Abstracts
Permanent URI for this collection
Browse
Recent Submissions
Item Open Access ИЗУЧЕНИЕ ПОЛИМОРФИЗМОВ ГЕНОВ АССОЦИИРОВАННЫХ С РАЗВИТИЕМ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ В КАЗАХСКОЙ ПОПУЛЯЦИИ(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Сейдалин, Н.К.; Бенберин, В.В.; Шаназаров, Н.А.; Жаппаров, Е.И.; Арипжанова, Г.О.; Бабенко, Д.Б.Введение. Рак молочной железы (РМЖ) является самой распространенной злокачественной опухолью у женщин. Заболеваемость РМЖ неуклонно возрастает. Распространенность, высокий индекс инвалидизации, экономические затраты на лечение, смертность – делают эту проблему не только медицинской, но и социальной. Разнообразие геномных аберраций и полученные в результате этого нарушения регуляции биологических путей, объясняют разнообразное клиническое поведение опухолей молочной железы. Определение соответствующих зародышевых мутаций остается одним из основных направлений исследований для лучшего понимания биологических эффектов этих аберраций. Методы. Исследование является проспективным, диагностическим исследованием. Сформирован перечень из 128 однонуклеотидных полиморфизмов ассоциированных с прогнозом и течением рака молочной железы в различных этнических популяциях. Проведено формирование групп пациентов в соответствии с критериями включения для забора биологического материала 500 пациенток казахской популяции с морфологически подтвержденным раком молочной железы и 500 женщин контрольной группы. Осуществлен забор биологического материала (венозная кровь) у пациентов и лиц контрольной группы. Проведено выделение ДНК из биологического материала и лабораторный анализ на наличие однонуклеотидных полиморфизмов генов в биологических образцах. Статистическая обработка результатов исследования включала в себя расчет равновесия Харди – Вайнберга, анализ ассоциации на основе обобщенных линейных моделей, анализ ассоциации между полиморфизмами и фенотипом доминантной генетической модели наследования. Результаты. В группе РМЖ, на основе логистической регрессии при использованием доминантной модели наследования с применением поправки Бонферонни была выявлена связь фенотип-генотип (использовалась поправка Бонферонни для значений P при множественном сравнении). Полиморфизмы rs2740574, rs2032582, rs2229774, rs2227945, rs121434592, rs139785364, rs1800056, rs11571746, rs2981582имели статистическую значимую (р<0.05) связь с течением РМЖ в казахской популяции при использовании доминантной модели наследования. Выводы. В группе РМЖ, на основе логистической регрессии с применением поправки Бонферонни, была выявлена связь в группе РМЖ и генетическими вариантами rs2740574, rs2032582, rs2229774, rs2227945, rs121434592, rs139785364, rs1800056, rs11571746, rs2981582при использовании доминантной модели наследования.Item Open Access TARGETED NEXT GENERATION SEQUENCING REVEALS NEW INSIGHTS INTO THE GENETIC BASIS OF INHERITED ARRHYTHMIA IN KAZAKHSTANI PATIENTS(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Akilzhanova, A.; Guelly, C.; Abilova, Zh.; Rakhimova, S.; Akhmetova, A.; Kairov, U.; Trajanoski, S.; Akilzhanova, G.; Kozhamkulov, U.; Abdrakhmanov, A.; Bekbosynova, M.Introduction:Ventricular arrhythmias are caused by mutations of ion channels and their interacting proteins. Most arrhythmia syndromes are inherited in an autosomal dominant manner, such that first-degree family members have a 50% chance of inheriting the disease. Identification of the mutation allows for predictive genetic testing in other living family members. Variable penetrance is common in all arrhythmia syndromes, the same mutation in the same family causing wide variation in phenotype. This suggests that other factors such as genetic modifiers and environmental factors may influence the phenotype. Recent advances in genetic sequencing techniques and the potential of therapeutic intervention in patents with inherited cardiac arrhythmias have garnered this group of disorders much attention in the scientific community. The purpose of the study was to identify the mutational spectrum of ventricular tachycardia (VT) in Kazakhstani patients. Material and Methods: using predeveloped a targeted panel of 96 known cardiac disease genes, associated with cardiomyopathy and arrhythmia we screened 92patients, diagnosed with VT and dilated cardiomyopathy (VT DCM) or idiopathic VT (iVT). Results. Targeted sequencing and stepwise filtering of the annotated variants identified a total of 307 unique variants in 74 genes totaling up in 456 variants for the overall study group. Variants included one in/del variant, four splice-site variants and 451single-nucleotide variants (SNV) within the coding exonic regions. Seven (0.15%) of the SNVs were unique stop-gain variants, three of those residing in the TTN gene. 168 HGMD mutations (61unique) were observed in 37 genes. According to ACMG variants were classified as 9 pathogenic (KCNJ2R218Q and TTN R5338X in iVT patients, KCNQ1c.477+1G>A, LMNA Q353X, MYH7 F244L, TTN L17465X and W21011X, DSG2c.2334+1G>A, GAA W746C in VT DCM patients), 11likely pathogenic, 97 variants with uncertain significance and rest as benign were observed. Conclusions: Individuals presenting with VT either secondary to DCM or of idiopathic etiology carry multiple rare mutations and potentially pathogenic sequence variants in cardiac risk genes in a similar pattern and at a comparable frequency. Further studies are needed to identify more mutations causing VT in a larger cohort of patients. Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan (AP05134683).Item Open Access GENETIC VARIANTS, METABOLOME, AND GUT MICROBIOME BIOMARKERS FOR OBESITY AND AGING IN RANDOMLY SELECTED KAZAKH INDIVIDUALS(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Akilzhanova, Ainur; Rakhimova, Saule; Kozhamkulov, Ulan; Kairov, Ulykbek; Kushugulova, Almagul R.; Terwilliger, Joseph; Lee, JosephObjective: Metabolic syndrome (MS) is a cluster of inter-related and heritable metabolic traits, which collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2diabetes. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Genome, Metabolome variations and gut microbiome can predict disease risk and diagnosis and help to understand molecular pathophysiology. We aimed toassess plasma metabolom differences and gut microbiome as well as genetic variants among Kazakh population to identify and characterize the genetic, metabolic profiles and host-gut microbiota interactions. Methods: Kazakhs were recruited into study after signing of informed consent in Astana, Kazakhstan. Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) (Metabolon, USA) and NGS16S rRNA gene-sequence-based methods were used. Bioinformatic and statistical analyses were performed. Results: Subjects were stratified by age (young <45y, old ≥45y), gender and BMI. 853 different biochemical indicators of the main pathways for the metabolism were identified in plasma. Results demonstrate alterations in various metabolic pathways in older participants compared to younger subjects. Metabolic differences included changes in metabolites associated with the metabolism of fatty acids, steroidogenesis, secondary carnitine metabolism, inflammation and oxidative stress. Microbiomes of older persons are characterized by a high level of microorganisms involved in the processing of plant substrates, butyrate- producing bacteria and also has higher values of opportunistic microorganisms, representatives of the Tenericutes family. The biodiversity index of the microbiome of older persons is reduced in comparison with the biodiversity index in younger participants. This may indicate the influence on the microbiome characteristics of such factors as genotype, nutrition, lifestyle.Genetic risk factors associated with the obesity and hypertension were identified. Conclusions: Understanding plasma metabolome and gut microbiome is essential to the development of future personalized strategies of healthcare. Genome-wide association studies (GWAS) have been widely utilized albeit with modest success in identifying variants that are associated with more than two metabolic traits. Further studies with detailed analysis are needed to clarify host-gut genetic and metbolome interactions. Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan (BR05236508).Item Open Access GENOTYPING OF MYCOBACTERIUM TUBERCULOSIS ISOLATES AMONG RECURRENT CASES OF TUBERCULOSIS IN KAZAKHSTAN(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Akhmetova, A.; Akilzhanova, A.; Toksanbaeva, B.; Bismilda, V.; Chingissova, L.; Kozhamkulov, U.Introduction: Tuberculosis still remains one of the major health problems in Kazakhstan. According to the World Health Organization data (2018), Kazakhstan is on the list of 30 countries with high rates of multidrug resistant tuberculosis in the world. MIRU-VNTR analysis is widely used genotyping method of M. tuberculosis. The aimof this work is to characterize biological diversity of M. tuberculosis clinical isolates among recurrent cases of tuberculosis in Kazakhstan. Materials and methods: 95 clinical isolates of M. tuberculosis were collected from different regions of Kazakhstan among recurrent cases of tuberculosis. Genotyping of all isolates was performed by 15 MIRU-VNTR approach. PCR products were visualized on 2% agarose gel stained with ethidium bromide. Quantity 1(BioRad) program was used to determine the PCR fragment size and calculate the number of tandem repeats in each MIRU-VNTR locus. 15-digit allelic profiles of all clinical isolates were uploaded to MIRU-VNTRplus web application to identify M. tuberculosis families. Phylogenetic tree was built using UPGMA (Unweighted pair group method with arithmetic mean) algorithm. Results: 40 genotypes were detected based on15 MIRU-VNTR genotyping results. 31(32,6%) genotypes were unique and found only in one isolate in the collection. The rest 64 (67,4%) M. tuberculosis clinical isolates were clustered into 9 clusters which included from 2to 34 isolates in one cluster. 87,4% of all clinical isolates were belonged to Beijing family. The second meaningful family that is found among the isolates was LAM family (10,5%). URAL and CAS families were identified in the rest 2,1% cases. Conclusion: Thus, 15 MIRU-VNTR typing of 95 clinical isolates of M. tuberculosisshowed that Beijing family strains that are associated with drug resistance prevail among recurrent cases of tuberculosis in Kazakhstan (87,4%).Item Open Access DRUG RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS CLINICAL ISOLATES FROM NEW TB CASES IN KAZAKHSTAN(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Kozhamkulov, U.; Akhmetova, A.; Rakhimova, S.; Daniyarov, A.; Molkenov, A.; Bismilda, V.; Chingissova, L.; Kairov, U.; Akilzhanova, A.Introduction: Nowadays and worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent. The global incidence of drug-susceptible TB, multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in the past decade led to decreased efficiency of chemotherapy. In Kazakhstan, the 2019 WHO report estimates the TB incidence in 2018 to be 68 per 100 000 population and the MDR-TB incidence to be 26/100,000 (WHO, 2019). Therefore, the goal of the study is to analyze clinical isolates from new TB Kazakhstani patients by determining drug resistance, genotyping and whole genome sequencing. Methods: 192M.tuberculosis drug resistant strains from new TB cases were analyzed. Resistance to the first-line anti-TB drugs were determined using absolute concentration method on L-J media and BACTEC MGIT-960. Spoligotyping was performed using commercially available kit “Ocimum Biosolutions Inc”. The whole genome sequencing was carried out on Roche 454 GS FLX+ platform. Results: The structure of 192drug resistant isolates showed that 98 (51.04%) were MDR, 55 (28.65%) – polyresistant, 39 (20.31%) – monoresistant. Genotyping results showed that W-Beijing family identified in 143 (74.48%) cases, T – 23 (11.98%), LAM – 11(5.73%), Haarlem - 10 (5.21%), U – in 4 (2.08%) and MANU-2– 1(0.52%) case only. W-Beijing family M.tuberculosis was a dominant genotype and composed more than 50% of two resistant groups: polyresistant - 70.9% and MDR - 87.75% clinical isolates of M.tuberculosis. Missense mutation of rpoB gene at codon 531with amino acid substitution Ser/Leu was the prevalent among mutations responsible for rifampicin resistance (87.75%). In case of isoniazid resistance, the most prevalent (96.94%) mutation was substitution at codon 315 Ser/Thr including 3 cases (3.06%) with double mutation when replacement simultaneously took place at katG gene and -15 position of promoter mabA (fabG)-inhA operon. Conclusion: MDR strains are predominant among resistant strains and mostly belong to Beijing family in Kazakhstan. W-Beijing is the most common genotype among all categories of drug resistant M.tuberculosis. As such MDR-TB should be a national priority in National TB Program for Kazakhstan. Acknowledgements: grant# АР05134737 MES RK.Item Open Access SNPS ASSOCIATED WITH MYOCARDIUM REMODELING IN HYPERTENSION IN THE KAZAKH POPULATION(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Sibagatova, A.; Benberin, V.; Karabayeva, R.; Vochshenkova, T.; Nagimtayeva, A.; Akhmetova, K.; Babenko, D.Introduction: Cardiovascular Disease (CVD) is the leading cause of mortality in Kazakhstan. Among all CVDs, hypertension is the most common and leads to remodeling of myocardium, which significantly increases cardiovascular risk. Some studies have been carried out to elucidate the genetic markers associated with target organ damage in hypertension, but not in Kazakh population. The aim of this study is to find out SNPs associated with myocardium remodeling in Kazakh population. Materials and methods: The sample size is 500 people There were 2groups of 250 hypertensive individuals, age - up to 61years. 1. Group without remodeling 2. with myocardial remodeling (MR) LVMI ≥115 in men, ≥95 in women, relative wall thickness ≥0.43 Clinical, laboratory, instrumental data were gathered. Рeripheral blood was taken for genotyping for SNPs known by association with target organ remodeling in HTN based on GWAS Catalog - EMBL-EBI and Varsome Clinical and PubMed publications. Genotyping was made using QuantStudio 12K Flex Real-Time PCR System by array technology. Results: Out of SNPs, seven SNPs were associated with myocardium remodeling. rs17016480 OR=1.80 (1.07-3.02) p=0.029, rs923109* OR=0.45 (0.20-1.03) p=0.033, rs11646213 OR=1.69 (1.14-2.53) p=0.009, rs113296370 OR=1,14 (0,68-1,93) p=0.036, rs591044 OR=0,49 (0,27-0,87) p=0.0095, rs2407103 OR=2.04 (1.18-3.52) p=0.011rs7016717 OR=3,74 (1.20-11.67) p=0.026 * marked polymorphisms associated with myocardium remodeling, but differing from the Hardy-Weinberg inheritance equilibrium in the control group.Item Open Access WHOLE TRANSCRIPTOME SEQUENCING ANALYSIS OF PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA FROM KAZAKHSTAN(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Sharip, A.; Rakhimova, S.; Molkenov, A.; Kozhamkulov, U.; Zhukov, Y.; Omarov, M.; Akilzhanova, A.; Kairov, U.Introduction: Esophageal cancer is the eighth most common cancer worldwide and sixth in Kazakhstan. Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer and diagnosed at late stage. The aim of the project was to identify genetic basis of ESCC by analyzing differentially expressed genes (DEGs) from whole-transcriptome sequencing of Kazakhstani patients. Materials and Methods: Tissue samples were obtained from 25 ESCC-affected individuals immediately after Ivor-Lewis esophagectomy from Oncology Center in Nur-Sultan. Whole transcriptome sequencing was performed following the TruSeq RNA Protocol. STAR software and DESeq2package have been used for mapping and defining differentially expressed genes. Functional analysis of DEGs was performed using various R packages. Results: The study sized 14 men and 11women, average age of patient 65.5±7.7 years 88% of the patients were diagnosed with advanced stages T3-T4. Analysis of tumor and normal esophageal tissues identified 7 DEGs, comprising 883 upregulated and 314 downregulated genes (with adjusted p-value <0.05). We found significant 4 up-regulated and 6 down-regulated KEGG pathways (p-value<0.05). Top 300 DEGs were mapped to PPI network and functional enrichment analysis was performed on identified three modules of closely connected nodes (genes). Conclusion: ESCC with moderate dysplasia is the most common histologic subtype of esophageal cancer in our patients and is characterized by a poor prognosis.High-throughput sequencing approach allows identifying molecular pathways involved in esophageal carcinogenesis that could improve diagnosis and treatment strategies. Acknowledgments: Work was supported by grant projects #AP05134722, #AP05135430 and #AP05136106 from the Committee Science and Ministry of Education and Science at the Republic of Kazakhstan.Item Open Access POTASSIUM CHANNEL GENES KCNQ1, KCNE1/2, KCNH2 (HERG) MUTATIONS IN PATIENTS WITH ATRIAL FIBRILLATION IN KAZAKHSTAN(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Abilova, Zhannur; Rakhimova, Saule; Akhmetova, Ainur; Zhalbinova, Madina; Nuralinov, Omirbek; Rashbayeva, Gulzhaina; Akilzhanova, Gulbanu; Abdrakhmanov, Ayan; Bekbosynova, Mahabbat; Akilzhanova, AinurBackground: Atrial fibrillation (AF) is a common arrhythmia of substantial public health importance, a major risk factor for stroke, heart failure, and other cardiovascular morbidities. Recent evidence demonstrates a heritable component underlying AF, and genetic discoveries have identified common variants associated with the arrhythmia. Aim: This study aims to report the spectrum of KCNQ1, KCNE1, KCNE2, KCNH2 (HERG) mutations in Kazakhstani patients with AF. Methods: Patients with AF were recruited at National Research Center for Cardiac Surgery, Nur-Sultan, Kazakhstan. Genomic DNA of the 104 cases with AF and 87 healthy relatives were analyzed for mutations in all protein-coding exons and their flanking splice site regions of the genes KCNQ1, KCNE1, KCNE2 and KCNH2 (HERG) using targeted next generation sequencing and validated by bidirectional Sanger sequencing. Results: In total, a disease-causing mutation was identified in 59 of the 104 (56.5%) index cases. Of these, altered sequence variants in the KCNQ1 gene accounted for 14.5 % of the mutations, whereas a KCNE1 mutation accounted for 43.5 % of the mutations, KCNE2 for 1.4% and KCNH2 for 40.6%. The majority of the distinct mutations were found in a single case (80 %), whereas 20 % of the mutations were observed more than once. We found two sequence variants in KCNQ1 exon 13 (S546S G1638A) and exon 16 (Y662Y C1986T) in 15 patients (14.5 %). In KCNE1 gene in exon 3 mutation, S59G A280G was observed in 42 of 104 patients (43.5%) and KCNE2 exon 2 T10K C29A in 1 patient (1.4 %). Screening KCNH2 (HERG) gene revealed sequence variants C789A (I263N), T1467C (I489I), C1539T (F513F) in exon 6, G2832T (E944D) in exon 12 and (R1047L G3541T), C3153T (R1051R) in exon 13. Genetic cascade screening of 87 relatives to the 104 index cases with an identified mutation revealed 26.9 % mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death. Conclusion: In this cohort of Kazakhstani index cases with AF, a disease-causing mutation in potassium channel genes KCNQ1, KCNE1/2, KCNH2 (HERG) was identified in 56.5 % of the referred patients. Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan (AP05134683).Item Open Access ЦИТОПРОТЕКТОРНЫЙ ПОТЕНЦИАЛ ЭКСТРАКТОВ КЛЮКВЫ, БРУСНИКИ, ЧЕРНИКИ(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Жуликеева, А.; Сегизбаева, Г.; Шульгау, З.; Харитонова, М.; Гуляев, А.; Кривых, E.; Сергазы, Ш.Терапевтический потенциал северных ягод связывают с высоким содержанием полифенольных субстанций. Экстракты клюквы, брусники, черники вследствие высокого содержания полифенолов, способны обладать антиоксидантными и цитопротекторными свойствами. В данном исследовании изучали цитопротекторные эффекты полифенольных экстрактов клюквы, черники, брусники на клеточных культурах invitro. Стандартизацию экстрактов проводили по общему фенольному числу – 10 мг/мл. Вероятные цитопротекторные свойства экстрактов северных ягод оценивали в МТТ-тесте на первичной культуре альвеолярных макрофагов кролика и перевиваемой клеточной культуре НЕК293 (humanembryonickidney, АТСС® CRL-1573™). Число альвеолярных макрофагов кролика в каждой лунке планшета составило 106 клеток в 1мл среды, клеток НЕК293 – 104 кле- ток. Экстракты клюквы, черники и брусники изучали в разведениях 1:10 и 1:100. В лунки вноси- ли исследуемые соединения (0,1мл): экстракты клюквы, черники и брусники в разведениях 1:10 и 1:100; доксорубицин в конечной концентрации 1мкг/мл и 10 мкг/мл; доксорубицин 10 мкг/мл + экстракты клюквы, брусники, черники в разведении 1:100; контроль – клетки без добавления ис- следуемых субстанций. Альвеолярные макрофаги крорлика инкубировали при 37°C в атмосфере CO2(5%) в течение 2часов, НЕК293 – в тчение 48 часов. Жизнеспособность клеток в контроле при- нимали за 100%. Эксперименты были выполнены в трёх повторностях. При добавлении к альве- олярным макрофагам экстрактов северных ягод в разведении 1:100 жизнеспособность клеток в сравнении с контролем не менялась, цитотоксическое действие отсутствовало, при внесении экстрактов в разведении 1:10 жизнеспособность клеток увеличивалась. Введение доксорубицина приводило к дозозависимому снижению жизнеспособности клеток. Присутствие в питательной среде экстрактов северных ягод нивелировало цитотоксическое действие доксорубицина. При инкубации клеток НЕК293 с экстрактами северных ягод в разведениях 1:100 жизнеспособность клеток сохранялась, при увеличении концентрации экстрактов жизнеспособность клеток расла. Цитотоксический доксорубицин ингибирует жизнеспособность клеток, но внесение экстрактов северных ягод в среду инкубации способствует сохранению жизнеспособности клеток. Способность полифенольных экстрактов предохранять клетки альвеолярных макрофагов и НЕК293 при различных режимах инкубации от воздействия цитотоксических эффектов наглядно выявляется в экспериментах с доксорубицином. Считаем, что эти результаты дают нам основания для предположения о наличии цитопротекторного потенциала у полифенольных экстрактов северных ягод. Входящие в состав экстрактов клюквы, брусники, черники полифенолы (флавоноиды, антоцианы и проантоцианидины), как антиоксиданты, способны защищать клетки от оксидативного повреждения, присутствующего в механизме цитотоксичности доксорубицина.Item Open Access ИЗУЧЕНИЕ ФУНКЦИОНАЛЬНЫХ СВОЙСТВ МИКРООРГАНИЗМОВ, ВЫДЕЛЕННЫХ ИЗ ВЕРБЛЮЖЬЕГО МОЛОКА(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Кудайбергенова, А.Изучение пробиотических свойств микроорганизмов, на сегодняшний день получило широкое распространение, но не утратило актуальности. Препараты на основе молочнокислых бактерий используются для лечения и профилактики заболеваний, связанных с разнообразными формами нарушения состава нормальной микрофлоры желудочно-кишечного тракта благодаря их антагонистической способности воздействия на патогенные микроорганизмы. Молочнокислые бактерии являются одним из основных классов кислотообразующих организмов в пищевой промышленности, и они играют жизненно важную роль во многих пищевых продуктах и кормить брожением. Мы выделили и провели молекулярную идентификацию из сырого верблюжьего молока. Образцы молока были получены от здоровых верблюдов, с соблюдениями правил санитарной гигиены. Вымя было трижды вымыто с дистиллированной водой перед сбором молока и высушено одноразовым полотенцем. Первые три потока молока были отброшены. Образцы молока собирались в стерильные пробирки, помещены в холодильную камеру и доставлены в лабораторию в течении 24 часов. Выделение молочнокислых бактерий проводили путем посева, предварительно подготовив разведение 10 мл молока в стерильном солевом растворе 90 мл концентрацией 8,5 гр/л. И последующем разведении в стерильном солевом растворе до 10-8 и посеве 1мл на среду Man-Rogosa (MRS) и Saburo для выделения дрожжей. Изоляты полученные после выделения были морфологически изучены, прошли окраску по Грамму и каталазный контроль. Для определения видового уровня были отобраны грамположительные, каталаза-отрицательные штаммы. После проведено генотипирование с использованием 16S рибосомальной ДНК. Результаты:, были обнаружены 13 различных штаммов относящихся к Lactobacillusparacasei, Lactobacilluskefiri, Enterococcusfaecium и 14 видов дрожжей. Дальнейшие исследования будут направлены на изучение функциональных пробиотических свойств, таких как устойчивость к повышенной кислотности, ферментам и желчи, синтез бактерицидных веществ и антагонистическая активность, протеолитическую активность, способность к адгезии и др.Item Open Access ГЕНОМНАЯ ХАРАКТЕРИСТИКА КИШЕЧНЫХ ШТАММОВ KL. PNEUMONIAE, ВЫДЕЛЕННЫХ У НОВОРОЖДЕННЫХ ДЕТЕЙ В РОДИЛЬНОМ ДОМЕ(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Николаева, И.; Шайхиев, Г.; Григорьева, Т.; Васильев, И.Кl. pneumoniae являются одними из первых колонизаторов кишечника новорожденных и способны вызывать местные и системные заболевания в форме инфекции и мочевых путей, менингита, пневмонии, неонатального сепсиса. В связи со способностью клебсиелл длительно сохраняться во внешней среде, в стационарных условиях формируются внутрибольничные клоны с множественной антибиотикорезистентностью, устойчивостью к дезинфектантам и наличием генов, кодирующих «острова патогенности». Учитывая выше изложенные данные, актуальным является изучение антибиотикорезистентности и вирулентности штаммов Kl. pneumoniae, колонизирующих детей в родильных домах.Проведено генотипирование секвенированных последовательностей 8 штаммов Kl. pneumoniae, выделенных из фекалий у здоровых новорожден- ных детей на 4-5 день жизни. Полногеномные секвенирования проводились на платформе IlluminaMiSeq в режиме paired-end, 2-250 п.о. с использованием наборов NexteraXTDNALibraryPreparationKit (IlluminaInc., США), согласно инструкциям производителя. Результаты: У всех штаммов обнаружены гены бета-лактамаз, в том числе blaOXA-1обнаружены у 60%, blaTEM-30 – у 70%, blaCTX- M-15 – у 70%, blaSHV – у 100% штаммов. Гены устойчивости к аминогликозидам обнаружены у 90%, фторхинолонам – у 40%, сульфаниламидам – у 80%, хлорамфениколу – у 70%, тетрацикли- ну – у 50% и триметоприму – у 70% штаммов Kl. pneumoniae. Гены иерсиниабактина обнаружены у 70%, аэробактина, сальмохелина, колибактина и гипермукоидности – у 60%, K- и О-антигенов – у 100% штаммов. 60% штаммов Kl. pneumoniae имели сходный набор генов, соответствующий «гипервирулентному» и одновременно мультирезистентному генотипу Kl.pneumoniae и относились к сиквенс-типу ST23. Выявлено наличие генных детерминант множественной лекарственной устойчивости и вирулентности у штаммов Kl. pneumoniae, выделенных у здоровых новорожден- ных детей, что характерно для госпитальных штаммов микробов и может иметь клиническое и эпидемиологическое значение.Item Open Access ОПРЕДЕЛЕНИЕ ПРОБИОТИЧЕСКИХ СВОЙСТВ ДРОЖЖЕЙ SACCHAROMYCESCEREVISIAE(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Сапарбекова, А.; Латиф, A.; Ахмедова, З.Введение: В традиционной ферментированной пище образуются ряд веществ потенциально полезные для здоровья человека. Использование пробиотических культур, позволяют получить продукцию, содержащую эти культуры, за счет различных механизмов благотворно влияющие на микрофлору кишечника. Важным начальным событием в бактериальном патогенезе является приверженность бактерий через их поверхностные органеллы прикрепляться к клеткам кишечника хозяина. Использование S. cerevisiae как пробиотика у людей может противодействовать адгезии патогенов к тканям хозяина, обеспечивая альтернативные места адгезии энтеробактериям и таким образом предотвращают инфекции. Они также могут устранить патогены из желудочно- кишечного тракта инфицированных пациентов выводя их из организма в связанном с дрожевыми клетками состоянии. Методы: В качестве источников дрожжевых культур использовали смывы с поверхности сокосодержащих ягод, произрастающих в туркестанской области, а также свежих соков, полученных в стерильных условиях, в том числе сок граната, вишни, черешни, винограда, арбузный сок, сок столовой свеклы, сок сахарного сарго. Выделение и идентификация высокоактивных штаммов проводили общепринятыми в микробиологии методами. Результаты: В результате проведенных селекционных работ были отобраны штаммы Saccharomycescerevisiae выделенные из винограда, сока сахарного сарго и гранатового сока. Наиболее перспективными оказались SaccharomycescerevisiaeGul -8 и SaccharomycescerevisiaeAz- 12спос- бные относительно быстро сбраживать фруктовые соки, также ведущим фактором являлось высокое качество продукции: органолептические показатели, естественный фруктовый запах, без появления мутности и приятный слегка сладкий, слабо кислый вкус. Исследование антагонистических свойств к условно патогенным микроорганизмам показало, что штамм SaccharomycescerevisiaeAz- 12вызвал значительное сокращение количества клеток P. аeruginosa, E. coli и S. aureu при их совместном культивировании. В нашем исследовании мы использовали седиментационные и микроскопические методы для оценки адгезии бактериальных клеток к пробиотической клеточной стенке дрожжей. В методе седиментации на основе субъективной оценки размера гранул, были получены явно положительные результаты для S. aureus. Предот- вращение прилипания и транслокации бактерий в кишечных эпителиальных клетках связано с тем, что клеточная стенка SaccharomycescerevisiaeAz-12обладает способностью связывать энтеро- патогены. Выводы: Способность дрожжей связывать бактериальные клетки происходит из-за присутствия маннопротеинов в структуре клеточной стенки, и поэтому она не является уникальной особенностью, присущей SaccharomycescerevisiaeAz-12, а скорее универсальная особенность всех штаммов рода Saccharomyces. Тем не менее, сканирующая электронная микроскопия показывает, что бактерии Staphylococcusaureus, были более сильно связаны с поверхностью SaccharomycescerevisiaeAz- 12, чем на поверхности не пробиотических штаммов S. cerevisiae.Item Open Access CLINICAL EVALUATION OF THE EFFECTIVENESS OF MARE’S MILK IN PSORIASIS(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Algazina, T.; Yermekbayeva, B.; Batpenova, G.; Kozhakhmetov, S.; Kushugulova, A.According to the world health organization, the prevalence of psoriasis in the world is about 2%. However, according to a number of studies, this figure is significantly higher in developed countries and can range from 4.6 to 7%. According to official statistics in the Republic of Kazakhstan, psoriasis takes the third place in the structure of dermatoses, giving way to eczema, associated with this ailment of allergic skin diseases and mycoses. Moreover, the majority of patients diagnosed for the first time in their life are people aged 16 to 30 years. The aim of the study was to evaluate the clinical effect of Mare’s milk in the complex treatment of psoriasis patients of mild and moderate severity. The study included 20 patients with mild to moderate psoriasis, whose average age was 34.95±4.11years. In addition to standard psoriasis therapy, patients received freeze-dried Mare’s milk at 60 mg / day for 12weeks. Evaluation of the effectiveness of Mare’s milk was carried out using the dynamics of the Psoriasis Area Severity Index (PASI). Evaluation of the effectiveness of including Mare’s milk in standard therapy for psoriasis was carried out taking into account the dynamics of the dermatological status at the 6th and 12th weeks of treatment: a decrease in the PASI index by 68% and 88% (p=0.0003), respectively. In general, the dynamics of the overall PASI index for mild psoriasis decreased PASI from 10±0.62to 3.52±0.7, with an average severity of 29.51±0.7 to 3.05±0.5. The degree of severity of individual components of the psoriatic process – erythema, infiltration and peeling decreased. Complex therapy of psoriasis with the inclusion of Mare’s milk, which has a prebiotic and immunomodulating effect, to the standard therapy of psoriasis, helps to achieve an earlier and more stable resolution of the skin manifestations of the disease.Item Open Access STRUCTURAL CHANGES IN THE MICROBIOME IN RATS WITH DSS-INDUCED COLITIS(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Kozhakhmetov, S.; Babenko, D.; Tuyakova, A.; Nurgaziyev, M.; Nurgozhina, A.; Muhanbetganov, N.; Chulenbayeva, L.; Sergazy, S.; Gulyayev, A.; Kushugulova, A.Microflora plays a critical role in the initiation and development of inflammatory bowel disease (IBD). There are many facts accumulated about the effect of intestinal dysbiosis on the pathogenesis of Crohn’s disease and ulcerative colitis (UC). A biological preparation based on intestinal bacteria can modulate the intestinal normoflora in IBD. We evaluated the effect of the biological drug on rat intestinal microbiome in DSS-induced colitis.Rats were divided into 4 groups: without a colitis model (n = 7); with a colitis model received (n=6); experimental group animals (with a colitis model) received a 10% DSS solution for 7 days, and biology product intragastrically at a dose of 500 mg/kg body weight once per day for 7 days (n = 7); comparison group animals (with a colitis model) received a 10% DSS solution for 7 days and as a treatment the 5-ASA (5-aminosalicylic acid) intragastrically at a dose of 100 mg / kg of animal body weight once for 7 days (n = 6). In our work, we found a decrease in bactericides after 7 days of 10% DSS. An increased in the biodiversity index in the control group is associated with an increase in the following genera: Murimonas, Victivallales, Anaerofustis and etc. Wang W. et. al. shows a decrease in the number of Lactobacillus and Bifidobacteria were significantly reduced in DSS-induced colitis. In our study, the use of biological product show to the partial restoration of certain types of intestinal bacteria such as gram-positive Clostridium XVIII, Faecalibacterium, gram-negative Microbacter, Phascolarctobacterium producing SCFAs, etc.Item Open Access EFFECT OF MARE’S MILK PREBIOTIC SUPPLEMENTATION ON THE GUT MICROBIOME AND THE IMMUNE SYSTEM DURING AND AFTER ANTIBIOTIC THERAPY(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Nurgaziyev, M.; Aitenov, Y.; Khassenbekova, Zh.; Akpanova, S.; Rysbekov, K.; Kozhakhmetov, S.; Nurgozhina, A.; Sergazy, Sh.; Chulenbayeva, L.; Ospanova, Zh.; Tuyakova, A.; Mukhambetganov, N.; Sattybayeva, R.; Urazova, S.; Galymgozhina, N.; Gulyaev, A.; Kushugulova, A.Antibiotic treatment can severely affect the gut microbiome with short-term and long-term consequences. Probiotic and prebiotic supplements are widely prescribed to modulate the composition and function of the human gut microbiome. The current study aims to determine the impacts of mare’s milk prebiotic on the diversity of gut bacterial communities and the local immune system when administered during and after a course of antibiotic therapy. Six children aged 4 to 5 years diagnosed with bilateral bronchopneumonia were prescribed cephalosporin (Cefuroxime) antibiotics. During the 60 days of the study, 3 children consumed mare’s milk prebiotics whereas the other 3 did not. Fecal samples were collected daily during antibiotic therapy and every 5 days after antibiotic therapy. Total DNA was isolated and taxonomic composition of the gut microbiome was analyzed by sequencing of the 16S rRNA gene (V1-V3 region). To evaluate the local immune status the MILLIPLEX MAP platform was used. Counts of 11genera were reduced, which did not recover until the last day of the study. The abundance of Bacteroides were not significantly altered in both groups. Christensenella, Rothia, Abiotrophia, Acinetobacter, Anaerotruncus, Holdemania and Turicibacter numbersare significantly increased at day 5 and remained at the same level during the study period. Cephalosporin administration also reduced pro-inflammatory and anti-inflammatory cyto/ chemokines (MIP1α, TNFα, GMCSF, GCSF, sCD40L, FGF2, TGFα, IL1α, IP10).Item Open Access SPECIFICATIONS OF NUTRITION WITH HEALTHY AND PATHOLOGICAL CONDITIONS OF PSORIASIS(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Nurgozhina, A.; Yermekbayeva, B.; Gulyayev, A.; Kozhakhmetov, S.; Sergazy, S.; Nurgaziyev, M.; Aitenov, Y.; Chulenbayeva, L.; Tuyakova, A.; Kushugulova, A.Psoriasis is a long-lasting autoimmune disease characterized by patches of abnormal skin. 183 participants in the experiment were selected for the study, half of which are with psoriasis disease. All participants in the study passed the EPIC-Norfolk Food Frequency Questionnaire, which was completed once and included a diet over the past week. The aim of the study was to identify the intakes of different nutrients in two groups by age. AfterquestionnaireFETAtoolwasusedtoanalyzeallanswers (http://www. srl.cam.ac.uk/epic/epicffq/). The output was the results for all nutrients and macro and microelements that are in the food. Significant differences in patients were in eight nutrients, namely: betacarotene, carotene, fructose, potassium, potatoes, fruits, nuts and seeds, and vegetables. All differences are in favor of healthy patients. patients with psoriasis had a diet with low income of fruits and vegetables which brought to the deficiency in some nutrients and vitamins. The used tool for converting food frequency questionnaire data into nutrient and food group values can be used widely for different study populations.Item Open Access ISOLATION FROM THE KAZAKH TRADITIONAL FOOD PRODUCTS OF A NEW STRAIN OF LACTIC ACID BACTERIA PRODUCING THE HUMAN PLASMINOGEN RECEPTOR(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Shaikhin, S.; Abitayeva, G.; Abilhadirov, A.; Dossova, A.; Pirmanova, A.; Tynybaeva, I.Lactobacillus bacteria are one of the most important groups of the human intestinal microbiota that promote health. Adhesion to host tissues represents a crucial early step in the colonization process of either pathogens or commensal bacteria. Plasminogen - binding may also contribute to bacterial adhesiveness and invasiveness by nonproteolytic mechanisms. Plasminogen (Plg) binds to bacterial cell surface receptors, as well as to receptors on eukaryotic cells and may thus function as a bridge between the bacteria and the epithelium. The project aims to isolate a new strain of lactobacilli producing a protein- receptor for human plasminogen (Plg-R) from traditional Kazakh food products and to study the mechanism of reception. Lactic acid bacteria (LAB) strains isolated from traditional home-made food products and identified using 16S rRNA nucleotide sequence analysis; samples of extracellular proteins obtained from the cell-free supernatant (CFS) of the 24-hour culture after pH adjustment to 8.0 to dissociate acidic cell surface proteins, followed by concentration. Screening for Plg binding in CFS of LAB isolates carried out by Western Blotting assay. The Plg-R was purified from cell lysates after ultrasonic homogenization by Q-sepharose chromatography and the isoelectric point and subunit structure were determined by Mono P column chromatography and Sephadex G-75 gel filtration respectively. Screening of 35 isolates of LAB for Plg binding revealed a strain L. plantarum 30 isolated from homemade butter with maximal Plg-binding activity. The Plg-R band with comparatively high intensity migrated in the region of 47 K on the PAA gel with SDS and showed pI=4.8. The Plg binding was inhibited by adding an analog of lysine ɛ-aminocaproic acid (EACA). The Plg-R eluted in the exclusion volume in gel-filtration, which indicates the quaternary structure. A new strain from the homemade butter which produces the Plg-R was isolated. The inhibition by EACA of the Plg binding with receptor indicates the specificity of the binding which realized via lysine residues on the molecule of Plg-R. The properties of Plg-R are similar to the glycolytic moonlighting enzyme enolase and identification of the Plg-R in progress.Item Open Access ENGINEERING CHEMOKINE-BASED CCR5 BLOCKERS TO TACKLE INFECTIOUS AND INFLAMMATORY DISEASES(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Vangelista, LucaThe C-C chemokine receptor type 5, CCR5, is expressed on various cell types and is involved in a large number of pathophysiological conditions. In recent years, CCR5 gained a huge attention, as it was found to play a central role in several infectious (e.g., HIV-1and Staphylococcus aureus), inflammatory and autoimmune diseases, and in major pathologies such as cancer and atherosclerosis. Most importantly, CCR5, the major HIV-1cellular co-receptor and the exclusive one in primary infections, is the molecular portal for HIV-1entry and transmission. Interestingly, the CCR5 Δ32gene deletion encodes for a truncated nonfunctional protein, providing resistance to HIV-1infection in homozygous individuals. Consequently, CCR5 and its ligands present a great potential for targeted therapies based on the development of high-affinity receptor antagonists and CCR5 gene editing. Gene editing of CCR5 to introduce the naturally occurring Δ32mutation has the aim to provide protection from HIV-1infection and possibly eradication of the virus from infected individuals. However, individuals naturally carrying the Δ32mutation may have adjusted their chemokine system to compensate for CCR5 absence, hence the de novo introduction of this mutation might bring some pathophysiological burden. Besides gene editing, biochemical CCR5 blockade via the development of potent CCR5 antagonists is a seemingly more realistic large scale therapeutic approach. Significant efforts are under way to understand the fine structural details of the interaction between CCR5 and its ligands and maraviroc, a small chemical drug, has been developed and FDA-approved as HIV-1entry inhibitor acting as CCR5 antagonist. CCL5 is a natural chemokine ligand for CCR5, a small globular protein with a very stable fold. Previous research from my group produced the engineered CCL5 mutant CCL5 5p125m, the most potent in vitro CCR5 antagonist HIV-1inhibitor reported to date (1000 fold more potent than maraviroc). My ongoing research at NU is aimed at the 3D structure rational design and production of even more potent CCL5 derivatives and their investigations as inhibitors in the expanding therapeutic perspective of CCR5 blockade for a growing number of pathological conditions.Item Open Access ISOLATION OF NATURAL REPRESENTATIVES OF CARP LACTOFLORA TO CREATE PATHOGEN CONTROL AGENTS THAT CAN BE ALTERNATIVE TO ANTIBIOTICS(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Urazova, M.; Zakarya, K.; Sarmurzina, Z.; Bissenova, G.; Abitayeva, G.; Shevtsov, A.; Tekebayeva, Zh.; Tynybayeva, I.; Abzhalelov, A.Currently, the microbiome of commercial fish species is being actively studied. In reviews, mainly based on metagenome analysis features and formation of intestinal microflora of various fish species of North America, Asia and Europe have been presented. Results of these researches showed that lactic acid bacteria (LAB) are common microbial group of intestinal microbiota of fish (Wu et al., 2012; Ye et al., 2014; Borsodiet al., 2017; Wang et al., 2018). In our research a characteristic of 22lactic acid bacteria isolated from Common Carp (Cyprinus carpio) intestines were studied. All of them were tested for their ability to inhibit growth of Aeromonas punctate, Shewanella xiamenensis, Pseudomonas aeruginosa,Pseudomonas taiwanensis.In sum, 7 isolates with high antagonistic activity were selected. 16S rDNA gene sequencing identified them as Lactobacillus fermentum(4), Lactobacillus casei/paracasei (2) and Pediococcus pentosaceus (1). All identified isolates can grow in wide temperature range (10° C to 37° C) and in presence of bile. Earlier the species of Lactobacillus, Lactococcus, Streptococcus, Enterococcus,Pediococcus and Carnobacteriumgenera were isolated from carp intestines (Bucio et al., 2006; Wang et al., 2018). We isolated only strains, belonging to 3 species (Lactobacillus fermentum, Lactobacillus casei/paracasei and Pediococcus pentosaceus). It is low rate of species diversity. Perhaps this is due to the conditions, when we made isolationof LAB. It wasmade at the transition period from wintering to active spawning.The climate of Central and Northern Kazakhstan is severe and it is characterized by a cold winter lasting 5,5-6 months. Long wintering is a stress for an animal, and its microflora too. During the wintering period, carps do not feed, the composition of their microflora becomes poorer.The dominance of somespecies among intestinal LAB during cold period should be due to their specific characteristics, such as resistance to low temperatures and unfavorable environmental factors.Selective 7 strains could be alternatives to antibiotics for freshwater aquaculture in Kazakhstan.Item Open Access ИСПОЛЬЗОВАНИЕ НЕЙРОСЕТЕВОГО МОДЕЛИРОВАНИЯ ДЛЯ РАННЕГО ПРОГНОЗИРОВАНИЯ ПАРКИНСОНИЧЕКОГО СИНДРОМА ПРИ ХРОНИЧЕСКОЙ ИШЕМИИ МОЗГА(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Андронова, М.А.; Статинова, Е.А.; Сайко, Д.Ю.; Андронова, И.А.; Черний, Т.В.Введение: В последние годы отмечается тенденция к омоложению хронической ишемии мозга (ХИМ), поэтому важно на основе комплексного клинико-неврологического и клинико-инструмен- тального обследований обеспечить раннюю диагностику паркинсонического синдрома у боль- ных ХИМ. Методы: в работе использованы клинические, нейропсихологические, электрофизиологические (ЭЭГ, ЭКГ и вариабельность ритма сердца), ультразвуковые (транскраниальная допплерография), статистические (построение и анализ нейросетевых моделей в пакете StatisticaNeuralNetworks 4.0) методы. Результаты: Для проведения кластеризации данных исследуемых в многомерном пространстве признаков использовали сети Кохонена. Все показатели больных ХИМ были дифференцированы на два нейрона в выходном слое, и были разделены на два кластера (Cl 1и Cl 2). Выводы: На основании кластерного анализа были разработаны «математические модели» ХИМ с доминированием паркинсонического синдрома (ПС) (Cl 1) и без ПС (Cl 2) в количественных пара- метрах (Ме(ДИ±95%)) клинических, неврологических, нейропсихологических, нейрофизиологиче- ских и гемодинамических показателей.
- «
- 1 (current)
- 2
- 3
- »