Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart

POLYFLUOROALKYL-2-(HET)ARYLHYDRAZONO-1,3-DICARBONYL COMPOUNDS IN INTRAMOLECULAR CYCLIZATION REACTIONS

This work was financially supported by the Program UB RAS (Grant number 18-3-3-13)

Микроволновые характеристики композитного материала на основе эпоксидного полимера с добавлением графеновых и ферритных наноматериалов

The radio absorption properties of polymer composite materials with ferrite and graphene additives in the microwave frequency range (26-38 GHz) were studied. It was shown that graphene-like structures have a significant effect on the ability of composite materials to shield from electromagnetic radiation.Проведены исследования взаимодействия электромагнитного излучения микроволнового диапазона с полимерными радиопоглощающими композитными материалами, содержащими наноразмерные ферритные и графеновые добавки. Установлено, что преимущественно слоистые графеновые структуры оказывают существенное влияние на способность композитных материалов к экранированию электромагнитного излучения данного спектрального диапазона

Генетические механизмы распознавания бактерий рецепторами врожденного иммунитета крупного рогатого скота

The research identified a list of molecules involved in the mechanisms of innate immunity in cattle and the recognition of bacterial pathogens. The current list of molecular receptors has expanded to include TLR receptors and the recently defined NOD-like receptors (NLRs): NOD, NALP, NAIP, and IPAF. TLR molecules are designed to transmit a ligand-binding signal on the cell surface or endosome and activate specific molecules of bacterial origin in the cytosol, such as peptidoglycans, RNA, toxins and flagellins. The obtained data on the molecular structure of TLR and NLR receptors indicate their anti-inflammatory role, mediated by signals through nuclear transcription factor κB and activation of caspase-1 in the inflammasome. It has been shown that the role of immunosensors of extracellular and intracellular perception of bacteria in regulating inflammation is synergistic. Mutations in TLR and NOD receptors are associated with autoimmune inflammatory syndromes. This review examines the body's ways of recognising intracellular pathogens, describes the problem of their mimicry from the animal immune system, and the molecular mechanisms of such interactions. Variants of molecular interactions of innate immune receptors with peptidoglycans, bacterial DNA and toxins, cell wall compartments, and bacterial flagellin receptors are also considered. This study aimed to analyse the current understanding of the genetic and molecular structure of the immune response to bacterial environmental factors and the mechanisms and characteristics of the reaction of the animal body.В ходе исследований определен перечень молекул, вовлеченных в механизмы врожденного иммунитета крупного рогатого скота и распознавания бактериальных патогенов. Современный перечень молекулярных рецепторов расширился и теперь иммуносенсоры включают: рецепторы TLR, а также недавно определенные NOD-подобные рецепторы (NLR): NOD, NALP, NAIP и IPAF. Молекулы TLR предназначены для передачи сигнала связывания лиганда на поверхности клетки или эндосомы и активации в цитозоле специфичных молекул бактериального происхождения, таких как пептидогликаны, РНК, токсины и флагеллины. Полученные данные о молекулярной структуре рецепторов TLR и NLR указывают на их противовоспалительную роль, опосредованную сигналами через κB-фактор ядерной транскрипции и активацией в инфламмасоме каспазы-1. Показано, что роль в регуляции воспаления иммуносенсоров неклеточного и внутриклеточного восприятия бактерий синергетична. Мутации в TLR- и NOD-рецепторах связаны с аутоимунными воспалительными синдромами. В данном обзоре рассмотрены способы организма распознавать внутриклеточные патогены, описана проблема их мимикрии от иммунной системы животных, молекулярные механизмы таких взаимодействий. Рассмотрены также варианты молекулярных взаимодействий рецепторов врожденного иммунитета с пептидогликанами, бактериальной ДНК и токсинами, компартментами клеточных стенок, а также рецепторами бактериального флагеллина. Целью данного исследования был анализ современного понимания генетической и молекулярной структуры иммунного ответа на бактериальные факторы окружающей среды, а также анализ механизмов и особенностей реагирования организма животных

Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals

4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity. The polyfluoroalkyl residue in 4-AHPs led to the appearance of an anticarboxylesterase action in the micromolar range. An NH-fragment and/or methyl group instead of the polyfluoroalkyl one in the 4-AHPs promoted antioxidant properties in the ABTS, FRAP and ORAC tests, as well as anti-cancer activity against HeLa that was at the Doxorubicin level coupled with lower cytotoxicity against normal human fibroblasts. Some Ph-N-substituted 4-AHPs could inhibit the growth of N. gonorrhoeae bacteria at MIC 0.9 μg/mL. The possibility of using 4-AHPs for cell visualization was shown. Most of the 4-AHPs exhibited a pronounced analgesic effect in a hot plate test in vivo at and above the diclofenac and metamizole levels except for the ones with two chlorine atoms in the aryl group. The methylsulfonyl residue was proved to raise the anti-inflammatory effect also. A mechanism of the antinociceptive action of the 4-AHPs through blocking the TRPV1 receptor was proposed and confirmed using in vitro experiment and molecular docking. © 2022 by the authors.FFSN-2021-0005; Russian Foundation for Basic Research, РФФИ: 20-03-00312; Russian Science Foundation, RSF: 21-13-00390This work was financially supported by the Russian Science Foundation (grant No 21-13-00390 for V.I.S.): the synthesis and analysis of compounds, antimicrobial evaluation, cytotoxicity, analgesic and anti-inflammatory activity, mechanism of analgesia, molecular docking; by the Russian Foundation for Basic Research (grant No 20-03-00312 for Y.V.B.): esterase profile of compounds; antioxidant activity in ABTS and FRAP tests were performed in the frame of IPAC RAS State Targets Project FFSN-2021-0005