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Anastasia I Ryzhkova,1,2 Margarita A Sazonova,1,3 Vasily V Sinyov,1 Elena V Galitsyna,4 Mariya M Chicheva,4 Alexandra A Melnichenko,4 Andrey V Grechko,5 Anton Yu Postnov,1 Alexander N Orekhov,3,6 Tatiana P Shkurat4 1Laboratory of Medical Genetics, National Medical Research Center of Cardiology, Moscow, Russian Federation; 2Department of Virology, K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology-MVA, Moscow, Russian Federation; 3Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation; 4Department of Genetics, Southern Federal University, Rostov-on-Don, Russian Federation; 5Federal Research and Clinical Center of Reanimatology and Rehabilitology, Moscow, Russian Federation; 6Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow Region, Russian Federation Abstract: There are several types of mitochondrial cytopathies, which cause a set of disorders, arise as a result of mitochondria’s failure. Mitochondria’s functional disruption leads to development of physical, growing and cognitive disabilities and includes multiple organ pathologies, essentially disturbing the nervous and muscular systems. The origins of mitochondrial cytopathies are mutations in genes of nuclear DNA encoding mitochondrial proteins or in mitochondrial DNA. Nowadays, numerous mtDNA mutations significant to the appearance and progress of pathologies in humans are detected. In this mini-review, we accent on the mitochondrial cytopathies related to mutations of mtDNA. As well known, there are definite set of symptoms of mitochondrial cytopathies distinguishing or similar for different syndromes. The present article contains data about mutations linked with cytopathies that facilitate diagnosis of different syndromes by using genetic analysis methods. In addition, for every individual, more effective therapeutic approach could be developed after wide-range mutant background analysis of mitochondrial genome. Keywords: mitochondrial cytopathy, mitochondrial dysfunction, mtDNA mutation, mitochondrial gene mutation

Transforming growth factor β1 (TGF-β1) plays an important role in the pathogenesis of many allergic diseases, including atopic dermatitis (AD). Objective: to study the role of TGF-β1 in the pathogenesis of AD in children. Materials and methods. A survey was conducted of 34 patients with AD and 20 healthy children. TGF-β1 in serum were determined by ELISA using kits of Human TGF beta1 Platinum ELISA. Definition Arg25Pro gene polymorphism of TGF β1 was carried out using allele-specific polymerase chain reaction. Results. It was found that patients with AD showed a significant increase in the concentration of TGF-β in the serum (222,37±68,58 PG/ml) compared with the control group (3,03±0,41 ng/ml) [p = 0.001]. The concentration depends on the severity and duration of the illness. Frequency of genotypes for the polymorphism Arg25Pro TGF β1 gene among patients with AD had significant differences from the control group (p < 0.05). Moreover, among patients who are heterozygotes for the gene Arg25Pro TGF β1, was significantly more observed moderate (77.78 %) and severe (33,33%) the course of the disease. Conclusion. The obtained results confirm the importance of TGF-β1 in the pathogenesis of AD.

Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of asthma. It activates neoangiogenesis, thus contributing to disruption of the microcirculation in the bronchi and increasing the intensity of exposure to the elements of the inflammatory cascade. So, the goal of this research was to evaluate the role of C-634G VEGFA gene polymorphism in the pathogenesis of childhood asthma. In the analysis of the blood no statistically significant differences has been revealed in the genotype frequencies and allele on investigated polymorphism between the control group of children and the group of children with asthma. The most frequently registered one is homozygous polymorphism of VEGFA gene. The influence of the polymorphic C-634G of VEGFA gene on the concentration of serum IgE is not revealed.

Early stages of individual development are defined by active cell division and differentiation processes. Intercellular signaling molecules as well as proliferation control and DNA stabilizing factors act as basic functional groups. Changes in genome stability maintaining genes functioning can cause the mutation number increase during blastomeric cleavage and differentiation. Thereby the goal of current work was to investigate the frequencies of cell cycle and DNA reparation control genes polymorphic variants in women with normally progressing pregnancies and in women with first trimester pregnancy loss. The present case-control study included 151 women with spontaneous abortion and 134 women with normally progressing pregnancies. Polymorphisms Pro72Arg in TP53, Asp148Glu in APEX1 and Lys751Gln in ERCC2 were detected by allele-specific PCR. When analyzed separately, the allele and genotype distributions of the polymorphisms in the two groups were similar. However, in MDR analysis the interaction between the genotypes TP53, APEX1, XPD showed to be associated to early pregnancy loss.

The involvement of GDF15 protein in modulating the processes of cellular migration and adhesion, tissue remodeling and inflammatory responses suggests that this factor may be of high importance for pregnancy establishment and its further maintenance. Analyzing pregnancy-associated dynamics of the factor confers a valuable addition to the case-control studies and can help advance our understanding of the fundamentals of the factor’s involvement in pregnancy. However, as seen from the systematic literature review presented in this paper, current data set significant questions on roles of GDF15 in pregnancy. Additionally, a significant controversy is seen in the literature regarding the gestational dynamics of GDF15. Thus, we tried to contribute to the field by assessing the dynamics of serum GDF15 protein in the course of the physiological human pregnancy. We found that serum maternal GDF15 levels increase by almost two orders of magnitude with progression of pregnancy from the mid-first trimester towards the early second trimester and then towards the term. These data were further compared with those found in the literature.

Background: This study aimed to evaluate diagnostic possibilities of the high-resolution carotid ultrasonography for determining early manifestations of atherosclerosis taking into account gender and lipid profile differences of patients. Patients and methods: In this case-control setting, we included 431 subjects aged 55 to 79 years with no history of hypertension, ischemic heart disease, heart attack, stroke and other cardiovascular diseases. Non-invasive assessment of carotid intima-media thickness (CIMT) was held by high-resolution carotid ultrasonography. Results: We detected the atherosclerotic lesions in more than 50% of the patients. The appearance of atherosclerotic plaques in carotid arteries was associated with gender and alterations in the lipid spectrum of blood. Conclusion: The high-resolution carotid ultrasonography combined with blood lipid spectrum test could be considered as a screening method to reveal early atherosclerosis.

Objectives: In this study, we examined the relationship between the AGT gene M235T and T174M polymorphisms and CHD risk in Rostov population. Material and Methods: We studied two groups of patients with clinical and coronary angiography evidence of CHD and age- and gender-matched controls, respectively. AGT gene M235T and T174M polymorphisms were analyzed by polymerase chain reaction. Results: The frequency distribution of AGT (M235T) genotypes among patients and controls (M235T: 28.5% and 16.2%; 235T: 22.4% and 7.3%, respectively) was statistically different (P = 0.03 and 0.001, respectively). CHD odds ratio associated with M235T heterozygotes and 235T homozygotes were 2.63 (1.1-6.1) and 4.88 (1.7-13.8), respectively. Conclusion: This study demonstrates the contribution of AGT gene M235T polymorphism, but not the AGT (T174M), to the presence of CHD risk in Rostov population. Genetic association studies involving very large sample size are needed to provide conclusive evidence on the effects of the AGT gene and other genes within the RAS system on risk of CHD.

This is a mini-review capturing the views and opinions of selected participants at the 2021 IEEE BIBM 3rd Annual LncRNA Workshop, held in Dubai, UAE. The views and opinions are expressed on five broad themes related to problems in lncRNA, namely, challenges in the computational analysis of lncRNAs, lncRNAs and cancer, lncRNAs in sports, lncRNAs and COVID-19, and lncRNAs in human brain activity.

Several maternal genetic variations are known to play an important role during pregnancy since they can affect mother health and/or fetal growth. The frequency of these variants is variable among different populations. This study aimed to investigate thrombophilia, folate metabolism and hypertension genetic variants in reproductive age women of Rostov region (Russia) and then assess their linkage disequilibrium (LD) and heterogeneity among populations. A total of 3108 reproductive age women were included (33.75 ± 5.13 years). Twenty-one genetic variants were detected with RT-PCR. LD was tested according to (D') coefficient and p value. The highest frequency of mutant allele in studied population was as follows: PAI-1 rs1799768, MTRR rs1801394, AGT rs699, and AGTR2 rs1403543. We showed a high possibility of coinheritance of MTHFR rs1801133 with rs1801131 and AGT rs699 with rs4762 (D'=0.992 and 0.999, respectively). In addition, comparative analysis showed F7 rs6046, FGB rs1800790, MTR rs1805087, and AGT rs699 significantly more frequent among Rostov females by 1.3-1.5 times than European. MTHFR rs1801133, ADD1 rs4961, AGTR2 rs1403543, NOS3 rs2070744, and rs1799983 were with higher frequencies in Europeans than those in the studied group. Our data could be used as a reference for further associative studies of targeted genetic variations in different pregnancy complications specifically in this population., (© 2023 University College London (UCL) and John Wiley & Sons Ltd.)

Obesity develops largely due to genetic factors, with the genetic polymorphism of lipid metabolism enzymes being of particular importance. However, it is still unclear how the genetic variants of one of the key enzymes in lipid transport, lipoprotein lipase (LPL), are associated with the endocrine function of mesenchymal tissues in obesity. The current study was aimed at the investigation of the LPL rs328 gene variant association with adipokines and myokines levels, as well as lipid metabolism indices in the blood of children and adolescents of both genders with obesity. We found that LPL polymorphism rs328 is not characterized by the differences in the levels of hormones, adipokines, and myokines and in the blood of healthy children and adolescents; however, it significantly affects these indices during obesity in gender-dependent manner. The shifts in hormones, adipokines, and myokines manifest mostly in the obese individuals with Ser447Ser genotype rather than with 447Ter genotype. Obese boys homozygous for Ser447Ser have more elevated leptin levels than girls. They also demonstrate lower adiponectin, apelin, prolactin, and osteocrine levels than those in obese girls with the same genotype. The gender-based differences are less pronounced in individuals with 447Ter genotype than in the homozygotes for 447Ser. Thus, we conclude that the polymorphism rs328 of the lipoprotein lipase gene is accompanied by the changes in hormones, adipokines, and myokines levels in the blood of children and adolescents with obesity in gender-dependent manner., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2023 Alexander V. Shestopalov et al.)

Long non-coding RNAs (lncRNAs) play important roles in the maintenance of metabolic homeostasis. Recently, many studies have suggested that lncRNAs, such as Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and Imprinted Maternally Expressed Transcript (H19), might participate in the pathogenesis of metabolic disorders such as obesity. We conducted a case-control study with 150 Russian children and adolescents aged between 5 and 17 years old in order to assess the statistical association between the single nucleotide polymorphisms (SNPs) rs3200401 in MALAT1 and rs217727 in H19 , and the risk of developing obesity in this population. We further explored the possible association of rs3200401 and rs217727 with BMI Z-score and insulin resistance. The MALAT1 rs3200401 and H19 rs217727 SNPs were genotyped using Taqman SNP genotyping assay. The MALAT1 rs3200401 SNP was identified as a risk factor for childhood obesity ( p < 0.05) under the dominant and allelic models, and the CT heterozygous genotype was associated with the risk of increased BMI and with insulin resistance. The H19 rs217727 SNP had no significant association with obesity risk (all p > 0.05). Our findings thus suggest that MALAT1 SNP rs3200401 is a potential indicator of obesity susceptibility and pathogenesis in children and adolescents.

Glucocorticoid therapy is widely used in the treatment of various pathologies. Sensitivity to glucocorticoids  (GC) has a serious impact not only on the effectiveness of their action, but also on the severity of side effects, the formation of risk factors and the development  of cardiovascular diseases (CVD). Variability of sensitivity to GC causes different phenotypes and severity of metabolic disorders underlying  CVD. Among  them, one can distinguish  a decrease in muscle mass and strength, obesity, glucose and lipid metabolism impairment, and others. Glucocorticoids carry out their effects by binding to the glucocorticoid receptor (GR), and therefore this is considered a critical point in their action. This review presents data on the significance of the glucocorticoid  receptor structure, examines the main single nucleotide polymorphisms (SNP) of the NR3C1 gene associated with hypersensitivity  or relative resistance to glucocorticoids  in the context of metabolic disorders and the development of CVD. The association of the four most studied SNP of the GR gene with metabolic risks is described in detail: BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), GR-9ß (rs6198). Their determination can contribute to clarifying the prognosis of both the effectiveness of GC and the development of metabolic disorders, and subsequent early correction of CVD risk factors.

We conducted this meta-analysis to estimate associations between CDKN2B antisense (CDKN2B-AS) rs2383207 polymorphism and susceptibility to atherosclerosis. A systematic literature research of Google Scholar and PubMed was performed to identify eligible studies. Overall, eight studies were included for meta-analyses. The association was assessed by statistical odds' ratio (OR) with 95% confidence interval (CI). RevMan software (Cochrane Collaboration, 5.3. Copenhagen) was used for the meta-analysis. Pooled overall analyses showed that rs2383207 polymorphism was associated with the risk of atherosclerosis in the whole population. Additional analyses by ethnicity revealed that rs2383207 polymorphism was associated with susceptibility to atherosclerosis in Asians and Caucasians. Our results suggest that rs2383207, might serve as genetic biomarkers of atherosclerosis. Further, studies will be required to confirm the observed association.

Uterine leiomyoma is the most common benign gynecological tumor in women of reproductive age. It has been diagnosed approximately in 5 to 69% of women and was symptomatic in 30% of them. The underlying pathobiology of uterine leiomyoma is not well understood yet, but it can be defined as an estrogen-dependent tumor. Thus, this meta-analysis aimed to investigate ESR1rs9340799 (XbaI, A351G), ESR1rs2234693 (Pvull, T397C), and COMT rs4680 (Val158Met) polymorphisms, which affect estrogen functioning and metabolism, in association with UL risk. According to PRISMA protocol, systematic searching of databases resulted 24 included studies. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were used to evaluate associations of the three targeted polymorphisms with uterine leiomyoma risk in dominant model of inheritance. Meta-analysis included 4969 women diagnosed with uterine leiomyoma and 4934 controls. ESR1 (XbaI, A351G) polymorphism showed no significant association with uterine myeloma risk (OR = 1.19, 95% CI 0.98-1.45, P = 0.07). ESR1 (Pvull, T397C) was associated with a higher risk of uterine leiomyoma, but only in Asian (OR = 1.78, 95% CI 1.30-2.45, P = 0.0004) and COMT (Val158Met) according to our data is significantly associated with a lower risk of leiomyoma (OR = 0.83, 95% CI 0.71-0.97, P = 0.02). Our updated meta-analysis provided statistical evidence for the protective role of COMT (Val158Met) in association with the susceptibility to uterine leiomyoma and the possible role of ESR1 (Pvull, T397C) as a risk factor of this tumor., (© 2022. Society for Reproductive Investigation.)

In the present work, a pilot creation of four cybrid cultures with high heteroplasmy level was performed using mitochondrial genome mutations m.12315G>A and m.1555G>A. According to data of our preliminary studies, the threshold heteroplasmy level of mutation m.12315G>A is associated with atherosclerosis. At the same time, for a mutation m.1555G>A, such a heteroplasmy level is associated with the absence of atherosclerosis. Cybrid cultures were created by fusion of rho0-cells and mitochondria from platelets with a high heteroplasmy level of the investigated mutations. To create rho0-cells, THP-1 culture of monocytic origin was taken. According to the results of the study, two cybrid cell lines containing mutation m.12315G>A with the heteroplasmy level above the threshold value (25% and 44%, respectively) were obtained. In addition, two cybrid cell lines containing mutation m.1555G>A with a high heteroplasmy level (24%) were obtained. Cybrid cultures with mtDNA mutation m.12315G>A can be used to model both the occurrence and development of atherosclerosis in cells and the titration of drug therapy for patients with atherosclerosis. With the help of cybrid cultures containing single nucleotide replacement of mitochondrial genome m.1555G>A, it is possible to develop approaches to the gene therapy of atherosclerosis.

Despite the fact that the role of mitochondrial genome mutations in a number of human diseases is widely studied, the effect of mitochondrial heteroplasmy in the development of cardiovascular disease has not been adequately investigated. In this study, we compared the heteroplasmy levels of mtDNA from leukocytes for m.3256C>T, m.3336T>C, m.12315G>A, m.5178C>A, m.13513G>A, m.14459G>A, m.14846G>A, m.15059G>A, m.652insG and m.1555A>G mutations in CVD-free subjects and CVD patients in samples derived from Russian and Mexican populations. It was demonstrated that heteroplasmy level of m.5178C>A was associated with CVD in Russian men, and m.14459G>A - in Russian women. Mitochondrial heteroplasmy level of m.13513G>A and m.652insG were associated with CVD in Mexican men, and only m.652insG- in Mexican women. The levels of heteroplasmy for mitochondrial mutations m.3336T>C, m.5178C>A, m.14459G>A, m.14846G>A and m.1555A>G were significantly higher in CVD-free Mexican men, and for m.3256C>T, m.3336T>C, and m.14459G>A - in CVD-free Mexican women.

Cardiovascular disease (CVD) is a leading cause of mortality worldwide. Proper mitochondrial function is necessary in tissues and organs that are of high energy demand, including the heart. Mitochondria are very sensitive to nutrient and oxygen supply and undergo metabolic adaptation to the changing environment. In CVD, such an adaptation is impaired, which, in turn, leads to a progressive decline of the mitochondrial function associated with abnormalities in the respiratory chain and ATP synthesis, increased oxidative stress, and loss of the structural integrity of mitochondria. Uncoupling of the electron transport chain in dysfunctional mitochondria results in enhanced production of reactive oxygen species, depletion of cell ATP pool, extensive cell damage, and apoptosis of cardiomyocytes. Mitophagy is a process, during which cells clear themselves from dysfunctional and damaged mitochondria using autophagic mechanism. Deregulation of this process in the failing heart, accumulation of dysfunctional mitochondria makes the situation even more adverse. In cardiac pathology, aberrations of the activity of the respiratory chain and ATP production may be considered as a core of mitochondrial dysfunction. Indeed, therapeutic restoration of these key functional properties can be considered as a primary goal for improvement of mitochondrial dysfunction in CVD. Key messages Mitochondrial dysfunction plays a crucial role in cardiovascular disease pathogenesis. Cardiovascular disease is associated with altered mithochondrial biogenesis and clearance. In cardiovascular disease, impaired mitochondrial function results in decreased ATP production and enhanced ROS formation.

Myocardial infarction is one of the clinical manifestations of coronary heart disease. In some cases, the cause of myocardial infarction may be atherosclerotic plaques which occurred in the human aorta. The association of mtDNA mutations with atherosclerotic lesions in human arteries was previously detected by our research group. In this study, we used samples of white blood cells collected from 225 patients with myocardial infarction and 239 control persons with no health complaints. DNA was isolated from the blood leukocyte samples. Then, PCR fragments of DNA were obtained. They contained the investigated regions of 11 mitochondrial genome mutations (m.5178C>A, m.3336T>C, m.652delG, m.12315G>A, m.14459G>A, m.652insG, m.14846G>A, m.13513G>A, m.1555A>G, m.15059G>A, m.3256C>T). According to the obtained results, three mutations of the human mitochondrial genome correlated with myocardial infarction. A positive correlation was observed for mutation m.5178C>A. At the same time, a highly significant negative correlation with myocardial infarction was observed for mutation m.14846G>A. One single-nucleotide substitution of m.12315G>A had a trend towards negative correlation. These mutations can potentially be useful for creating molecular/cellular models for studying the mechanisms of myocardial infarction and designing novel therapies. Moreover, these mutations can possibly be used for diagnostic purposes.

Aim. This review article describes literature sources devoted to the investigation of mitochondrial dysfunction using cytoplasmic hybrids (cybrids). The presented studies were carried out on cultures of cybrid cell lines HL60, MOL T-4, A549, 143B, HeLa, Arpe-19, HEK-293, SH-SY5Y and NT2. According to the analysis of scientific world literature, some of the most promising models for studying mitochondrial dysfunction are cell cultures without mitochondria (rho0) and cytoplasmic hybrids containing one or several mutations of mitochondrial genome. In the review scientific researches on studying biochemical and molecular cellular pathological processes in cybrid cells in various human diseases such as Alzheimer's disease and mild cognitive impairment, MERRF and MELAS syndromes, Leber's optic atrophy and Parkinson's disease were considered. Material dedicated to cybrids as potential models for the study of treatment possibilities was presented separately. Conclusion. The analyzed in the review rho0-cell cultures and cybrid lines containing mtDNA mutations may be models for the study of mitochondrial genome dysfunctions, biochemical and molecular cellular pathological processes. It is worth noting that in various cell cultures, similar tendencies are observed in functional activity changes of rho0-cell and cybrids compared with native cell lines. For example, such tendencies as reduction of oxygen consumption level, morphological changes of mitochondrial structure, resistance to apoptosis, reduction of ATP consumption level, increase in glucose consumption, activity deterioration of some respiratory chain complexes.

In the present study, the frequencies of genotypes and alleles of candidate genes with respect to polymorphisms associated with increased pregnancy loss in the first trimester of pregnancy, including MMP1–1607insG, MMP9 A–8202G, and TIMP1 С536T, were reported. The frequency of homozygotes for allele MMP9 A–8202 was increased by a factor of two among women with miscarriage in the first trimester compared to the control. Significant models of interaction of genes MMPs and TIMP1 were revealed. The genotypes of genes MMP1 (rs1799750), MMP9 (rs11697325), and TIMP1 (rs11551797) increasing the risk of pregnancy loss in the first trimester were determined.

Cardiovascular diseases are currently a basic cause of mortality in highly developed countries. The major reason for genesis and development of cardiovascular diseases is atherosclerosis. At the present time high technology methods of molecular genetic diagnostics can significantly simplify early presymptomatic recognition of patients with atherosclerosis, to detect risk groups and to perform a family analysis of this pathology. A Next-Generation Sequencing (NGS) technology can be characterized by high productivity and cheapness of full genome analysis of each DNA sample. We suppose that in the nearest future NGS methods will be widely used for scientific and diagnostic purposes, including personalized medicine. In the present review article literature data on using NGS technology were described in studying mitochondrial genome mutations associated with atherosclerosis and its risk factors, such as mitochondrial diabetes, mitochondrial cardiomyopathy, diabetic nephropathy and left ventricular hypertrophy. With the use of the NGS technology it proved to be possible to detect a range of homoplasmic and heteroplasmic mutations and mitochondrial genome haplogroups which are associated with these pathologies. Meanwhile some mutations and haplogroups were detected both in atherosclerosis and in its risk factors. It conveys the suggestion that there are common pathogenetic mechanisms causing these pathologies. What comes next? New paradigm of crosstalk between non-pharmaceutical (including molecular genetic) and true pharmaceutical approaches may be developed to fill the niche of effective and pathogenically targeted pretreatment and treatment of preclinical and subclinical atherosclerosis to avoid the development of chronic life-threatening disease.

Background and Objectives: Oxidative status-based interactomic profiling is a promising approach for fundamental integrative cell biology, diagnostics, and therapy. However, this approach has been neither utilized as a method nor tested as a tool. Thus, we aimed (1) to develop an oxidative status pathway state assessment-based analytical procedure relying on NFE2L2/AP1 pathway evaluation, and (2) to preliminarily assess its responsiveness, performance and diagnostic properties when applied to deciphering stress conditions of the academic examination period and academic term. These conditions were chosen as those representing a common model of mild, everyday-life stressors causing shifts in oxidative status., Methods: To meet the aim of the study, we performed a repetitive-measurements study collating gene expression of NFE2L2/AP1 pathway targets and controllers under the two stress conditions using semi-quantitative reverse transcription-polymerase chain reaction., Results: Surprisingly, even with some sensitivity limitations of the methods employed, a pathway state analysis approach based on a multiple target-to-controller ratio calculation was highly responsive and yielded very high receiver operating characteristics in deciphering the model stress conditions., Conclusion: Although further testing of the approach is required, the interactomic pathway activation assaying concept was preliminarily experimentally proven to be a highly promising clinical diagnostic tool that may easily be adapted for current tasks.

The sample of women with physiologic pregnancy consisting of 40 females with fetus normosomia and 8 females with fetus macrosomia were examined. The examination covered the evaluation of changes in concentration of ghrelin, somatotropin, insulin-like growth factor-I, insulin, leptin and thyroid hormones in mother and umbilical blood. In females with fetus macrosomia the changes in concentration of hormones regulating trophism, energy balance and anabolic processes in organisms of mother and fetus were detected

Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H(2) from its oxidized form that appears as a result of the antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis.

The ability of cationic plastoquinone derivative 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to modify processes of spontaneous and induced mutagenesis was studied. It is shown that daily introduction of this compound into male Wistar rats in doses of 25 and 250 nmol/kg during two weeks decreases spontaneous level of chromosome aberrations in anaphase in the eye cornea from 0.39 +/- 0.09 to 0.13 +/- 0.08 and 0.14 +/- 0.05, respectively. The level of 8-hydroxy-2'-deoxyguanosine in blood serum of the investigated animals decreases from 32.12 +/- 1.55 to 25.90 +/- 2.26 and 25.76 +/- 1.50 ng/ml, respectively. These facts indicate that the decrease in spontaneous clastogenesis is caused by decreased level of DNA damage by endogenous reactive oxygen species. A higher dose of SkQ1 also decreases to control level chromosome aberrations caused by oxygen under pressure of 0.5 MPa for 60 min. It is also shown in experiments with bacterial biosensors that SkQ1 is able to efficiently protect cells against genotoxic effect of UV radiation at 300-400 nm.

Influence of infrared cold laser emission (IRCL) on the dynamic equilibrium between lipid peroxidation and tension of the antioxidant defense system in rat's tissues (blood, brain, retina, cornea) was evaluated in animals with circulatory cerebral hypoxia induced by occlusion of the left carotid artery. Tissues of white rats were examined for IRCL effects on hemiluminescence, malonic dialdehyde, SOD and catalase activities on the background of circulatory cerebral hypoxia. Data of the experiment evidenced an antioxidant effect of posthypoxic IRCL therapy as it reduces intensity of the free radical processes in plasma, cerebral tissues and retina. The experiment demonstrated the IRCL ability to modulate LPO, to stiffen the antioxidant defense system in the event of eye diseases originated from circulatory hypoxia of the ocular analyzer.

Effects of infrared cold laser radiation (IRCLR) on mutagenesis and proliferation of the corneal epithelium were studied with laboratory white mice subjected to instigated circulatory hypoxia of the brain. The experiment was to reveal whether IRCLR influences the frequency of chromosomal rearrangements and to allow calculation of the corneal cells mitotic index for circulatory brain hypoxia. Laser radiation was shown to reconstitute the normal frequency of chromosomal aberrations as well as the mitotic cycle in epithelial cells of the mice cornea. Data of the experiment are promising from the standpoint of antihypoxic use of IRCLR in ophthalmology.

The paper deals with the impact of infrared low-intensity laser radiation (IRLILR) on a mutation process and the proliferative activity of the animal cornea during stimulation of circulatory brain hypoxia. During an experiment on laboratory albino rats, IRLILR was studied for its impact on the level of chromosomal rearrangements and the mitotic index in the corneal cells was calculated in circulatory brain hypoxia. Laser exposure during stimulation of circulatory brain hypoxia favors normalization of the level of chromosomal aberrations and a mitotic cycle in the rat corneal epithelial cells. The experimental findings suggest that IRLILR may be used in ophthalmological care for antihypoxic purposes.

Effects of 24-hr breathing air mixtures containing xenon (XBM) and krypton (KBM) were compared in terms of hormonal status, and blood biochemical indices and morphology in laboratory animals. Some changes observed in blood and hormone indices could be a nonspecific adaptive response. Hence, we should elicit whether these effects are quickly reversible or long. For several indices krypton was a more favorable factor than xenon. However, some of its effects invite to delve into effects of different krypton concentrations on organism.

A historical review of allantoin research is presented. An increased allantoin level in the trophoblast and serum of pregnant women has been demonstrated. Allantoin concentration decreased in placental tissues and increased in the serum in developing placental insufficiency.

The purpose was to look into the effects of 24-hr. exposure in a normoxic air-argon environment (AAE) on the epitheliocyte proliferative system, i.e. chromosomal aberrations dynamics and cornea proliferative activity, in laboratory mice. Argon was found to significantly decrease the percentage of spontaneous mutations in cells and, probably, to induce reversible inhibition of cell division. Subsequent experiments may not only disclose the still unknown properties and advantages of argon but also shed light on cell mechanisms triggered by the noble gases in general.

Polymorphism of Shereshevsky-Turner syndrome (STS) was studied in 233 patients who were examined at medical genetic services of the Research Institute of Obstetrics and Pediatrics (Rostov-on-Don) and Rostov Regional Hospital from 1978 to 1998. The subjects examined were residents of the Rostov oblast (administrative region) (RO) and some settlements in the northern Caucasus (NC). The mean incidence rate of STS was 3.8 per 10,000 newborns in this region in the period studied. Most STS cases were accounted for by the X trisomy (60 and 66.6% in the RO and NC, respectively). The mosaic form of STS was found in 25% of cases in both RO and NC. Other cytogenetic forms were found in 13.5 and 8.33% of patients from the RO and NC, respectively. The clinical polymorphism of STS, dynamics of its manifestation during ontogeny, and anthropometric parameters of the patients were studied. The effects of the age of parents, the season and month of conception, occupational hazards at the parents' workplaces, and the place of residence on the risk of STS were analyzed. Factor analysis was used to determine the sets of the main clinical signs characteristic of different STS cytogenetic forms in the RO and NC populations.

We studied the level of lipid peroxidation and the activity of antioxidant enzymes (superoxide dismutase and catalase) in various tissues of adult Xenopus laevis after an initial exposure to hyperbaric oxygenation at the developmental stage 38. We have found that irrespective to the mode of treatment, the level of lipid peroxidation and activity of antioxidant enzymes in the brain, lungs, and blood of these animals were higher as compared to control animals. We demonstrate that, after the exposure of adult animals to hyperoxia, if they were earlier subjected to hyperbaric oxygenation (0.2 MPa) at stage 38, there was no intensification of lipid peroxidation or changes in the activity of superoxide dismutase and catalase. In adult animals initially subjected to hyperbaric oxygenation at the same stage of development but at the pressure--0.7 MPa, the second exposure to hyperoxia led to a drastic intensification of lipid peroxidation in the brain; in some animals, an increased level of lipid peroxidation products in the lungs was observed.

The levels of tissue antioxidant uric acid in relation to chromosomal aberrations and leaving erythrocytic chromatin were determined in the spleen, bone marrow and blood of rats exposed to toxic hyperoxia (0.7 MPa O2, convulsions). Considerable growth of the uric acid levels and the rate of chromosomal aberrations in all tissues was observed within the first hours after treatment. The article discusses mechanisms of uric acid formation, redistribution and disintegration in tissues under extreme conditions. Specificity of the uric acid metabolism in tissues was shown with the help of the correlation analysis of uric acid concentrations. Inverse relationship between uric levels and chromosomal impairments noted in some cases permits to make a supposition about genoprotective properties and adaptogenic role of uric acid during oxidative stress.

The effect of different regimens of hyperbaric oxygenation (0.2 MPa and 0.4 MPa for 1 or 3 hour) has been investigated in the culture of diploid and triploid human fibroblasts, picked out from aborts. The quantity of marked thymidine in nuclei of cells depends on both the value of pressure and time of treatment. HBO causes stimulant effect under 3-hour treatment. Influence of different regimens of HBO on human fibroblasts reveals high resistance of triploid to oxidative stress in comparison with diploid fibroblasts.

Mice were exposed to helium-oxygen conditions (3.6 MPa, 5 sessions). Compression lasted for 6 h, isopression - 5 days, decompression - 18 h. The interval between sessions was 10 days. The present study has revealed that hyperbary increases the level of diene conjugates and shift bases in the erythrocyte membranes and plasma only after 1 and 3 sessions. Superoxide dismutase is suppressed after 3 and 5 sessions. Catalase activity remains unchanged. The effect of hyperbary on the induction of chromosome aberrations in bone marrow, cornea of the eye and germinal tissues has been studied. Bone marrow has been detected as more sensitive to hyperbary. Induction of aberrations in bone marrow cells has observed for 3 months.

Cytogenetical consequences of high oxygen pressure action (HOB) have been studied in professional and nonprofessional divers after deepening. Blood samples of subject from both groups were treated with HBO in vitro to compare individual reaction of the somatic cells genome to HOB. The present study reveals that HBO increases the level of chromosome aberrations, and individual response to HBO differs. There is a correlation between the level of chromosome aberrations in vivo and in vitro. This indicates that blood treatment in vitro can reveal the sensitivity of the genome in human before HBO treatment. According to the data in vitro 2 groups of the genome response to HBO: up to 20% and higher than 20% aberrations are distinguished.

Patients with several diseases have been examined for detection of chromosome aberrations in peripheral blood cells after 10 sessions of hyperbaric oxygen (HBO) at 0.15-0.20 MPa for 40 min. The present study reveals that HBO increases the level of chromosome aberrations, and that individual reactions to HBO differ. Pure erythrocytes treated with high-pressure oxygen (HBO) at 0.7 MPa for 1 h are clastogenic for intact syngeneic lymphocytes. The effect of HBO (0.3 MPa, 5 sessions of 1 h daily) on induction of chromosome aberrations in somatic cells and germinal tissues of rat males has been studied. Induction of aberrations in bone marrow cells after HBO was seen for 3 months. In lymphocytes of patients, it was seen for 9 months. Chromosome rearrangements at the first meiotic division were detected only 90 days after exposure. HBO affects neither the functional nor the morphological condition of gonads and does not induce dominant lethals. It is proposed that a high quantity of chromosome breaks in cells of somatic tissues is an adaptive reaction of organisms to HBO.

This paper presents cytogenetic data obtained from peripheral blood of patients who were treated with hyperbaric oxygenation (HBO) at 0.15-0.2 MPa for 40 min daily during 10 days. The patients showed a significant increase of chromosome aberrations mainly caused by chromatid and chromosome breaks. The level of induced aberrations showed individual variations. These results suggest that HBO may have an indirect effect on the genetic apparatus of human somatic cells.

The effect of higher oxygen pressures (0.3 MPa, 5 sessions 1 h each daily) on induction of chromosomal aberrations in somatic cells and germinal tissues of rat males has been studied. Appearance of aberrations in bone marrow cells after HBO was recorded for 3 months, in cells of eye cornea epithelium--during 3 weeks after the end of sessions. Chromosome rearrangements in the first meiotic division were detected only 90 days after sessions. HBO affects neither functional nor morphological conditions of gonads and induces no dominant lethals. It is suggested that mutagenesis in bone marrow cells is an adaptive process, preventing mutagenic consequences of HBO in the cells of germinal tissue.

High pressure of oxygen induces chromosomal rearrangements in metaphases of human peripherical blood cells treated in vitro. An increase in the percentage of rearrangements was detected in the third mitosis, due mainly to chromatid breaks. The data of cytogenetical analysis of lymphocytes of human blood treated in vivo at 3 ata for 30 min are presented. A differential character of distribution spectrum of chromosomal aberrations induced after in vivo and in vitro treatment was noted. Some unusual alterations in chromosome morphology are described, namely, solid, not stained clear lense-like bodies surrounded by chromatin and localised in the long arm of chromatids.

The effect of hyperbaric oxygenation was investigated in bone marrow cells of rats, at prolongated and fractionated regimes usually employed in medicine. As a result of this study, it was pointed out that fractionated treatment of animals at I ata I h during 5 and 10 days affects the rats cytogenetically and causes several chromosomal damages. Prolongated treatment with high pressure oxygen was of a less mutagenic activity. The data obtained suggest nondirect action of this mutagen on the genetic apparatus.