Issue 3 | September 2024
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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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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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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This work is devoted to the study of mRNA expression patterns and the relative content of selenoproteins in mice with TAA-induced liver fibrosis and TAA-induced HCC. The main objective of this study is to evaluate the activation or suppression of selenoprotein synthesis during HCC progression and directly in the tumor in one TAA-treated mouse model, which is a pilot study and allows us to closely approximate the situation observed during HCC progression in vivo. It was found that as HCC progresses, there is an increase in the mRNA expression of thioredoxin reductases TXNRD1 and TXNRD2, deiodinase DIO3, glutathione peroxidases GPX1, GPX2, GPX4, and an inverse correlation in the expression of mRNA was characteristic of GPX3. In addition, the mRNA expression of endoplasmic reticulum resident selenoproteins: SELENOM, SELENON, SELENOT and SELENOS changed significantly. Also, in tumor liver samples and directly in the tumor itself, an increase in the expression of the selenoprotein SELENOP was recorded. The information obtained from the results of this work will significantly complement the existing data on the role of mammalian selenoproteins in various liver pathologies and in oncogenesis in general.
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The study of the severity and consequences of infectious diseases is a relevant subject of research throughout the world, which was directly demonstrated by the situation with the 2020-2023 coronavirus pandemic. In our study, we analyzed a distribution of genotypes and alleles frequency of polymorphic variants of the IL6 rs1800795, TNFA rs1800629 and LZTFL1 rs10490770 gene polymorphisms, which were previously linked to the pathogenesis of COVID-19, in populations of Burzyan Bashkirs, Sterlibashevsky Bashkirs, Permsky Bashkirs, Kazan Tatars, Chuvash, Udmurts, Mari, Komi and Mordvins. Statistically significant differences were identified in the IL6 rs1800795 between the populations of the Burzyan Bashkirs and the Mari and Komi (p < 0.05). The Sterlibashevsky Bashkirs, Permsky Bashkirs and Udmurts also statistically significantly differed from the Komi population (p < 0.05). When studying the TNFA rs1800629, statistically significant differences were identified between the populations of Sterlibashevsky and Permsky Bashkirs and the Udmurts population (p < 0.05). Analysis of the LZTFL1 rs10490770 revealed statistically significant differences only between the Udmurt and Mari populations (p < 0.05). The data indicate that despite the geographic proximity of the examined populations of the Volga-Ural region, they were able to preserve the uniqueness of their gene pool.
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The aim: determination of correlation dependence of adaptogenic defense reactions in rats in the acute phase of pain stress on laser-puncture exposure to low-intensity IR radiation. Material and methods. Four groups of rats were used in the work: "experimental", which received after the injury a 10-day course of PPBM, and three comparison groups ("intact", "no exposure" and "placebo"). The intensity of lipid peroxidation, specific activity of antioxidant enzymes, protein concentration, malonic dialdehyde content in blood plasma and erythrocytes were determined by spectrophotometric method. Microcirculation indices were evaluated according to the previous series of our studies. Emotional and behavioral reactions were studied in the "open field" test. Results. Normalization of metabolic, microcirculatory and behavioral indices was registered in the experimental group. The correlation coefficients between the microcirculation index and the data of behavioral activity under pain stress were significantly less than the correlation coefficients between oxidative stress and cognitive functions, which confirms the determining role of oxidative metabolism disturbance in the formation of cognitive disorders. Conclusion: the registered adaptation and stress-limiting effect of PPBM in conditions of experimental pain stress allows us to recommend the technology of laser acupuncture for use in complex rehabilitation of patients with pain syndrome.
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A hypothesis is proposed about the role of evolutionary relationship of retroelements with transfer RNAs (tRNAs) on their processing to form small non-coding RNAs. This is evidenced by the use of tRNA as primers for reverse transcriptase, origin of SINE2 from tRNA, use of LINE1 enzymes by tRNA for pseudogenes formation. Under the influence of RISC enzymes, tRFs are formed from tRNA, that control gene expression at the epigenetic level. Non-coding RNAs formed from transcripts of retroelements are characterized by similar properties. An assumption has been made about the functioning of a species-specific epigenetic network between such non-coding RNAs formed from retroelements and tRNAs. Decoding such a network may open up the possibility of creating new epigenetic agents for the treatment of human diseases, and will also allow us to determine mechanisms of genetic code emergence in evolution. One of the bases for this network formation may be the distribution and composition of tRNAs and retroelements in the genome. I have provided data on this network mechanisms formation, describing the similar functional properties of tRNAs and retroelements, their influence on the same targets and pathways in the human organism. I suppose that the relationship between tRNAs and retroelements arose as an integral property of living things when life arose in RNA world, where tRNAs were originally used to perform many regulatory catalytic functions, one of which was later transformed into the transfer of amino acids for protein synthesis.
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The paper presents an analysis of literature data on the characteristics of microbiocenoses across a wide range of infectious and somatic pathologies, as well as the results of our research on changes in the composition of the gastrointestinal tract microbiota in patients with various diseases. It is demonstrated that the microbiota responds consistently to any pathological changes occurring in the host organism, primarily manifested as a disruption in the balance between anaerobic (bifidobacteria, lactobacilli, bacteroids, clostridia, etc.) and aerobic components of the microbiocenosis. The predominance or suppression of specific types of microorganisms is primarily influenced by the composition of the individual's indigenous microbiota, rather than the specific pathology associated with dysbiosis.
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Background: previous studies have implicated the INSIG2 rs6726538 single nucleotide polymorphism (SNP) as a potential risk factor for cervical cancer. Our objective was to examine the correlation between this genetic variation and the vulnerability of Iraqi women to cervical cancer. Methods: this case-control study analyzed rs6726538 genotypes and allele frequencies in 109 cervical cancer cases and 109 healthy controls. Logistic regression calculated odds ratios (OR) and 95% confidence intervals (CI). The rs6726538 SNP was genotyped using tetra-primer ARMS-PCR. Results: the AT genotype occurred more frequently in cases than controls (52.2% vs 34%, OR 0.783, 95% CI 0.38-1.25, p = 0.0391). The TT genotype was less common but showed a non-significant decreased cancer risk versus AA (OR 0.336, 95% CI 0.17-0.96, p = 0.0707). The T allele was significantly higher in cases (36.3% vs 20.6% in controls, p = 0.0023), while the A allele was higher in controls (79.4% vs 63.7% in cases, p = 0.05). Conclusion: this preliminary data indicates that the rs6726538 T allele and TT genotype may be associated with increased cervical cancer risk, while the A allele and AA genotype could have a protective effect. However, larger studies are required to validate these initial findings on how this SNP may impact cervical cancer susceptibility.
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In the present study, we investigated the effect of α1-adrenergic receptor stimulation on the electrical activity of the right atrium cardiomyocytes with imposed rhythm in rats of different ages using methoxamine and methoxamine against the background of selective blockade of phospholipase C inhibitor (U-73122). Methoxamine increased the duration of the repolarization phase of the action potential. However, there were no changes in the other electrophysiological parameters studied. U-73122 markedly blocked all effects of α1-adrenoreceptor stimulation on the parameters of the electrical activity of working cardiomyocytes in 7-, 21-, and 100-day-old rats.
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Discovering alternate methods to treat cancer has been the focus of several investigations. The preventive benefits of β-glucan against liver damage, toxicity, and alteration in antinuclear antibody (ANA), alpha-fetoprotein (AFP), and anti-double strand DNA antibody (anti-dsDNA) caused by Ehrlich ascites carcinoma (EAC) are investigated in this study. A total of 40 mice weighing between 20-25 g, were divided randomly into four groups: the control group, the β-glucan group (200 mg/kg bw/day for two weeks), the EAC group, and the EAC+β-glucan group. The most recent research demonstrated that EAC damaged the liver and increased serum levels of AFP, anti-dsDNA, alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). However, compared to the control, serum total proteins and albumin levels considerably decreased. EAC therapy with β-glucan enhanced liver structure and function. As a result, it is possible that suggests that β-glucan can help prevent and treat liver toxicity.
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Mycobacterium tuberculosis, a species of pathogenic bacteria in the Mycobacteriaceae family, is the infectious agent that causes tuberculosis (TB), one of the most progressive bacterial pathogens in human history. The pathogen is the first cause of mortality linked to a single pathogen worldwide, especially in poor and developing countries. There are two clinical manifestations of disease caused by this bacterium: pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). A single nucleotide polymorphism (SNP) in the human caspase recruitment domain-containing protein 8 (CARD8) gene of TB infection plays a critical role in the disease progression. Combining this SNP with the CARD8 polymorphism increased the effect, indicating a new link between the CARD8 gene and TB infection. The present study was conducted to determine the association between the polymorphism of the CARD8 gene and EPTB infection in humans. The study included patients (males and females) infected with PTB (n = 50), and EPTB (n = 50), as well as 50 healthy individuals as a control group. Blood samples were collected from all the participants and used to isolate DNA. Using a self-designed nested tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR) assay, the genotypes in CARD8 A/T SNPs were identified. The results showed that there were no significant differences between the types of patients themselves and no significant differences between patients and healthy individuals in the results of ARMS-PCR. The findings of the present study revealed a correlation between patients with EPTB and polymorphisms in CARD8 (rs2043211).
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The potential role of proteolytic enzymes in impeding the growth of cancer by the anti-angiogenesis process has gained attention recently. This review explores proteolytic enzymes that have been studied for their capacity to obstruct the development of new blood vessels that are essential for the growth of tumors. These enzymes include matrix metalloproteinase and serine proteases. The mechanisms by which these enzymes inhibit angiogenesis including degradation of extracellular matrix proteins and inhibition of signaling pathways involved in blood vessel formation are discussed. Also, proteolytic enzymes’ possible therapeutic applications as anti-angiogenesis drugs in the treatment of cancer are highlighted.
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Background: the nucleus pulposus NP pulls on the ruptured annulus fibrosus AF, bulging the intervertebral disc IVD and releasing chemicals that may irritate nerves and cause inflammation and pain. This produces histological changes to the IVD, including less gelatinous NP, cracks and fissures, decreased matrix water content, and proteoglycan composition changes. Aim of study: this study aims to investigate the histopathological changes in the Herniated Disc HD tissue, as well as cartilage histopathology grade and stage assessment. Materials and methods: fourty tissue samples of lumbar HD obtained after the operations were kept in 10% formalin. Then all HD sections were processed, and embedded, after that, 5 μm thick glass mounted sections were stained with Hematoxylin and Eosin and Alcian blue (pH 0.02) and examined microscopically for histopathological changes and grading scoring was also conducted based on cell density, structural alterations of collagen fibers, and proteoglycan degeneration. Results: hemorrhage with fibrin deposition, mucous degeneration around chondrocyte clones and degeneration, increased chondrocyte density, expanded lacunae with degenerated chondrocytes, fiber disorientation, cleft formation, mucoid matrix changes, and inflammatory cell infiltration with fibrocyte prefiltration were the most histopathological changes in HD samples. Along with necrotic chondrocyte increase and tissue fiber alterations. Histological cell density grade indicated different-sized clones. All HD tissues revealed collagen fiber structural alterations, with gradients (52.5%) being most common. All HD samples showed mucous (proteoglycans) degradation, especially in gradients abundantly present and intermediate between 1 and 3 (45% and 42.5%). Conclusions: histopathological changes in intervertebral disc associated with HD infection.
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A varicocele is the most common rectification cause of male infertility. It is an abnormal dilation of the veins of the pampiniform plexus in the spermatic cord. It is estimated to affect 10-15% of men and adolescents. The aim of the current study was to investigate the immunological parameters, gene expression profiles, and their correlations in varicocele and non-varicocele oligospermic patients compared to healthy controls, providing insights into the molecular mechanisms underlying male infertility. A total of 120 males were involved in this study over the period from October 2023 to January 2024. Blood and semen samples were collected from patients who were diagnosed with varicocele confirmed oligospermia (40 samples) and non-varicocele oligospermic patients (40 samples), in addition to 40 apparently healthy males as control. The level of IL-18 and IL-37 was estimated in the serum of tested groups using Enzyme Linked Immunosorbent Assay (ELISA) technique. The serum levels of the pro-inflammatory cytokine IL-18 were significantly elevated in all patient groups compared with control. Interestingly, the anti-inflammatory cytokine IL-37 was also significantly increased. The gene expression of heat shock protein A2 (HSPA2) was detected using reverse transcriptase polymerase chain reaction (RT-PCR). The fold of gene expression results by RT-PCR technique revealed a significant downregulation of HSPA2 (0.3453 ± 0.311-fold) gene expression in varicocele patients and a 0.154 ± 0.13-fold decrease in non-varicocele oligospermia compared with control. However, no significant correlation was found between the expression of HSPA2 and the levels of IL-18 and IL-37.
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