Stabilized melanocortin analog peptide ACTH(6–9)PGP (HFRWPGP) possesses a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we ...present a study of the proproliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6–9 (HFRW) linked with the peptide prolyine–glycyl–proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H2O2, tert-butyl hydroperoxide, and KCN and demonstrated proproliferative activity. The mechanism of its action was the modulation of proliferation-related NF-κB genes and stimulation of prosurvival NRF2-gene-related pathway, as well as a decrease in apoptosis.
Endocannabinoid anandamide (AEA) and paracannabinoid lysophosphatidylinositol (LPI) play a significant role in cancer cell proliferation regulation. While anandamide inhibits the proliferation of ...cancer cells, LPI is known as a cancer stimulant. Despite the known endocannabinoid receptor crosstalk and simultaneous presence in the cancer microenvironment of both molecules, their combined activity has never been studied. We evaluated the effect of LPI on the AEA activity in six human breast cancer cell lines of different carcinogenicity (MCF-10A, MCF-7, BT-474, BT-20, SK-BR-3, MDA-MB-231) using resazurin and LDH tests after a 72 h incubation. AEA exerted both anti-proliferative and cytotoxic activity with EC
in the range from 31 to 80 µM. LPI did not significantly affect the cell viability. Depending on the cell line, the response to the LPI-AEA combination varied from a decrease in AEA cytotoxicity to an increase in it. Based on the inhibitor analysis of the endocannabinoid receptor panel, we showed that for the former effect, an active GPR18 receptor was required and for the latter, an active CB2 receptor. The data obtained for the first time are important for the understanding the manner by which endocannabinoid receptor ligands acting simultaneously can modulate cancer growth at different stages.
Prostanit is a novel drug developed for the treatment of peripheral arterial diseases. It consists of a prostaglandin E
(PGE
) moiety with two nitric oxide (NO) donor fragments, which provide a ...combined vasodilation effect on smooth muscles and vascular spastic reaction. Prostanit pharmacokinetics, however, remains poorly investigated. Thus, the object of this study was to investigate the pharmacokinetics of Prostanit-related and -affected metabolites in rabbit plasma using the liquid chromatography-mass spectrometry (LC-MS) approach. Besides, NO generation from Prostanit in isolated rat aorta and human smooth muscle cells was studied using the Griess method. In plasma, Prostanit was rapidly metabolized to 1,3-dinitroglycerol (1,3-DNG), PGE
, and 13,14-dihydro-15-keto-PGE
. Simultaneously, the constant growth of amino acid (proline, 4-hydroxyproline, alanine, phenylalanine, etc.), steroid (androsterone and corticosterone), and purine (adenosine, adenosine-5 monophosphate, and guanosine) levels was observed. Glycine, aspartate, cortisol, and testosterone levels were decreased. Ex vivo Prostanit induced both NO synthase-dependent and -independent NO generation. The observed pharmacokinetic properties suggested some novel beneficial activities (i.e., effect prolongation and anti-inflammation). These properties may provide a basis for future research of the effectiveness and safety of Prostanit, as well as for its characterization from a clinical perspective.
The deadwood contributes to an increase in soil heterogeneity due to the changing the microrelief (by the formation of windthrow-soil complexes), as well as changes in physical and chemical ...characteristics of decaying wood directly during xylolysis. We hypothesized that fallen logs as an element of microrelief influence the species composition and cover structure of vascular plants. We studied the influence of Picea abies (L.) Karst fallen logs of moderate and advanced decay stages on the horizontal distribution and heterogeneity of vascular plant cover in different microsite types (small boreal grass type, blueberry type, small boreal grass-blueberry type, herbs, and blueberry type) in old-growth middle taiga spruce forest in the Kivach State Nature Reserve (Republic of Karelia, Russia). The fallen deadwood acts as a factor of heterogeneity, causing reversible changes in the homogeneity of the original plant cover. The decaying logs influence the horizontal distribution of small herbs by changing the occurrence and density of shoots of Oxalis acetosella L., Maianthemum bifolium (L.) F.W. Schmidt, Vaccinium myrtillus L., and Vaccinium vitis-idaea L., as well as the occurrence of Luzula pilosa (L.) Willd. and Calamagrostis arundinacea (L.) Roth. Its impact on the heterogeneity parameters can be traced up to 20 cm from the log. The differences in vascular plant cover between fallen logs and the surrounding forest floor depend on the soil conditions of the microsite. The heterogeneity of conditions created by the logs smoothed out with increasing decay class, resulting in decreasing differences in the heterogeneity parameters of vascular plant cover between deadwood and forest floor. The changes in the homogeneity of the initial vascular plant cover by deadwood and the gradual smoothing of heterogeneity between the logs and the forest floor in rich and poor conditions have different, mainly opposite, trends. Finally, the structure of the vegetation cover reaches a state that is typical of particular growth conditions beyond deadwood.
Cholines acylated with unsaturated fatty acids are a recently discovered family of endogenous lipids. However, the data on the biological activity of acylcholines remain very limited. We hypothesized ...that acylcholines containing residues of arachidonic (AA-CHOL), oleic (Ol-CHOL), linoleic (Ln-CHOL), and docosahexaenoic (DHA-CHOL) acids act as modulators of the acetylcholine signaling system. In the radioligand binding assay, acylcholines showed inhibition in the micromolar range of both α7 neuronal nAChR overexpressed in GH4C1 cells and muscle type nAChR from Torpedo
, as well as Lymnaea stagnalis acetylcholine binding protein. Functional response was checked in two cell lines endogenously expressing α7 nAChR. In SH-SY5Y cells, these compounds did not induce Ca
rise, but inhibited the acetylcholine-evoked Ca
rise with IC
9 to 12 μM. In the A549 lung cancer cells, where α7 nAChR activation stimulates proliferation, Ol-CHOL, Ln-CHOL, and AA-CHOL dose-dependently decreased cell viability by up to 45%. AA-CHOL inhibited human erythrocyte acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by a mixed type mechanism with
= 16.7 ± 1.5 μM and
= 51.4 ± 4.1 μM for AChE and
= 70.5 ± 6.3 μM and
= 214 ± 17 μM for BChE, being a weak substrate of the last enzyme only, agrees with molecular docking results. Thus, long-chain unsaturated acylcholines could be viewed as endogenous modulators of the acetylcholine signaling system.
The 100th anniversary of the highest court instance of Russia determines the relevance of studying the Supreme Court of the RSFSR as a historical and legal phenomenon, formed as the highest judiciary ...authority on fundamentally different organizational approaches than before. The article studies certain specifics of the highest instance of Russia’s judiciary, including legal forms of its organization, activities of the Supreme Court of the RSFSR, structural intra-system relationships, and its place and role in the development of Russia’s statehood. The research offers analysis of theoretical concepts and judicial legislation during the preceding period between the two judicial reforms (of 1864 and of 1922). It aims at revealing certain features of the legal model of the Supreme Court of the RSFSR in 1922 as the first created national form of an organizationally autonomous court of the highest judicial instance in terms of its place and role in the system of Soviet justice. The research methodology is based on comparative-legal and historical-legal approaches. The author refers not only to legal acts, but also to publications of the party and Soviet leaders of the first years of the Soviet power, devoted to the issues of formation of a unified judicial system and its supreme body. The prerequisites for the formation of the Supreme Court of the RSFSR associated with requests for stability and clarity of the rule of law, uniformity of judicial practice in the conditions of the New Economic Policy have been highlighted. The article draws conclusions concerning the legal status of the Supreme Court of the RSFSR, highlights its features as the highest level in a unified judicial system, and determines the legal nature, the place and the role of the Supreme Court of the RSFSR in the system of judiciary, where it was endowed with organizational and managerial powers in respect of people’s investigators, collegium of defense counsellors, bailiffs and public notary offices.
BACKGROUND: in the 1990s Russian cosmonauts performed six long-duration missions on Mir that went from 312 to 438 d. In 2015 a mission on the International Space Station that continued for 340 d, 8 ...h, and 47 min was successfully accomplished. It was a joint U.S./Russian mission
completed by Scott Kelly and Mikhail Kornienko (KM).METHODS: The intensity of in-flight physical exercises and postflight motor changes were measured in KM and in the six cosmonauts who made shorter flights (173.3 ± 13.8 d) on ISS while using similar countermeasures against
the adverse effects of microgravity.RESULTS: It was found that both parameters varied similarly in spite of the difference in the duration of ISS missions. KM maintained adequate physical performance throughout the entire flight; moreover, the level of postflight changes he displayed
was comparable to that recorded in the group of cosmonauts who completed 6-mo missions on ISS.DISCUSSION: In summary, the 1-yr mission has clearly demonstrated the high efficacy of the countermeasures used by KM.Fomina EV, Lysova NYu, Kukoba TB, Grishin AP, Kornienko MB. One-year mission on ISS is a step towards interplanetary missions. Aerosp Med Hum Perform. 2017; 88(12):1094-1099.
Background: There is a need for the systematization, generalization and analysis of the structural changes of the myocardium, occurring in patients with myocarditis. This disease is rare; therefore, ...structured information in the field of radiological diagnostics is still insufficient within national publications. Aim: The study purpose was to determine the significance and specificity of changes observed in cardiac magnetic resonance images in patients with myocarditis, and to compare the obtained results with the literature data. Methods: 7 patients, including children aged 4 and 6, with a verified diagnosis of myocarditis were retrospectively examined. Results: The analysis of the obtained images revealed the most common changes related to myocarditis, such as myocardial edema, impaired myocardial contractility, increased delayed accumulation of the contrast agent. The pathophysiological mechanisms of the found structural changes were analyzed and described. Conclusion: Magnetic resonance imaging is the most important non-invasive method for diagnosing myocarditis, which allows one to identify the lesion of the heart muscle, to assess the extent of its damage, to differentiate myocarditis from other diseases, as well as to assess the dynamics when evaluating the effectiveness of therapy.
Evolution of Russian Microgravity Countermeasures Yarmanova, Eugenia N.; Kozlovskaya, Inessa B.; Khimoroda, N. N. ...
Aerospace medicine and human performance,
12/2015, Volume:
86, Issue:
12
Journal Article
Peer reviewed
INTRODUCTION: Countermeasures to prevent or partially offset the negative physiologic changes that are caused by the effects of microgravity play an important role in supporting the performance of ...crewmembers in flight and their safe return to Earth. Research conducted in Russia
on the orbital stations Salyut and Mir, as well as simulation experiments on the ground, have demonstrated that changes that occur during extended spaceflight in various physiologic systems can be prevented or significantly decreased by using countermeasures. Hardware and techniques used on
the ISS have been substantially improved to reflect the experience of previous extended missions on Russian orbital stations. Countermeasures used during early ISS missions consisted of the U.S. treadmill (TVIS), cycle ergometer (ВБ-3), a set of resistance bands, a postural muscle
loading suit (Penguin-3), electrical stimulator (Tonus-3), compression thigh cuffs (Braslet-М), a lower body negative pressure (LBNP) suit (Chibis), a lower body g-loading suit (Kentavr), and water/salt supplements. These countermeasures are described in this article.Yarmonova EN,
Kozlovskaya IB, Khimoroda NN, Fomina EV. Evolution of Russian microgravity countermeasures. Aerosp Med Hum Perform. 2015; 86(12, Suppl.):A32-A37.
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•We synthesized four types of (non-)solvated REE(III) carboxylates with different structures.•All dimeric and polymeric complexes characterized by single-crystal X-ray ...diffraction.•M2(piv)6(Hpiv)6 show a reversible phase transition to a commensurate modulated modification.•Magnetic properties of the lanthanide complexes M2(piv)6(Hpiv)6 were investigated.
The rare-earth metal(III) complexes M2(piv)6(Hpiv)6 (monoclinic, P21/c, 1), M2(piv)6(Hpiv)6·Hpiv (monoclinic, C2/c, 2), M(piv)3n (trigonal, P63/m, 3), and (Hpiv)2(iPrOH)2Sm2(piv)6·2Hpiv (triclinic, P-1, 4), where piv is (CH3)3CCO2−, were synthesized, and their structures were determined by single-crystal X-ray diffraction (SC-XRD). The crystallization was shown to be controllable by varying the nature of the salting-out agent – the non-coordinating organic solvent in the M(OAc)3·4H2O–Hpiv system. The following bulky single-phase samples were obtained: dimers 1 or 2 with M = Pr, Nd, Sm, Eu, and Gd using hexane C6H14; dimer 1 or 1D polymer 3 with M = Y, Er, and Yb using EtOH; dimers 2 or 4 with M = Sm using iPrOH. A reversible phase transition to a commensurate modulated modification (P21/c) was observed for crystals of 1 (Pn). The magnetic properties of complexes 1a (Pr), 1b (Nd), 4 (Sm), 1d (Eu), 1f (Dy), 1 g (Ho), and 1 h (Er) were investigated.
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