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排序方式: 共有470条查询结果,搜索用时 31 毫秒
151.
Mariia Larkina Evgenii Plotnikov Ekaterina Bezverkhniaia Yulia Shabanova Maria Tretyakova Feruza Yuldasheva Roman Zelchan Alexey Schulga Elena Konovalova Anzhelika Vorobyeva Javad Garousi Torbjrn Grslund Mikhail Belousov Vladimir Tolmachev Sergey Deyev 《International journal of molecular sciences》2022,23(21)
Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [99mTc]Tc-(HE)3-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)3), provided clear imaging of HER2 expressing breast cancer 2–4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E3C), Gly-Gly-Gly-Cys (G3C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)3-linker (designated as G3-(G3S)3C) would further improve the contrast of imaging using 99mTc-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9–5 nM. Biodistribution of [99mTc]Tc-G3-G3C, [99mTc]Tc-G3-(G3S)3C, and [99mTc]Tc-G3-E3C in mice was compared with the biodistribution of [99mTc]Tc-(HE)3-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-(HE)3-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications. 相似文献
152.
Aleksey M. Krasnyi Alsu A. Sadekova Tatyana Y. Smolnova Vyacheslav V. Chursin Natalya A. Buralkina Vladimir D. Chuprynin Ekaterina Yarotskaya Stanislav V. Pavlovich Gennadiy T. Sukhikh 《International journal of molecular sciences》2022,23(18)
The aim of this study was to evaluate the levels of ten energy metabolism factors: C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1 (total), resistin, and visfatin, and to determine the expression of GLP1R receptors, CD10, CD26 proteases, and pro-inflammatory marker CD86 by macrophages in the peritoneal fluid (PF) in patients with endometriosis. The study included 54 women with endometriosis and a control group of 30 women with uterine myoma without signs of endometriosis. The levels of factors in PF were assessed by a multiplex method. Expression of GLP1R receptors, CD10, CD26 proteases, and CD86 by macrophages was evaluated using flow cytometry. It was found that in women with endometriosis, the concentrations of ghrelin, GLP-1, glucagon, and visfatin in PF were reduced (p = 0.007, p = 0.009, p = 0.002, p = 0.008, respectively). At the same time, there was a noted increase in the CD10 protease expression by peritoneal macrophages (p = 0.044). Correlation analysis showed a positive correlation of ghrelin and GLP-1 levels with CD86 macrophage expression (p = 0.044, p = 0.022, respectively) in the study group; a positive correlation was also found between the levels of GLP-1, glucagon, and visfatin with CD26 macrophage expression (p = 0.041, p = 0.048, p = 0.015, respectively) in PF. No correlations were found in the control group. These results indicate that a decrease in the levels of ghrelin, GLP-1, glucagon, and visfatin in PF may contribute to endometriosis development through their impact on the expression of pro-inflammatory markers of PF macrophages. 相似文献
153.
Dmitry Rasskazov Irina Chadaeva Ekaterina Sharypova Karina Zolotareva Bato Khandaev Petr Ponomarenko Nikolay Podkolodnyy Natalya Tverdokhleb Oleg Vishnevsky Anton Bogomolov Olga Podkolodnaya Ludmila Savinkova Elena Zemlyanskaya Vadimir Golubyatnikov Nikolay Kolchanov Mikhail Ponomarenko 《International journal of molecular sciences》2022,23(15)
Synthetic targeted optimization of plant promoters is becoming a part of progress in mainstream postgenomic agriculture along with hybridization of cultivated plants with wild congeners, as well as marker-assisted breeding. Therefore, here, for the first time, we compiled all the experimental data—on mutational effects in plant proximal promoters on gene expression—that we could find in PubMed. Some of these datasets cast doubt on both the existence and the uniqueness of the sought solution, which could unequivocally estimate effects of proximal promoter mutation on gene expression when plants are grown under various environmental conditions during their development. This means that the inverse problem under study is ill-posed. Furthermore, we found experimental data on in vitro interchangeability of plant and human TATA-binding proteins allowing the application of Tikhonov’s regularization, making this problem well-posed. Within these frameworks, we created our Web service Plant_SNP_TATA_Z-tester and then determined the limits of its applicability using those data that cast doubt on both the existence and the uniqueness of the sought solution. We confirmed that the effects (of proximal promoter mutations on gene expression) predicted by Plant_SNP_TATA_Z-tester correlate statistically significantly with all the experimental data under study. Lastly, we exemplified an application of Plant_SNP_TATA_Z-tester to agriculturally valuable mutations in plant promoters. 相似文献
154.
Anastasia Khokhlova Tatiana Myachina Xenia Butova Anastasia Kochurova Ekaterina Polyakova Michael Galagudza Olga Solovyova Galina Kopylova Daniil Shchepkin 《International journal of molecular sciences》2022,23(15)
Leptin is a pleiotropic peptide playing an important role in the regulation of cardiac functions. It is not clear whether leptin directly modulates the mechanical function of atrial cardiomyocytes. We compared the acute effects of leptin on the characteristics of mechanically non-loaded sarcomere shortening and cytosolic Ca2+ concentration ([Ca2+]i) transients in single rat atrial and ventricular cardiomyocytes. We also studied the functional properties of myosin obtained from cardiomyocytes using an in vitro motility assay and assessed the sarcomeric protein phosphorylation. Single cardiomyocytes were exposed to 5, 20, and 60 nM leptin for 60 min. In ventricular cardiomyocytes, 60 nM leptin depressed sarcomere shortening amplitude and decreased the rates of shortening and relaxation. These effects were accompanied by a decrease in the phosphorylation of cMyBP-C, an increase in Tpm phosphorylation, and a slowdown of the sliding velocity of thin filaments over myosin in the in vitro motility assay. In contrast, in atrial cardiomyocytes, the phosphorylation of cMyBP-C and TnI increased, and the characteristics of sarcomere shortening did not change. Leptin had no effect on the characteristics of [Ca2+]i transients in ventricular cardiomyocytes, while 5 nM leptin prolonged [Ca2+]i transients in atrial cardiomyocytes. Thus, leptin-induced changes in contractility of ventricular cardiomyocytes may be attributed to the direct effects of leptin on cross-bridge kinetics and sarcomeric protein properties rather than changes in [Ca2+]i. We also suggest that the observed differences between atrial and ventricular cardiomyocytes may be associated with the peculiarities of the expression of leptin receptors, as well as signaling pathways in the atrial and ventricular myocardium. 相似文献
155.
Kseniya M. Achasova Elena N. Kozhevnikova Mariya A. Borisova Ekaterina A. Litvinova 《International journal of molecular sciences》2021,22(19)
The mucus layer in the intestine plays a critical role in regulation of host–microbe interactions and maintaining homeostasis. Disruptions of the mucus layer due to genetic, environmental, or immune factors may lead to inflammatory bowel diseases (IBD). IBD frequently are accompanied with infections, and therefore are treated with antibiotics. Hence, it is important to evaluate risks of antibiotic treatment in individuals with vulnerable gut barrier and chronic inflammation. Mice with a knockout of the Muc2 gene, encoding the main glycoprotein component of the mucus, demonstrate a close contact of the microbes with the gut epithelium which leads to chronic inflammation resembling IBD. Here we demonstrate that the Muc2−/− mice harboring a gut protozoan infection Tritrichomonas sp. are susceptible to an antibiotic-induced depletion of the bacterial microbiota. Suppression of the protozoan infection with efficient metronidazole dosage or L-fucose administration resulted in amelioration of an illness observed in antibiotic-treated Muc2−/− mice. Fucose is a monosaccharide presented abundantly in gut glycoproteins, including Mucin2, and is known to be involved in host–microbe interactions, in particular in microbe adhesion. We suppose that further investigation of the role of fucose in protozoan adhesion to host cells may be of great value. 相似文献
156.
Anna Tyrtyshnaia Sophia Konovalova Anatoly Bondar Ekaterina Ermolenko Ruslan Sultanov Igor Manzhulo 《International journal of molecular sciences》2021,22(19)
The search for methods of cognitive impairment treatment and prevention in neurological and neurodegenerative diseases is an urgent task of modern neurobiology. It is now known that various diseases, accompanied by dementia, exhibit a pronounced neuroinflammation. Considering the significant docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids’ therapeutic potential, we decided to investigate and compare anti-inflammatory activity of their N-acylethanolamine derivatives. As a result, we found that both N-docosahexaenoylethanolamine (synaptamide) and N-eicosapentaenoylethanolamine (EPEA) prevents an LPS-mediated increase in the proinflammatory cytokines TNF-α and IL-6 production in the SIM-A9 microglia culture. In an in vivo experiment, synaptamide reversed an increase in LPS-mediated hippocampal TNF-α and IL-1β, but EPEA did not. However, both compounds contributed to the microglia polarization towards the M2-phenotype. Synaptamide, rather than EPEA, inhibited the Iba-1-positive microglia staining area increase. However, both synaptamide and EPEA prevented the LPS-mediated astrogliosis. A study of BDNF immunoreactivity showed that synaptamide, but not EPEA, reversed an LPS-mediated decrease in BDNF production. Despite the more pronounced anti-inflammatory activity of synaptamide, both compounds were effective in maintaining a normal level of hippocampal long-term potentiation in neuroinflammation. The results indicate a high therapeutic potential for both compounds. However, some tests have shown higher activity of synaptamide compared to EPEA. 相似文献
157.
158.
When Russia's housing allowance programme, the country's first means‐tested programme, was introduced in 1994, it was truly innovative. However, there were difficulties from the start, many arising from the division of authority for setting programme parameters among different levels of government and the potential for variation in the treatment of similar households in different cities. In 1996, the programme's original simple basis for benefit determination was seriously impaired by the introduction of different principles for very low‐income households. Moreover, local governments have exhibited a willingness to vary benefits from year‐to‐year, depending on political and budgetary considerations. The analysis presented here documents the impact of these variations on participation rates in a sample of Russian cities. Large inequities are obviously present in the treatment of similar households from city to city. Indeed, it is questionable whether the programme as currently configured is fulfilling the social safety net function envisioned for it in the original legislation. 相似文献
159.
Shishatskaya EI Voinova ON Goreva AV Mogilnaya OA Volova TG 《Journal of materials science. Materials in medicine》2008,19(6):2493-2502
Microspheres have been prepared from the resorbable linear polyester of β-hydroxybutyric acid (polyhydroxybutyrate, PHB) by
the solvent evaporation technique and investigated in vitro and in vivo. Biocompatibility of the microspheres has been proved
in tests in the culture of mouse fibroblast cell line NIH 3T3 and in experiments on intramuscular implantation of the microspheres
to Wistar rats for 3 months. Tissue response to the implantation of polymeric microspheres has been found to consist in a
mild inflammatory reaction, pronounced macrophage infiltration that increases over time, involving mono- and poly-nuclear
foreign body giant cells that resorb the polymeric matrix. No fibrous capsules were formed around polymeric microparticles;
neither necrosis nor any other adverse morphological changes and tissue transformation in response to the implantation of
the PHB microparticles were recorded. The results of the study suggest that polyhydroxybutyrate is a good candidate for fabricating
prolonged-action drugs in the form of microparticles intended for intramuscular injection. 相似文献
160.
The primary objectives of the housing reforms in the Russian Federation were to reduce the balance of the state housing stock by privatisation and to raise rental payments in order to permit the market to achieve a more efficient utilisation of the housing stock by allocating available housing to those with effective housing demand. Part of these objectives also included improving the quality of maintenance in state housing by breaking up the monopolies of state maintenance firms and replacing them with private firms procured through competitive bidding procedures. Moscow, in particular, has been a forerunner in implementing housing reform policies, including shifting from state maintenance firms to contracted private ones. Using Moscow and other Russian cities as illustrations for reforms in maintenance and managementbrings to light the benefits of private maintenance and also problems which must be overcome, not only throughout Russia but in nearly all the countries of the formerSoviet bloc. This paper evaluates the institutional changes of maintenance and sources of funding for maintenance in Moscow during the reforms; it shows evidence of improved quality of housing maintenance through the use of contracted private firms; and providesa general overview of competitive maintenance and condominium formation throughout Russia. 相似文献