Haemophilus influenzae is one of the most common causative agents of community-acquired pneumonia (CAP). Gene recombinations and high polymorphism make it difficult to diagnose the pathogen even by methods of molecular genetics. The development of DNA microarrays for H. influenzae detection in clinical samples of patients with CAP is promising. The aim of this work was to evaluate the possibility of detection of H. influenzae in clinical samples of patients with CAP using DNA microarray. Oligonucleotide probes were selected using disprose program and sequences from NCBI Nucleotide. Probes capable of cross-linking with H. haemolyticus and H. parainfluenzae DNA were removed in order to exclude nonspecific interaction. Probes were tested as part of DNA microarray design using samples of nucleic acid from tracheal aspirates of children with CAP. H. influenzae detection frequency in clinical samples was determined using sputum samples, tracheal aspirates and pharyngeal swabs of children and adults with CAP. The prevalence of the hybridization signal of the specific probes over 3 standard deviations of the hybridization signal of the negative control probes was interpreted as positive. The results were validated by PCR. 22 probes for H. influenzae detection with DNA microarray were selected. The hybridization signal of probes exceeded the threshold while testing samples containing H. influenzae DNA and did not exceed the threshold value while testing negative samples. H. influenzae detection frequency among patients with CAP was assessed. The results can be used for development of diagnostic tools for establishing the etiological factor of CAP.
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 013_Филатова_148-158.pdf | 808.63 KB |
The aim of this study was to evaluate the effects of two variants of the Daedaleopsis confragosa fungus extract, F-1368 strain, differing in polysaccharide concentration, on five human cancer cell lines (U-87 MG, C-33 A, SK-Mel-28, MDA-MB-231, SW620) in vitro. Standard cytotoxicity assessment methods, including MTT-assay and clonogenic assay, were employed. Additionally, an experiment was conducted on laboratory SCID mice with heterotopic xenografts of human glioblastoma U-87 MG, where the test preparations were administered subcutaneously into the tumor area. Tumor sizes were measured using a caliper, and upon euthanasia, xenografts were histologically examined with hematoxylin-eosin staining under a light microscope. Results from MTT and clonogenic assays demonstrated that F-1368 extracts reduced the viability, mitochondrial function, and proliferative activity of tumor cells in vitro. However, a threefold increase in polysaccharide concentration in one of the extracts did not significantly enhance its cytotoxicity against tumor cells in vitro. Furthermore, one extract was tested on U-87 MG cell xenografts, revealing a reduction in tumor growth in SCID mice. The maximum tumor growth inhibition index for U-87 MG cells reached 50.7% at 21 days post-commencement of extract injections. These findings suggest that the D. confragosa F-1368 strain holds promise for investigating both in vitro and in vivo models of antitumor activity and identifying potential bioactive molecules or compounds.
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| 012_Соловьева_139-147.pdf | 641.57 KB |
The aim was to study macrolide resistance of erm B -positive H.pylori in patients with newly diagnosed and recurrent helicobacteriosis in Nizhny Novgorod. Materials and methods: PCR detection of H.pylori DNA in gastric juice and biotopes of the mucous membrane of the gastric antrum was performed in 3450 patients with gastroenterological diseases. To identify the ermB gene associated with macrolide resistance, domestic commercial PCR test systems were used. Results: from 2005 to 2023 there was a progressive reduction in visits for gastric and duodenal ulcers. The dynamics of primary and secondary genetic H.pylori macrolide resistance increased continuously from 2011 to 2014 and stabilized thereafter. From 2014 to 2023, the proportion of patients with ermB gene positive H.pylori infection increased approximately 2-fold (to 17.0% in 2018). In patients with a history of eradication therapy, the minimum detection rate of the ermB gene was established in 2011. Since 2012, there has been an increasing detection rate of secondary H.pylori macrolide resistance to 35.4% in 2022. Conclusions: during the observation period, a progressive reduction in the proportion of patients with gastric and duodenal ulcers among patients with gastroenterological diseases was revealed. The study of primary and secondary H.pylori macrolide resistance showed an increase in the detection rate of resistant isolates in Nizhny Novgorod. The study of genetic H.pylori macrolide resistance is necessary when re-identifying in patients with a history of eradication therapy and in patients who took clarithromycin for other reasons for the optimal selection of drugs included in the re-treatment regimen of infection.
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| 011_Перфилова_129-138.pdf | 771.68 KB |
Gastric cancer (GC) is one of the most common cancer types in the world with a high mortality rate. It is assumed that polymorphisms of the NFKB1 gene that disrupt its expression predispose to the development of epithelial cancer, including GC. The aim of this study is to explore the association of polymorphism rs28362491 of NFKB1 gene with the risk of GC development for individuals from the Volga-Ural region of Russia. The samples for the study were the DNA of 374 patients with GC and 365 healthy donors of various ethnicities (Russians, Tatars, Bashkirs). It was shown that in all studied groups the most common heterozygous genotype ID of the polymorphic locus rs28362491 of the NFKB1 gene, alleles I and D occur with similar frequencies. Also, it has been established that for Tatars, allele D of the rs28362491 polymorphic locus of the NFKB1 gene is a marker of an increased risk of developing GC, and allele I and genotype II are markers of a reduced risk of developing GC. Meta-analysis showed statistically significant differences in the distribution of allele frequencies of the polymorphic locus rs28362491 of the NFKB1 gene between patients with cancer and controls when combining samples of Tatars and Bashkirs. We hypothesize that polymorphism rs28362491 of the NFKB1 gene may contribute to the genetic structure of susceptibility to GC.
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| 010_Нургалиева_120-128.pdf | 624.21 KB |
Epigenetic regulation of spatiotemporal gene expression in ontogenesis is determined by programmed species-specific activations of retroelements in successive cell divisions. Evolutionary selection of this genome control mechanism is aimed at achieving a mature state, after which unprogrammed activation of retroelements occurs, which expression products stimulate interferon response, aseptic inflammation and aging-associated diseases development, such as atherosclerosis. Interferon in atherosclerosis stimulates pro-inflammatory macrophage phenotype, which contributes to pathological immune response, foam cell formation and atherosclerosis progression. Activation of retroelements occurs under the influence of viral infections, which role in atherosclerosis development has been proven, which confirms my hypothesis. Dysfunctional foam macrophages produce HERV-K102, which stimulates innate immunity, HERV-K HML2 expression correlates with macrophage immune activation and interferon response. Data were obtained on association with atherosclerosis of microRNAs derived from retroelements, which are involved in the disease pathogenesis due to their influence on cholesterol metabolism (miR-498, -520d), immune processes (miR-1257, -28, -2909), activation of DNMT1 (miR-1264) and EZH2 (miR-630), gene expression in endothelial cells (10 specific miRNAs), vascular smooth muscle cells (14 specific miRNAs) and macrophages (miR-320b, -326, -378, -384), contributing to pathological phenotype of these cells. In atherosclerosis microRNAs derived from retroelements interact with circular RNAs (miR-495, -576, -579, -630, -633, -637, -942) and long non-coding RNAs (miR-326, -4731, -495, - 616, -641, -664a) the key sources of which are retroelements. Role of ANRIL, NEAT1, PAPIA, MAARS, VINAS, H19, AK136714, MIAT, and interaction of Alu elements with ANRIL and NEAT1, identified in atherosclerosis development. The data obtained can become the basis for targeted effect on retroelements activation in atherosclerosis using microRNAs.
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| 09_Мустафин_108-119.pdf | 449.97 KB |
The focus of this review is on the study of aberrant metabolism in brain cells in Parkinson's disease. Parkinson's disease is the second most prevalent neurodegenerative disorder, characterized by the aggregation of the pathological protein α-synuclein, loss of dopaminergic neurons in the compact part of the substantia nigra, leading to a combination of motor and non-motor symptoms. While the hallmark motor symptoms of PD are well-documented, emerging research sheds light on intricate metabolic changes occurring at the cellular level, providing new insights into the pathophysiology of the disease. Studying the role of endogenous small molecules in protein-metabolite intermolecular interactions, conformational rearrangements of protein molecules, especially membrane receptors and transporters in regulating blood-brain barrier permeability, modulation of signaling transduction processes in neuroinflammation and neurodegeneration, remains pertinent.
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| 08_Колотьева_90-107.pdf | 1.89 MB |
Injury to the proximal part of the equine suspensory ligament (SL), called proximal suspensory desmitis (PSD), commonly causes lameness in horses. PSD is extremely difficult to manage and treat, with present methods often unable to achieve full recovery, especially in chronic cases. The present study was the first to use gene therapy to restore moderate and severe injuries of the proximal suspensory ligament in horses. Plasmid DNA encoding species specific bone morphogenetic protein 2 (bmp2) and vascular endothelial growth factor (vegf164) was injected into the site of proximal suspensory ligament injury, followed by box rest and a controlled exercise program. Clinical observations and ultrasound imaging were used to evaluate effectiveness over a period of 12 months. No negative side effects were observed. Clinical improvements were observed, especially in the forelimb affected horses, by day 30. In horses with chronic hindlimb PSD, few clinical improvements were reported. Echogenicity and the fiber alignment scoring improved but no concomitant changes to cross section area, dorsopalmar thickness or lateromedial width of the proximal suspensory ligament were observed. The transfer of bmp2 and vegf164 genes into the equine PSL exhibited beneficial effects in horses with acute or subacute forms of lesions, primarily in the forelimb.
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| 07_Закирова_74-89.pdf | 1.15 MB |
Heavy metals, due to their ability to bioaccumulate and are highly toxic even in low concentrations, are the most dangerous environmental pollutants, especially in industrialized countries. The purpose of the study was to evaluate the degree of cadmium accumulation, as well as the expression of the Mt1a and Mt2a genes, in the kidneys of rats using two experimental models of subchronic intoxication with cadmium chloride. A total of 80 adult white outbred rats of both sexes were equally distributed into four groups: a control group (negative control), group 1 (0.001 mg/kg/day CdCl2), group 2 (0.01 mg/kg/day CdCl2), 3rd group (0.1 mg/kg/day CdCl2). After three months of exposure, 10 animals (5 males and 5 females) were randomly selected from each group and euthanized, followed by kidney samples for cadmium analysis and gene expression assessment. The remaining animals (n = 40) were left for an additional 30 days without treatment, before being sacrificed to collect tissue. The results showed that 1 month after cadmium withdrawal, the processes of redistribution of the metal in the body are still ongoing, which is expressed in a greater accumulation of cadmium in the kidneys. We also recorded an increase in the Mt1a gene expression and a decrease in the Mt2a gene expression in the kidneys of animals that went through the remission stage compared to animals without it. These data suggest that even after Cd withdrawal, there may be long-term negative effects on the kidneys.
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| 06_Валова_66-73.pdf | 719.38 KB |
Obesity is recognized as a multifactorial health condition characterized by excess body fat accumulation. Orlistat is a well-known effective anti-obesity therapeutic drug, however, like many other medications on the market, it has certain unpleasant side effects. Medical herbs have recently acquired popularity in the treatment of obesity. The current project's intention was to evaluate the effect of treatment with Artemisia annua extract (AAE) to ameliorate hepato-renal dysfunction in obese rats. 40 male Sprague Dawley (SD) rats were divided into 4 groups (n = 10). The 1st group (Gp1) served as a negative control, and Gp2 was used as a positive control and given a high-fat diet (HFD) for a period of 12 weeks. For a period of 8 weeks, Gp3 and Gp4 received HFD and daily treatments of orlistat (30 mg/kg) or AAE (150 mg/kg), respectively. Hematological, biochemical, and histopathological parameters were determined. The results demonstrated that obese rats, Gp2, had hepato-renal impairment. Moreover, hepato-renal dysfunctions were exacerbated when orlistat was administered to obese rats of Gp3. In contrast, AAE-treated obese rats, Gp4, have shown alleviated hematological changes and resulted in considerable improvements in hepato-renal function. Taken together, AAE administration demonstrated potential ameliorative effects against hepato-renal dysfunctions in obese rats when compared to treatment with orlistat.
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| 05_Hasan_47-65.pdf | 3.26 MB |
Herniated (prolapsed) discs HD is a multifactor disease that afflicts around 9% of the global population and occurs when the nucleus pulposus NP bulges and pushes on the ruptured annulus fibrosus AF, releasing substances that may irritate the surrounding nerves and cause inflammation that leads to extensive histopathological and immunological changes. The aim of this study is to demonstrate the etiological role of IL-10, IL-17 levels, CD4+, and CD68 in the pathogenesis of herniated disc in Iraqi patients. The immunohistochemical analysis was performed on 30 excised HD specimens taken during endoscopic discectomy, and stored in the fixative solution (formalin 10%). Cytokines (IL-10 and IL-17) were measured by using their Enzyme-Linked Immunosorbent Assay ELISA kits, in sera of 40 patients who were diagnosed with HDs as a case group, in addition to 20 healthy as a control group. The results revealed that the CD4+ expression was negative in 70% of the HD samples, while only 8 HD samples were negative for CD68 expression. On the other hand, results of ELISA analysis recorded high levels of IL-10 with low levels of IL-17 in HD patients sera compared with control sera. According to the above it can concluded that immunohistochemical analysis of HD tissues showed infiltration of CD4+ and CD68. Also compared to controls high levels of IL-10 in HD samples combined with low levels of IL-17.
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| 04_Dhilal_40-46.pdf | 748.85 KB |
Breast cancer (BC) is one of the most common causes of death among women in the world. This study investigated the role of global DNA methylation (5mC) and hypoxia-inducible factor 1 alpha (HIF-1α) levels in BC disease progression. Blood samples were collected from 40 patients with benign breast tumors, 40 patients with malignant breast tumors, and 40 healthy subjects. Patients with malignant breast tumors were divided into two groups: women in stage II (low-level), and patients in stages III and IV (high-level). Genomic DNA was isolated from whole blood samples from the subjects and used for global DNA methylation. Furthermore, the levels of HIF-1α expression were measured. The results showed that the levels of 5mC in patients with BC and benign breast tumors were considerably lower (0.538 ± 0.03 and 0.432 ± 0.04%, respectively), compared to the control (0.619 ± 0.05%). Furthermore, there was a significant (p ≤ 0.05) decrease in levels of 5mC in BC patients at stages III and IV compared to control. However, there were no significant differences between low-level and high-level stages. The HIF-1α levels of patients in both the benign breast tumors and BC were insignificant (923.35 ± 72.42 and 1386.03 ± 102.01pg/ml, respectively), compared to the control (825.5 ± 62.36 pg/ml). Although, BC patients at low levels showed no significant difference in HIF-1α levels compared with patients at high levels. The findings indicated that variations in 5mC levels across different stages and types of breast tumors may serve as a prognostic indicator for the development of BC and also implicated HIF-1α in the development of BC.
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| 03_Basim_28-39.pdf | 542.34 KB |
This study was designed to assess the harmful impact of Duprost on the testes of experimental animals. The animals were divided into 3 categories: control, acute, and chronic; the last two were further divided into subgroups. All acute subgroups were given a lonely oral dosage of 0.5, 0.12, 0.08, and 0.04 mg/kg for 24 hours. The chronic subgroups were given a daily dosage of 0.12, 0.08, 0.04 mg/kg for 42 days. The sections of treated testes of acute and chronic sets showed pathological alterations mainly in dosages (0.12 mg/kg and 0.08 mg/kg). The higher dosages cause cellular depletion, necrosis and lysis of the testicular interstitium, hyperplasia and increased thickness of the interstitium. Moreover, there was marked hypertrophy, marked tubular dilation and deterioration with severe degeneration and necrosis of lining epithelium with a loss of stereocilia in epididymis tissue.
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| 02_Ban Jasm_16-27.pdf | 1.66 MB |
Ionising radiation from radiotherapy can cause thyroid disease, autoimmune antibodies, and haematological invasion. Ionising radiation affects the immune system, and surpassing the body's tolerance can damage the hematopoietic system, causing early symptoms and serious consequences. The study used ELISA technique to determine autoantibodies and thyroid hormones in whole blood samples from Iraqi physician in Baghdad city for nuclear medicine which exposed daily to radiotherapy according to their routine job. CBC were also determined using autoanalyzer. A group of healthy control patients was also studied. Blood samples from Iraqi doctors who were routinely exposed to radiation were examined, a statistically significant decrease (P ≤ 0.01) in the serum levels of the Triiodothyronine (T3) and Thyroxine 4 (T4) and a statistically significant elevation (P ≤ 0.01) of Anti-Thyroid peroxidase Ab (Anti-TPO Ab), Anti-Thyroglobulin Ab (anti-Tg Ab), and antinuclear antibody (ANA) serum levels in female were seen in contrast to the healthy control group. Compared to healthy controls, female workers had less RBCs and Hb. For that, it can be concluded that the exposure to radiotherapy is effective in female more than male workers in Baghdad city for nuclear medicine which can be due to the effect of radiation low dose on female autoimmune system.
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| 01_Bahaa_5-15.pdf | 777.34 KB |
This review analyzes current trends in the development of traditional (open-loop) methods of non-invasive brain stimulation, as well as promising directions for the development of closed-loop methods of adaptive neurostimulation. The main focus is on studies using non-invasive magnetic and electrical stimulation, as well as acoustic and audiovisual stimulation. The possibilities and prospects for using these technologies as a tool in carrying out a wide range of rehabilitation procedures are analyzed. The results of the authors' own research in this direction are presented.
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| 014_Федотчев_Парин_147_155.pdf | 272.87 KB |
The effect of gas-discharge plasma radiation on the biochemical parameters of blood and urine of intact animals and animals with acute alcohol intoxication was investigated. Measurements of the content of medium-mass molecules (MMM), creatinine, urea, glucose, lactate and hemoglobin in the blood and 14 physicochemical indicators of the urine test were carried out. Acute alcohol intoxication (AAI) was simulated by intraperitoneal injection of 33% ethanol at a dose of LD50. The treatment was carried out by an experimental pulsed (10 Hz) device generating radiation of spark discharge plasma. It was revealed that exposure to plasma radiation does not lead to changes in the biochemical parameters of blood and urine of intact animals. In the model of AAI, the development of protein-creatininia, urobilinogenuria, and an increase in the specific gravity of rat’s urine was observed. The total level of MMM and hemoglobin in the blood increased, lactic acidosis developed. After exposure to plasma radiation in animals with AAI, blood and urine parameters normalized, which is probably associated with the activation of the organism's adaptive and antioxidant reserves. Thus, the positive effect of spark discharge plasma radiation on the organism during acute ethanol intoxication has been shown.
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| 013_Трофимова_137-146.pdf | 562.24 KB |
The heritability of human psychological well-being ranges from 36 to 48%. GWAS conducted between 2016 and 2019 identified 364 SNPs significant for well-being. A significant association with psychological well-being has been shown for the APOE, OXTR, OXT, NMUR2, CNR1, CRHR1, and CYP19A1 genes. The greatest influence on psychological well-being is exerted by allelic variants of the MAYA, 5-HTT, СOMT genes, and the CTRA gene group (conservative transcriptional response to adversity). Brain functioning is influenced by the peculiarities of VNTR distribution in the regulatory regions of the 5-HTT, SLC6A3, AVPR1A, FUS, OXT, PARK7, POMC, TACR3, TRPV1 and TRPV3 genes. These features are due to the individual distribution of SVA (SINE-VNTR-Alu) retroelements, which belong to transposons that are drivers of epigenetic regulation. Features of activation of retroelements located in the regulatory regions of genes may affect the individual level of well-being. This is evidenced by the association with psychological well-being of DRD4, MAOA, SLC6A3, 5-HTT genes alleles, determined by the length of VNTR in their regulatory regions. Evidence of retroelements role in well-being regulation is that retroelements are sources of protein-coding genes and microRNAs involved in brain functioning. The Arc gene, derived from retroelements, is characterized by transport into neuronal dendrites with translation regulation. We analyzed the MDTE DB database on transposon-derived microRNAs and scientific literature. According to the results, 12 miRNAs, derived from transposons, are associated with major depressive disorder. The data obtained indicate the influence of transposons on psychological well-being, which is assessed by the absence of depression.
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| 012_Мустафин_123-136.pdf | 698.34 KB |
Currently, data are accumulating on the antioxidant properties of bilirubin and its protective role in various diseases. This review considers the dose-dependent effect of bilirubin on its cytoprotective and antioxidant properties, the relationship between the level of bilirubin and the pathophysiological manifestations of bronchial asthma, in the pathogenesis of which chronic inflammation induced by oxidative stress plays a significant role. The article also focuses on the potential therapeutic use of bilirubin in the treatment of bronchial asthma.
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| 011_Кубышева_115-122_a.pdf | 351.47 KB |
Pancreatic cancer (PC) is one of the most aggressive malignant neoplasms. Next-generation sequencing (NGS) was performed in 223 patients from Nizhny Novgorod with morphologically verified pancreatic cancer (PC) treated at the Oncological Dispensary of the Nizhny Novgorod Region in 2021-2022. The patients were conditionally divided into two subgroups: The first subgroup (184 patients) underwent PCR testing at the Nizhny Novgorod Regional Oncology Dispensary and then next-generation sequencing (NGS) of the coding regions of the BRCA1/2 genes at the National Medical Research Centre of Radiology of the Ministry of Health of the Russian Federation. The second subgroup (39 patients) underwent NGS of the coding regions of cancer-associated genes at the Centre for Personalised Medicine of the Moscow Clinical Scientific and Practical Centre named after A.S. Loginov. Germline mutations in the BRCA1/2 genes were detected in 6 patients with pancreatic cancer (3.3 ± 1.3%), including one case in the BRCA1 gene and 5 in the BRCA2 gene. Various pathogenic mutations in genes (ATM, FANCC, POLE, NBN, BLM, SMARCA4, MUTYH, FANCG) associated with different oncological syndromes were found in 9 patients (23.1 ± 1.2%). The high prevalence rates of different pathogenic variants in PC patients, regardless of age and family history of oncology, indicate the need for medical genetic counselling followed by NGS. The detection of germline mutations in genes of hereditary tumour syndromes in PC patients will help to identify high-risk groups for tumor development in relatives and enable early diagnosis.
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| 010_Колесникова_103-114.pdf | 556.72 KB |
Ophthalmic diseases are common problems in dogs of various breeds and ages. In recent years, ophthalmologists have been paying more attention to stem cell (SC) therapies, since the renewal and regeneration of any tissue in the adult body depends on somatic SC, and eye tissues are no exception. The aim of the present work was to determine the influence of allogenic mesenchymal stem cells (MSC) in healing ulcerative keratitis of dogs. Our research showed that subconjunctival injections of allogeneic MSCs from adipose tissue was clinically safe for use in dogs during the follow-up period. These injections contributed to the decrease of the clinical manifestations of ulcerative keratitis in dogs, as evidenced by a decrease the intensity and area of the affected areas of the cornea compared to classic therapy.
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| 09_Закирова-94-102.pdf | 677 KB |
A major problem of medicine is the prevention, treatment and rehabilitation of patients with congenital malformations of the maxillofacial region. This is due to their frequency, the severity of anatomical and functional disorders, as well as the complexity of social adaptation of patients. Cleft lip and palate are highly common malformations with a significant variation of risk factors. The updating of epidemiological data in certain regions of Russia makes it possible to identify the dominant causal mechanisms of the occurrence of defects, to determine the necessary directions for improving preventive and diagnostic measures, treatment and tactics of dispensary supervision of patients. The analysis of the incidence of congenital malformations of the maxillofacial region in the city of Nizhny Novgorod and the Nizhny Novgorod region of Russia over the past 19 years has been carried out. The risk factors for the development of anomalies, the structure of morbidity, the type and nature of the therapeutic measures carried out were determined.
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| 08_Алешина_86-93.pdf | 562.94 KB |
