In clinical practice, the metabolic syndrome can lead to multiple complications, including diabetes. It remains unclear which component of the metabolic syndrome (obesity, inflammation, hyperglycemia, or insulin resistance) has the strongest inhibitory effect on stem cells involved in beta cell regeneration. This makes it challenging to develop effective treatment options for complications such as diabetes. In our study, experiments were performed on male C57BL/6 mice where metabolic disorders have been introduced experimentally by a combination of streptozotocin-treatment and a high-fat diet. We evaluated the biological effects of Bisamide Derivative of Dicarboxylic Acid (BDDA) and its impact on pancreatic stem cells in vivo. To assess the impact of BDDA, we applied a combination of histological and biochemical methods along with a cytometric analysis of stem cell and progenitor cell markers. We show that in mice with metabolic disorders, BDDA has a positive effect on lipid and glucose metabolism. The pancreatic restoration was associated with a decrease of the inhibitory effects of inflammation and obesity factors on pancreatic stem cells. Our data shows that BDDA increases the number of pancreatic stem cells. Thus, BDDA could be used as a new compound for treating complication of the metabolic syndrome such as diabetes.
Nuclear anomalies of different types appear in cells in response to the action of ionizing radiation after the passage of the first mitotic division. In this article, we present the results of the study of the frequency of occurrence of three types of nuclear anomalies (“tailed” nuclei, nucleoplasmic bridges, and dumbbell-shaped nuclei) in vitro in human lymphocytes cultured with cytochalasin B when exposed to X-rays at doses of 0.0, 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, and 2.0 Gy. To stop the cell cycle of cultured lymphocytes after the first mitotic division, a cytokinesis block was performed using cytochalasin B. Dose-dependent curves of the occurrence of lymphocytes containing “tailed” nuclei, nucleoplasmic bridges, or dumbbell-shaped nuclei after irradiation have been constructed. At the same time, frequencies of occurrence of chromosomal aberrations (dicentric and ring chromosomes) in the culture of lymphocytes exposed to the same radiation doses were studied. Comparison of the frequencies of occurrence of dicentric and ring chromosomes with frequencies of occurrence of nuclear anomalies allows us to conclude that these nuclear anomalies are formed as a result of chromosomal aberrations arising in lymphocytes under the action of ionizing radiation. More than that, most of the chromosomal aberrations are converted into dumbbell-shaped nuclei in vitro in the culture of lymphocytes in the cytochalasin block.
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The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing β-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1β and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor β-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor β-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing β-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice.
Radiation exposure leads to a large number of victims who seek medical help in the first hours. To provide medical care, it is necessary to correctly establish the fact and dose of radiation by bioindication and biodosimetry methods. Lymphocytes containing nuclear anomalies are easily detected cells of peripheral blood and are suitable as objects of bioindication in the case of radioactive exposure to a large number of people. Among these anomalies we distinguish micronuclei, "tailed" nuclei, nucleoplasmatic bridges, dumbbell-shaped nuclei, etc. This review observes the main types of these nuclear anomalies of lymphocytes in the light of their common origin from dicentric chromosomes. We recommend using these alterations in peripheral blood lymphocytes nuclei as the simplest biomarkers in the framework of bioindication tests when it is necessary to work with a large number of victims.
The Belarus-American (BelAm) Thyroid Study cohort consists of persons 0–18 years of age at the time of exposure to radioiodines from the 1986 Chernobyl nuclear power plant accident who have undergone serial thyroid screenings with referral for fine-needle aspiration biopsy (FNAB) using standardized criteria. We investigated thyrocyte nuclear abnormalities in cytological samples from FNABs in 50 BelAm subjects with thyroid nodules and 43 control patients from Leningrad, Russia, unexposed to Chernobyl fallout. Nuclear abnormalities such as internuclear chromosome bridges and derivative nuclei with broken bridges (i.e., “tailed” nuclei), formed from dicentric and ring chromosomes, may be cellular markers of radiation exposure. In the exposed BelAm cohort, thyrocytes with bridges were present in 80% of subjects with single-nodular goiters compared with 27% of unexposed controls. The average frequency of thyrocytes with bridges was also significantly higher in the BelAm subjects than in controls as was the mean frequency of thyrocytes with tailed nuclei. In the case of multi-nodular goiters, thyrocytes with bridges were present in 75.0% of exposed BelAm patients compared with 16.7% of unexposed controls. Thyrocytes with tailed nuclei were observed in all of the BelAm subjects but in only 35% of controls, and the mean frequency of tailed nuclei was significantly higher. Unusually long bridges were detected in 29% of BelAm patients with single-nodular goiters and 35% of cases with multi-nodular goiters, while no such abnormalities were observed in the follicular thyroid epithelium of patients from the Leningrad region. Further study is needed to understand whether these phenomena represent irradiation consequences in the human organism.
Helicobacter pylori grows and multiplies in the gastrointestinal tract (GIT) in about half of the world's population. The prevalence of diseases associated with this bacterium is steadily increasing, which makes it necessary to search for optimal therapy aimed at eradication of this bacterium. Such diseases, for example, include gastric ulcer (GU) and chronic gastritis (CG). Unfortunately, modern possibilities for eradication therapy do not always make it possible to cure patients, and relapses often occur if it is cured. Nowadays, a particular topical issue has arisen, which concerns the resistance of Helicobacter pylori to therapies, because the effectiveness of medication used in clinics decreases every year. One of the mechanisms favouring tolerance to antibiotics is the transformation into a different morphological form -coccoid. This form of the bacterium was discovered quite a long time ago. Nevertheless, the question of its importance in clinical practice remains open to this day. Modern studies are aimed at understanding the role of coccoid forms of H. pylori in the survival of the population of these bacteria and at clarifying their role in the pathogenesis of gastrointestinal diseases. It is not known whether it is necessary to evaluate the contamination of a given morphological form of a bacterium of the gastric mucosa in clinical practice and its influence on the development of diseases etc. This article presents an overview and analysis of modern ideas about H. pylori coccoid forms and answers to the main questions posed in the last 10 years regarding the study of coccoid forms. Additionally, our results present a comparison of expression of virulence factors in coccoid and spiral forms of H. pylori.
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