Production of reactive oxygen species by neutrophils and macrophages of F1 hybrid mice (C57Bl6xCBA) in response to stimulation with cucurbit(n)urils (n = 6, 7, 8)

Background. Due to their very small size, nanomaterials, in particular cucurbiturils, have unique physical and chemical properties that find their application in medicine. However, the toxicity of cucurbiturils is not fully understood; in particular, we are interested in the immunological safety of their use. One of the mechanisms of nanotoxicity is the formation of reactive oxygen species (ROS) by macrophages and neutrophils. Hyperproduction of ROS can lead to oxidative stress and further damage to cell DNA with loss of physiological function and development of pathology.   The aim. Evaluation of the effect of cucurbit[n]urils (n = 6, 7, 8) on the production of reactive oxygen species by mice macrophages and neutrophils.   Materials and methods. F1 hybrid mice (CBAxC57Bl/6) aged 2 months (n = 11) were used in the work. Evaluation of superoxide radical production by peritoneal mouse neutrophils and macrophages was carried out by spectrophotometric method for determining the reduction of p-nitroblue tetrazolium (NBT) to formazan.   Results. It was shown that CB[6] and CB[7] at concentrations of 0.5 and 0.3 mM do not have an inhibitory effect on ROS synthesis, but, on the contrary, significantly increase ROS production by macrophages. In addition, CB[6] 0.3 mM increases the level of ROS in neutrophils.   Conclusion. Cucurbiturils can lead to an increase in the production of ROS in immunocompetent cells, depending on the concentration used (0.3 mM and higher)

Cucurbituril-based Supramolecular complexes with platinum compounds influence on expression of CTLA-4 on Regulatory T cells

Tumors are a leading pathology in the population. Chemotherapy cannot provide adequately and effectively to cure patients. Some medicine, such as cytostatic, are characterized by a wide range of side effects and resistance of solid tumors to chemotherapy by these medicines. In recent research, the mechanisms of action of cytotoxic agents have been described, and the most appropriate causes of resistance have been suggested. Drug delivery system based on Cucurbit[7]uril (CB[7]) was used to minimize side effects and overcome resistance. CB[7] has ability to form host-guest supramolecular complexes with oxaliplatin and carboplatin.It is important to consider the immune system maintain to a great role, and platinum compounds are able to have an immunomodulatory effect on immunocompetent cells. There is convincing evidence about the cytotoxic response against tumor cells is also associated with immunomodulating properties. A specific immune microenvironment with high frequency of suppressor cells is made by tumors. FoxP3+ regulatory T cells are recruited by the tumor, an increased number of these cells and expression levels of CTLA-4 and PD-1 on them contribute to the progression of the tumor process. These markers correlate with recurrence and poor survival of the patients. Therefore, it is necessary that antitumor therapy agents have an effect on a subpopulation of regulatory T cells and their functional activity. This study evaluated the effects of cucurbit[7] uril, platinum compounds, and supramolecular complexes on FoxP3+ regulatory T cells and the expression of immune checkpoint molecules.In this study peripheral blood cells from volunteers (n = 8, average 29.0±2.4) were used. Mononuclear cells obtained in the standard protocol were incubated for 72 h at concentrations of 0.3 and 0.1 mM for carboplatin and oxaliplatin, respectively, as well as complexes and CB[7] in equivalent dosages. Next, the samples were labeled with monoclonal antibodies to determine the phenotype and expression of immune checkpoint molecules by flow cytometry.We obtained the following results: The CB[7]-carboplatin complex in stimulated and non-stimulated cultures significantly reduced the number of FoxP3+ regulatory T cells compared to the control. At the same time, carboplatin and the CB[7]-carboplatin complex reduced the expression of CTLA-4 in an non-stimulated culture compared to CB[7].Complexes of Cucurbit[7]urils with platinum compounds are a perspective antitumor agent with immunomodulatory properties

The nature of the intertext in flash fiction

The study aims to investigate the nature of the intertext in flash fiction. For this purpose, the concepts of intertext, intertextuality, reminiscence, allusion and their artistic nature, its various manifestations are analyzed in the stories of writers of the period of independence of Kazakhstan as a method. As a result, the blemish of the appearance of Bukir (Hunchback), who considered himself an incomparable artist, was reflected in his mind and feelings. In conclusion, writers criticized the character and his surroundings through death, exposing lies and truth and pursuing moral and aesthetic goals.El estudio tiene como objetivo investigar la naturaleza del intertexto en la ficción flash. Para este propósito, los conceptos de intertexto, intertextualidad, reminiscencia, alusión y su naturaleza artística, sus diversas manifestaciones se analizan en las historias de escritores del período de independencia de Kazajstán como método. Como resultado, la mancha de la aparición de Bukir (Jorobado), quien se consideraba un artista incomparable, se reflejó en su mente y sentimientos. En conclusión, los escritores criticaron al personaje y su entorno a través de la muerte, exponiendo mentiras y verdades y persiguiendo objetivos morales y estéticos

Influence of Cucurbiturils on the Production of Reactive Oxygen Species by T- and B-Lymphocytes, Platelets and Red Blood Cells

Reactive oxygen species (ROS) are highly reactive chemical molecules containing oxygen. ROS play an important role in signaling and cell homeostasis at low and moderate concentrations. ROS could be a cause of damage to proteins, nucleic acids, lipids, membranes and organelles at high concentrations. There are a lot of cells that can produce ROS to maintain functional activity. It is known that metal nanoparticles can increase production of ROS in cells. However, the effect of cucurbiturils on ROS production is still unknown. In our study, we evaluated production of ROS by the immune (T-, B-lymphocytes, NK-cells) and non-immune cells (red blood cells, platelets), as well as tumor cells line (1301, K562) after treatment with cucurbiturils in vitro. Assessment of reactive oxide species (ROS) were provided by using dihydrorhodamine 123 (DHR 123). Fluorescence intensity and percentage DHR123 were measured by flow cytometry. Platelets, erythrocytes and activated T-helpers were changed the level of ROS production in response to stimulation with cucurbiturils. It was found that the percentage of these ROS-producing cells was reduced by cucurbiturils. Thus, cucurbiturils may affect the production of ROS by cells, but further research is needed in this area