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Genetics of macrovascular complications in type 2 diabetes

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World Journal of Diabetes 2021年第8期12卷 1200-1219页

作者： Ziravard n Tonyan Yulia A nasykhova Maria M danilova Andrey S Glotov Department of Genomic Medicine D.O.Ott Research Institute of ObstetricsGynecology and ReproductologySaint-Petersburg 199034Russia Laboratory of Biobanking and Genomic Medicine of Institute of Translation Biomedicine St.Petersburg State UniversitySaint-Petersburg 199034Russia

Type 2 diabetes mellitus(T2DM)is a metabolic disorder that currently affects more than 400 million worldwide and is projected to cause 552 million cases by the year ***-term vascular complications,such as coronary artery disease,myocardial infarction,stroke,are the leading causes of morbidity and mortality among diabetic *** recent advances in genome-wide technologies have given a powerful impetus to the study of risk markers for multifactorial *** date,the role of genetic and epigenetic factors in modulating susceptibility to T2DM and its vascular complications is being successfully studied that provides the accumulation of genomic *** the future,this will provide an opportunity to reveal the pathogenetic pathways in the development of the disease and allow to predict the macrovascular complications in T2DM *** review is focused on the evidence of the role of genetic variants and epigenetic changes in the development of macrovascular pathology in diabetic patients.

关键词： Type 2 diabetes Epigenetics Genetics Macrovascular complications

Pathological changes in the cellular structures of retina and choroidea in the early stages of alloxan-induced diabetes

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World Journal of Diabetes 2018年第12期9卷 239-251页

作者： Irina danilova Svetlana Medvedeva Svetlana Shmakova Margarita Chereshneva Alexey Sarapultsev Petr Sarapultsev Department of Biology and Fundamental Medicine Institute of Natural Sciences and Mathematics Ural Federal University Named After the First Pres.of Russia B.N.Yeltsin Laboratory of Morphology and Biochemistry Institute of Immunology and Physiology Ural Division of Russian Academy of Sciences Laboratory of Immunophysiology and Immunopharmacology Institute of Immunology and Physiology Ural Division of Russian Academy of Sciences Institute of Chemical Engineering Ural Federal University Named After the First Pres. of Russia B.N. Yeltsin Laboratory of Immu-nophatophysiology Institute of Immunology and Physiology Ural Division of Russian Academy of Sciences

AIM To investigate the temporal sequence of pathological changes in the cellular structures of retina and choroidea in the early stages of diabetes in laboratory *** Experimental type 1 diabetes was modeled by three intraperitoneal injections of an alloxan solution into 30 male nonlinear rats at 16 wk of age. The 30 th and 60 th days from the final alloxan injection were chosen as the endpoints. Light and electron microscopy and morphometric and immunohistochemical studies were performed on histological slices of eyeballs from experimental *** Diabetic disturbances progressed to 60 d of the experiment. Thus, in the retina, a partial destruction of photoreceptors accompanied by interstitial edema was observed. The morphometric analysis revealed a reduction in the thickness of the retina. A reduction in the number of blood vessels of the choroid with disturbances of the endothelial cells and the vascular walls and a persistent reduction in the number of melanocytes were observed. The number of proliferating Ki-67 positive cells decreased, and the number of macrophages increased with diabetes *** The starting point in the development of destructive changes involves early reduction in the number of melanocytes of the choroidea and alterations in the retinal pigment epithelium.

关键词： Alloxan Diabetes Diabetic retinopathy Early stage Morphology Histological changes

The correctional modification of inflammatory response at the experimental acute pancreatitis

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Advances in Bioscience and Biotechnology 2012年第4期3卷 442-448页

作者： Alex P. Sarapultsev Oleg n. Chupakhin Maxim А. Rantsev Petr А. Sarapultsev Irina G. danilova Svetlana U. Medvedeva Larisa P. Sidorova Federal State Autonomous Educational Institution of Higher Professional Education Ural Federal University named after the first President of Russia B. N. Yeltsin Ekaterinburg Russia Institute of Immunology and Physiology of the Ural Branch of the RAS Ekaterinburg Russia The IJ Postovsky Institute of Organic Synthesis the Ural Branch of the RAS Ekaterinburg Russia

This study investigated the effects of the L-17 compound of the group of substituted 5R1, 6H2-1,3,4- thiadiazine-2-amines on the possibility of inflammatory reaction evolvement correction in experimental acute pancreatitis. The study was based upon recent clinical and experimental work which demonstrated the role of local and systemic inflammatory reactions in pancreatonecrosis. Pancreatonecrosis modeling in rats was performed in accordance with the author’s modification of ligation model of acute pancreatitis. The biochemical and hematological analysis were performed in all groups at day 1. For microscopic analysis, five histological slices of each animal were analyzed. The main group, consisting of 15 animals with the average body weight 223 g each, got intraperitoneal injection of L-17 compound, dozed 40 mg/kg in an hour after surgery of pancreatitis formation. Later on, a 40 mg/kg doze of L-17 compound was repeatedly injected as often as once every 24 hours. Already during the 1st day of the experiment, no leucopenia was observed and the signs of proliferative inflammation were detected. Later, at the background of L-17 compound introduction (5th day of the experiment) the necrosis area got surrounded by demarcation bank, and further on (by the 7th day) had been entirely replaced by granulation tissue. Thus, the application of L-17 compound in experimental acute pan-creatitis results in replacement of destructive purulent inflammation by exudative-proliferative one, prevents lympho- and monocytopenia development, minimizes amylase and pancreatic ferments level during the first day of development of the disease and cuts down the lethality rate as result of pancreatonecrosis complications twofold.

关键词： L-17 Compound Experimental Model Inflammation Acute Pancreatitis

Effect of antigens on colony forming efficiency of stromal clonogenic cells and expression of cytokine genes in primary cultures of bone marrow and spleen of mice

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Advances in Bioscience and Biotechnology 2011年第5期2卷 315-319页

作者： U.F. Gorskaya T.A. danilova M.V. Mezentseva I.M. Shapoval V.G. nesterenko 不详

Presence of microbial cells preparation (HCL – extract of group A streptococcus) in primary cell cultures of bone marrow (BMCC) and spleen (SCC) of CBA mice induced the expression mRnA of proinflammatory cytokines genes: IL-2, IL-6 and IL-8 in BMCC;in SCC cultures mRnA IL-1 β and IL-6 appeared and mRnA IL-4 disappeared. Injection of S. typhimurium antigen complex to mice CBA increased 5 times colony forming efficiency (CFE) and, respectively, content of stromal precursor cells (CFU-F) in femur bone marrow and 9 times in spleen of these animals with maximum at the first day. In both primary BMCC and SCC from immunized animals expression of proinflammatory cytokines genes IL-1 β, IL-6, IL-8 and TnF- α was revealed - in BMCC on 1 - 3 day after immunization, and in SCC – up to 15 days. In CBA mice injected with polyvinylpyrrolidone (PVP) CFE and number of CFU-F in BMCC and SCC increased 1, 9 and 1, 8 times only and expression of genes IL-6, IL-8 and TnF- was observed only on the first day. In СВА/n xid mice there was neither increase CFU-F in the corresponding organs, nor expression of proinflammatory cytokines genes in primary cultures. The data suggest the possibility of positive participation of stromal cells in the development on of immune response in organism. Degree of activation of stromal tissue in immunized mice, apparently, correlates with the degree of immune response, supposing a close relationship between stromal tissue and immune system.

关键词： Stromal Cells-Immunity