Opera Medica et Physiologica

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Invited review
Printed December 02, 2024;
Published ahead of print December 01, 2024; Printed December 02, 2024; OM&P 2024 Volume 11 Issue 4, pages 60-70; doi:10.24412/2500-2295-2024-4-60-70
Abstract Full Text

Molecular genetic studies make it possible to determine associations of multifactorial diseases (MFDs) with many specific SNPs, which influence on MFDs etiopathogenesis is often difficult to explain. This is due to the one-sided focus of strategies in the search for mechanisms of these SNPs influence, which are mainly limited to determining the role of protein-coding genes, near or within which these polymorphisms are located. This article provides data on the mechanisms of SNP influence on MFDs etiopathogenesis due to changes in the transposable elements, which leads to their activation, dysfunction or susceptibility to exogenous viral infections. As a result, the relationship of transposable elements with specific proteins, non-coding RNA and epigenetic factors changes, which is a predisposing factor for MFDs development. Indeed, most disease-associated SNPs are located in intronic and regulatory regions of genes, and in intergenic regions. Transposable elements of the human genome are also localized in these places. Therefore, the association of specific SNPs with certain MFDs is due to the different activities of specific transposable elements. Determining the influence of SNPs on transposable elements is promising in bioinformatics studies with the construction of maps of the distribution of these elements in the genome within genes and in intergenic regions with the identification of changes in their structure under the influence of polymorphisms. Using neurodegenerative diseases as an example, it has been shown that pathological functioning and activation of retroelements due to SNPs in the regions of their location in the human genome leads to these MFDs development.

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07_Мустафин_60-70.pdf478.11 KB

Full-length research paper
Printed December 02, 2024;
Published ahead of print December 01, 2024; Printed December 02, 2024; OM&P 2024 Volume 11 Issue 4, pages 51-59; doi:10.24412/2500-2295-2024-4-51-59
Abstract Full Text

During cardiac surgery, as well as on-pump CABG, it is crucial to monitor arterial blood parameters in order to assess the condition of patients and risks that might occur in the operating room. In some cases, the cardiac activity of patients undergoing on-pump CABG cannot be self-restored and resuscitation measures are required. Thus, the aim of the study was to analyze the differences between the two groups of patients (self-restoration of cardiac activity vs additional resuscitation measures were required) and identify arterial blood parameters potentially indicating that the patient is at risk. The data of 21 patients were analyzed with Python packages. Statistically significant differences were found between the control group (self-restoration of cardiac activity) and the test group (additional resuscitation measures were required) in the following arterial blood parameters: the levels of sodium, chloride, glucose and blood osmolality. We believe that hyponatremia and blood hypoosmolality might be a reason for cell edema which creates a greater load on the heart and leads to inability of self-restoration of cardiac activity.

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06_Киселева_51-59.pdf1.33 MB

Full-length research paper
Printed December 02, 2024;
Published ahead of print December 01, 2024; Printed December 02, 2024; OM&P 2024 Volume 11 Issue 4, pages 40-50; doi:10.24412/2500-2295-2024-4-40-50
Abstract Full Text

Over the past three decades, the majority of norovirus outbreaks and sporadic cases have been caused by strains of the GII.4 genotype. Notably, this period has seen a periodic change in the norovirus variants within the GII.4 genotype, with some variants acquiring epidemic distribution. Currently, six polymerase gene variants classified as P-type GII.P4 (GII.P4US95, GII.P4FarmingtonHills, GII.P4Hunter, GII.P4Yerseke, GII.P4DenHaag, and GII.P4NewOrleans) are represented in public nucleotide sequence databases, corresponding to GII.4 genotype variants of the gene encoding the main capsid protein VP1 of norovirus. In this study, the nucleotide sequence of the complete RdRp gene was obtained for a strain from Nizhny Novgorod, identified as GII.4Sydney[P4NewOrleans]. According to the results of Bayesian phylogenetic analysis based on RdRp GII.P4 gene sequences available in the GenBank database divided the analyzed strains into clusters according to polymerase variant. Within these clusters, lineages of intervariant recombinants are formed in accordance with the affiliation of the capsid protein variants associated with this polymerase variant. Analysis of the deduced amino acid sequences revealed substitutions specific to different polymerase variants that have emerged and become established within the norovirus population. It appears that the emergence of new norovirus variants within the GII.4 genotype involves selection for strains in which the polymerase and major capsid protein genes have coevolved, conferring certain advantages that facilitate further dissemination. These findings are highly relevant for advancing therapeutic strategies targeting RdRp inhibition for norovirus treatment and for development of specific prophylactic agents.

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05_Епифанова_40-50.pdf1.5 MB

Full-length research paper
Printed December 02, 2024;
Published ahead of print December 01, 2024; Printed December 02, 2024; OM&P 2024 Volume 11 Issue 4, pages 35-39; doi:10.24412/2500-2295-2024-4-35-39
Abstract Full Text

The effect of molecular hydrogen (H2) on the functional state of spermatozoa through signaling pathways was studied. In the work, drugs that affect elements of intracellular signaling cascades were used to study the mechanisms of action of H2. We used the adenylatecyclase stimulator – forskolin, the Ca2+-channel blocker – verapamil, and the proteinkinase C inhibitor – staurosporine. We studied concentrations of MDA, ATP, the percentage of total motility and the average speed of spermatozoa under the action of H2 against the background of the action of drugs and without the action of drugs. It was shown that the concentration of MDA in all series did not change. Forskolin causes an increase in sperm motility and velocity. The use of H2 increased the effects stimulated by forskolin: sperm motility and average velocity increased. The concentration of ATP, the percentage of motility and the velocity of sperm decreased under the action of staurosporine and verapamil. The combined action of H2 and verapamil as well as the combined action of H2 and staurosporine determined an increase in sperm motility and velocity. Thus, H2 had a modulating effect through signaling pathways and caused an increase in the functional indices of sperm.

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04_Дерюгина_35-39 +.pdf501.86 KB

Full-length research paper
Printed December 02, 2024;
Published ahead of print December 01, 2024; Printed December 02, 2024; OM&P 2024 Volume 11 Issue 4, pages 21-34; doi:10.24412/2500-2295-2024-4-21-34
Abstract Full Text
Chronic kidney disease biomarkers are not studied well yet. Klotho and fibroblast growth factor 23 can be used as sensitive chronic kidney disease biomarkers, as well as single nucleotide polymorphisms of renin-angiotensin-aldosterone system genes may signal the risk of a genetic predisposition to this pathology. In this regard, the purpose of our work is to study the association of polymorphisms of renin-angiotensin-aldosterone system genes with physiological indicators of end-stage renal disease. Levels of fibroblast growth factor 23, Klotho, urea, creatinine, albumin, C-reactive protein, complete blood count parameters were considered in end-stage renal disease patients and control group. Also single nucleotide polymorphisms of AGT (rs4762), AGTR1 (rs5186) and AGTR2 (rs1403543) genes were determined. As a result, a statistically significant increase of fibroblast growth factor 23, urea and creatinine in the plasma of patients with end-stage renal disease was revealed. Statistically significant relationships were found between the complete blood count parameters, between albumin level and parathyroid hormone, between mean corpuscular hemoglobin and C-reactive protein. No difference of the frequency of polymorphisms of the studied genes between the groups was found.  An increase of albumin and decrease of Klotho levels were recorded in carriers of the heterozygous genotype of the rs5186 polymorphism and in the case of a complete replacement for the wild allele in the FGFR2 gene (rs1403543) in the group of patients with end-stage renal disease. In the control group a relationship was found between the levels of urea, albumin and creatinine and the carriage of rs4762 and rs1403543 polymorphisms.
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03_Давыдова_21-34.pdf1.35 MB

Full-length research paper
Printed December 02, 2024;
Published ahead of print December 01, 2024; Printed December 02, 2024; OM&P 2024 Volume 11 Issue 4, pages 13-20; doi:10.24412/2500-2295-2024-4-13-20
Abstract Full Text

This study investigates the effects of omaveloxolone, a Keap1 inhibitor, on mitochondrial network (MN) dynamics and cell survival under oxidative stress in control fibroblasts and fibroblasts from a Parkinson's disease patient with a PINK1 mutation. The PINK1-mutant fibroblasts showed increased sensitivity to hydrogen peroxide-induced stress. Omaveloxolone pre-treatment improved cell viability under stress conditions in both cell types. Under normal conditions, PINK1-mutant fibroblasts exhibited lower MN connectivity compared to control cells. Oxidative stress reduced MN density in both cell types, while omaveloxolone treatment normalized MN connectivity in PINK1-mutant cells and maintained higher MN connectivity under stress. Similar effects were observed for mitochondrial branch length. Omaveloxolone (50 nM) also increased mitophagy in both cell types under normal conditions. Our findings demonstrate that omaveloxolone exerts protective effects by maintaining mitochondrial dynamics and activating mitophagy. It enhances mitophagy under normal conditions and supports MN structure under oxidative stress, improving cell viability in both control and PINK1-mutant fibroblasts. These results highlight omaveloxolone's potential as a therapeutic agent for protecting cells in diseases associated with impaired mitochondrial dynamics, particularly Parkinson's disease linked to PINK1 mutations.

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02_Бережнов_13-20.pdf1.72 MB

Full-length research paper
Printed December 02, 2024;
Published ahead of print December 01, 2024; Printed December 02, 2024; OM&P 2024 Volume 11 Issue 4, pages 5-12; doi:10.24412/2500-2295-2024-4-5-12
Abstract Full Text

This study investigates the effects of the α1-adrenergic receptor agonist methoxamine at various concentrations (10−9 to 10−6 M) on the frequency and characteristics of spontaneous action potentials in right atrial preparations of newborn and adult rats. In newborn rats, methoxamine at all studied concentrations significantly increased the duration of the action potential repolarization phase, while in adult rats, decreasing it. Interestingly, in adult rats, methoxamine at a concentration of (10−6 M), exhibited a dual effect, decreasing the duration of the action potential repolarization phase in some samples while increasing it in others. Stimulation of α1-adrenergic receptors by methoxamine in working cardiomyocytes of the right atrium in both age groups led to an increase in the frequency of action potential generation; however, this effect was more pronounced in newborn rats. These findings highlight the age-dependent effects of α1-adrenergic receptor stimulation on cardiac electrical activity, suggesting that the mechanisms underlying these responses may differ significantly between newborn and adult rats.

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01_Mansour_5-12.pdf680.23 KB

Full-length research paper
Printed September 20, 2024;
Published ahead of print September 20, 2024; Printed September 20, 2024; OM&P 2024 Volume 11 Issue 3, pages 174-188; doi:10.24412/2500-2295-2024-3-174-188
Abstract Full Text

Introduction. Acute limb ischemia is a critical condition requiring immediate revascularization. The risk of complications is affected by age, coronary heart disease, chronic kidney disease, respiratory failure, diabetes mellitus, thrombosis etiology, urgency and duration of surgery. The aim of the study was to evaluate the influence of the presented risk factors on the results of open revascularization for acute thrombosis in patients with acute COVID-19. Materials and methods. The results of open surgical treatment of acute limb ischemia of Rutherford class II in patients with acute COVID-19 (86 patients, group I) and 50 patients without COVID-19 (group II) were analyzed. Results. In-hospital mortality was 73.2% in group I and 12% in group II. Most deaths in group I were due to early rethrombosis. Risk factors - coronary heart disease, chronic kidney disease, diabetes mellitus, age >75 years had a greater negative impact in group I against the background of coronavirus infection. Conclusion. In patients in the acute stage of COVID-19, open revascularization is associated with a higher risk of complications and mortality in the early postoperative period relative to patients who underwent surgery without coronavirus infection. The impact of all the identified risk factors increases against the background of COVID-19, a statistically significant increase in the odds ratio of developing postoperative complications was found for such perioperative risk factors as: coronary heart disease, respiratory failure, polyvalent etiology of thrombosis and age over 75 years, among the intraoperative factors, the emergency nature of the operation and the duration of the surgical intervention are significant.

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15_Nikolsky_174-188.pdf746.49 KB

Full-length research paper
Printed September 20, 2024;
Published ahead of print September 20, 2024; Printed September 20, 2024; OM&P 2024 Volume 11 Issue 3, pages 158-173; doi:10.24412/2500-2295-2024-3-158-173
Abstract Full Text

The transition of the ion channel between the open and closed states is traditionally considered random. Current experimental data indicated the presence of oscillatory modes of regulation of open/closed states, and possible connections between these modes. The canonical methods Fourier or wavelet transforms, fractal analysis and mathematical modelling can evaluate open/closed states oscillatory modes, but cannot describe their relationship to each other. We first applied the method of bispectral analysis to solve this problem. The well-described potassium channels potential-dependent Kv, calcium-dependent KCa and the modelled potassium channel KcsA were studied. The relationship between fluctuations open/closed lifetimes at frequencies ~0.1, ~1 and ~10 Hz was shown. These frequencies correspond to rhythmic processes in cardiovascular and nervous systems functioning, including those regulated by potassium channels. The normalised integrated bispectrum index was chosen to quantitatively evaluate the interrelation of ion channel opening/closing states. The normalised bispectrum index notable increased upon alteration of the membrane potential from 0 to 20 mV. The obtained data expand our understanding of ion channel functioning principles and can be used in the search for new approaches to the pathological states (channelopathies) therapy.

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14_Astashev_158-173.pdf2.01 MB

Full-length research paper
Printed September 20, 2024;
Published ahead of print September 20, 2024; Printed September 20, 2024; OM&P 2024 Volume 11 Issue 3, pages 152-157; doi:10.24412/2500-2295-2024-3-152-157
Abstract Full Text

Сholelithiasis is a multifactorial process that is influenced by both environmental and genetic factors. Some evidence suggests that total plasma homocysteine correlates with the presence of gallstones, suggesting that hyperhomocysteinemia is a risk factor for cholelithiasis. The aim of this work was to analyze the association of polymorphic variants of the methylenetetrahydrofolate reductase MTHFR (rs1801133 (677C > T), rs1801131 (1298A > C)) and methionine synthase reductase MTRR (rs1801394 (66A > G)) genes with the development of gallstone disease in individuals from the Republic of Bashkortostan. DNA samples from 196 patients with cholelithiasis and 274 healthy individuals aged 23-87 years living in the Republic of Bashkortostan were used as research material. Genotyping was performed using the real-time PCR method. It has been established that the rs1801133*T allele and the rs1801133*TT genotype of the MTHFR gene are markers of an increased risk of developing cholelithiasis. An association was established between the rs1801133*TT genotype of the rs1801133 polymorphic variant of the MTHFR gene and the moderate severity of cholelithiasis and hereditary burden in patients with cholelithiasis. A study of the polymorphic variant of the MTRR gene revealed that the rs1801394*G allele increases the risk of cholelithiasis. Analysis of associations of the polymorphism rs1801131 of the MTHFR gene with the development of cholelithiasis did not reveal statistically significant differences between the compared groups of patients and controls. Determination of homocysteine levels and genetic testing of MTHFR and MTRR polymorphisms in patients with cholelithiasis may be useful in clinical practice.

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13_Fedorova_152-157.pdf560.97 KB

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