Ergodicity Breaking and Self-Destruction of Cancer Cells by Induced Genome Chaos.

During the progression of some cancer cells, the degree of genome instability may increase, leading to genome chaos in populations of malignant cells. While normally chaos is associated with ergodicity, i.e., the state when the time averages of relevant parameters are equal to their phase space averages, the situation with cancer propagation is more complex. Chromothripsis, a catastrophic massive genomic rearrangement, is observed in many types of cancer, leading to increased mutation rates. We present an entropic model of genome chaos and ergodicity and experimental evidence that increasing the degree of chaos beyond the non-ergodic threshold may lead to the self-destruction of some tumor cells. We study time and population averages of chromothripsis frequency in cloned rhabdomyosarcomas from rat stem cells. Clones with frequency above 10% result in cell apoptosis, possibly due to mutations in the BCL2 gene. Potentially, this can be used for suppressing cancer cells by shifting them into a non-ergodic proliferation regime.

Antidiabetic Effects of Bisamide Derivative of Dicarboxylic Acid in Metabolic Disorders.

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.

Analyzing the Effects of Single Nucleotide Polymorphisms on hnRNPA2/B1 Protein Stability and Function: Insights for Anticancer Therapeutic Design.

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is a pivotal player in m6A recognition, RNA metabolism, and antiviral responses. In the context of cancer, overexpression of hnRNPA2/B1, abnormal RNA levels, and m6A depositions are evident. This study focuses on two significant nonsynonymous single nucleotide polymorphisms (nsSNPs) within hnRNPA2/B1, namely, F66L and E92K. Our structural analyses reveal decreased stability in these mutants, with E92K being predicted to undergo destabilizing post-translational methylation. Furthermore, our extensive analysis of 44,239 tumor samples from the COSMIC database uncovers that amino acid position 92 exhibits the second-highest mutation frequency within hnRNPA2/B1, particularly associated with breast and lung cancers. This experimental data aligns with our theoretical studies, highlighting the substantial impact of the nsSNP at position 92 on hnRNPA2/B1's stability and functionality. Given the critical role of pre-mRNA splicing, transcription, and translation regulation in cellular function, it is important to assess the impact of these nsSNPs on the stability and function of the hnRNPA2/B1 protein to design more efficient anticancer therapeutics.

Karyopathological traits of thyrocytes and exposure to radioiodines in Belarusian children and adolescents following the accident at the Chernobyl nuclear power plant.

The Belarus-American (BelAm) thyroid study cohort consists of persons who were 0-18 years of age at the time of exposure to radioactive iodine fallout from the 1986 Chernobyl nuclear power plant accident and 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 75 BelAm subjects with single and multiple thyroid nodules and 47 nodular goiter patients from Leningrad, Russia, unexposed to Chernobyl fallout. Nuclear abnormalities examined included internuclear chromosome bridges and derivative nuclei with broken bridges (i.e., "tailed" nuclei), which are formed from dicentric and ring chromosomes and thus may be cellular markers of radiation exposure. Among subjects with single-nodular goiter, thyrocytes with bridges were present in 86.8% of the exposed BelAm cohort compared with 27.0% of unexposed controls. The average frequency of thyrocytes with bridges and with tailed nuclei was also significantly higher in the BelAm subjects than in controls. Among subjects with multinodular goiters, thyrocytes with bridges were present in 75.7% 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 40% of controls, and the mean frequencies of bridges and tailed nuclei were significantly higher in the exposed group. Unusually, long bridges were detected in 29% of BelAm patients with single-nodular goiters and 35% of those with multinodular goiters, while no such abnormalities were observed among patients from the Leningrad region. In the exposed subjects from BelAm, we also found positive correlations between their estimated dose of Iodine-131 from Chernobyl fallout and the frequency of tailed nuclei (p = 0.008) and bridges (p = 0.09). Further study is needed to confirm that these phenomena represent consequences of radiation exposure in the human organism.

Colonization by Various Morphological Forms of Helicobacter pylori in the Gingival Sulcus and Antrum of the Stomach.

BACKGROUND: Helicobacter pylori eradication therapy can be considered effective if the result of its implementation is removed including all roots and rootlets from which surviving H. pylori can repopulate in the gastric mucosa. One of the reasons for the ineffectiveness of eradication therapy can be the continuous presence of viable coccoid forms of H. pylori in the oral cavity. Therefore, anti-Helicobacter eradication therapy should be supplemented by the sanitation of the oral cavity. OBJECTIVES: The objective of this study is to determine the frequency of occurrence of H. pylori in the gastric mucosa and in the oral cavity in patients with chronic periodontitis or with chronic gastritis using immunocytochemical method and to evaluate the pathophysiological relationship between periodontitis and HP-associated acid-dependent stomach diseases mediated by H. pylori. METHODS: A group of patients with chronic gastritis (70 participants, 46 women, 24 men, age: 24 - 55 years) and another group with chronic periodontitis before the start of surgical treatment (61 participants, 30 women, 31 men, age: 20 - 60 years) were examined for НР bacterial cells using immunocytochemical methods of staining gastric biopsy and exfoliate samples from the gingival sulcus surface. The participants did not take any antimicrobial medication before and during the examination. Routine staining was also performed to view microbiota in smears for both groups. The participants signed a voluntary consent agreement to undergo routine medical examinations and join the study at the Nikiforov Russian Centre of Emergency and Radiation Medicine, EMERCOM of Russia, where the ethical committee was made. RESULTS: Immunocytochemical method could identify all stages of bacillary-coccoid transformation of H. pylori which accounted for 63.4-67.5% of cases. HP-antigenpositive bacteria were found in the oral cavity in both groups of examined patients. It was apparent that spiral forms of H. pylori were dominant over coccoid forms in the gastric mucosa in the antrum of the stomach, whereas coccoid forms of H. pylori were frequently found more in the oral cavity. Helicobacteriosis in the oral cavity was identified in chronic periodontitis. CONCLUSION: We found certain pathogenetic connections between inflammatory lesions of the oral cavity and diseases of the internal organs of the gastrointestinal tract. Accordingly, we suggest the necessity to use proper medication for oral cavity sanitation along with anti-Helicobacter eradication therapy to influence the HP reservoir in the oral cavity and gingival sulcus. Additionally, bacterial cells of HP reside in the oral cavity in coccoid forms; therefore, the coccoid form of HP should become the second principal target in treating HP.

Increased Level of Interleukin-8 in Female Genital Tract After HP Eradication Lines.

BACKGROUND: Antibiotics are known to be effective in treating bacterial infectious disease. Changes in microflora and mucosal dysbiosis may take place after antibiotic treatment. We investigated in this research the effect of anti-Helicobacter pylori treatment (AHT) on local immunity of the female genital tract. METHODS: The study identified the levels of cytokines IL-8 and TNF-α in vaginal secretion in a group of female patients with Helicobacter-associated acid-related diseases who were or were not treated with antibiotics against Helicobacter Pylori. RESULTS: Research outcomes turned out that the secretory cytokine (chemokine) IL-8 is dramatically increased in the vaginal mucosa in patients treated with antibiotics, specifically in post-menopause women. CONCLUSION: Helicobacter pylori eradication treatment affects the immune status of the female genital tract.

Clinical and laboratory importance of detecting Helicobacter pylori coccoid forms for the selection of treatment.

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.

The Frequency of Lymphocytes Containing Dumbbell-Shaped Nuclei Depends on Ionizing Radiation Dose and Correlates with Appearance of Chromosomal Aberrations.

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.