), and more advanced heart valve calcification (p=0.038). CONCLUSION: Successful parathyroid hormone level control with vitamin D receptor activators was associated with higher serum Klotho, selective agents having shown greater effect. Long-term treatment with selective vitamin D receptor activators may contribute to cardiovascular calcification prevention by modifying Klotho levels.

[Low serum Klotho level as a predictor of calcification of the heart and blood vessels in patients with CKD stages 2-5D].

Cardiovascular calcification (CVC) makes a significant contribution to the manifestation of cardiovascular complications in patients with chronic kidney disease. Early CVC markers are currently being actively studied to optimize cardio-renoprotective strategies. We performed a prospective comparative analysis of the following factors: FGF-23, a-Klotho, sclecrostin, phosphate, parathyroid hormone, the estimated glomerular filtration rate (eGFR), central systolic pressure as an independent determinant of CVC. MATERIALS AND METHODS: The study included 131 patients with chronic kidney disease 25D st. Serum levels of FGF-23, Klotho, and sclerostin were evaluated using the ELISA method. Vascular augmentation (stiffness) indices, central arterial pressure (using the SphygmoCor device), calcification of heart valves and the degree of aortic calcification (aortic radiography) were also investigated. The observation period was 2 years. RESULTS: According to the Spearman correlation analysis, the percent of calcification increase and the change in Klotho level are most related. According to ROC analysis, a decrease in serum levels of Klotho by 50 units or more is a significant predictor of an increase in aortic calcification of 50% or more with a sensitivity of 86% and a specificity of 77%. Using logistic regression analysis, it was found that a serum Klotho level 632 pg/L predicts an eGFR below a median level of 48 ml/min/1.73 m2 with a sensitivity of 85.5% and a specificity of 78.5%. Wherein OR 17.477 (CI 95% 8.04637.962; p0.001). CONCLUSION: The factor most associated with CVC is Klotho. Decreased serum level of Klotho is a predictor of aortic calcification. In addition, the initial serum level of Klotho is a predictor of eGFR after 2 years.

[Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs]. / Vliianie benz[a]pirena na ékspressiiu AhR-reguliruemykh mikroRNK v legkikh samok i samtsov krys.

Smoking is the main risk factor for lung cancer, mainly due to presence of nitrosamines and polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BP) in tobacco smoke composition. The genotoxic effect of BP is based on the high DNA-binding ability of its metabolites, while the epigenetic effects are mediated by a change in the expression of cancer related genes or regulatory RNAs. It has been shown that women have a higher risk to develop lung cancer upon smoking rather than men. We hypothesized that crosstalk between signaling pathways activated by BP and estrogens could underlie the sex-dependent differences in miRNAs expression. To test this hypothesis, male and female rats were subjected to short-term or long-term BP exposure. Using in silico analysis, miRNAs containing the ER- and AhR-binding sites in the promoters of the genes (or host genes) were selected. During chronic exposure of BP the expression of miR-22-3p, -29a-3p, -126a-3p, -193b-5p in the lungs of male rats were significantly increased, while the level of miRNA-483-3p were decreased. Expression of miRNA-483-3p was up-regulated during chronic BP exposure in the lungs of female rats and the levels of other studied miRNAs were unchanged. In turn, changes in the expression of miRNAs were followed by changes in the expression of their target genes, including PTEN, EMP2, IGF1, ITGA6, SLC34A2, and the observed changes in female and male rat lungs were varied. Thus, our results suggest that sex-dependent epigenetic effects of BP may be based on different expression of AhR- and ER- regulated miRNAs.

[The impact of the COVID-19 epidemic on the elderly mental health and psychosocial support.]

The spread of the COVID-19 epidemic is accompanied by psychosocial problems that have negative consequences for the mental health (MH) and quality of life (QoL) of the majority of the population. The elderly (65+ individuals) with chronic somatic diseases and reduced adaptation reserves are particularly at risk. In General, the epidemic highlighted the growing problems of psychosocial work with the 65+ cohort in the conditions of progressive aging of the population of many developed and developing countries. These problems are directly related to the preservation of MH and QoL of elderly people, people with disabilities, and others. Additional reserves should be sought to support these categories of individuals. In particular, the use of remote tele-consulting and assistive information technologies that enhance the communication capabilities of older persons is relevant. The article analyzes publications that offer practical recommendations for reducing the negative effects of the COVID-19 pandemic on MH and QoL in a cohort of 65+ individuals. As a starting point of the discussion, the article by A.G.Golubev et al., in which the issues of public support for 65+ persons are considered to be the most relevant in the field of gerontology in the context of emergency response to the spread of the COVID-19 epidemic, is considered.

Methane hydrate emergence from Lake Baikal: direct observations, modelling, and hydrate footprints in seasonal ice cover.

This paper provides a novel report of methane hydrates rising from bottom sediments to the surface of Lake Baikal, validated by photo and video records. The ascent of hydrates in the water column was confirmed by hydroacoustic data showing rising objects with velocities significantly exceeding the typical speeds (18-25 cm s-1) of gas bubbles. Mathematical modelling along with velocity and depth estimates of the presumed methane hydrates coincided with values observed from echograms. Modelling results also showed that a methane hydrate fragment with initial radius of 2.5 cm or greater could reach the surface of Lake Baikal given summer water column temperature conditions. Results further show that while methane bubbles released from the deep sedimentary reservoir would dissolve in the Lake Baikal water column, transport in hydrate form is not only viable but may represent a previously overlooked source of surface methane with subsequent emissions to the atmosphere. Methane hydrates captured within the ice cover may also cause the formation of unique ice structures and morphologies observed around Lake Baikal. Sampling of these ice structures detected methane content that exceeded concentrations measured in surrounding ice and from the atmosphere demonstrating a link with the methane transport processes described here.

[Low protein diet with essential amino acids ketoanalogues combination can affect serum FGF-23 and Klotho levels in chronic kidney disease 3b-4 stages patients: randomized pilot study].

Protein restriction diet (PRD) with ketoanalagues of essential amino acids (KA) combination can improve of chronic kidney disease (CKD) course while, the precise mechanisms of PRD + KAA action in CKD are not known yet. We have conducted a prospective, randomized, controlled study of PRD and KAA patient's group in compare with PRD without KAA group in regarding to serum Klotho and FGF-23 levels in patients with CKD. MATERIALS AND METHODS: The study included 79 CKD 3b-4 stages patients, non - diabetic etiology, used PRD (0.6 g/kg/day). The patients were randomized in two groups: 42 patients, received PRD + KAA (Group 1) and 37 patients continued the PRD without KAA (Group 2). Serum FGF-23 (Human FGF-23 ELISA kit with antibodies to native FGF-23 molecule, Merk Millipore MILLENZFGF-23-32K), Klotho (Human soluble Klotho with antiKlotho monoclonal antibodies, IBL-Takara 27998-96Well) levels, as well as instrumental examination: bioimpedance analysis [assess of muscle body mass (MBM), fat body mass (FBM), body mass index (BMI) and others]; sphygmography [assess of augmentation (stiffness) indices (AI), central (aortal) blood pressure (CBP) by «Sphygmacor¼ device]; as well as echocardiography [assess of cardiac (valvular) calcification score (CCS) and left ventricular myocardium mass index (LVMMI)], were studded in addition to conventional examination. RESULTS AND DISCUSSION: To the end of 14th month of the study the PRD group reached a body mass index (BMI) decrease (p=0.046), including MBM in men (p=0.027) and woman (p=0.044). In addition, higher FGF-23 (p=0.029), and lower Klotho (p=0.037) serum levels were revealed in the PRD group compared to the PRD+KAA group as well as the increase in AI (p=0.034), CCS (p=0.048), and LVMMI (p=0.023). CONCLUSION: Use of PRD + KAA provides adequate nutrition status and more efficient correction of FGF-23 and Klotho imbalance in CKD progression that may contribute to alleviation of both cardiovascular calcification and cardiac remodeling in CKD. Importantly, a prolonged PRD use without supplementation of KAA may lead to malnutrition signs.

[Serum troponin-I as a marker of fibroblast growth factor-23 (FGF-23) cardiotoxic effect, in patients with chronic kidney disease].

AIM: It has been established that an increased fibroblast growth factor (FGF-23) serum levels significantly contribute to the heart and blood vessels remodeling in patients with chronic kidney disease (CKD). But the precise mechanisms of the FGF-23 cardiac effect are currently being actively studied. At the same time, it is believed that the cardiac effects of FGF-23 may be due to the increasing deficit of Klotho protein as CKD progresses. In parallel with these changes, a number of studies indicate the persistence of the detectable troponins serum levels in CKD patients, even in the absence of clear clinical manifestations of cardiovascular diseases (CVD). The aim of the study was to confirm / exclude the existence of a causal relationship between elevated FGF-23, reduced Klotho and elevated troponin-I (as the most specific troponin in CKD). MATERIALS AND METHODS: The study included 130 CKD stages 1-5D patients without clinically pronounced symptoms of СVD (Coronary artery disease, CCS class 2-4, Chronic heart failure, NYHA 24, myocarditis, pericarditis, arrhythmias), as well as the severe arterial hypertension (BP >160/90 mm Hg), according to the laboratory and instrumental methods of examination. The selected group of patients was studied: serum levels of FGF-23 (Human FGF-23 ELISA kit), Klotho (Human soluble Klotho with antiklotho monoclonal antibodies), troponin-I (high - sensitive assay), and also data from instrumental examination methods: electrocardiography (ECG), echocardiography (left ventricular myocardial mass index (LVMI), cardiac (valvular) calcification score (CCS) using a semi - quantitative point scale), sphygmagraphy (augmentation (stiffness) indices of vessels (AI), pulse wave velocity (PWV), central (aortic) blood pressure (CBP), blood supply of subendocardium (BSE) - using "Shygmacor" device (Australia)). RESULTS AND DISCUSSION: The changes in serum levels of FGF-23, Klotho and troponin-I (Tr-I) depended on the stage of CKD. The following correlations were identified: FGF-23 and: Tr-I (r=0.601; p.

[The Modern Characteristics of Anti-Tuberculosis Care Support of Population of the Chechen Republic].

Despite a steady tendency of decreasing of indices of morbidity of tuberculosis of population of the Chechen Republic, the problems related to early diagnosis of tuberculosis and organization of specialized medical care of patients continue to be unresolved. The questionnaire survey of administrators of anti-tuberculosis medical organizations of the Chechen Republic was carried out with the purpose of establishing difficulties in medical care support of patients with tuberculosis and determining main directions of their overcoming. The results of study demonstrated that main problems are asocial behavior of patients, inadequate staffing of institutions with medical and paramedical personnel, absence of proper relationship with other medical organizations, inadequate level of financing. The administrators indicated as main directions of solving problems increasing of remuneration of labor of medical personnel of anti-tuberculosis medical organizations, development of social defense of patients, physicians and population, alteration of actual normative legal base according to modern social economic conditions, enhancement of preventive direction of work, optimization of manning table and standards of work load of physicians and also development of tactics of treatment and re-organization of dispensary observation of patients with tuberculosis.

[Predictors of hepatic insufficiency in obstructive jaundice]. / Prediktory pechenochnoi nedostatochnosti pri mekhanicheskoi zheltukhe.

AIM: To develop predictive model for hepatic insufficiency in obstructive jaundice. MATERIAL AND METHODS: Obstructive jaundice was modeled by the author's method on 48 mini pigs, while morpho-functional features of erythrocytes were studied by using of INTEGRA Aura atomic force microscope (NT-MDT, Zelenograd, Russia). Histological specimens were stained with hematoxylin and eosin. Discriminant analysis was used to create predictive model for hepatic insufficiency. RESULTS: Mathematical model of hepatic insufficiency prediction has been developed. Sensitivity and specificity of this model were 94.1% and 74.2% respectively. Total percentage of correct predictions was 81.3%. CONCLUSION: Severe obstructive jaundice contributes erythrocyte's transformation from biconcave to dome-shaped followed by changes of its physical properties. Erythrocyte's volume and activity of cytolysis enzymes are the most informative to predict hepatic insufficiency. Our model allows us to diagnose this complication at early stages and to correct pre-, intra- and postoperative therapy.

Fibroblast growth factor-23 (FGF-23) / soluble Klotho protein (sKlotho) / sclerostin glycoprotein ratio disturbance is a novel risk factor for cardiovascular complications in ESRD patients receiving treatment with regular hemodialysis or hemodiafiltration.

AIM: Aim of the study was to explore the role of the FGF-23/sKlotho/sclerostin ratio disturbance in the determining of cardiovascular risk in end stage renal disease (ESRD) patients, receiving treatment with regular hemodialysis (НD) or hemodiafiltration (НDF) online in Russia. MATERIALS AND METHODS: 42 patients with ESRD, at the age of 18-55 years, treated with HD or HDF on line for at least 6 months, were examined. 22 (52.3%) patients received traditional HD, the remaining 20 (47.7%) - HDF online. In all the patients, in addition to a general examination, the serum levels of FGF-23, sKlotho, sclerostine (by ELISA), their associations with cardiovascular risk factors (left ventricular hypertrophy (LVH), acute coronary syndrome (ACS), serum troponin I levels) with the numbers of techniques (ECG; Eho-CGF (with calculation of left ventricular myocardium mass index (LVMMI), as well as the relative thickness of the walls of the left ventricle (RWT); sphygmography (central (aortal) blood pressure (CBP), subendocardial blood flow (SBF) - by «Sphygmocor¼), and the effect of regular HD and HDF on serum levels of the studied markers, were assessed. RESULTS: An independent effect of FGF-23 on the risk of LVH, as well as on the increase of serum troponin I in the studied ESRD patients [ß=3.576 p<0.01, and ß=1.115, p<0.05, respectively] was found. Serum Klotho was the factor most associated with the CBP [ß=-0.023; p<0.001]. The increased serum sclerostin was correlated with a lower incidence of both reduced SBF [r=0.492; p<0.05], symptoms of coronary heart disease [r=-0.449; p<0.05] and rhythm disturbances [r=-0.446; p<0.05]. In addition, in HD patients higher FGF-23 and lower Klotho and sclerostine serum levels were associated with: inadequate dialysis syndrome (Kt/V <1.1; r=0.463; p<0.05), chronic inflammation (C-reactive protein >10 mg/L; r=0.612; p<0.01), and with a decrease in serum albumin level (<35 g/l; r=0.459; p<0.05). The FGF-23/sKlotho/sclerostin ratio disturbance was more pronounced in patients treated with traditional HD then HDF online. A direct correlation (r=0.445; p<0.05) was established between FGF-23 serum levels and serum phosphorus, which was more pronounced in HD patients (r=0.545; p<0.01). CONCLUSION: In HD and HDF ESRD patients, higher serum FGF-23 and lower sKlotho and sclerostin levels were associated with a chronic inflammation, malnutrition, secondary hyperparathyroidism, and may considered as predictors of cardiovascular complications such as LVH, ACS, rhythm disturbances, persisting of subincreased serum troponin I.

Quality of life of chronic kidney disease patients on renal replacement therapy.

The study demonstrated the results of the comparative analysis of various types of renal replacement therapy effects on the quality of life patients with terminal stage of chronic kidney disease on the basis of standardized questionnaires. It has been shown that the quality of life is significantly improved after a kidney transplantation. At the same time, it has also been found that the introduction of home dialysis, epoetins, active metabolites of vitamin D, calcimimetics in the clinic care expanded the opportunities for the labor rehabilitation of the dialysis patients and made their quality of life comparable with the same of the kidney transplant recipients.

[Hygienic assessment of indoles in the diet of medical students].

A number of studies have shown the relationship between the regular consumption of cruciferous vegetables and the risk of malignant tumors in certain localizations, the activation of mechanisms of alimentary adaptation of the organism under conditions of alien loads, by inducing enzymes of the biotransformation system of xenobiotics. The cruciferous vegetables are distinguished by the presence of minor components, such as indole-3-carbinol, formed during the hydrolysis of glucosinolates. The aim of the investigation was a retrospective study of the content of indoles in students' diet with subsequent quantitative analysis in different comparison groups. The study involved 250 students from a medical university aged 21 to 27 years. To assess the actual nutrition, the developed questionnaires were used, which included the most common products in the Moscow region, sources of indole glucosinolates. It was found that 44% of the respondents didn't include cruciferous vegetables in the diet, and of those who consumed sources of indoles (56% of respondents), only about half received them in the recommended amount. It should also be noted that as in men, in women the most commonly used in the diet product as a source of indoles was cabbage, it was included in the diet of 68% of the respondents who used cruciferous vegetables, rarely pekin cabbage was used (16.3%) and broccoli (16.3%). Cauliflower, radishes, Kale and horseradish was included in the diet of 7.8-14.9% of the students. Less often turnip was consumed - only by 2.1% of the students. No significant differences in the consumption of indoles in the student with deficient, normal or overweight was revealed. Also, there was no correlation between excess weight and the consumption of various indoles sources. The obtained results testify to the extremely low level of alimentary intake of indole-3-carbinol.

Search of MicroRNAs Regulating the Receptor Status of Breast Cancer In Silico and Experimental Confirmation of Their Expression in Tumors.

MicroRNA whose expression depends on the receptor status of breast cancer were selected using bioinformatic analysis. The expression of 9 microRNAs (16, 17, 21, 27, 125, 146, 155, 200a, and 221) was analyzed in 76 samples of breast cancer with various receptor phenotypes. The expression of microRNAs 155, 27, and 200a did not differ in various types of breast cancer. The data on positive correlation between the expression of microRNA-21 and microRNA-221 and negative receptor status of the tumor were confirmed. The expression of the tumor suppressing microRNA-125b decreased in samples of breast cancer expressing HER2 and ER and in triple negative breast cancer, which characterizes it as a universal marker of breast cancer. An increase in the expression of microRNA-16 was shown in samples of breast cancer expressing HER2 and ER. The expression of microRNA-17 decreased in triple negative breast cancer and increased in ER+, PR+, and HER+ types of breast cancer. MicroRNAs 16, 17, 21, 125b, 146b, and 221 can be promising markers for differential diagnostics of various phenotypes of breast cancer.

[Risk factors for anemia in the early stages of chronic kidney disease]. / Faktory riska razvitiia anemii na rannikh stadiiakh khronicheskoi bolezni pochek.

AIM: To identify the early markers of anemia in chronic kidney disease (CKD) in patients with chronic glomerulonephritis (CGN) and glomerulonephritis (GN) in systemic diseases. SUBJECTS AND METHODS: Seventy-nine patients with some male preponderance who were aged 21 to 65 years (45.3±11.1 years) and had CKD (CGN and GN) in systemic diseases (systemic lupus erythematosus and Wegener's granulomatosis) in the early stages (Stages I-II) of CKD were examined. GN was diagnosed by a lifetime renal biopsy. Systemic diseases were diagnosed according to the criteria for each nosological entity. The stages of CKD were defined according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria; the glomerular filtration rate (GFR) was calculated using the CKD EPI equation (2012). According to the presence or absence of anemia, all the patients included in the study were divided into 2 groups: 1) 43 (54.4%) anemic patients; 2) 36 (45.6%) non-anemic patients (a control group). In addition to general clinical examination adopted for a nephrology department, special studies, such as determination of the serum levels of hepcidin, interferon-γ (IFN-γ), soluble Klotho protein (s-Klotho), as well as iron, ferritin, and transferrin saturation (TSAT) ratio, were performed to solve the set tasks. RESULTS: Forty-three anemic patients who had a hemoglobin level of 110 (100; 119) g/l and 36 control patients who had the similar values were noted to have statistically significantly (p<0.001) higher levels of IFN-γ (11 (10; 14) and 0.2 (0.09; 0.6) ng/ml), hepcidin (26 (25; 27) and 5.1 (3.8; 5.9) ng/ml) and C-reactive protein (1.5 (1.1; 2.1) and 0.3 (0.2; 0.6) mg/dl), and lower levels of s-Klotho protein (12 (10; 18) pg/ml) and TSAT (18 (14; 19)%. Forty-three patients with anemia were also found to have a statistically significantly (p<0.01) lower GFR (65 (62; 87) and 80.5 (62; 90) ml/min) and higher systolic blood pressure (145 (125; 160) and 120 (115; 16) mm Hg) as compared with those in 36 control patients. At the same time, the compared groups displayed no statistically significant differences in serum ferritin levels (123 (110; 150) and 115 (100; 140) µg/l). Among 43 CKD patients with anemia, its detection rate in the presence of systemic diseases was 3.2 times higher than that in CGN patients (41.7 and 12.7%). ROC analysis revealed that in the CKD patients with CGN and GN, the serum hepcidin level ≥ 25 ng/ml, with the sensitivity and specificity being of 89.7% and 74%, respectively (p > 0.001), was associated with the development of anemia. Moreover, the hemoglobin level of<120 g/ l was found to have an independent impact on the risk of reducing serum s-Klotho production. CONCLUSION: In Stage I-II CKD patients with CGN and GN in the presence of systemic diseases, elevated serum hepcidin levels should be regarded as a predictor for anemia of chronic disease (ACD). Herewith, the decrease in hemoglobin levels <120 g/l is associated with the reduced production of the nephroprotective factor s-Klotho. The treatment of ACD for Stages I-II CKD should encompass intravenous administration of iron in order to increase its content and availability for erythropoiesis.

[Antiviral activity and possible mechanisms of action of moraprenil phosphates during experimental infection caused by herpes simplex type 1 virus].

AIM: Study of antiviral activity of moraprenil phosphates (MPP) against herpes simplex type 1 virus (HSV1) in vitro and during experimental infection caused by HSV1 in mice. MATERIALS AND METHODS: Activity of MPP in vitro was tested by the ability to suppress formation of symplasts in VERO cells infected with HSV1, strain VR-3. A series of MPP that suppress virus-induced symplast-formation by 30 times was selected for in vivo experiments. Anti-viral activity of MPP in vivo was studied in HSV-1 infected mice after administration of either prophylaxis or therapy regimens. RESULTS: MPP at the dose of 20 microg/mice during s/c administration exhibited a pronounced prophylactic-therapeutic effect. Effectiveness of MPP during clinically evident herpes against the background of developing neurologic symptoms was demonstrated for the first time. Visual observation of the mice, that had received MPP as the first clinical symptoms of the disease appeared, has shown that against the background of preparation injection the clinical signs have ceased after 2 - 3 days and did not registered at least for the whole duration of the observation period (14 days). CONCLUSION: Active herpes infection is accompanied by the increase of FoxP3 expression in-thymus was shown. Possible mechanisms of anti-viral effect of MPP are discussed.

[Microrna, evolution and cancer].

MicroRNAs are known as a posttranscriptional negative regulators of gene expression by binding to the 3'UTP of target mRNAs in cytoplasm. More than 1600 microRNAs expressed in human cells, are involved in the regulation of embryogenesis, differentiation, cell cycle, apoptosis, senescence, thus determining cell fate. Up to 60 % of protein coding genes are under their control. Various sets of microRNAs found in different human tissues under normal and pathological conditions, including cancer, suggest that miRNAs are involved in most cellular pathways. To date, there is no doubt that regulatory potential of the genome is largely determined by miRNAs. In our study, we performed a comparative phylogenetic analysis of the origin and evolution of the total set of 1048 miRNAs in the human genome and investigated the role of certain miRNAs in carcinogenesis of thyroid and mammary glands, as potential diagnostic and prognostic biomarkers of malignancy. Analysis of phylogenetic distribution of miRNAs in the human genome has shown four peaks of appearance of new miRNA genes in the evolution from Methazoa to H. sapiens. The highest amount of new miRNA genes appeared after divergence of H. s. from common ancestor with P. t. Expansion of transposable elements in genome was accompanied by the origin of new miRNA genes on the basis of their sequences. More than 14 % from 1600 miRNAs of human genome originated from mobile elements and still remain. Profiles of expression of 5 miRNAs, pertaining to oncomicroRNAs - miR-21, -221, -222, -155 and -205 - allow distinguishing ductal invasive carcinoma of mammary gland and thyroid papillary carcinoma. The data obtained suggest different ways and roles of participation of the same miRNAs in carcinogenesis of thyroid and mammary glands. So, these miRNAs and profiles of their expression might be used in the diagnosis and prognosis of cancer.