Ekaterina G. Batotsyrenova

Glioblastoma (GBM) is one of the most malignant and common human brain tumors. This tumor contains glioblastoma stem cells (GSCs), which drive tumor growth, progression, and metastasis even after surgical resection, radiation, and chemotherapy. Physiological changes within the body facilitate the adaptation, maintenance, survival, and proliferation of GBM cells. Underlying this cellular plasticity is the asymmetric division of GBM cells, which gives rise to diverse cancer cell types. Consequently, the issue of GBM plasticity is crucial for understanding tumor biology and developing effective therapeutic strategies. This review focuses on GBM heterogeneity, associated markers, microRNAs, long non-coding RNAs, signaling cascades (kinases, transcription factors), genes, and transitions between distinct cellular phenotypes. It examines the expression and regulation of GSC markers across various cellular states are influenced by cell cycle phases and the transition from a proneural (PN) to a mesenchymal phenotype (MES)— proneural-mesenchymal transition (PMT) which are associated with changes in cellular activity. The PN and MES of GBM cells are represented as a dynamic continuum of transitional states underlying the processes of self-renewal, proliferation, invasion migration, therapy resistance, and differentiation. Further research is needed to elucidate the molecular mechanisms of GBM cellular plasticity involved in angiogenesis, metastasis, and immunosuppression of the tumor microenvironment.

The aim of the study is to propose ways to optimize gastric lavage from food. Materials and methods. А series of simulations of gastric lavage through a gastric tube with a diameter of 1 cm from mashed potatoes, oatmeal and rice porridge using a Janet syringe and tap water with temperatures of 15 ^° C, 20 ^° C, 37 ^° C and 45 ^° C. Results. Regardless of the water temperature, it took the shortest time to wash the stomach model from mashed potatoes: Me 7.6 (Q1–Q3: 6.3–10.8) minutes. The evacuation time of oatmeal porridge was: Me 17.5 (Q1–Q3: 14.1–22.8). When using water with a temperature of 15 ^° C and 20 ^° C, it was not possible to remove rice porridge from the stomach model within 60 minutes, in other cases it took the longest time: Me 19.8 (Q1–Q3: 18.8–21.8) minutes. A decrease in the gastric lavage time was revealed with an increase in water temperature (pConclusion. An increase in the effectiveness of gastric lavage can be achieved by increasing the temperature of the water used (p<0.05). The developed original modification of the gastric lavage probe also made it possible to reduce the time of evacuation of stomach contents (p<0.05). After testing in experiments on laboratory animals and clinical studies, the data obtained can change approaches to gastric lavage in an urgent situation.

Currently, immuno-oncology is a rapidly developing field of medicine, primarily due to the integration of achievements in molecular biology and biotechnology (creation and production of modified cells and effector molecules), immunological physiology (understanding of subtle mechanisms of regulation of immune functions) and clinical medicine (adequate accompanying therapy, allowing manipulation of the patient’s immune system). A large number of tumors overexpress tumor-associated gangliosides (sialylated glycosphingolipids). For example, GD3, GD2 and GM2 are overexpressed in melanoma and neuroblastoma cells, increased expression of GD1a, GM1, GM2 is shown in carcinoma cells, GD2 is expressed by soft tissue sarcoma, osteogenic sarcoma and small cell lung cancer cells. The ratio of the number of gangliosides varies from one tumor type to another. In addition, gangliosides are found in neoplastic tissues that are not characteristic of normal transformed cells of this tissue. In particular, one such ganglioside is GD2. In normal cells, the expression of this ganglioside, as well as that of GM2, is restricted to nerve cells, but in the case of cancer transformation they are found in cells of malignant tumors. Numerous studies have shown that tumor-associated gangliosides arising from oncogenic transformation play a key role in invasion and metastasis of a number of tumors and induce tumor-associated angiogenesis. First of all, it has been established that tumor cells differ in the composition of gangliosides. the ganglioside composition of metastasis cells differs from the cells of the primary tumor focus and is characterized by a decrease in the content of complex gangliosides. Due to its high level of expression in a number of tumors and limited expression in normal tissues, ganglioside GD2 can be considered as an ideal potential target for the development of anti-tumor immunotherapies.

The efficacy of Strongylocentrotus droebachiensis gonad lyophilisate in combined poisoning with carbendazim and X-ray irradiation was assessed in rat biomodels. Two-week intragastric administration of the lyophilisate was shown to partially compensate for the changes caused by adverse factors, as the same time as exhibiting antioxidant, hemopoetic, and anabolic aciton.

Разработка и внедрение иммобилизованных препаратов ферментов является актуальным и перспективным направлением в современной фармацевтической практике. Лекарственные формы, в состав которых входит протеолитический фермент папаин (КФ 3.4.22.2), обладают противовоспалительным и регенерирующим действием и эффективны для лечения нарушений кожного покрова. В данной работе рассматриваются условия получения иммобилизованных препаратов папаина с применением в качестве носителей волокнистых полиэлектролитов на основе полипропилен-стирол-дивинилбензольной матрицы: слабокислотного катионообменника К-4 и высокоосновного анионообменника А-1. Адсорбционную иммобилизацию проводили при температурах 293±2К, 313±2К с использованием метода переменных концентраций в интервале 0.2-5.0∙10-2 ммоль/дм3, рН 6.5. Выявлено, что фиксация белка на волокнах при температуре 313±2К описывается моделью Ленгмюра. Анализ экспериментально полученных изотерм сорбции папаина при 293±2К показал, что с увеличением концентрации папаина во внешнем растворе процесс адсорбции обусловлен преимущественно взаимодействием в фазе носителя белковых макромолекул. Образование полимолекулярных слоев фермента описывается уравнением Брунауэра-Эммета-Теллера (БЭТ). Наиболее значимый вклад в полную сорбционную емкость волокнистых носителей вносит физическая сорбция. Сделано предположение, что при этом имеет место формирование супрамолекулярных структур в виде ассоциатов белка. Каталитическая активность гетерогенных биокатализаторов при рН 6.5 составляет 47-87% от ферментативной активности растворимого папаина. Проведен расчет равновесных параметров сорбции белка рассматриваемыми носителями (констант, характеризующих взаимодействия папаин-волокнистый носитель, папаин-папаин) и некоторых термодинамических характеристик исследуемого процесса иммобилизации (свободной энергии Гиббса, энтальпии, энтропии). Экспериментально подтверждена возможность применения данного способа иммобилизации папаина на волокнистых сорбентах.

Background. Medulloblastoma (MB) prognosis and response to therapy depend largely on genetic changes in tumor cells. Many genes and chromosomal abnormalities have been identified as prognostic factors, including amplification of MYC oncogenes, gains in 1q and 17q, deletions in 10q and 21p, or isochromosomes 17 (i(17)(q10)). The frequency of these abnormalities varies greatly between ethnic populations, but the frequency of specific abnormalities, such as MYCC and MYCN amplification, 17q gain, and deletions, in the Russian population is unknown. Objective: The aim is to study the frequency of MYCC and MYCN amplifications, 17q gain, and 17p deletion and determine their prognostic value in Russian patients with MB. Methods. This study was performed on MB cells obtained from 18 patients (12 boys and 6 girls, aged between 3 months and 17 years, with a median age of 6.5 years). Determination of cytogenetic aberrations was carried out using FISH assays with MYCC-SO, MYCN-SO, and MYCN-SG/cen2 probes, as well as cen7/p53 dual color probes and PML/RARα dual color probes (Abbott Molecular, USA). One-way ANOVA and Fisher’s F-test were used to compare the two groups. The differences were considered significant when p < 0.05. Results. In 77.7% of patients (14/18), the classical type of MB was present; in 16.7% (3/18), desmoplastic type; and in 5.6% (1/18), nodular desmoplasic types of neoplasms. Amplification of MYC genes was detected in 22.2% of Russian patients (n = 4 out of 18). Patients with MYC amplification had the worst overall survival (OS: 0% vs. 68%, p = 0.0004). Changes on the 17th chromosome were found in 58.3% of patients. Deletion of 17p occurred in 23.1%, and gain of 17q occurred in 46.2%. There were no significant differences in OS, clinical signs, or the presence of additional 17q material or 17p deletion among patients with MB. Conclusions: Amplification of the MYC gene is a predictor of poor overall survival to therapy and a high risk of metastatic relapse. This allows us to more accurately stratify patients into risk groups in order to determine the intensity and duration of therapy.

Introduction. Mercury poisoning has a cumulative effect. Mercury gradually accumulates in tissues and organs, which negatively affects the functions of all body systems, especially the brain. The aim of this study was to investigate the neuropeptides content in the blood plasma of Wistar rats after subchronic low-dose mercury acetate poisoning. Material and methods. During the study, rats was intragastrically administered mercury acetate at a dose of 4 mg/kg for 30 days. On days 30 and 44, the blood plasma of rats was tested for the levels of calcium-binding protein (S100), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), pigment epithelial-derived factor (PEDF), myelin basic protein (MBP). Results. The concentration of S100 protein in the blood plasma of the experimental group of rats decreased by 43,9%, and the concentration of MBP increased by 172,6%. Fourteen days after the end of the toxicant administration, the concentration of protein S100 in the blood plasma of poisoned animals was significantly lower by 132,7% compared to the control group. The content of MBP increased by 59,4% and neuron-specific enolase increased by 44,6%, the concentration of neuropeptides PEDF and GFAP changed insignificantly. Conclusions. The results obtained demonstrate that even low concentrations of mercury acetate, entering the body for a long time, affect the concentration of neuropeptides in blood plasma, which indicates negative changes in the central nervous system of rats.

Purpose of the study. To study the effect of sequential release of peptide extracts (PEE) from the pineal gland and pituitary gland of reindeer (Rangifer tarandus) on endogenous regulatory proteins (hypoxia-inducible factor 1 alpha (HIF1α), peroxisome proliferatoractivated receptor gamma (PPARγ), soluble phosphoenolpyruvate carboxykinase 1 (PEPCK) and melatonin in the blood serum of male rats under conditions of experimental light desynchronosis.Materials and methods. Modeling of light desynchronization was carried out on two-month laboratory white outbred male rats weighing 180 ± 20 g in the number of 144 individuals. The animals were divided by the method of randomization into three main groups: 1st group represented the control, in which the normal lighting regimen was modeled (LED lighting 500 lux day/night 12/12); the 2nd group was kept in the regimen of constant illumination; the third group was kept in a regimen of constant darkness. The formation of light desynchronization was carried out for 30 days. During the first 14 days of the formation of light desynchronosis, the rats were intranasally being administered with the test substances. After 30 days from the beginning of the experiment, the rats were euthanized for the collection of biological material. The blood serum HIF1α, PPARγ, PCK1 and melatonin levels of laboratory animals were analyzed by the enzyme immunoassay method (EIA).Results. The use of PEE in two doses during light deprivation has reduced the concentration of HIF1α in the blood serum, indicating improved oxygen utilization in the tissues of experimental animals. PEE in two doses has caused a sharp increase in the concentration of the transcription factor in blood serum PPARγ, which promotes the initiation of processes regulating the exchange of lipids and carbohydrates in adipose tissue. The application of peptide extracts in two doses has revealed a decrease in the activity of PCK1 under constant illumination. With constant exposure to PEE in doses 100 mg/kg, it promotes an increase in the concentration of melatonin in the blood serum, approximately equal to the level of the control group.Conclusion. The study revealed the chronobiotic effects of PEE on the concentration of regulatory proteins and melatonin in the blood serum of male rats in the conditions of light desynchronization. It should also be noted that these effects differ from the known effects of the delta-sleep inducing peptide, which may be due to a different mechanism of molecular action.

Background: Glioblastoma multiforme (GBM) is a very malignant brain tumor. GBM exhibits cellular and molecular heterogeneity that can be exploited to improve patient outcomes by individually tailoring chemotherapy regimens. Objective: Our objective was to develop a predictive model of the life expectancy of GBM patients using data on tumor cells’ sensitivity to chemotherapy drugs, as well as the levels of blood cells and proteins forming the tumor microenvironment. Methods: The investigation included 31 GBM patients from the Almazov Medical Research Centre (Saint Petersburg, Russia). The cytotoxic effects of chemotherapy drugs on GBM cells were studied by an MTT test using a 50% inhibitory concentration (IC₅₀). We analyzed the data with life expectancy by a one-way ANOVA, principal component analysis (PCA), ROC, and Kaplan–Meier survival tests using GraphPad Prism and Statistica 10 software. Results: We determined in vitro the IC₅₀ of six chemotherapy drugs for GBM and 32 clinical and biochemical blood indicators for these patients. This model includes an assessment of only three parameters: IC₅₀ of tumor cells to carboplatin (CARB) higher than 4.115 μg/mL, as well as levels of band neutrophils (NEUT-B) below 2.5% and total protein (TP) above 64.5 g/L in the blood analysis, which allows predicting with 83.3% probability (sensitivity) the life expectancy of patients for 15 months or more. In opposite, a change in these parameters—CARB above 4115 μg/mL, NEUT-B below 2.5%, and TP above 64.5 g/L—predict with 83.3% probability (specificity) no survival rate of GBM patients for more than 15 months. The relative risk for CARB was 6.41 (95 CI: 4.37–8.47, p = 0.01); for NEUT-B, the RR was 0.40 (95 CI: 0.26–0.87, p = 0.09); and for TP, it was 2.88 (95 CI: 1.57–4.19, p = 0.09). Overall, the model predicted the risk of developing a positive event (an outcome with a life expectancy more than 10 months) eight times (95 CI 6.34–9.66, p < 0.01). Cross k-means validation on three clusters (n = 10) of the model showed that its average accuracy (sensitivity and specificity) for cluster 1 was 74.98%; for cluster 2, it was 66.7%; and for cluster 3, it was 60.0%. At the same time, the differences between clusters 1, 2, and 3 were not significant. The results of the Sobel test show that there are no interactions between the components of the model, and each component is an independent factor influencing the event (life expectancy, survival) of GBM patients. Conclusions: A simple predictive model for GBM patients’ life expectancy has been developed using statistical analysis methods.

Mercury poisoning has a cumulative effect. Mercury gradually accumulates in tissues and organs, which negatively affects the functions of all body systems, especially the brain. The aim of this study was to investigate the neuropeptides content in the blood serum of Wistar rats after subchronic low-dose mercury acetate poisoning. During the study, rats was intragastrically administered mercury acetate at a dose of 4 mg/kg for 30 days. On days 30 and 44, the blood serum of rats was tested for the levels of calcium-binding protein (S-100), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), pigment epithelial-derived factor (PEDF), myelin basic protein (MBP). The concentration of S-100 protein in the blood serum of the experimental group of rats decreased by 43.9%, and the concentration of MBP increased by 172.6%. Fourteen days after the end of the toxicant administration, the concentration of protein S-100 in the blood serum of poisoned animals was significantly lower by 132.7% compared to the control group. The content of MBP increased by 59.4% and neuron-specific enolase increased by 44.6%, the concentration of neuropeptides PEDF and GFAP changed insignificantly. The results obtained demonstrate that even low concentrations of mercury acetate, entering the body for a long time, affect the concentration of neuropeptides in blood serum, which indicates negative changes in the central nervous system of rats.