In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg ...effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Association between lymphocyte activation and formation of immune tolerance, as well as pregnancy outcome, in the case of immunocytotherapy (ICT) was studied in women with idiopathic recurrent ...pregnancy loss (IRPL). The content and phenotypic characteristics of activated T lymphocytes and NK cells were investigated in the peripheral blood of IRPL patients with different pregnancy outcomes (pregnancy prolongation to the full term and habitual miscarriage). The fraction of activated cells in the subpopulation of cytotoxic T lymphocytes (CD3
+
CD8
+
/CD3
+
CD8
+
CD69
+
) before ICT was significantly lower in women who lost the pregnancy. After ICT, the fraction of these cells during weeks 5-6 of pregnancy in woman with miscarriage was higher than in women with pregnancy prolonged to the full-term. Excessive content of activated cytotoxic lymphocytes can be a mechanism underlying impaired maternal immunotolerance to fetal alloantigens, which is a leading factor of early pregnancy loss. The obtained data confirm the involvement of activated Th17 cells and FOXP3
+
Treg cells in the formation of tolerance to paternal antigens of the fetus. Comparison of the decrease in the fraction of CD4
+
CD25
high
RORt
+
lymphocytes at the early gestation period (5-6 weeks) and significant upregulation of the IL-17 production by
in vitro
stimulated whole blood cells in women with miscarriage with the same parameters in women with prolonged pregnancy suggested an imbalance between pro-inflammatory Th17 cells and Treg cells. No such imbalance in the content effector T lymphocytes was observed in women with the full-term pregnancy. Taken together, our data indicate an important role of gestational activation of lymphocytes in the formation of maternal immune response to fetal alloantigens necessary for the prolongation of pregnancy.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Density fluctuations in I-mode discharges in ASDEX Upgrade are studied. The I-mode specific weakly coherent mode (WCM) appears at the transition from the L to I-mode. The WCM but also the turbulence ...in general are strongly modulated by a low frequency mode which can be related to the geodesic acoustic mode (GAM). The GAM induces an energy transfer away from the central WCM frequency, indicating an underlying instability responsible for the WCM. During the I-mode magnetic fluctuations close to the WCM frequency are intensified, which can be assigned to the geodesic Alfvénic oscillation. The geodesic Alfvénic oscillation is already present in the L-mode, and does not follow changes of frequency of the WCM, therefore it is not responsible for the WCM.
The Yakutsk Extensive Air Shower Array has been continuously operating for more than 50 years (since 1970) and up until recently it has been one of world’s largest ground-based instruments aimed at ...studying the properties of cosmic rays in the ultra-high energy domain. In this report we discuss results recently obtained at the array—on cosmic rays’ energy spectrum, mass composition and directional anisotropy—and how they fit into the world data. Special attention is paid to the measurements of muonic component of extensive air showers. Theoretical results of particle acceleration at shocks are also briefly reviewed. Future scientific and engineering plans on the array modernization are discussed.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In recent years new data have been obtained on the role of intestinal dysbiosis in the pathogenesis mechanisms of neuroinflammation and neurodegeneration in Alzheimer's disease (AD), as well as on ...the influence of dietary patterns (Mediterranean diet, MIND diet) and probiotics on the correction of dysbiosis and slowing down the development of cognitive disorders. It seems reasonable to draw the attention of practicing physicians to the need to prevent cognitive dysfunction through dietary correction, probiotics and prebiotics intake.
of the research was to study the possibility of using certain dietary patterns, as well as intake of probiotics and prebiotics for the correction of dysbiosis and early prevention of cognitive dysfunction, basing on the analysis of published data on the bidirectional communication between the colon microbiota and the brain and microbiota changes in patients with cognitive dysfunction and AD.
. We searched domestic and foreign literature devoted to gut microbiota, the "gut-brain" axis, microbiota disorders in AD patients; mechanisms of neuroinflammation and neurodegeneration; the role of dietary patterns, in particular MIND diet, pre- and probiotics in the prevention of cognitive dysfunction - via PubMed search engine, SemanticScholar Google Internet search platform and domestic scientific electronic library Cyberleninka. 72 literature sources were analyzed.
. Intestinal dysbiosis and disruption of intestinal barrier integrity play an important role in the pathogenesis of neuroinflammation and neurodegeneration. Changes in the microbiota in patients with cognitive impairment and AD are associated with disease severity and are generally characterized by increased numbers of Gram-negative microorganisms in Bacteroidetes and Proteobacteria phyla and decreased numbers of Gram-positive microorganisms in Firmicutes and Actinobacteria phyla. An increase in gram-negative microorganisms abundance leads to elevated release of lipopolysaccharides (LPS) that disrupt the integrity of the intestinal mucous barrier and, through a series of steps, initiate neuroinflammation. Course application of probiotics containing representatives of Bifidobacterium and Lactobacillus genera, in particular, Bifidobacterium breve A1 и Lactobacillus plantarum С29 strains, leads to improved cognitive function, which can be explained by anti-inflammatory and antioxidant effects. Long-term prospective studies of the effects of dietary patterns such as the Mediterranean diet and the MIND diet clearly show delayed regression of cognitive function in older adults without initial dementia as well as in patients with AD. For example, according to various studies, individuals who have strictly adhered to the Mediterranean diet for 6-9 years have a 23-39% lower risk of developing cognitive impairment. Adherence to the MIND diet for 6 years has a statistically significant association with higher verbal memory scores. Correction of gut dysbiosis, including through the administration of probiotics, prebiotics and bringing the diet to the MIND diet pattern, is the most affordable and rational method for early prevention of cognitive dysfunction.
. A promising strategy in the early prevention of neuroinflammation, cognitive impairment and dementia is to maintain the balance of the gut microbiota. The solution to this problem is achieved by adjusting the dietary pattern, increasing the use of dietary fiber and prebiotics and reasonable use of probiotics.
Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease characterized by acute onset, fever, malaise, and back pain. As the disease progresses, hemorrhagic disturbances and ...kidney dysfunctions predominate. The examination of tissue collected postmortem supports the premise that virus replication is not responsible for this pathology; therefore, it is widely believed that virus-induced immune responses lead to the clinical manifestations associated with HFRS. The overproduction of inflammatory cytokines is commonly reported in subjects with HFRS and has given rise to the hypothesis that a so-called “cytokine storm” may play a pivotal role in the pathogenesis of this disease. Currently, supportive care remains the only effective treatment for HFRS. Our data show that serum levels of interferon (IFN)-γ, interleukin (IL)-10, CCL2, and IL-12 are upregulated in HFRS cases when compared to healthy controls and the level of upregulation is dependent on the phase and severity of the disease. Furthermore, we observed an association between the mild form of the disease and elevated serum levels of IFN-γ and IL-12. Collectively, these observations suggest that the administration of exogenous IFN-γ and IL-12 may provide antiviral benefits for the treatment of HFRS and, thus, warrants further investigations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A method for modifying sesquiterpene lactones using the click chemistry methodology has been developed. A series of conjugates of alantolactone and dehydrocostus lactone with alkoxy substituted ...benzylazides was obtained and their cytotoxic profile with respect to tumor cells of the A549, SH-SY5Y, Hep-2 and HeLa lines was evaluated. It has been shown that derivatives containing dehydrocostus lactone motif in their structure exhibit the highest cytotoxic activity.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The indolocarbazole derivative LCS-1269 has a multitarget mechanism of action on tumors and blocks vasculogenic mimicry. The hydrophobic character of LCS-1269 hampers the development of an injectable ...dosage form (IDF), the need for which was determined in series of
in vitro
and
in vivo
biological experiments. The purpose of this study was to select an excipient composition for creating a model IDF of LCS-1269 with high antitumor activity and low toxicity and to develop the technology for LCS-1269 IDF production. Acomposition of a model IDF of LCS-1269 including EtOH (95%), Kollidon 17 PF, and polysorbate 80 and the technology for obtaining a true solution were developed during preliminary experimental studies. The selected model was lyophilized to exclude EtOH from the composition and to increase the shelf life of the compound.
The structural, electrical, and magnetic properties of lithium zinc ferrite prepared by ceramic technology have been studied. The composition of lithium zinc ferrite is Li
0.4
Fe
2.4
Zn
0.2
O
4
with ...1 and 2 wt % bismuth oxide. The addition of Bi
2
O
3
prior to sintering of the samples has been shown to affect the structural, electrical, and magnetic properties of the ferrite. A significant increase in density from 4.47 to 4.65 g/cm
3
and a decrease in porosity from 4.8 to 2.3% have been observed when the concentration of bismuth oxide has been increased to 2 wt %. The Bi
2
O
3
-containing samples have higher specific electrical resistivity compared to that of the additive-free lithium zinc ferrite. The introduction of bismuth oxide has reduced the specific saturation magnetization from 70.55 to 54.76 G cm
3
/g. The Curie temperature has not changed significantly. An optimal combination of macroscopic properties of ferrite has been found at 1 wt % Bi
2
O
3
concentration.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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