Design and Synthesis of Isosteviol Triazole Conjugates for Cancer Therapy

One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using “click” chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development

A method for partial estimation of electromagnetic wave diffraction by a longitudinal baffle in an endless waveguide

Background. A 2D problem of diffraction of a TE-polarized electromagnetic wave in an infinite waveguide with a longitudinal baffle is studied. The mathematical formulation of this physical problem is equivalent to a boundary value problem for the Helmholtz equation with Dirichlet-type boundary conditions and matching conditions. To solve this problem, the method of partial regions is used. In accordance with this method, the solution of the problem in each subdomain is sought in the form of a series with unknown coefficients, which are found from the matching conditions at the media interface. Using the method of integral-summation identities, this boundary value problem is reduced to an infinite system of linear algebraic equations (SLAE) with respect to unknown coefficients. Results. An SLAE corresponding to the 2D problem of diffraction in an infinite waveguide with a longitudinal baffle is derived. Computational experiments have been carried out. Resonance effects are found, which are obtained in cases where the frequency of the incident wave is close to the natural frequencies of the subregions corresponding to the branched part of the waveguide. Diagrams of electromagnetic fields at resonant frequencies are constructed. The energy values of the electromagnetic field are calculated for various wave numbers. Conclusions. From the results of computational experiments, we can conclude that the accuracy of fulfillment of the boundary conditions of matching depends on the SLAE truncation parameter. To check the accuracy of fulfillment of the boundary conditions, the concept of the matching residual is introduced. It is shown that resonance phenomena are observed at frequencies of the incident wave close to the eigenvalues of the subregions corresponding to the branched part of the waveguide

(S)-N-(N-(((2R,3S,4R,5R)-5-(6-Amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)sulfamoyl)-5-oxopyrrolidine-2-carboxamide

Aminoacyl sulfamides represent a family of high-affinity inhibitors of the specific aminoacyl tRNA synthetase activity. In this paper we describe the synthesis of a novel sulfamide adenosine derivative 4 bearing pyroglutamyl fragment (pGlu-SA)

EFFECT OF THE ETHYLMETHYLHYDROXYPYRIDINE SUCCINATE ON THE OXIDATIVE MODIFICATION OF SERUM PROTEINS IN PATIENTS WITH ISCHEMIC STROKE

Aim. To study the effect of ethylmethylhydroxypyridine succinate (EMHPS) on the protein oxidative modification (POM) in patients with acute ischemic stroke. (IS) Material and methods. Patients with IS (n=80) and 20 healthy subjects matched for age and sex (control group) were included in the study. IS patients were split into 2 groups: group 1 (n=39) received EMHPS in addition to standard treatment, and group 2 (n=41) - the standard therapy only. POM was studied by optical density of dinitrophenylhydrazone in wave lengths of 356, 370, 430, 530 nm in 1, 3 and 15 days after IS in patients of the both groups and in control. Results. Significant disorders of the antioxidant system were determined in patients with IS in the range of aldehyde and ketone derivates of dinitrophenylhydrazone in comparison with patients of control group. The highest POM level was observed in patients with atherothrombotic IS: optical density indexes of neutral and alkaline aldehyde and ketone derivates in blood serum proteins were maximal in all wave lengths. Next in order of POM levels decreasing followed patients with cardioembolic and haemodynamic IS and lastly patients with lacunar IS. POM increasing tendency was observed after 3 days in all patients with IS, especially in patients with atherothrombotic IS. A positive POM trend was found in all patients of the group 1 (p&lt;0.05) in 15 days after disease onset. Patients with lacunar IS demonstrated optical density indexes in 530 nm wave length even comparable to those in the control group (0.18±0.01 and 0.2±0.03, respectively; p&gt;0.05). Conclusion. EMHPS inclusion in the treatment of IS patients has a positive effect on the POM changes.</p

Gene expression profiling leads to discovery of correlation of matrix metalloproteinase 11 and heparanase 2 in breast cancer progression

Background In order to identify biomarkers involved in breast cancer, gene expression profiling was conducted using human breast cancer tissues. Methods Total RNAs were extracted from 150 clinical patient tissues covering three breast cancer subtypes (Luminal A, Luminal B, and Triple negative) as well as normal tissues. The expression profiles of a total of 50,739 genes were established from a training set of 32 samples using the Agilent Sure Print G3 Human Gene Expression Microarray technology. Data were analyzed using Agilent Gene Spring GX 12.6 software. The expression of several genes was validated using real-time RT-qPCR. Results Data analysis with Agilent GeneSpring GX 12.6 software showed distinct expression patterns between cancer and normal tissue samples. A group of 28 promising genes were identified with ≥ 10-fold changes of expression level and p-values < 0.05. In particular, MMP11 and HPSE2 were closely examined due to the important roles they play in cancer cell growth and migration. Real-time RT-qPCR analyses of both training and testing sets validated the gene expression profiles of MMP11 and HPSE2. Conclusions Our findings identified these 2 genes as a novel breast cancer biomarker gene set, which may facilitate the diagnosis and treatment in breast cancer clinical therapies

Relevance of Implementing Digital Strategies and Tools for Small Business

Данное исследование посвящено изучению такого понятия как digital­стратегия фирмы и применению инструментов продвижения. Актуальность изучаемых в статье вопросов развития бизнеса посредством современных цифровых инструментов подтверждается тенденцией развития интернет­маркетинга. В статье рассмотрены понятия digital­стратегии, обобщены основные инструменты продвижения в сети Интернет, проанализированы метрики анализа эффективности инструментов. Автором сделаны выводы о необходимости внедрении digital­инструментов.This study is devoted to the study of such a concept as a company's digital strategy and the use of promotion tools. The relevance of the issues of business development studied in the article using modern digital tools is confirmed by the trend in the development of Internet marketing. The article discusses the concepts of digital strategy, promotion tools, describes methods for analyzing the effectiveness of tools. The author draws conclusions about the need to introduce digital tools