The Investigation of Molecular Networks Involved in Diabetes Remission Achieved by Metabolic Bariatric Surgery

Poster (download) Shan Zaidi, Ancha Baranova, Ph.D. Department of Biology, George Mason University University, Fairfax, VA, USA Bariatric surgery, which is primarily used to treat obesity, has shown to elicit a remission in type 2 diabetes mellitus in 40 – 50% of patients. After analysis of existing literature concerning metabolic control exerted by gut hormones, we prioritized oxyntomodulin (OXM), peptide YY (PYY), pancreatic polypeptide (PPY), ghrelin, and glucagon-like peptide 1 (GLP-1) as important soluble contributors to anti-diabetic effects of bariatric surgery. To find support for this hypothesis, analysis of diabetes-associated genetic networks was performed in Pathway Studio environment. Lowered concentrations of PYY in plasma may contribute to both type 2 diabetes and obesity. The list of molecules with levels elevated post-surgery include GLP-1 and agonists for its receptors, well-known to improve insulin and normalize glucagon defects in diabetic patients. OXM inhibits ghrelin release, thus, displaying a potential for a development as novel therapeutic. We conclude that comprehensive understanding of the post-bariatric changes in gut hormones milieu may produce novel targets for the development of novel anti-diabetic medications.

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The role of microRNA-370 in Steroid-Resistant Focal Segmental Glomerulosclerosis

Poster (download) Sepideh Zununi Vahed, sepide.zununi@gmail.com, Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran Seyedeh Mina Hejazian, smhjz.biotech@gmail.com, Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran Mohammadreza Ardalan, ardalan34@yahoo.com, Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran Dysregulated levels of microRNAs may be involved in the pathogenesis and response to steroid therapy in patients with focal segmental glomerulosclerosis (FSGS). An in-silico analysis indicated that miR-370 is contributed to biological adhesion, cation transport, regulation of ion transport, cation transmembrane transport, and metal ion transport in FSGS.

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Why we need more complex gene diagnostic: the case study of exome from patient with congenital glaucoma

Video (download) Dinara Ivanoshchuk1, Mikhail Voevoda2, Natalia Konovalova3, Konstantin Gunbin41ICG SB RAS, Novosibirsk, Russia, dinara@bionet.nsc.ru2ICG SB RAS, Novosibirsk, Russia, voevoda@bionet.nsc.ru3TSMA, Tumen, Russia, doctork@bk.ru4ICG SB RAS, Novosibirsk, Russia, genkvg@bionet.nsc.ru Usually, a detailed analysis of well-known diseases-related genes for the presence of pathogenic variants does not give any meaningful result, despite the good agreement between the patient’s diagnosis and the available data on the mutations manifestation in these genes. This study, we try to disentangle such a cases using gene network aware exome analysis and variants prioritization.

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Semi-quantitative analysis of serum proteome in patients with bipolar disorder

Poster (download) Seregin Alexander Alexandrovich1, Smirnova Lyudmila Pavlovna2, Simutkin German Gennadievich31Mental Health Research Institute Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk, Russia, apocalips1991@mail.ru2Mental Health Research Institute Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk, Russia, lpsmirnova@yandex.ru3Mental Health Research Institute Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk, Russia, ggsimutkin@gmail.com The work analyzed the protein spectrum of blood serum of 45 with bipolar disorder. Protein recruitment in BD was mainly associated with the immune response, regulation of transport processes through the cell membrane and cellular communication, the development of neurons and oligodendrocytes, and cell growth. Cadherin-5 and vascular endothelial growth factor receptor 1 are a marker of endothelial dysfunction. The detection of these proteins suggests the presence of endothelial dysfunction in the pathogenesis of BD. The detection of myelin 1 transcription factor and the literature data on the effect of mutations in the MYT1L gene on the risk of major depressive disorder suggest the MYT1 protein as a potential BD biomarker. The results may help to discover new pathways associated BD.

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IL1b T-31C and VEGFРђ C+936T SNPs may be used as prognostic markers of rheumatoid arthritis treatment inefficiency

Poster (download) Vitaly Omelchenko1, Elena Letyagina2, Alla Shevchenko3, Yuliya Kurochkina4, Anna Akimova5, Maxim Korolev61Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, v.o.omelchenko@gmail.com2Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, elena_letyagina@list.ru3Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, shalla64@mail.ru4Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, juli_k@bk.ru5Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, calor844@gmail.com6Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, kormax@bk.ru Objectives: The aim of our study was to analyze the association between some SNPs and treatment of rheumatoid arthritis with biological drugs. Patients and methods: We studied 368 Russian patients with rheumatoid arthritis. All of them were treated in accordance with the standard recommendations. Fifty seven patient received biological disease-modifying antirheumatic drugs. Single nucleotide polymorphisms (TNFО± C-863A, TNFО± G-308A, TNFО± G-238A, IL1ОІ T-31РЎ, IL4 РЎ-590T, IL6 G-174C, IL10 A-1082G, IL10 РЎ-592Рђ, VEGFA C+936T, VEGFA C-2578A) were determined by restriction fragment length polymorphism analysis of PCR-amplified fragments (PCR-RFLP) or RT-PCR. Results: The IL1ОІ T-31C and VEGFA C+936T SNPs were association with bDMARDs treatment. Homozygotes IL1b -31CC and VEGFРђ +936 CC were more frequently in bDMARDs group compare with patients without bDMARDs (28.1% vs 17.1%, p=0.044 and 80.4% vs 66.6%, p=0.041). Other polymorphisms didn’t demonstrate any significant differences. Conclusions: Our data suggest, that IL1ОІ T-31C and VEGFA C+936T SNPs can be used as part of a comprehensive assessment of the prognosis of the treatment effectiveness.

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The development of compensatory processes in the liver and kidney in conditions of distant tumor growth

Poster (download) Nataliya Bgatova1, Asel Rakhmetova2, Saule Bakhbaeva3, Viktoriia Makarova4, Iuliia Taskaeva51Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences,Novosibirsk, Russia, n_bgatova@ngs.ru2Pavlodar State University; Pavladar, Kazakhsta, asel-rakhmetova@mail.ru3Pavlodar State University; Pavladar, Kazakhstan, saule0577@mail.ru4Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences Novosibirsk, Russia, shedina_vika@mail.ru5Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences Novosibirsk, Russia, inabrite@yandex.ru Development of malignant tumor accompanied endogenous intoxication of an organism having a mixed nature, in particular due to dysfunction of organs detoxification and excretion damaging effect of tumor metabolism. The active process of moving toxic and biologically active substances formed during tumor progression from the primary focus by blood and lymph flow leads to damage of distant organ. The aim of this work was to identify structural changes in the liver and kidney under the conditions of modeling distant tumor growth. For modelingВ  tumor growth, hepatocarcinoma-29 (G-29) cells were used. G-29 cells were injected into the muscle of the right thigh of CBA mice [1]. The material for research was collected after 3, 7, 13, and 30 days of the experiment. The structure of the liver and kidney was studied by the method of light and electron microscopy. Both destructive and compensatory changes in the liver and kidney were revealed in conditions of distant tumor growth. In the liver, a decrease a size of hepatocytes and concentration of organelles, as well as development of autophagy, as a mechanism for maintaining intracellular homeostasis, were noted. In the kidney at the early stages of the development of the tumor growth, structural signs of filtration barrier disorde were shown. Subsequent development of compensatory hypertrophy of podocytes and glomerular capillary endothelium, as well as autophagy in the epithelium of the proximal nephron were noted.

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The role of NGS in diagnosis of hereditary ophthalmic pathology

Andrey Marakhonov1, Tatyana Vasilyeva2, Vitaly Kadyshev3, Rena Zinchenko41Research Center for Medical Genetics, marakhonov@generesearch.ru2Research Center for Medical Genetics, valyeva_debrie@mail.ru3Research Center for Medical Genetics, vvh.kad@gmail.com4Research Center for Medical Genetics, renazinchenko@mail.ru Here we discuss the requirements, efficiency, place as well as performance of next generation methods in DNA diagnosis of hereditary ophthalmic diseases.

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Proteomic Analysis of Extracellular Vesicles Produced by Placental Mesenchymal Stem Cells

Anastasia Khutornenko1, Anastasia Zharikova2, Vasily Popkov3, Sergey Kovalchuk4, Kirill Goryunov5, Yulia Shevtsova6, Egor Plotnikov7, Dmitry Zorov8, Denis Silachev91Laboratory of Cell Technologies, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia, bioingenier@gmail.com2Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia, azharikova89@gmail.com3The A.N. Belozersky Institute Of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, popkov.vas@gmail.com4Laboratory of Bioinformatic methods for Combinatorial Chemistry and Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia, xerx222@gmail.com5Laboratory of Cell Technologies, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia, kirishgor@gmail.com6Laboratory of Cell Technologies, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia, yulshevtsova@yandex.ru7A.N. Belozersky Institute of Physico-Chemical Biology; Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia, plotnikov@belozersky.msu.ru8A.N. Belozersky Institute of Physico-Chemical Biology; Reserch Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia, zorov@belozersky.msu.ru9A.N. Belozersky Institute of Physico-Chemical Biology; Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia, d_silachev@oparina4.ru Mesenchymal stem/stromal cells (MSCs) have therapeutic potential in many pathological conditions, that is explained mostly by their paracrine action. MSCs secrete extracellular vesicles (EVs) packed with proteins, DNA, RNA and lipids. One of the easily accessible and reach sources of MSCs is placenta. In order to reveal possible pathways, by which EVs produced by placenta-derived MSCs (EVs-PMSC) could realize their therapeutic potential we conducted proteomic analysis of EVs-PMSC and subsequent bioinformatic analysis of identified proteins using Reactome pathway database. Identified peptides were mapped to 2093 proteins. Among the 2093 proteins, 972 proteins were identified in at least four LC-MS/MS analyses out of eight. According to Reactome the most significant ‘top three’ 1st level pathways for detected EVs-PMSC proteins were ‘Cellular responses to external stimuli’; ‘Immune system’; ‘Developmental biology’. Some of the most enriched pathways in the group ‘Cellular responses to external stimuli’ were: ‘Response of EIF2AK4 (GCN2) to amino acid deficiency’; ‘Cellular response to hypoxia’; ‘Detoxification of Reactive Oxygen Species’. Some of the most enriched pathways in the group ‘Immune System’ were: ‘Class I MHC mediated antigen processing & presentation’; ‘Neutrophil degranulation’; ‘Interferon Signaling’. The most enriched pathway in the group ‘Developmental biology’ was ‘Axon guidance’. Thus far, concerning most enriched pathways EVs-PMSC proteome is expected to: 1) provide protection against stress (amino acid deficiency, hypoxia, ROS) to the damaged tissues; 2) possess immunomodulation properties; 3) facilitate axon guidance. The result (the top list of enriched pathways) leads to the notion that EVs-PMSC could be effective in terms of neuroprotection.

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