Search

The aim. This review aims to provide a comprehensive understanding of dichloroacetic acid derivatives. We aim to cover all aspects of these compounds, including their chemical properties, various synthesis methods, and their wide range of applications in medicinal chemistry. By exploring their diverse roles in drug development, we aim to highlight their importance and potential in shaping future pharmaceutical innovation. Materials and methods. Bibliosemantic and analytical methods are used in the research. Results. Our studies confirm the potential effectiveness of dichloroacetic acid and its derivatives in the treatment of cancer and other diseases. These compounds can induce the apoptosis process, which is the programmed cell death, and inhibit the cancer cells' growth. This is particularly effective when dichloroacetic acid and its derivatives are used in combination with other therapeutic methods, as indicated in the patents cited in our study. Dichloroacetic acid and its derivatives have also shown the ability to lower blood glucose and cholesterol levels. This indicates the possibility of their use for diabetes, hyperlipidemia, and lactic acidosis treatment. Diabetes, hyperlipidemia, and lactic acidosis are serious conditions that can lead to significant health problems. Therefore, the possibility of using dichloroacetic acid and its derivatives for the treatment of these conditions opens new perspectives in medical science. Conclusions. Our findings point to the prospects of further research in the field of new therapy methods development and the use of dichloroacetic acid derivatives as potential drugs to improve the effectiveness of cancer and other diseases treatment. We believe that these compounds have great potential for further study and may play an important role in future medical innovation. [ABSTRACT FROM AUTHOR]

Проблематика. Експериментальне вивчення протипухлинної дії нанокомплексів (НК), що складаються з наночастинок GdYEuVO4 і холестерину, свідчить про доцільність їх використання в онкологічній практиці. Механізм реалізації протипухлинної дії НК може бути пов’язаний з утворенням під їхнім впливом активних форм кисню (АФК), які зумовлюють загибель пухлинних клітин. Мета. Вивчення прооксидантних і протипухлинних властивостей НК, що складаються з наночастинок GdYEuVO4 і холестерину, в системі in vitro. Методика реалізації. Експерименти проводили на клітинах асцитної аденокарциноми Ерліха (АКЕ), які перещеплювали внутрішньочеревно мишам лінії BALB/c. На 7-му добу розвитку АКЕ клітини виділяли та in vitro обробляли НК протягом 3 год. Контролем були клітини, не оброблені НК. Формування внутрішньоклітинних АФК визначали методом проточної цитометрії з використанням набору Fluorometric Intracellular ROS Kit, рівень метаболічної активності клітин АКЕ – за допомогою МТТ-тесту колориметричним методом, кількість клітин у стані апоптозу або некрозу оцінювали з використанням проточної цитометрії та набору реагентів FITC Annexin V Apoptosis Detection Kit I. Результати. Інкубація клітин АКЕ з НК приводить до більш ніж трикратного посилення порівняно з контролем формування АФК. Під впливом НК також відбувається майже двократне пригнічення метаболічної активності клітин АКЕ, що супроводжувалося зменшенням на 25 % кількості життєздат­них клітин АКЕ. Показано, що НК належать до тих унікальних сполук, які одночасно можуть викликати кілька видів загибелі клітин, але загибель пухлинних клітин після обробки НК відбувалася переважно унаслідок некрозу. Висновки. Цитотоксична дія НК відносно клітин АКЕ реалізується за рахунок їхніх прооксидантних властивостей. Отримані результати можуть бути враховані при створенні нових стратегій терапії злоякісних новоутворень.

The aim of the research - to determine the level of BAX, caspase-3, GRP78, IRE1 and Beclin-1 in the cerebral cortex of rats with chronic ethanol consumption and under conditions of exposure to the germanium complex with nicotinic acid (MIGU-1). Materials and methods. Female rats had free access to 20 % C2H5OH as the only source of fluid for 110 days. Starting from the 90th day, the animals were injected with MIGU-1 (10 mg/kg/day, IP). The expression level of BAX, caspase-3, GRP78, IRE1 and Beclin-1 in the tissue was determined by Western blot analysis. Results. In rats with chronic ethanol consumption, the level of BAX-dimer increased by 2.06 times (p˂0.001). The introduction of MIGU-1 caused a decrease in the level of BAX-dimer by 1.42 times (p˂0.05). In rats with chronic ethanol consumption, the level of caspase-3 increased by 2.12 times (p˂0.05), cleaved caspase-3 increased by 6.37 times (p˂0.05). When MIGU-1 was administered, the level of caspase-3 decreased by 1.73 times (p˂0.05). Under the conditions of MIGU-1 administration, protein bands of cleaved caspase-3 were reduced to an undetectable level. In rats with chronic ethanol consumption, the level of GRP78 increased by 1.72 times (p˂0.05). After administration of MIGU-1, no changes in the level of GRP78 were recorded. Long-term ethanol consumption increased the levels of IRE1 by 1.74 times (p˂0.05) and p-IRE1 by 2.7 times (p˂0.001). In the presence of MIGU-1, the levels of IRE1 and p-IRE1 did not change. Under the conditions of chronic ethanol consumption, an increase in the levels of Beclin-1 by 2.33 times (p˂0.001) and p-Beclin-1 by 4.69 times (p˂0.001) was observed. Administration of MIGU-1 did not affect the level of Beclin-1, while the level of p-Beclin-1 decreased by 3.09 times (p˂0.001). Conclusions. Long-term ethanol consumption triggers metabolic changes in the cerebral cortex, resulting in ER stress, UPR activation, autophagy, and apoptosis. Administration of MIGU-1 alleviates ER stress by selectively inhibiting specific branches of apoptosis through effects on Beclin-1 levels, suggesting an effect of MIGU-1 on neuronal survival under chronic ethanol consumption. [ABSTRACT FROM AUTHOR]

Aim. PFKFB3 is glycolytic activator that overexpressed in human lung cancer and plays a crucial role in multiple cellular functions including programmed cell death. Despite the many small molecules described as PFKFB3 inhibitors, some of them have shown disappointing results in vitro and in vivo. On the other hand KAN0438757, selective and potent, small molecule inhibitor has been developed. However, the effects of KAN0438757, in non-small cell lung carcinoma cells remain unknown. Herein, we sought to decipher the effect of KAN0438757 on proliferation, migration, DNA damage, and programmed cell death in non-small cell lung carcinoma cells Methods. The effects of KAN0438757 on cell viability, proliferation, DNA damage, migration, apoptosis, and autophagy in non-small cell lung carcinoma cells were tested by WST-1, real-time cell analysis, comet assay, wound-healing migration test, and MMP/JC-1 and AO/ER dual staining assays as well as western blot analysis. Results. Our results revealed that KAN0438757 significantly suppressed the viability and proliferation of A549 and H1299 cells and inhibited migration of A549 cells. More importantly, KAN0438757 caused DNA damage and triggered apoptosis and this was accompanied by the up-regulation of cleaved PARP in A549 cells. Furthermore, treatment with KAN0438757 resulted in increased LC3 II and Beclin1, which indicated that KAN0438757 stimulated autophagy. Conclusions. Overall, targeting PFKFB3 with KAN0438757 may be a promising effective treatment approach, requiring further in vitro and in vivo evaluation of KAN0438757 as a therapy in non-small cell lung carcinoma cells. [ABSTRACT FROM AUTHOR]

The aim of our work is to assess the viability and determine the types of death of blood leukocytes in rats with polycystic ovary syndrome (PCOS) under conditions of intermittent cold exposure. The study was performed on 40 immature female rats of the WAG population, aged 27 days, divided into 5 groups of 8 animals each. Group 1 included intact rats. In group 2, rats were subcutaneously injected with 0.2 ml of purified and sterilized olive oil daily for 25 days. In group 3, rats were exposed to periodic cold exposure daily for 25 days. In group 4, dehydroepiandrosterone-induced PCOS was modeled in rats. In group 5, rats were injected with dehydroepiandrosterone against the background of periodic cold exposure. Leukocyte viability and death pathways were determined using a FACS Canto II flow cytometer (Becton Dickinson, USA). Rats with dehydroepiandrosteroneinduced PCOS showed a decrease in the percentage of viable leukocytes and an increase in the percentage of leukocytes in the early stage of apoptosis, while the number of leukocytes in the late stage of apoptosis and necrotic leukocytes did not change. In rats, on the background of the introduction of dehydroepiandrosterone under conditions of intermittent cold exposure, the percentage of viable leukocytes, as well as leukocytes at different stages of apoptosis and necrosis, corresponded to the physiological norm. Thus, the authors revealed a decrease in the viability of neutrophilic leukocytes in the blood of rats with dehydroepiandrosterone-induced PCOS due to the activation of apoptosis processes, as evidenced by an increase in the percentage of leukocytes at the initial stages of apoptosis. Intermittent cold exposure (4 h daily at +4°C for 25 days) against the background of dehydroepiandrosterone administration to rats had an anti-apoptotic effect, normalizing the viability of neutrophilic blood leukocytes. [ABSTRACT FROM AUTHOR]

The subject of the study (observations). Questions of the apoptotic process in the development of fibroplastic changes in pneumoconiosis in miners. The purpose of the study – to substantiate the contribution of the genetic factor associated with genome polymorphism in the development of dust pathology in miners. Identification of gene variants as markers of individual predisposition to the development of pneumoconiosis. Research methods. Theoretical basis.

Unfavorable working conditions of miners are a risk factor for the development of fibroplastic and neoplastic processes. The literature does not sufficiently cover the issues of fibrous transformation, histogenetic mechanisms of neoplastic processes in PC with subsequent neoplastic transitions of this tissue. Occupational dust pathology of respiratory organs in Kuzbass remains relevant due to its high prevalence among workers of the coal industry. Entering the body, various components of coal cause the development of pneumoconiotic fibrosis. New ideas about the histogenesis of fibrosis in recent years have shifted to the molecular level and appeal to the state of cellular receptors, the expression of some genes and the repression of others, the study of apoptosis processes, changes in cellular phenotype, as well as endothelial damage, which is the platform on which pathological processes occur in the future. The relevance of the problem. The Kemerovo region is the largest coal mining region in Russia, it is here that 58 % of the «black» fuel in the country is obtained. The Kuznetsk Coal Basin, the richest coal deposit in the world, is located on the territory of Kuzbass. Of the total reserves, 140 billion tons of coal are suitable for mining. At the same time, the coal industry is associated with difficult and dangerous working conditions, which are risk factors for occupational dust pathology of the respiratory organs. The aim of the study was to identify trigger morphological mechanisms of the development of oncological pathology in miners with signs of pneumofibrosis, based on pathomorphological, immunohistochemical studies of changes in the tissue of the airways during epithelial-mesenchymal transformation, apoptotic activity, proliferation of smooth muscle cells (MMC) and endothelial dysfunction. Materials and methods. Histological, morphometric and immunohistochemical studies of pulmonary histione obtained during 60 autopsy operations of a group of Kuzbass miners. All structural elements of lung tissue were studied. Immunohistochemical study was performed using monoclonal antibodies (proliferation marker Ki-67; oncogene of proapoptotic activity Vcl-2; endothelial function factors CD-31 and CD-34, macrophage factor NAM 56). The object of the study was histological, immunohistochemical and morphometric changes under microscopy, as well as interstitial correlations of these structures. Morphometric measurement of straight and curved linear dimensions of structures and their areas was carried out on an Olympus CX 31 microscope with a Nikon digital sight – Fi1 digital video camera. Morphometry was performed in structures without signs of traumatic effects. Results. Coal industry workers have pronounced changes in lung tissue, which manifest themselves in pronounced fibroplastic tissue transformation. These pathological changes cause the development of EMT with a likely transition to neoplastic tissue. The main source of fibrosis development in the lungs are activated myofibroblasts, the precursors of which can be as resident fibroblast-like cells. Dedifferentiated epithelial cells, MMCs, as well as endothelial cells can act as a source. Conclusions. The idea of fibrous tissue as a precursor of neoplastic processes in PC is only one facet of the histogenetic understanding of cellular transformation as a mechanism of the main pathological changes in pneumoconiosis. Intracellular changes occurring in PC should serve as a foundation for further in-depth study of complex pathogenetic aspects in medicine.

Objective: to determine the presence of changes in peripheral blood parameters, characterizing its redox state, and the level of apoptosis of lymphocyte in radiologists-x-ray technologies who, due to their official duties, are exposed to small doses of ionizing radiation. Object and methods: The work was performed on blood samples of 45 professionals radiologists-x-ray technologies and 52 conventionally healthy individuals (control group). The content of malondialdehyde and sulfhydryl groups of proteins and peptides (-SH) in blood plasma was determined; catalase enzyme activity and the ratio of pro-antioxidant processes in hemolysates, the level of superoxide anion-radical (O2-*) generation, the total production of free radical compounds (reactive forms of oxygen and nitrogen) and the level of apoptosis of peripheral blood lymphocytes (PBL). Results: The content of malondialdehyde in the blood of professionals was increased by 1.49 times and the content of -SH was decreased by 1.67 times compared to conventionally healthy individuals. An increase in the level of O2-* production by 1.56 times was observed for PBL. The obtained results indicate a shift in the ratio between antioxidant and pro-oxidant processes towards the latter, which is confirmed by a 1.49-fold increase of this index. The level for PBL apoptosis was reduced by 1.35 times. For professionals, against the background of increased generation of O2- *, a reliable direct correlation was observed between the indicator of apoptosis and the total production of free radical compounds, and between the latter and the level of apoptosis of lymphocytes, which was not noted for the conventionally healthy individuals group. Conclusion: A change in the ratio between pro- and antioxidant processes in the blood was found for professionals who are in contact with sources of ionizing radiation, which indicates the possibility of the development of oxidative stress, and the consequence of a reduced level of apoptosis of lymphocytes may be the danger of accumulating genetic damage in these cells. [ABSTRACT FROM AUTHOR]

Aim. To study the effect of vaginal probiotic therapy on the outcome of human papillomavirus (HPV) infection.Materials and methods. The study included HPV-infected patients: 29 patients with normal vaginal flora and 146 patients with a deficiency of vaginal lactobacilli, of which 117 patients received vaginal probiotic therapy. In samples obtained before and after the therapy, the effect of the probiotic on the change in the ratio of living, apoptotic, and necrotic vaginal epithelial cells after preliminary exposure to oxidative stress was studied.Results. It was found that probiotics reduce the number of infected epithelial cells that survived the oxidative damage and shift the balance of cell death forms towards apoptosis. Vaginal probiotic therapy in patients with a deficiency of lactobacilli increased the frequency of HPV elimination by 2.5 times and reduced the likelihood of treatment failure from 1.5 to 4 times, depending on the viral load. The probiotic therapy made the structure of HPV outcomes in Lactobacillus-deficient patients similar to that in patients with normal vaginal flora.Conclusion. Vaginal probiotic therapy improves outcomes of HPV infection in patients with a deficiency of lactobacilli by reducing the number of survived infected cells and shifting the cell death pattern towards apoptosis.

Процессы апоптоза и некроза являются механизмами программируемой гибели клеток, отличающиеся друг от друга механизмами их реализации. Данные процессы в пределах физиологической нормы представляют интерес в оценке их влияния на активность иммунных реакций. Цель. Выявить характер взаимосвязи уровня некроза и апоптоза лимфоцитов периферической крови и выраженности реакций иммунной системы у практически здоровых людей. Материалы и методы. Проведено обследование 77 человек. Клинический анализ периферической крови проведён на гематологическом анализаторе Sysmex XS-500i (Япония). Изучение содержания апоптотических и некротических клеток выполнено на проточном цитометре Epics XL (Beckman Coulter, США). ИФА в сыворотке крови определено содержание цитокинов, иммуноглобулинов (Bender MedSystems, Австрия) и серотонина (DRG, Германия). Результаты исследования обработаны с использованием пакета прикладных программ Statistica 6 (StatSoft, США). Результаты. Установлено, что повышенный уровень некротизированных лимфоцитов сочетается с увеличением числа апоптотических лимфоцитов, Т-хелперов, лимфоцитов CD95+, IgA, IgE, IgG на фоне сокращения уровня клеток с рецепторами к белкам главного комплекса гистосовместимости класса II и к Fc-фрагменту IgE, провоспалительных цитокинов (IFN-γ, IL-6) и серотонина. Некротическая гибель не ассоциирована с клеточным цитолизом по содержанию цитотоксических Т-лимфоцитов и натуральных киллеров, но обратно взаимосвязана с реакцией фагоцитоза нейтрофилов. Заключение. Таким образом, некротическая гибель лимфоцитов в пределах физиологических границ в отличие от апоптоза повышает активность иммунных реакций. Некрозу и апоптозу подвергаются преимущественно зрелые В-клетки с рецепторами к IgE и белкам главного комплекса гистосовместимости класса II.

This literature review is devoted to the molecular mechanisms of oogenesis and depletion of the ovarian reserve. One of the factors in this process is constantly changing environment of the ovaries, both during intrauterine development and the postnatal period. Numerous mechanisms and factors affecting the internal environment of the female gonad are described, such as stem cell factor (SCF), which regulates migration of primordial germ cells and survival of early oocytes, insulin-like growth factor I (IGF-I), and leukocyte migration inhibitory factor (LMIF). The capabilities of the endocrine system, namely sex steroids, which can both replenish the number of germ cells and deplete the ovarian reserve through the expression of apoptotic markers, were shown. Apoptosis causes degeneration of most of the germ cells formed during oogenesis. The molecular mechanisms and factors involved in this process are numerous.Pathways mediated by mitochondria of germ cells and external pathways mediated by receptors of the cell surface were described. A mediator between two apoptotic pathways was established – the Bid protein (BH3-interacting domain death agonist), the activation of which triggers the apoptosis mechanism of the intrafollicular microenvironment. Some other factors were identified that mediate programmed germ cell death and result in diminished ovarian reserve: eukaryotic elongation factor 2 kinase (eEF-2 K), PUMA and NOXA genes, the absence of growth factors and members of tumor necrosis factor (TNF) family. Changes in the epigenetic modification of chromatin in the follicular and germ cells, oxidative stress, decreased DNA repair, and the involvement of the genes BRAC1, RAD51, ERCC2, and H2AX associated with this process can also affect reproductive health and the ovarian reserve. A significant role of mitochondrial dysfunction of follicular cells in depletion of the ovarian reserve is of great interest, which leads to impaired oocyte competence, deteriorates the gamete quality, and depletes the ovarian reserve. Therefore, oogenesis depends on a huge number of factors and the internal environment of the ovaries, the knowledge of which can maintain the stability of the reproductive function and preserve the quality of the ovarian reserve.

Background. Recent studies demonstrated immunosuppressive properties of vascular endothelial growth factor (VEGF-A) and identified VEGF-A as a key mediator of tumor-induced immunosuppression. Placental growth factor (PlGF) is another member of VEGF family in which dramatic elevation is associated with effective immune adaptation in successful pregnancy, whereas low concentrations are related to pregnancy complications resulting from the activation of immune system. Previously, we have shown that activated T cells express VEGF receptor type 1 (VEGFR-1), and PlGF inhibits T cell proliferation in VEGFR-1–dependent manner.The aim of the present study was to further characterize PlGF effects on T cell responses in vitro.Materials and methods. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated with anti-CD3 monoclonal antibodies (a-CD3) in the absence or presence of PlGF and assessed for IL-10 production, programmed cell death and the expression of inhibitory receptors (PD-1, CTLA-4, Tim-3) in CD4+ and CD8+ T cell subsets.Results. The addition of PlGF to PBMC cultures activated with a-CD3 resulted in increased percentages of IL- 10-producing CD4+ and CD8+ T cells. Besides, PlGF promoted CD8+ T cells apoptosis while did not affect programmed cell death within CD4+ T cells. Notable, T cell activation with a-CD3 in the presence of PlGF was accompanied by the enhancement of PD-1-expressing cells in CD8+ T cell subset and Tim-3-expressing cells in both CD4+ and CD8+ T cells, and by the increased expression of PD-1 and Tim-3 on T cells.Conclusion. Our in vitro findings indicate that PlGF can inhibit T cell responses due to the increasing interleukin-10 (IL-10) production, promoting CD8+ T cell apoptosis and enhancing the expression of PD-1 and Tim-3 inhibitory receptors. Given the elevated levels of PlGF in successful pregnancy and its decrease in gestation complications, the obtained data also suggest that PlGF-mediated suppression may be implicated into the governing immune evasion in pregnancy.

Aim: analysis of all known markers of proliferation, apoptosis, autophagy and angiogenesis in the pathogenesis of Barrett’s esophagus and esophageal adenocarcinoma with the purpose of improvement of diagnostics and treatment quality.Materials and methods. Analysis of the available scientific sources by Russian and foreign authors.Results. Data on all the known markers has been structured and is supposed to be integrated into clinical practice in the diagnosis and treatment of Barrett’s esophagus and esophageal adenocarcinoma at various stages of disease development.

The effect of synthetic leu-enkephalin (dalargin) on apoptosis and necrosis in leukocytes after cold stress on the morphological characteristics of cells and using fluorescent dyes Hoechst 33342 as well as propidium iodide was studied. The degree of cold stress influence depending on the duration of incubation of cell suspension at 0-2 and 37°C on the initiation of apoptosis and necrosis on the morphological characteristics of cells was determined. It has been proven that the ratio of apoptotic cells to necrotic ones was maximal after the use of the regimen as follows: preliminary incubation of leukocytes at 37°C - 15 min, cell exposure at 0-2°C - 15 min and subsequent incubation of leukocytes at 37°C. It has been confirmed that pre-incubation of cells with neuropeptide to cold stress affects the effectiveness of the protective action of dalargin, in particular, contributes to a significant (p ≤ 0.05) reduction in the percentage of leukocytes with morphological signs of apoptosis and necrosis. It was found that a consistent increase in temperature after cold stress to 37°C did not affect the percentage of cells with morphological signs of apoptosis and necrosis. It has been validated that the percentage of leukocytes with the apoptosis and necrosis signs after cold stress was significantly reduced after incubation of leukocytes with dalargin at a concentration of 10-9 mol/l. [ABSTRACT FROM AUTHOR]

Background. The universal molecular characteristics of malignancy are activation of cell proliferation and inactivation of apoptotic cell death. Besides genes-regulators of the processes other molecules are involved, including mucins and Cdx-2. Aim. To conduct comparative and correlation analysis of indexes of immunohistochemical expression of Ki-67, p53, caspase-3, as well as MUC-1 and Cdx-2 in distal colonic polyps. Methods. Pathohistological and immunohistochemical studies of biopsies of adenomas and hyperplastic polyps from 40 patients were carried out. Results. Distal colonic polyps are characterized by medium proliferation level: the median of Ki-67 expression for hyperplastic polyps is 42,20 (35,27; 52,38) %, while the median for adenomas is 65,39 (52,28; 76,23) % (р˂0,05). The polyps are characterized by low p53 expression levels: the median of the marker expression for hyperplastic polyps is 1,53 (1,17; 3,16) %, for adenomas – 9,15 (8,26; 12,39) % (р˂0,05). The studied polyps are characterized by low apoptosis levels: the median of caspase-3 expression for hyperplastic polyps is 33,78 (30,28; 42,34) CUOD, for adenomas – 22,19 (16,84; 40,51) CUOD (р˂0,05). Distal colonic polyps are characterized by medium MUC-1 and Cdx-2 expression levels: the medians of the markers expression for hyperplastic polyps are 62,13 (34,20; 71,85) CUOD and 71,81 (62,36; 77,77) CUOD, for adenomas – 80,25 (52,14; 95,21) CUOD and 95,14 (81,19; 112,17) CUOD, respectively (р˂0,05). The correlation analysis revealed several correlations: reverse medium strength correlation between p53 and caspase-3 expression levels (r = -0,57, р˂0,05), direct medium strength correlation between caspase-3 and MUC-1 expression levels (r = 0,52, p˂0,05) take place in hyperplastic polyps, whereas reverse strong correlation between caspase-3 and MUC-1 expression levels 1 (r = -0,88, p˂0,05) takes place in adenomas. Conclusions. Distal colonic adenomas differ by higher proliferation and p53 expression levels, comparing to hyperplastic polyps, and by lower apoptosis level that is associated with higher MUC-1 expression level as well. Hyperplastic polyps differ by higher apoptosis level that is associated with lower MUC-1 expression level. Cdx-2 expression increases on benign adenoma stage and does not correlate with proliferation and apoptosis indexes.

Relevance. Impairment of apoptosis regulation in P19 cells is correlated with generation of oxidative stress. Under hypoxia, changes in mitochondrial functions occur, which may exacerbate oxidative stress in the tumor cell. The aim of the study was to evaluate the effects of N-ethylmaleimide and 1,4-dithioerythritol on implementation and regulation of apoptosis in P19 cells under hypoxia in vitro.Materials and methods. P19 cells (mouse teratocarcinoma) cultured under hypoxia served as the material for the study. For redox status modulation, 5mM N-ethylmaleimide and 1,4-dithioerythritol in the final concentrations of 5 mM were used. The intracellular concentration of calcium ions, the transmembrane potential and the number of Annexin V, CD95 and CD120 positive cells were determined by flow cytometry. The levels of reduced, oxidized and protein-bound glutathione, protein SH groups, hydroxyl radical and protein carbonyl derivatives were measured by spectrophotometry.Results. The alteration in the redox status of the glutathione system under hypoxia, accompanied by oxidative modification of proteins (glutathionylation and carbonylation), influences the metabolism in the tumor cell on the whole. Under the effects of 1,4-dithioerythritol, an SH group protector, this alteration promotes formation of additional mechanisms to escape apoptosis, whereas under the effects of N-ethylmaleimide, an SH group blocker, it, on the contrary, promotes apoptosis activation.Conclusions. The changes in the redox homeostasis of the tumor cell and modulation of oxidative modification of proteins (glutathionylation and carbonylation) under hypoxia are one of the promising approaches to targeted regulation of cell death.

The studies were conducted on 2-3-months-old males of C57BL/6 mice weighing 20-24 g. Obtaining and operating with adipose tissue-derived mesenchymal stem cell (MSC) culture was performed in a sterile laminar box under conditions of asepsis and antiseptics. The adipose tissue-derived MSC of the 2, 4, 7 and 12 passages were analyzed. Morphometric analysis was performed using a light microscopy. Morphometric parameters such as cell and nucleus area or nuclear-cytoplasmic ratio were calculated using the Axiovision light microscope (Carl Zeiss, Germany) and Image J 1.45 software. Trypan blue dye used for investigation of the viability of MSC. The morphological characteristics of adipose tissue-derived MSC during the process of cultivation changes: at the first passages of cultivation, the cells are spindle-shaped with two, at least three, long cytoplasmic processes, which are located bipolar. Near the nucleus, the Golgi complex is clearly visible - a sign of active cells. At later passages, cells have a small cytoplasmic processes and the bipolar arrangement of processes changes by stellar arrangement. Golgi complex is also clearly visualized. The indicator of the nuclearcytoplasmic ratio in MSC from adipose tissue is significantly reduced at the 7th passage to 0.2189 ± 0.0122 (P < 0.01), and at the 12th passage to 0.1111 ± 0.0086 (P < 0.001) compared to the 2nd passage. The coefficient of proliferation of adipose tissue-derived MSC is significantly reduced at 12th passage. The viability of MSC from adipose tissue with an increasing of a number of passages significantly reduces and at the 12th passage of cultivation reaches 84.67 ± 1.36 (P < 0.05). The content of apoptotic cells that exhibited sensitivity to serum-free cultivation significantly increased at the 7th and 12th passages and was 21.33 ± 1.36 (P < 0.05) and 23.67 ± 0.97% (P < 0.05), respectively. [ABSTRACT FROM AUTHOR]

The study of indicators of cellular renewal of epithelial cells of the gastric mucosa in atrophic gastritis can optimize diagnostic and therapeutic approaches, given that this form of gastritis is a precancerous disease. Markers of proliferation and apoptosis of Ki-67, PCNA, p53 and bcl-2 in gastrobioptates of patients aged 45–60 years with non-atrophic and atrophic gastritis were determined by immunohistochemistry. As a result of the study, the proliferative-apoptotic status of epithelial cells of the gastric mucosa was determined, which leads to a conclusion about the reduction of reparative processes.

За даними досліджень, частота летальності серед пацієнтів похилого та старечого віку після проведення аортокоронарного шунтування складає від 3 до 11 %, разом з тим, як ускладнення виникають у 30–40 % випадках. Одним із найчастіших порушень, яке можна спостерігати в ранній післяопераційний період, та яке безпосередньо загрожує життю пацієнтів, є післяопераційна кардіальна дисфункція. Важливу роль у її патогенезі займає зростання загибелі кардіоміоцитів шляхом апоптозу. Мета дослідження – вивчити вираження впливу на апоптичні реакції різних схем анестезіологічного забезпечення у пацієнтів з ішемічною хворою серця (ІХС) при аортокоронарному шунтуванні (АКШ) в умовах штучного кровообігу. Матеріали і методи. У дослідження включено 20 пацієнтів з ІХС, яким виконували АКШ-3 в умовах штучного кровообігу. Середній вік хворих склав (68,5±4,1) року. Чоловіків було 70,0 %, жінок – 30,0 %. Залежно від схеми анестезіологічного забезпечення, усіх пацієнтів поділили на 2 групи: перша (10 осіб) – із використанням в якості гіпнотика “Cевофлуран”; друга групи (10 осіб) – із застосуванням засобу “Пропофол”. Локальний захист міокарда – штучна елeктричнa фібриляція. Зразки біоптату міокарда забирали з вушка правого передсердя. Гістологічні зрізи використовували для проведення імуногістохімічних досліджень із застосуванням первинних антитіл проти білків ВAX, Bcl-2 та каспази – 3 (DAKO). Результати досліджень та їх обговорення. При схемі анестезіологічного забезпечення із застосуванням севофлурану як гіпнотика, експресія антиапоптичного гена Вcl-2 виявлялась у 5 разів (р=0,003) вищою, порівняно з аналогічними значеннями, отриманими від пацієнтів, де використовували пропофол. Експресія проапоптичних генів Срр-32 і ВАХ в групі з анестезією севофлураном була у 3 (р=0,032) і 2 разів (р=0,011) відповідно, достовірно меншою, порівняно з показниками при використанні пропофолу. Висновки. За рахунок підвищення експресії антиапоптичного гена Вcl-2 і зниження експресії проапоптичних генів Срр-32 і ВАХ, севофлуран достовірно менше, порівняно з пропофолом, впливає на активацію апоптозу, внаслідок чого зменшується вірогідність програмованої клітинної загибелі міокардіоцитів.

Objective – to conduct an analytical review of modern sources of scientific literature on the pathogenesis of uterine fibroids and risk factors of its development. Materials and methods. Conducted analysis of 38 foreign and 22 domestic sources on this topic. Results. Based on the analysis of the latest scientific data, the review describes the key factors that trigger the development of uterine fibroids; presented modern theories of pathogenesis of this disease. Despite of learning a large number of researched pathogenetic mechanisms of uterine fibroids, at present there is no single clear opinion about the etiology and pathogenesis of this tumor, and many questions remain unresolved. Conclusion. Our analysis shows that uterine myoma is a multifactorial disease and can develop through various pathogenetic mechanisms, which requires further study.

Background. It’s well known that colonic polyps can be precursors of colorectal cancer. But exact immunohistochemical parameters, including proliferation and apoptosis levels of polyps’ cells, that may have prognostic value, still not known. Objective. To study the features of immunohistochemical expression of proliferation and apoptosis markers by distal colonic polyps’ cells. Methods. Pathomorphological and immunohistochemical studies of biopsies of distal colonic polyps from 30 patients (the age ranged from 41 to 83 years) were carried out. Results. Distal colonic polyps are characterized by the medium proliferation level of epithelial cells [Me=62.40% (48.65; 76.23) for adenomas, Me=26.23% (22.19; 48.88) for hyperplastic polyps], the low proliferation level of stromal cells [Me=2.94% (1.23; 4.35) for adenomas, Me=1.18% (1.10; 1.86) for hyperplastic polyps], the low p53 expression level of epithelial and stromal cells [Me=2.39% (1.58; 8.26) and Me=1.23% (0.72; 1.49) for adenomas’ cells, Me=0,00% (0,00; 1,47) and Me=0,00% (0,00; 0,05) for hyperplastic polyps’ cells], and also by the low apoptosis level of epithelial and stromal cells [Me=31.84CUOD (19.53; 42.34) and Me=43.87CUOD (25.47; 73.09) for adenomas, Me=16.99CUOD (11.86; 39.85) and Me=28.64CUOD (19.20; 30.71) for hyperplastic polyps]. There are direct correlations between the expression levels of proliferation and apoptosis markers and also the dysplasia grade of the distal colonic adenomas: between the Ki-67 expression levels of epithelial and stromal cells and also the dysplasia grade (γ=0.65 and γ=0.70, respectively), between the p53 expression level of epithelial cells and the dysplasia grade (γ=0.53), between the caspase-3 expression levels of epithelial and stromal cells and also the dysplasia grade (γ=0.80 and γ=0.63, respectively). Moreover, there are direct correlations between the expression levels of proliferation and apoptosis markers of distal colonic polyps’ epitheliocytes: between the Ki-67 and p53 expression levels (r=0.71 for adenomas, r=0.79 for hyperplastic polyps), between the Ki-67 and caspase-3 expression levels (r=0.61 for adenomas), between the p53 and caspase-3 expression levels (r=0.59 for adenomas, r=0.79 for hyperplastic polyps). Conclusion. These data indicate the close association between the processes of proliferation, accumulation of p53 protein, and apoptosis of the distal colonic polyps’ cells.

The review describes main classes of extracellular microvesicular particles, mechanisms of their biogenesis and their potential role in the development of tuberculosis. Special attention is paid to apoptosis of macrophages infected with tuberculous mycobacteria, generation of apoptotic ectosome and involvement of the latter into the formation of anti-tuberculosis immune response. Conclusion: mechanisms of apoptotic blebbing, ectosomes and clearing of these particles possess the potential to become a new tool within pathogenetic therapy of tuberculosis.

Oxidative stress resulted to decrease in cells viability compared to the control (78 ± 5 % and 100 ± 6 %, respectively, р < 0,05). GK-2 and NGF prevented H2O2-induced HUVEC cells damages (95 ± 3 % for HA-2 and 97 ± 4 % for NGF vs. 78 ± 5 % for H2O2, p < 0.05). In control the number of cells with condensed chromatin was 9 ± 2, after the addition of H2O2 78 ± 9 (p < 0.05 compared with the control). The addition of NGF or GK-2 after H2O2 significantly reduced the number of such cells (44 ± 9 and 41 ± 8, respectively) (p < 0.05 compared to hydrogen peroxide) and prevented the development of morphological changes in nuclear chromatin. Thus GK-2, like NGF, in human endothelial cell culture HUVEC prevented the apoptosis development caused by hydrogen peroxide.

Цель исследования. Изучить влияние хлорида лития на эндотелиоциты в монослое in vitro под действием сывороток крови пациентов с синдромом системной воспалительной реакции (СВР) на фоне тяжелой сочетанной травмы. Материалы и методы. При проведении исследования использовали токсичную сыворотку крови 5 больных с тяжелой сочетанной травмой. В контроле использовали сыворотку крови 5 практически здоровых доноров. В разных сериях эксперимента эндотелиальные клетки линии EA.hy926 инкубировали с сывороткой крови здорового человека (контроль) и пациентов с СВР на фоне тяжелой сочетанной травмы. К образцам клеток добавляли хлорид лития в конечных концентрациях 0,01; 0,1; 1; 10 ммоль/л. После инкубации клетки снимали раствором трипсина-версена, фиксировали 70% этанолом и окрашивали йодистым пропидием. Клетки, содержавшие фрагментированную геномную дезоксирибонуклеиновую кислоту, анализировали с помощью проточной цитофлуориметрии. Результаты. Установлено, что токсичная сыворотка подавляла фосфорилирование киназы гликогенсинтазы 3β (GSK-3β) в эндотелиоцитах, а также вызывала расщепление Vascular endothelial (VE)-кадгерина, уменьшение количества клаудина и актина, инициируя разрушение межклеточных контактов эндотелиального монослоя и апоптоз эндотелиоцитов. Инкубация монослоя эндотелиоцитов с хлоридом лития в концентрации от 1 ммоль/л и выше практически полностью предотвращала разборку клаудина, актина и VE-кадгерина, а также более чем в 2 раза снижала интенсивность апоптоза эндотелиоцитов. Было обнаружено, что прединкубация с хлоридом лития в концентрации 1 ммоль/л не только предотвращала инактивацию GSK-3β, но и, наоборот, стимулировала ее фосфорилирование. Заключение. Хлорид лития предотвращает разборку клаудина и VE-кадгерина в межклеточных контактах, уменьшает количество апоптотических клеток в монослое эндотелиальных клеток линии EA.hy926 под действием сыворотки крови пациентов с СВР на фоне тяжелой сочетанной травмы, что может свидетельствовать о протекторном эффекте препарата на эндотелиальный барьер. Результаты настоящей работы позволяют высказать предположение о том, что защитный эффект хлорида лития на эндотелий реализуется через фосфорилирование GSK-3β.

Обзор литературы посвящен ключевым событиям патогенеза, новым классификационным критериям и подходам к лечению системной красной волчанки. Нарушенные процессы программируемой гибели клеток (апоптоз, нетоз и аутофагия) приводят к увеличению продукции апоптотических клеток, вследствие чего происходит «замусоривание» организма с дальнейшей B-клеточной гиперреактивностью. Системная красная волчанка (СКВ) - это мультисистемное аутовоспалительное заболевание с широким спектром клинических проявлений, охватывающим многие органы и ткани. EULAR/ACR2018г представил новые классификационные критерии СКВ, а также возможность treat-to-target терапии препаратами генной-инженерии (ГИБП) с целью получения стойкой ремиссии и снижения дозировки глюкокортикостероидов, вплоть до полной их отмены.

Перинатальна асфіксія є істотним чинником ризику розвитку неврологічного дефіциту і когнітивних порушень у новонароджених дітей. У гострому періоді, після перенесеної гіпоксії-ішемії, в головному мозку відбувається необоротна загибель частини клітин за типом некрозу. Пошкоджені таким чином клітини вже не можуть бути відновлені. У другу фазу ушкодження, яка обумовлена вторинною енергетичною недостатністю, варіанти загибелі клітин включають апоптоз, аутофагію, партанатос і ферроптоз. Ці типи руйнування клітин є регульованими, вони можуть модулюватися, у тому числі й фармакологічними засобами. Препаратом, який продемонстрував свої нейропротективні властивості та поліпшення нейро-когнітивних результатів у новонароджених дітей після перенесеної гіпоксії-ішемії, виявився еритропоетин. Результати досліджень серед недоношених дітей досить суперечливі. Поліпшення когнітивного розвитку недоношених дітей при ранньому профілактичному призначенні рекомбінантного людського еритропоетину отримано у дітей з гестаційним віком понад 28-м тижнів. У глубоконедоношених дітей, народжених в терміні менше 28-ми тижнів гестації, застосування еритропоетину не вплинуло на неврологічний розвиток або летальність при оцінці к 2-х річному віку. У доношених новонароджених застосування еритропоетину в ранні терміни після перенесеної гіпоксії-ішемії скорочує ризик розвитку церебрального паралічу і когнітивних порушень. Дослідження, що тривають, покликані отримати інформацію про вплив раннього використання еритропоетину на результати як недоношених, так і доношених новонароджених дітей при поєднанні еритропоетину та лікувальної гіпотермії.

В даний час в літературі є суперечлива інформація про протікання процесів морфогенезу простати людини. Більш пильне вивчення процесів морфогенезу в патологічно незміненій простаті можуть полегшити розуміння виникнення атипових форм залоз і м'язових пучків. Мета роботи. Дослідити в простаті плодів людини формування і перетворення залоз і м'язової тканини. Матеріали та методи. Проведено морфометричне дослідження на 19 простатах плодів людини від 14 до 40 тижнів внутрішньоутробного розвитку. Результати. Встановлено, що перетворення епітеліальних тяжів в залозисті трубочки не супроводжується збільшенням їх площі, так як утворення просвіту відбувається шляхом апоптозу. Простежено основні етапи перетворень епітеліальних тяжів в типові альвеолярно-трубчасті залози. При цьому незначному збільшенні питомої площі залозистої паренхіми в органі перетворення залоз, що розвиваються, відбувається переважно за рахунок їх каналізації (питома площа просвітів залоз збільшується в 3,8 рази - р

The article presents the review of pathophysiological mechanisms for the formation of the secondary immunological failure in severe craniocerebral injury: a stress-induced change in the functioning the neurohumoral axis, increase in the levels of catecholamines, cytokines, and activation of apoptosis of lymphoid cells.

Introduction. One of the crucial tasks in medicine is studying the molecular mechanisms of selective management of tumor cell apoptosis following conformational changes in protein molecules (ubiquitination).The purpose of the study. The aim of the project is to establish the role of ubiquitin and ubiquitinligase in dexamethasone-induced apoptosis in Jurkat cells.Materials and methods. The study was carried out on the Jurkat tumor cell line (intact cells and cells cultured in the presence of an apoptosis inducer dexamethasone in the final concentration of 10 µmol. In intact and dexamethasone-affected Jurkat cells, implementation of apoptosis and the amount of FAS-, TNF Receptor 1 and cells with reduced mitochondrial membrane potential were assessed by flow cytometry using FITC-conjugated Annexin V and Propidium Iodide. The levels of NF-κB, Apaf-1, ubiquitin and ubiquitin ligase were determined by Western blot analysis. The activity of caspase-3 was measured by spectrofluorometry.Results. When adding the apoptosis inducer dexamethasone to the Jurkat cell culture, we registered a fall in the concentration of ubiquitin and a rise in the level of ubiquitinligase against the backdrop of activated receptor(an increase in the amount of Annexin V positive cells, FASand TNF Receptor 1) and mitochondrialmediated (an increase in the number of cells with reduced mitochondrial membrane potential and elevation of Apaf-1 level) pathways of apoptosis, as opposed to the intact cell culture. We estimated the completion of apoptosis by determining the activity of caspase-3 in the investigated tumor cells.Conclusion. The obtained findings allow the conclusion that ubiquitination of regulatory and effector proteins in programmed cell death is one of the molecular mechanisms that regulates and selectively controls apoptosis in Jurkat cells.

The paper presents results of the ВНК-21/2-17 lineage cell cycle tests using flow cytometry. This cell line is widely used in biological industry that is why studying the ВНК-21/2-17 cell suspension pattern using the proposed technique and determination of tools and methods to prevent morphological and structural cell modifications in the culture affected by negative factors is of great interest. Flow cytometry allows to determine quantitative parameters of cell cycle phases and perform correlation between these phases and viability of the working cell population. It was mentioned that the general trend of this cell lineage suspension cultivation for 48 hours has a standard dynamics, herewith at all stages of the cell cycle the primary growth stage - G1 prevailed. Under unfavorable conditions of cultivation apoptotic debris could increase up to 31-59%, i. e. part of the cell population could be potentially non-reproductive. Unsuccessful cultivation stages associated with low pH content in the cultivator where pH was not maintained at the constant level were detected. During optimization of cell cultivation physical and chemical parameters proliferation intensity increased. Viable cell yield during cultivation when a specific pH was maintained was higher and at the synthetic stage G2 + M no cycle delay occurred.

Resume. Relevance. Alcoholic cardiomyopathy (ACM) is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Their underlying mechanisms are poorly known, leading to a lack of effective therapy. Related with oxidative stress DNA damage and cell death play an essential role in the development of alcoholic cardiomyopathy. The aim of present study - using previously developed translation model to evaluate the levels of DNA damage and apoptosis in the myocardium of rats with ACM and modulating effect of cardioprotective drugs. Methods. ACM was established by forced alcoholization of rats (10 % ethanol solution as the only source of drinking water for 24 weeks; mean daily ethanol consumption was 5.0-6.5 g/kg). Trimetazidine (20 or 30 mg/kg), fabomotizole (15 mg/kg) or their combination (20 + 15 mg/kg) were injected ip, daily during following 4 weeks of abstinence. DNA damage was evaluated using alkaline and neutral comet assay. Apoptosis was assessed by TUNEL assay in paraffin-embedded sections. Results. No DNA damage or apoptosis of the myocardial cells was observed in rats with alcoholic cardiomyopathy at the abstinence period. A decrease in the level of cardiomyocytes with a high degree of DNA fragmentation, referred to as “hedgehog” DNA comets and that are presumably cells at the stage of autophagic fragmentation of chromatin, was revealed. Treatment of rats at the abstinence period with cardioprotective drugs trimetazidine and fabomotizole or their combination raised “hedgehog” DNA comets level up to control value. Conclusion. Our findings allows considering the appearance of cardiomyocytes with highly fragmented DNA as an important mechanism for regulating and maintaining myocardial homeostasis in ACM.

One of the hereditary factors affecting the development of breast and ovarian cancer is the 5382insC mutation in BRCA1 gene. But, nearly 15 % of carriers of this mutation do not manifest cancer during their lifetime. At present, the features of the development of spontaneous and induced genomic instability in asymptomatic carriers of BRCA1 mutations are studied insufficiently. The aim of the work was to evaluate the effect of the 5382insC BRCA1 mutation on the radiosensitivity of lymphocytes of individuals without an established oncopathology. The cultivation of blood lymphocytes obtained from 9 women (3 individuals with the 5382insC BRCA1 mutation without established oncopathology, and 6 conditionally healthy volunteers) was carried out. Some of the cultures were irradiated with γ-quanta (IBL-237C emitter, power 2.34 Gy/min) at a dose of 1.0 Gy before cultivation. For evaluation of the relative level of DNA damage the method of Сomet assay was applied. It was found that spontaneous level of DNA damage in cultures of lymphocytes of carriers of the BRCA1 5382insC mutation was statistically significantly (p < 0.01) higher than in the control group. After exposure to ionizing radiation for lymphocyte cultures of individuals with BRCA1 5382insC mutation, a decrease (p < 0.01) in the level of cells with a high degree of DNA damage was observed while the apoptotic activity was found to be increased (p < 0.01). It has been suggested that an increase in the elimination of damaged cells due to apoptotic activity in response to the action of genome-damaging factors is one of the effective mechanisms that can significantly reduce the likelihood of cancer in asymptomatic carriers of the BRCA1 gene mutations. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Endocrinology / Mìžnarodnij Endokrinologìčnij Žurnal is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Activities of two classes of neutral proteases were studied: caspases and proteasomes, which are contained in extracellular vesicles generated by mesenchymal and hematopoietic human stem cells (MSCs and HSCs, respectively). The formation of apoptosomes induced by the cytochrome C and dATP did not occurred in these cells. The presence of TNFa in the culture medium of HSCs causes the appearance of caspase-3 intracellular activity. Herewith caspase activity was detected in exosomes also. This activity was completely inhibited by a non-substrate caspase inhibitor, emricasane, and it was not sensitive to proteasome inhibitors. It is assumed that the caspases' activity from the cultural medium is the sum of membrane (outer side of exosome membrane), intracellular and extracellular activities. Apparently, this activity refers to apoptosomes as it was revealed by gel filtration of cultural medium with TNFa free from exosomes. Thus, TNFa induces the appearance of neutrophils in the culture of HSCs or the generation of other differentiated cells that are capable of apoptosis, in contrast to HSCs or MSCs. Proteasomal activity increased noticeably in exosomes from HSCs after the addition of TNFa. In contrast to exosomes from MSCs, all activity of proteasomes in HSCs-produced exosomes had a membrane localization. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Endocrinology / Mìžnarodnij Endokrinologìčnij Žurnal is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Medicina Neotloznyh Sostoanij is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The goal of the study is to determine the particular features of pemphigus vulgaris (PV) morphogenesis and keratinocytes in the patients’ skin having morphological signs of acantholysis and apoptosis as well as changes in Langerhans cells. Materials and methods. Skin tissue samples taken from 46 PV patients were examined. The skin tissue samples underwent cytology, histopathology and immunohistochemistry examinations as well as transmission electronic microscopy. An increased number of CD1a+ (dendritic) cells and apoptotic Cpp3+ keratinocytes was revealed in the skin of the PV patients. According to the electronic microscopy data, keratinocytes with signs of apoptosis are present in fresh vesicles in the acantholysis area at early PV stages quite seldom; at the same time, Langerhans cells had morphologic signs of activation. As the number of keratinocytes with desmosome lysis signs grew, the number of apoptotic keratinocytes was increasing reliably. Conclusion. In case of PV, apoptosis has a secondary nature and develops as anoikis.

The method of DNA-electrophoresis was used to study apoptosis in the lymph nodes of the abdominal lymphodissection zone after local intraoperative photodynamic therapy (PDT) for the gastrointestinal cancers. Apoptosis (apoptotic ladder) was determined in the four cell populations of lymph nodes:– in the lymph nodes with metastases that have not been irradiated;– in the irradiated during PDT lymph nodes with metastases;– in the lymph nodes without metastases that have not been irradiated;– in the irradiated during PDT lymph nodes without metastases.The implementation of this study was possible due to intraoperative division of lymph nodes into two parts, one of which was removed while another one intentionally wasn’t removed and was irradiated (in human). It was also removed 60-90 minutes after PDT treatment and examined for apoptosis. As a result, it was found that apoptosis is detected in the irradiated during PDT lymph nodes with metastases. The obtained results show the fact that in the lymph nodes of the abdominal lymphodissection zone tumor cells selectively die by apoptosis as a result of the local intraoperative photodynamic therapy (PDT) for the gastrointestinal cancers while in non-malignant cells apoptosis doesn’t occur after PDT (p

In the present work we investigated the effect of germanium (Ge) citrate, which has antioxidant properties, on functional and metabolic activity of neutrophils, degree of DNA damage and pathways of thymus and lymph node cell death under the conditions of systemic endotoxemia in mice. It was found that the administration of E. coli lipopolysaccharide (LPS) (3 mg/kg) induced a systemic inflammatory process with significant damage to cells and organs. Introduction of LPS caused the activation of the nonspecific resistance cells (according to the nitroblue tetrazolium test and the lysosomal-cationic test), which is an important mechanism of the cytotoxic effect of LPS. There was severe damage to DNA of thymus and lymph node cells, reducing their viability and an increase in the number of cells with signs of apoptosis or necrosis. The use of Ge citrate under the conditions of LPS treatment reduced generation of reactive oxygen species in neutrophils, as evidenced by a decrease in the percentage of formazanpositive cells and the cytochemical index. The content of cationic proteins and inflammatory mediators, according to the average cytochemical coefficient, was also decreased. In addition, administration of Ge citrate resulted in a reduce of the degree of DNA damage in thymus and lymph node cells, as well as in weakening necrotic and apoptotic cell death. Thus, the use of Ge citrate had a protective effect on thymus and lymph node cells reducing their DNA damage and death, which can be mediated by the normalization of neutrophil functions revealed in our experiments. The data obtained indicate the promise of the use of Ge citrate in the complex prevention and treatment of endotoxin induced diseases in humans and animals. [ABSTRACT FROM AUTHOR]

Copyright of Problems of Cryobiology & Cryomedicine / Problemy Kriobiologii i Kriomediciny is the property of National Academy of Sciences of Ukraine Institute for Problems of Cryobiology & Cryomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The effect of sirtuins activator (resveratrol) on the functional state of oocytes (meiotic maturation) and cumulus cells (apoptosis and necrosis) was assesed using the model of systemic autoimmune damage created by immunizing the CBA line mice with kidney antigen suspension. The conducted researches revealed significant ovarial damages of mice under the conditions of experimental model. A significant decreasement of number of mature follicles isolated from the ovaries was observed and an increasement (compared with control) of the number of oocytes with atypical morphology (unevenly granulated cytoplasm, signs of fragmentation of the cytoplasm) was noted. It was shown that, under experimental conditions during cultivation, the percentage of cells that dissolved germinal vesicle and capable to form first polar body significantly decreased. We have shown that inhibition of ovarian function was accompanied by a significant changes in viability and loss of cumulus cells. After the cultivation of oocytes in a medium which contained activator of sirtuins - resveratrol (20 μM), a significant increasement of the percentage of oocytes that dissolved germinal vesicle and formed the first polar body was detected, as well as the increasement of number of viable cells and the decreasement of the number of cells with morphological signs of apoptosis and necrosis. [ABSTRACT FROM AUTHOR]

Aim of review. To present data on the role of mitochondrial and lysosomal dysfunction in pathogenesis of acute pancreatitis (AP). Summary. Hyperamilasemia, premature intralobular activation of digestive enzymes, accumulation of large vacuoles in acinar cells, activation of proinflammatory mediators, apoptosis and necrosis of acinar cells are the basic pathomorphological signs of AP. The mitochondrial dysfunction that develops at acute pancreatitis is followed by disorders of ATP synthesis and initiation of processes of apoptosis and necrosis. The lysosomal dysfunction at AP is manifested by autophagy disorders that leads to vacuolation of acinar cells and intralobular trypsin accumulation. Conclusion. At the recent time there is noticeable growth in frequency of acute pancreatitis cases and increase of mortality in patients with pancreatic necrosis. Mitochondrial and lysosomal dysfunction acts as pathogenic basis for AP, leading to energy deprivation of pancreatic cells. Mitochondrial and lysosomal dysfunction initiates processes of apoptosis, necrosis, activation of trypsinogen and vacuolation of acinar cells that this disease. Therefore new studies aimed for therapeutic impact on mitochondrions and lysosomes are required. Key words: acute pancreatitis, dysfunction of organellas, mitochondrion, lysosome, apoptosis, necrosis, autophagy.

Investigated is the effect of azoximer bromide (polioxidonium - PO) and dalargin (DA) on the immune system cell reactivity in the anti-tularemia vaccine prosess modeling in Balb/c mice. The animals were immunized subcutaneously with a dose of 104 live microbial cells of vaccine strain Francisella tularensis 15 NIIEG. PO or DA subcutaneously administered 60 min before vaccination, respectively, in doses of 4 mg and 2 mg. On 3rd and 21st days of immunogenesis the peripheral organs of the immune system and the contents of the abdominal cavity were investigated. Cell response to vaccination and investigated immunomodulators evaluated by flow cytometry (CyAn ADP) for two light scatter parameters and for changing the proliferating and apoptotic cell number. Additionally, for the characterization of changes in the functional status of lymphocytes nuclei the light microscopy was used and titers of specific antibodies were determined. Installed is the different response of intact mice lymphocytes and phagocytes to PO and DA introduction. As distinct from PO, DA stimulated the lymphocete proliferation and macrophage apoptosis by acting on their cytoplasmic granules. PO activated the migration of phagocytes with high cytoplasmic granules from mice abdominal cavity in the spleen. Only when using the PO as an immunomodulator in anti-tularemia vaccine process modeling recorded a significant increase in specific antibody titers against the background of a long-term functional splenocyte activation and macrophages reduced macrophage damage intensity in the spleen and abdomen.

The results of the experimental study of immune response of human skin malignant melanoma cells Mel 226 on photodynamic exposure are represented in the article. Photoinduced apoptosis of skin malignant melanoma was studied in vitro. The study showed that irradiation with the agent fotoditazin at dose of 0.5–2.5 µg/ml (6 and 10 min exposure 30 min before irradiation; irradiation parameters: wavelength of 662 nm, total light dose from 40 to 60 J/cm2) induced early apoptosis. The increase of the time of laser irradiation significantly accelerates the conversion of photosensitized tumor cells from early to late apoptosis.

The study of the functional morphology of rat sarcoma M-1 after photodynamic therapy using bacteriopurpurinimide disulfide derivative (disulfide-BPI) as a photosensitizer is described. The research methods included immunohistochemistry for PCNA and CD31, evaluation of mitotic activity and apoptosis of tumor cells, as well as computer analysis of microscopic images. Photoinduced antitumor effect was shown to be due to the destruction of sarcoma M-1 vascular bed, the rapid inhibition of proliferative activity and devitalization of tumor cells by apoptosis and necrosis. It is reasonable to suppose that in the early stages after photodynamic therapy destruction of the microvasculature and photocytostatic shock of tumor cells with subsequent development of necrosis are caused by direct influence of the light flux on sensitized cellular elements in parenchyma and stroma of tumors. The efficiency of photodynamic therapy with the novel photosensitizer is determined by the sequence of destructive and inflammatory changes in tumor parenchyma and surrounding tissues, as well as repopulation potential of tumor cells survived after treatment.