Low molecular weight compounds targeting chaperone proteins Hsp90 and Hsp70 have opened up a new avenue in the therapy of neoplasms. In 2020, we tested 3 Hsp70 inhibitors from the class of 4-aminopiperidine derivatives for their antitumor activity on in vivo models. The list of the tested compounds included N-(2-chlorobenzyl)-N-ethyl-1-(2-(methylthio)pyrimidin-4-yl)piperidin-4-amine (compound 1), 4-((methyl(1-(2-(methylthio)pyrimidin-4-yl) piperidin-4-yl)amino)methyl) benzonitrile (compound 2) and N-(2,6- dichlorobenzyl)-1-(1-(2-(ethylthio)pyrimidin-4-yl)piperidin-4-yl)-N-methylmethaneamine (compound 3). The aim of this study was to compare the efficacy of 4-aminopiperidine derivatives in vivo using the models of transplantable murine L1210 lymphocytic leukemia and B16 melanoma. Compounds 2 and 3 used in combination with cyclophosphamide exhibited high cytotoxic activity (р = 0.05) against L1210 leukemia (an 80-82% increase in survival time) and B16 melanoma (98-99.7% tumor growth delay). For L1210 lymphocytic leukemia, compounds 2 and 3 used in combination with cyclophosphamide fell into the low (+) therapeutic potential category. For B16 melanoma, compounds 1, 2 and 3 used in combination with cyclophosphamide fell into either low (+) or moderate (++) therapeutic potential categories. On the whole, the tested doses of the compounds used in combination with cyclophosphamide hold promise for the therapy of L1210 leukemia and B16 melanoma in mouse models. Our findings confirm the potential of low molecular weight Hsp70 inhibitors for combination chemotherapy against cancer.
VIEWS 157
COVID-19 belongs to the group of acute respiratory infections and it is often complicated with pneumonia. This study aimed to investigate manifestations of community-acquired pneumonia (CAP) epidemic process during the COVID-19 epidemic in the Russian Federation. We analyzed the official statistical data reporting the incidence of CAP in the Russian Federation in 2013–2020 and incidence of COVID-19 as registered in March–July 2020. The mean average annual CAP incidence rate that we calculated and the 2020 CAP incidence prediction allowed assessing the relationship between CAP and COVID-19. It is shown that the long-term dynamics of the incidence of CAP in the Russian Federation is characterized by a pronounced upward trend with an average annual growth rate of 6.4%. The share of adult population among the CAP cases is the largest; on average, it is 64.7% (95% CI [63.1; 66.3]). In 2020, against the background of SARS-CoV-2 circulation, the discrepancy between the actual incidence of CAP and the predicted figures reached and exceeded 558% (in July 2020). As the COVID-19 epidemic developed, the incidence of CAP was registered to increase. There was established a direct and significant correlation between the incidence of CAP and COVID-19 (rxy = 0.932; p <0.01).
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Wind affects functional state and health of human beings. Physical activity mitigates the risk of hypothermia, but not the discomfort felt in cold winds. Moreover, there appears a risk of body cooling and frostbite. This study aimed to assess the risk to health of a human being associated with the wind chill factor index in the various climatic zones of a Russian region. The calculation relied on the mean monthly daily temperature and wind speed values, minimum temperature and maximum wind values registered in the subarctic and continental climate zones during the two climatological normals determination observation periods, 19611990 (second period) and 1991–2020 (third period). In the third period, a significant decrease in wind strength was registered in the subarctic (8 months) and temperate continental (9 months) climates. The mean monthly temperatures increased in April by 3.5 °C (p = 0.006), April–June by 4.05 °C (p = 0.001) and 3.9 °C (p = 0.001). The maximum wind in the subarctic climate did not change, in the temperate continental zone it decreased within 9 months; the minimum temperature increased in 4 and 1 months. In the subarctic zone, the mean temperature and wind values made the ambient conditions uncomfortable for 6 months (versus 7), with one characterized as "extremely cold"; the cold exposure risk decreased during the "very cold" period; in the temperate climate zone, the potentially uncomfortable conditions period lasted for 4 months (versus 6). With wind at the maximum and temperature at the minimum, in the subarctic climate, the weather remained severe for 8 months a year in each of the determination periods ("uncomfortable, chilly" — 2 months, "cold, skin surface hypothermia" — 1 month, "extremely cold, possible hypothermia of the exposed parts of the body in 10 minutes" — 5 months); in the temperate continental climate zone, it was severe for 5 months of each year ("uncomfortable, chilly" — 2 months, "cold, skin surface hypothermia" — 3 month).
VIEWS 219