Genetic polymorphism of Y-chromosome in Kazakh populations from Southern Kazakhstan.

BACKGROUND: The Kazakhs are one of the biggest Turkic-speaking ethnic groups, controlling vast swaths of land from the Altai to the Caspian Sea. In terms of area, Kazakhstan is ranked ninth in the world. Northern, Eastern, and Western Kazakhstan have already been studied in relation to genetic polymorphism 27 Y-STR. However, current information on the genetic polymorphism of the Y-chromosome of Southern Kazakhstan is limited only by 17 Y-STR and no geographical study of other regions has been studied at this variation. RESULTS: The Kazakhstan Y-chromosome Haplotype Reference Database was expanded with 468 Kazakh males from the Zhambyl and Turkestan regions of South Kazakhstan by having their 27 Y-STR loci and 23 Y-SNP markers analyzed. Discrimination capacity (DC = 91.23%), haplotype match probability (HPM = 0.0029) and haplotype diversity (HD = 0.9992) are defined. Most of this Y-chromosome variability is attributed to haplogroups C2a1a1b1-F1756 (2.1%), C2a1a2-M48 (7.3%), C2a1a3-F1918 (33.3%) and C2b1a1a1a-M407 (6%). Median-joining network analysis was applied to understand the relationship between the haplotypes of the three regions. In three genetic layer can be described the position of the populations of the Southern region of Kazakhstan-the geographic Kazakh populations of Kazakhstan, the Kazakh tribal groups, and the people of bordering Asia. CONCLUSION: The Kazakhstan Y-chromosome Haplotype Reference Database was formed for 27 Y-STR loci with a total sample of 1796 samples of Kazakhs from 16 regions of Kazakhstan. The variability of the Y-chromosome of the Kazakhs in a geographical context can be divided into four main clusters-south, north, east, west. At the same time, in the genetic space of tribal groups, the population of southern Kazakhs clusters with tribes from the same region, and genetic proximity is determined with the populations of the Hazaras of Afghanistan and the Mongols of China.

Determination of Chemical Composition and Antimicrobial Activity of the CO2 Extract of Eryngium planum L.

The article presents parameters for obtaining a carbon dioxide extract from the subterranean part of Eryngium planum that contains a valuable set of organic substances and has a certain antimicrobial effect. Methods. Raw materials were collected in the Almaty region (Republic of Kazakhstan). The CO2 extract of Eryngium planum herbs was obtained under subcritical conditions. A gas chromatograph with a mass spectrometric detector was used to determine the compositional breakdown of the extract. Antimicrobial activity was determined by two methods: the micromethod of serial dilutions and the disk-diffusion method. Three microbial test strains were used: Staphylococcus aureus ATCC 6538-P, Escherichia coli ATCC 8739, and Candida albicans ATCC 10231. Results. To extract biologically active substances from the subterranean part of Eryngium planum L., we have chosen carbon dioxide extraction technology, a technology for processing carbon dioxide (CO2) raw materials, which allows us to extract various substances in high concentrations. Carbon dioxide extraction technology is an effective and environmentally safe way to isolate various biologically active substances contained in medicinal plant raw materials. In the composition of the CO2 extract of Eryngium planum L. 43 components were identified, the main of which are α-linolenic acid, 8.30%; myristic acid, 6.40%; caryophyllene, 6.92%; spatulous, 6.62%; and other main identified compounds and their percentage. Conclusions. The study showed that the CO2 extract of Eryngium planum L. contains biologically active compounds that have a pronounced antimicrobial effect against clinically significant microorganisms, such as Escherichia coli, Staphylococcus aureus, and Candida albicans.

Genetic Polymorphism of 27 Y-STR Loci in the Western Kazakh Tribes from Kazakhstan and Karakalpakstan, Uzbekistan.

Data on the genetic polymorphism of 27 Y-STR in Kazakhs of the Junior Zhuz has been presented and analyzed in relation to forensic features. A total of 464 representatives of the Western Kazakh tribes of Kazakhstan (Western Kazakhs, n = 405) and Uzbekistan (Karakalpakstan Kazakhs, n = 59) were examined by the Yfiler Plus set. The data are available in the YHRD under accession numbers YA006010 and YA006009. Genetic analysis (AMOVA and MDS) did not show significant differences between the two groups (Kazakhstan and Karakalpakstan Kazakhs) in terms of Y-chromosome diversity. Both groups are characterized by haplogroup C2a1a2 as a founder effect, which dominated two of the three tribes: Alimuly (67%), Baiuly (74.6%), and Zhetiru (25.8%). At the same time, the phylogenetic network for each tribe found its own clusters within C2a1a2. Western Kazakhs and Karakalpakstan Kazakhs present high values of unique haplotypes (84.44% and 96.61%), discrimination capacity (90.37% and 98.30%), and haplotype diversity (0.9991 and 0.9994). A set of 27 Y-STR loci distinguishes closely related individuals within the Western Kazakh tribes quite well. It is suitable for forensic application, and is also optimal for population genetics studies.

ITGA2 Gene Polymorphism Is Associated with Type 2 Diabetes Mellitus in the Kazakhstan Population.

Background and Objectives: Nowadays, every tenth adult in the world suffers from diabetes mellitus (DM). Diabetic retinopathy (DR) is the most common microvascular complication of type 2 DM (T2DM) and a leading cause of acquired blindness in middle-aged individuals in many countries. Previous studies have identified associations of several gene polymorphisms with susceptibility to microvascular complications of DM in various worldwide populations. In our study, we aimed to test the hypothesis of the associations of single nucleotide polymorphisms (SNP) of the VEGF (-2549I/D), RAGE (-429T/C and -374T/A), TCF7L2 (rs7903146), and ITGA2 (BglII) genes with a predisposition to DR among T2DM patients in the Kazakhstan population. Materials and Methods: We conducted a case-control study comparing the genotype distribution and allele frequencies between groups of DR patients (N = 94), diabetic patients without DR (N = 94), and healthy controls (N = 51). Genotypes were identified using the PCR-RFLP method. Results: In all cases, the genotype distribution corresponded to the Hardy-Weinberg equilibrium. The groups of diabetic patients with and without DR did not significantly differ in the genotype distribution of the SNPs studied. Differences between both groups of diabetic patients and healthy controls in four out of five SNPs were also not significant. At the same time, both groups of diabetic patients differed significantly from healthy controls in genotype distribution (p = 0.042 and 0.005, respectively) and allele frequencies (p = 0.021 and 0.002, respectively) of the BglII polymorphism in the ITGA2 gene. After adjusting for multiple comparisons, the differences between the group of diabetic patients without DR and the control group remained significant (pBonf = 0.027 for genotypes and pBonf = 0.009 for alleles). The BglII- allele was associated with diabetes: OR = 1.81 [1.09-2.99] for DR patients, and OR = 2.24 [1.34-3.75] for diabetic patients without DR. The association was also observed in the subset of Kazakhs. Conclusions: This study shows that the BglII polymorphism in the ITGA2 gene can be associated with T2DM but not with DR. According to our data, the risk allele for diabetes is the wild BglII- allele, and not the minor BglII+, which is considered as risky for DR.

Bioinformatics Analysis of the Interaction of miRNAs and piRNAs with Human mRNA Genes Having di- and Trinucleotide Repeats.

The variability of nucleotide repeats is considered one of the causes of diseases, but their biological function is not understood. In recent years, the interaction of miRNAs and piRNAs with the mRNAs of genes responsible for developing neurodegenerative and oncological diseases and diabetes have been actively studied. We explored candidate genes with nucleotide repeats to predict associations with miRNAs and piRNAs. The parameters of miRNAs and piRNA binding sites with mRNAs of human genes having nucleotide repeats were determined using the MirTarget program. This program defines the start of the initiation of miRNA and piRNA binding to mRNAs, the localization of miRNA and piRNA binding sites in the 5'-untranslated region (5'UTR), coding sequence (CDS) and 3'-untranslated region (3'UTR); the free energy of binding; and the schemes of nucleotide interactions of miRNAs and piRNAs with mRNAs. The characteristics of miRNAs and piRNA binding sites with mRNAs of 73 human genes were determined. The 5'UTR, 3'UTR and CDS of the mRNAs of genes are involved in the development of neurodegenerative, oncological and diabetes diseases with GU, AC dinucleotide and CCG, CAG, GCC, CGG, CGC trinucleotide repeats. The associations of miRNAs, piRNAs and candidate target genes could be recommended for developing methods for diagnosing diseases, including neurodegenerative diseases, oncological diseases and diabetes.

Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration.

There are different modalities of intercellular communication governed by cellular homeostasis. In this review, we will explore one of these forms of communication called extracellular vesicles (EVs). These vesicles are released by all cells in the body and are heterogeneous in nature. The primary function of EVs is to share information through their cargo consisting of proteins, lipids and nucleic acids (mRNA, miRNA, dsDNA etc.) with other cells, which have a direct consequence on their microenvironment. We will focus on the role of EVs of mesenchymal stem cells (MSCs) in the nervous system and how these participate in intercellular communication to maintain physiological function and provide neuroprotection. However, deregulation of this same communication system could play a role in several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, multiple sclerosis, prion disease and Huntington's disease. The release of EVs from a cell provides crucial information to what is happening inside the cell and thus could be used in diagnostics and therapy. We will discuss and explore new avenues for the clinical applications of using engineered MSC-EVs and their potential therapeutic benefit in treating neurodegenerative diseases.

Chemical Composition and Antimicrobial Activity of Subcritical CO2 Extract of Lepidium latifolium L. (Brassicaceae).

The genus Lepidium L. from Brassicaceae Burnett. family covers over 150 species with an almost cosmopolitan spread. In Kazakhstan, 21 species are described, of which four species are characterized by medicinal properties (L. crassifolium Waldst. et Kit., L. perfoliatum L., L. ruderale L., and L. latifolium L.), used in folk medicine as means of antibacterial, irritant, laxative, antitumor, analgesic, and anthelmintic action. Methods. Raw materials were collected from Almaty region (Republic of Kazakhstan). Lepidium latifolium L. herb's carbon dioxide extract (CO2 extract) was obtained by subcritical carbon dioxide extraction. A gas chromatograph with a mass spectrometric detector was used to determine the component composition of the extract. Antimicrobial activity was determined by two methods: the micromethod of serial dilution and the disc-diffusion method. Four microbial test strains were used: Staphylococcus aureus ATCC 6538-P, Escherichia coli ATCC 8739, Klebsiella pneumonia ATCC 10031, and Candida albicans ATCC 10231. Results. The technology of carbon dioxide extraction has undoubted advantages over traditional methods of extraction: it has a controlled selectivity in relation to groups of biologically active substances, allows deep extraction, and maximizes the release of rich complexes of compounds contained in plants. In this study, firstly, the CO2 extract was obtained under subcritical conditions from the aerial part of L. latifolium L., and the composition was determined. Hexane was the best solvent for CO2 extract, and 40 components were identified. Screening of antimicrobial activity of the L. latifolium's CO2 extract showed the essential activity of all clinically significant strains tested: Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Candida albicans. Conclusions. This research showed that the CO2 extract of the raw material of Lepidium latifolium L. contains biologically active compounds exhibiting an essential antimicrobial effect, and therefore it is possible to recommend for the development of various drugs for use in medical practice.

Combination of circulating miR-145-5p/miR-191-5p as biomarker for breast cancer detection.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. At present, there is a need to search for new, accurate, reliable, minimally invasive and cheap biomarkers in addition to existing methods for the diagnosis and prognosis of BC. The main goal of this study was to test the diagnostic value of six circulating miRNAs in Kazakh women. MATERIALS AND METHODS: TaqMan-based miRNA profiling was conducted using plasma specimens from 35 BC women patients and 33 healthy women samples (control group). RESULTS: The level of all seven miRNAs (including endogenous control) normalized by synthetic cel-miR-39 were significantly elevated in the group of BC patients. Normalization using miR-222-3p as endogenous control reduced differences in level of miRNAs between groups; as a result, only three miRNAs were significantly upregulated in the group of BC patients-miR-145-5p (P = 6.5e-12), miR-191-5p (P = 3.7e-10) and miR-21-5p (P = 0.0034). Moreover, ROC analysis showed that the use of miR-145-5p and miR-191-5p, both individually (AUC = 0.931 and 0.904, respectively) or in combination (AUC = 0.984), allows to accurately differentiate BC patients from healthy individuals. CONCLUSIONS: Two plasma miRNAs-miR-145-5p and miR-191-5p-are potential biomarkers for diagnosis of BC in the Kazakh population. The findings need to be further substantiated using a more representative sample.

Effect of lithium carbonate on autophagy and proliferative activity of isolated hepatocytes.

The hepatocytes were cultivated in the presence of lithium carbonate (LC) for drugs testing or possible source for transplantation in the treatment of hereditary or terminal liver diseases. The LC, as an inducer of autophagy, is a promising drug for maintaining cell homeostasis and has a significant effect on the ultrastructural organization of hepatocyte cells. Within current investigation, new mechanisms of the biological effects of lithium and the ultrastructural analysis of the primary culture of hepatocytes were studied via flow cytofluorometry, light, and electron microscopy methods. Obtained results demonstrate the absence of the toxic effect of 5 mM of LC on the primary hepatocyte culture. In addition, LC does not block the cell cycle at the G0/G1 stage after 24 h of hepatocyte cultivation and promotes the preservation of their viability by 48 h of the experiment. Moreover, LC does not stimulate hepatocyte apoptosis, induces autophagy and the preserves the proliferative activity of hepatocytes.