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排序方式: 共有230条查询结果,搜索用时 16 毫秒
51.
Oksana V. Salomatina Aleksandra V. Senkova Arseny D. Moralev Innokenty A. Savin Nina I. Komarova Nariman F. Salakhutdinov Marina A. Zenkova Andrey V. Markov 《International journal of molecular sciences》2022,23(11)
It is known that epoxide-bearing compounds display pronounced pharmacological activities, and the epoxidation of natural metabolites can be a promising strategy to improve their bioactivity. Here, we report the design, synthesis and evaluation of biological properties of αO-SM and βO-SM, novel epoxides of soloxolone methyl (SM), a cyanoenone-bearing derivative of 18βH-glycyrrhetinic acid. We demonstrated that the replacement of a double-bound within the cyanoenone pharmacophore group of SM with α- and β-epoxide moieties did not abrogate the high antitumor and anti-inflammatory potentials of the triterpenoid. It was found that novel SM epoxides induced the death of tumor cells at low micromolar concentrations (IC50(24h) = 0.7–4.1 µM) via the induction of mitochondrial-mediated apoptosis, reinforced intracellular accumulation of doxorubicin in B16 melanoma cells, probably by direct interaction with key drug efflux pumps (P-glycoprotein, MRP1, MXR1), and the suppressed pro-metastatic phenotype of B16 cells, effectively inhibiting their metastasis in a murine model. Moreover, αO-SM and βO-SM hampered macrophage functionality in vitro (motility, NO production) and significantly suppressed carrageenan-induced peritonitis in vivo. Furthermore, the effect of the stereoisomerism of SM epoxides on the mentioned bioactivities and toxic profiles of these compounds in vivo were evaluated. Considering the comparable antitumor and anti-inflammatory effects of SM epoxides with SM and reference drugs (dacarbazine, dexamethasone), αO-SM and βO-SM can be considered novel promising antitumor and anti-inflammatory drug candidates. 相似文献
52.
Innokenty A. Savin Marina A. Zenkova Aleksandra V. Senkova 《International journal of molecular sciences》2022,23(23)
Pulmonary fibrosis is a chronic progressive lung disease that steadily leads to lung architecture disruption and respiratory failure. The development of pulmonary fibrosis is mostly the result of previous acute lung inflammation, caused by a wide variety of etiological factors, not resolved over time and causing the deposition of fibrotic tissue in the lungs. Despite a long history of study and good coverage of the problem in the scientific literature, the effective therapeutic approaches for pulmonary fibrosis treatment are currently lacking. Thus, the study of the molecular mechanisms underlying the transition from acute lung inflammation to pulmonary fibrosis, and the search for new molecular markers and promising therapeutic targets to prevent pulmonary fibrosis development, remain highly relevant tasks. This review focuses on the etiology, pathogenesis, morphological characteristics and outcomes of acute lung inflammation as a precursor of pulmonary fibrosis; the pathomorphological changes in the lungs during fibrosis development; the known molecular mechanisms and key players of the signaling pathways mediating acute lung inflammation and pulmonary fibrosis, as well as the characteristics of the most common in vivo models of these processes. Moreover, the prognostic markers of acute lung injury severity and pulmonary fibrosis development as well as approved and potential therapeutic approaches suppressing the transition from acute lung inflammation to fibrosis are discussed. 相似文献
53.
54.
Savin Treanţă 《International journal of control》2020,93(3):611-618
ABSTRACTIn this paper, (strongly) b-V-KT-pseudoinvex multidimensional control problems are considered. Concretely, we introduce a generalised condition on the functionals involved in a multidimensional vector control problem and prove that a (strongly) b-V-KT-pseudoinvex multidimensional control problem is characterized so that all Kuhn–Tucker points are efficient solutions. In addition, the theoretical results derived in this paper are illustrated with an application. 相似文献
55.
M Savin 《Canadian Metallurgical Quarterly》1998,126(7-8):261-270
In chronic renal insufficiency resulting from destruction of the vast majority of nephrons, the surviving nephrons adapt their functions to the conditions of vigorous haemodynamic and osmolar overloads. They acquire an appropriate behaviour to preserve the principal renal functions and to achieve the balance of inner space. In the long period of time, similarly as in healthy people. Glomerulotubular balance as well as tubuloglomerular balance distinguish the remaining nephron function, while autoregulation of perfusion pressure along the glomerulus rapidly vanishes. All three regulation mechanisms are characteristic of the nephron function under physiologic conditions. Intense work of the remaining nephrons in chronic renal failure is under the high level controls of the group of hormones, among them are rennin-angiotensin system, arginine-vasopressin and atrial natriuretic peptide playing very important and particular roles. Comparison of different published studies emerge the idea that chronically increased arginine-vasopressin levels in chronic renal failure could block the autoregulation of blood flow and hydraulic pressure in glomeruli, which together with other mediator actions give high and fluctuating tense within remaining glomeruli, during every single cardiac cycle. It is probably the main event in the further course of kidney disease progression resulting in definite damage of the overloaded nephrons. Angiotensin II is one of reliably recognised mediators of unfavourable outcome in the process of nephron adaptation in chronic renal failure. Knowing the pathophysiologic processes in the remaining functionally adapted nephrons in chronic renal insufficiency determines a more adequate therapeutic approach in these patients. 相似文献
56.
V. K. Andreev V. I. Deev A. N. Savin 《Journal of Engineering Physics and Thermophysics》1985,48(1):10-12
Results are presented from a study of the effect of saturation pressure on the nonsteady critical heat flux during the boiling of liquid helium in a large volume.Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 48, No. 1, pp. 16–18, January, 1985. 相似文献
57.
58.
I. A. Nakrap A. N. Savin Yu. P. Sharaevskii 《Journal of Communications Technology and Electronics》2006,51(3):303-310
The results of an experimental investigation of electrodynamic characteristics of a meander microstrip line with a ferromagnetic film are presented for different values of an external magnetic field. It is found that, in the presence of a ferrite film, higher-order modes caused by perturbation of corresponding modes of a multilayered meander line are excited in the passband of a higher-order mode of the meander line. These modes propagate in dielectric substrates of the meander line and the ferromagnetic film. The effect of transmission of the active power in the stopband of the meander line with a ferromagnetic film is discovered. This effect also arises in the case of excitation of magnetostatic waves. 相似文献
59.
M. Ylnen H. Kattelus A. Savin P. Kivinen T. Haatainen J. Ahopelto 《Microelectronic Engineering》2003,70(2-4):337-340
The properties of amorphous metallic molybdenum–silicon–nitrogen (Mo–Si–N) films were characterised for use in nanoelectronic applications. The films were deposited by co-sputtering of molybdenum and silicon targets in a gas mixture of argon and nitrogen. The atomic composition, microstructure and surface roughness were studied by RBS, TEM and AFM analyses, respectively. The electrical properties were investigated in the temperature range 80 mK to 300 K. No transition into a superconductive state was observed. Nanoscale wires were fabricated using electron beam lithography with their properties measured as a function of temperature. 相似文献
60.
TC Chou XG Zhang A Balog DS Su D Meng K Savin JR Bertino SJ Danishefsky 《Canadian Metallurgical Quarterly》1998,95(16):9642-9647
A new class of 16-membered macrolides, the epothilones (Epos), has been synthesized and evaluated for antitumor potential in vitro and in vivo. Recent studies in these and other laboratories showed that epothilones and paclitaxel (paclitaxel) share similar mechanisms of action in stabilizing microtubule arrays as indicated by binding-displacement studies, substitution for paclitaxel in paclitaxel-dependent cell growth, and electron microscopic examinations. The present study examined cell growth-inhibitory effects in two rodent and three human tumor cell lines and their drug-resistant sublines. Although paclitaxel showed as much as 1, 970-fold cross-resistance to the sublines resistant to paclitaxel, adriamycin, vinblastine, or actinomycin D, most epothilones exhibit little or no cross-resistance. In multidrug-resistant CCRF-CEM/VBL100 cells, IC50 values for EpoA (1), EpoB (2), desoxyEpoA (3) (dEpoA), desoxyEpoB (4) (dEpoB), and paclitaxel were 0.02, 0.002, 0.012, 0.017, and 4.14 microM, respectively. In vivo studies, using i.p. administration, indicated that the parent, EpoB, was highly toxic to mice and showed little therapeutic effect when compared with a lead compound, dEpoB. More significantly, dEpoB (25-40 mg/kg, Q2Dx5, i.p.) showed far superior therapeutic effects and lower toxicity than paclitaxel, doxorubicin, camptothecin, or vinblastine (at maximal tolerated doses) in parallel experiments. For mammary adenocarcinoma xenografts resistant to adriamycin, MCF-7/Adr, superior therapeutic effects were obtained with dEpoB compared with paclitaxel when i.p. regimens were used. For ovarian adenocarcinoma xenografts, SK-OV-3, dEpoB (i.p.), and paclitaxel (i. v.) gave similar therapeutic effects. In nude mice bearing a human mammary carcinoma xenograft (MX-1), marked tumor regression and cures were obtained with dEpoB. 相似文献