The problem of opisthorchiasis caused by Opisthorchis felineus requires a search for alternative treatments, because the trematode can develop drug resistance and the existing drugs, such as praziquantel, may have undesirable side effects. This study aimed to identify the anti- opisthorchiasis and hepatoprotective properties of Populus tremula L. bark extract using in vitro methods. The PGF-PT active fraction with a high content of phenol glycosides was obtained though extraction. PGF-PT showed a dose-dependent anti-opisthorchiasis effect: the relative mobility index of maritae decreased from 98.2% at 250 µg/ml to 54.5% at 2000 µg/ml (p < 0.05), and the proportion of immobile specimens at 2000 µg/ml was 30% (p < 0.05). The probable mechanism of action is focal damage to the cells of the parasite’s superficial epithelium (tegument). PGF-PT exhibited a pronounced hepatoprotective effect in a lipotoxicity model based on HepG2 cells, as evidenced by normalized intracellular lipid accumulation and reduced oxidative stress. A high antioxidant activity of PGF-PT was shown in the model system (IC50 = 79.3 ± 1.0 µg/ml). Thus, the PGF-PT fraction has a complex effect — eliminating parasites and correcting metabolic disorders in the liver — which makes it a promising basis for new effective anthelmintic drugs.
VIEWS 399
An urgent problem of the role of Slavic expansion in shaping gene pools of the population of Europe is being analyzed actively using various methods to study ancient and current populations. However, it is difficult to solve due to the lack of consolidated data on the Y-haplogroups in Slavic-, Finnish-, and Turkic-speaking populations of European Russia. The study aimed to look into genetic portraits of Mordovian populations and Russians of the Ryazan Region relative to the surrounding populations of indigenous peoples of Central Russia. For the first time the Y-gene pool of the Volga–Oka region (10 populations, n = 1136 individuals) was assessed in a broad context of our own data on the gene pools of European Russia (based on a single panel of 35 Y-haplogroups, 80 populations, n = 9712). The analysis was performed by multidimensional scaling (MDS) and computed cartography (GeneGeo). The produced series of 35 maps of the Y-gene pool of Central Russia and maps of genetic distances from peoples of the Volga–Oka region describe the gene-geographic landscape of the region in detail. It has been shown that all the assessed Russian populations belong to the common “Slavic” cluster that also includes representatives of Western Slavs. The cluster of populations of the Ural–Volga region including three Finnish-speaking populations of Mordovia (Erzya, Moksha, Shoksha) and 7 Turkic-speaking populations of the Chuvash and Mishar turned out to be the most genetically close to the Russian populations of Central Russia. It has been hypothesized that this group of populations can be traced back to the gene pool of the ancient indigenous Finnish-speaking population of the Volga–Oka region. 
VIEWS 410
Quantitative processing of optoacoustic angiograms is an important task, the solution of which will potentially enable the early diagnosis of vascular diseases. The aim of this study is to refine and conduct biomedical validation of a software tool for the analysis of optoacoustic angiograms, focusing on the application of machine learning methods. The work was conducted on an open dataset containing three-dimensional optoacoustic angiograms of an experimental animal (mouse) in three temperature conditions: cold temperature (16 °C), room temperature (23 °C), and body temperature (30 °C), as well as a dataset with basic vascular features obtained by processing using Amira/Avizo (Thermo Fisher Scientific), a general-purpose software for visualization and analysis of scientific and industrial data. Various vascular features missing from previous work were developed and calculated, after which basic methods of unsupervised/supervised clustering and supervised classification were applied to determine different temperature conditions of vessel segments. Supervised classification methods demonstrated high overall accuracy: CatBoost — 98.9%, SGDClassifier — 95.7%, and logistic regression — 99.7%. The results are consistent with existing descriptions of vascular changes during temperature tests. The applied methodology is universal, meaning with minor modifications it can be adapted to patients. Therefore, the results of this study may potentially improve the diagnosis of vascular pathologies.
VIEWS 494
Synovial sarcoma is characterized by marked histological and molecular heterogeneity, and angiogenesis as well as innate immune cells are considered potential sources of prognostic markers and therapeutic targets. This study aimed to evaluate the relationship between the quantitative and spatial characteristics of mast cells and angiogenesis in the tumor microenvironment of synovial sarcoma, as well as their prognostic significance. Using immunohistochemistry (tryptase/ CD117, CD31/CD34, VEGF-A, α-SMA, CD3/CD8, CD68/CD163) and digital morphometry normalized to 1 mm2, we analyzed 140 cases of synovial sarcoma. The intrathumoral, peritumoral, and perivascular (≤50 µm from CD31+/CD34+ vessels) zones, as well as the mastocyte degranulation index, were evaluated separately. Mast cells were detected in all observations; their density and signs of degranulation were greatest in the perivascular zone. Perivascular mast cells were positively correlated with both microvascular density and VEGF-A expression, and inversely correlated with α-SMA pericyte coverage; these relationships remained significant even after accounting for CD163+ macrophages. A high microvascular density and increased perivascular mast cell counts were associated with an unfavorable survival prognosis, while pronounced CD8+ infiltration predicted better outcomes. The developed integral Mast-Angio Score, which combines perivascular density, mast cell degranulation, microvascular density, and VEGF-A expression, improves the accuracy of prognostic stratification and can serve as a morphological basis for justifying combined antiangiogenic and immune therapy.
VIEWS 572
A T cell receptor (TCR), an αβ heterodimer, recognizes peptide antigens presented by self molecules of the major histocompatibility complex (MHC). A significant number of T cell clonotypes are alloreactive: they can interact with various allelic variants of MHC and the associated peptides. Currently, it is unclear whether the effectiveness of the allogeneic immune response depends on the diversity of the TCR repertoire. Seeking to experimentally narrow the diversity of T cell clonotypes, we used mice with transgenic expression of the β-chain TCR (TCRβ) in this work. We analyzed how the TCRß-transgenic mice on the CBA/Lac (H-2k) background respond to EL-4 (H-2Kb) lymphoma cells in vivo with the aim to assess the effect of a narrower repertoire on the allogeneic immune response. The study has shown that transgenic mice develop a weak immune response to transplant antigens, and the formed pool of cytotoxic T cells is 1.5–1.7-fold smaller than that in wild-type animals. Consequently, the mice failed to reject the allogeneic tumor, leading to 100% mortality rate. The results of this work are consistent with the data from our earlier studies that employed another TCRß-transgenic model. They confirm that the decreased diversity of the TCR repertoire impairs the response to alloantigens, allowing the tumor to evade the immune response and progress in the allogeneic recipient.
VIEWS 447
MicroRNAs are resistant to RNases and are highly specific for various pathological conditions, particularly inflammation, allowing them to be considered inflammation biomarkers. They were detected in all body fluids, and miR146a plays a key role in the pathogenesis of inflammation. A total of 180 male white Wistar rats were selected for the study. All animals were 8–10 weeks old and weighed 200–250 grams. The animals were divided into five groups of 36 each. The first received saline solution intramuscularly, while the others underwent experimental modeling of obesity and knee arthrosis. The second group received 1.0 ml of saline solution intramuscularly, while the third, fourth, and fifth groups received dexamethasone at doses of 1 ng/ml, 10 ng/ml, and 100 ng/ml, respectively. Blood samples for the study were collected on days 3, 5, and 10. The obtained parameters were analyzed at the statistical significance level (p < 0.05). Increased miR146a levels were observed in animals in the second group compared to the others, due to the development of inflammation associated with obesity and concomitant gonarthrosis. In the third group, expression levels decreased slightly, remaining high. In the fourth group, with the use of 10 ng/ml dexamethasone, miR146a expression levels decreased most significantly on days 3 and 5. In the fifth group, virtually no changes were observed, with the parameter decreasing only slightly. The 10 ng/ml dexamethasone dose demonstrated the greatest efficacy during the experiment, possessing the greatest anti-inflammatory activity compared to the other doses.
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