Change in the karyotype of the embryo as a cause of spontaneous abortion in the first trimester

Currently, one of the most actual health problems in the world is the problem of a spontaneous abortion. Chromosomal abnormalities are one of the main reasons of early abortion, stillbirth or the birth of a child with multiple congenital malformations. The results of karyotyping of chorionic villi from 149 patients with diagnoses of "undeveloped pregnancy" or "anembryonia" were presented in the article. Metaphase chromosomes were used for cytogenetic research of the embryos. The samples were obtained from cytotrophoblast cells of chorionic villi by the "direct" method, without culture, according to standard technique. A GTG-method was used for staining the chromosome slides. The cytogenetic study of chorionic villi makes it possible to identify the karyotype abnormalities, which caused the fading of pregnancy, since the chorion karyotype corresponds to the embryo karyotype The slide analysis was carried out in accordance with the international system of the human cytogenetic nomenclature. As a result of the cytogenetic study, changes in the karyotype were revealed in 53.39 % of the samples, namely, genomic mutations – aneuploidy and polyploidy. Among the aneuploidies, we found the embryos with trisomy in the autosomes 5, 13, 16, 18, 20, 21, and 22. In addition, the karyotypes with trisomy and monosomy of the X chromosome, as well as the male karyotypes with an additional copy of the X or Y chromosome were present The polyploids in the study group were represented by triploid and tetraploid karyotypes of embryos. All the above mentioned karyotype disorders were found in both full and mosaic forms. Further, some non-developing embryos contained a chimeric karyotype - "chi46,XX/46,XY". In the study group, the prevailing were the embryos with a tetraploid karyotype in a mosaic form (6.71 %), Klinefelter syndrome in a mosaic form (6.04 %), and a triploid karyotype in a mosaic form (6.04 %). A statistically significant increase in the incidence of stillbirths with mosaic tetraploid karyotype was found in 2020. The share of this pathology was 25. %. Currently, there is no reliable information on the effect of the SARS-CoV-2 virus on the embryonic genome. Nevertheless, it is known that members of the coronavirus family are responsible for serious complications during pregnancy - pregnancy fading, fetal growth retardation, premature birth, death of the mother or fetal death in the neonatal period. In this connection, we can hypothesize that mitotic disorders and, as a consequence, appearance of embryos with a tetraploid karyotype seem to be associated with a mild SARS-CoV-2 infection that occurs in pregnant women in an inconspicuous form

Синтез цис- та транс-3-(4-гідроксифеніл)циклобутанкарбонових кислот та дослідження їх похідних як лігандів рецептора GPR-40

Aim. To synthesize cis- and trans-isomers of 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid and evaluate the biological activity of their derivatives against GPR-40.Results and discussion. Cis- and trans-isomers of 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid were synthesized. The derivatives of this compound were tested as GPR-40 agonists and exhibited the micromolar activity.Experimental part. The methyl ester of 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid was obtained as a mixture of cis/trans-isomers in 3 steps starting from a commercially available 3-oxocyclobutanecarboxylic acid. Further transformation of this compound into isomerically pure 3-(4-hydroxyphenyl)cyclobutanecarboxylic acids was achieved in five steps based on the chromatographic separation of diastereomeric amide derivatives. New GPR-40 ligands were obtained by O-alkylation of a phenolic oxygen atom of the corresponding carboxylic acid methyl ester. The biological activity of the agonists synthesized was studied using a fluorometric bioassay and the engineered Chinese hamster ovary (CHO) stable cell line expressing the human GPR-40.Conclusions. An effective synthetic approach to 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid allowing to isolate two single cis/trans-stereoisomers of this compound has been developed. In order to demonstrate the possibility for the bioisosteric replacement of the ethylene moiety in the structures of free fatty acid receptor (FFAR) agonists by the cyclobutane ring, four new GPR-40 ligands possessing the micromolar activity have been synthesized.Received: 22.08.2020 Revised: 11.10.2020 Accepted: 17.10.2020Мета. Синтезувати цис- та транс-ізомери 3-(4-гідроксифеніл)циклобутанкарбонової кислоти та виявити біологічну активність їх похідних щодо рецептора GPR-40.Результати та їх обговорення. Було синтезовано цис- та транс-ізомери 3-(4-гідроксифеніл)циклобутанкарбонової кислоти, а також їх похідні, що виявили мікромолярну активність як агоністи рецептора GPR-40.Експериментальна частина. Метиловий естер 3-(4-гідроксифеніл)циклобутанкарбонової кислоти було одержано у вигляді суміші цис- та транс-ізомерів у три стадії, виходячи з комерційно доступної 3-оксоциклобутанкарбонової кислоти. Подальше перетворення цієї речовини на ізомерно чисті 3-(4-гідроксифеніл)циклобутанкарбонові кислоти було досягнуто у п’ять стадій, що ґрунтувалося на хроматографічному розділенні діастереомерних амідних похідних. Нові ліганди рецептора GPR-40 одержано шляхом О-алкілування за фенольним атомом оксигену відповідного метилового естеру кислоти. Біологічну активність синтезованих агоністів досліджено на стабільній лінії клітин яєчників китайського хом’яка (CHO), яка експресує людський рецептор GPR-40, за допомогою флуориметричного біотесту.Висновки. Розроблено ефективний підхід до синтезу 3-(4-гідроксифеніл)циклобутанкарбонової кислоти, що дозволяє одержати її у вигляді двох індивідуальних цис/транс-стереоізомерів. Для демонстрації можливості біоізостерної заміни етиленової ланки в структурі агоністів рецепторів вільних жирних кислот (FFAR) на циклобутанове кільце було також синтезовано чотири нові ліганди GPR-40, що мали мікромолярну активність.Received: 22.08.2020 Revised: 11.10.2020 Accepted: 17.10.202

Comparative analysis of the DNA isolated from thyme leaves using different methods

Background. The base for a molecular analysis is DNA of high quality. For DNA isolation, different kits or classical methods are used. For mass analysis, isolation with kits is a very expensive process. So, the objective of our investigation was to find a cheap method for high-quality DNA isolation from leaves of various thyme cultivars.Materials and methods. Leaves cut from thyme accessions (Thymus mastichina L. cv. ‘Svetliachok’, T. striatus Vahl. cv. ‘Jubileiniy’, T. vulgaris L. cv. ‘Fantasia’, and T. vulgaris cv. ‘Jalos’.) maintained ex situ in the collection of the Nikita Botanical Gardens were used as the material for the analysis. Light microscopy was used to study leaf anatomy and localize essential oil on leaf cross sections. Essential oil was extracted on Ginsberg devices, and phenolic content was measured with The Folin–Ciocâlteu reagent (FCR). Commercial kits (DiamondDNATM, PureLink® Plant Total DNA Purification Kit) and classical methods (CTAB, CTAB with 2% polyvinylpyrrolidone) were used for DNA isolation. DNA quality was evaluated spectrophotometrically, with electrophoresis (horizontal, automated system Agilent 4200 TapeStation) and PCR.Results. The analysis showed that the leaf blade mesophyll of four thyme cultivars had inclusions with essential oil. The content of essential oil and phenolic compounds was measured biochemically. Since the plants were characterized by the presence of secondary metabolites, DNA was isolated by different methods. Spectrophotometry demonstrated that the classical CTAB method and CTAB with 2% PVP provided the best results. Using an automated electrophoresis system, the presence of high-molecularweight DNA (more than 52000 bp) in significant amounts was detected in the samples isolated with DiamondDNATM kit and CTAB + 2% PVP.Conclusion. Among the tested kits and methods, CTAB + 2% PVP provided thyme DNA suitable for PCR and, presumably, for genome library preparation. The low cost of reagents for this technique makes it applicable for future mass analysis of plant material

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Component composition of essential oil in the North American <i>Pinus</i> L. species introduced to the Southern Coast of Crimea

Background. Studying essential oils in conifers is of great scientific and practical interest due to their high bactericidal properties. Their volatiles play an important role in combating pathogenic microflora and removing harmful microorganisms from the air, thus benefiting human health. Conifers are highly effective as part of parklands and urban landscaping.Materials and methods. Pinus radiata D. Don, P. sabiniana Douglas and P. coulteri D. Don grown on the Southern Coast of Crimea were studied. Essential oil was extracted from pine needles by hydrodistillation on Ginsberg devices, and its component composition was analyzed using gas–liquid chromatography on a 6890N system with a 5973N mass selective detector.Results. Among the studied species, P. radiata manifested high essential oil content in needles: 0.15% on the wet weight basis (0.36%, dry weight). Under the conditions of the southern coast of Crimea, the major essential oil components in P. radiata were β-pinene (29.5% of the total essential oil), α-pinene (21.2%) and limonene (12.4%); in P. sabiniana, phenylethyl butyrate (20.5%), limonene (15.2%) and α-pinene (13.7%); in P. coulteri, β-pinene (11.6%), δ-cadinene (11.0%) and α-pinene (10.6%). In the essential oil of P. radiata monoterpenes dominated (74.9%); in P. sabiniana, monoterpenes (38.7%) and their derivatives − alcohols (25.3%) and esters (20.5%); in P. coulteri, sesquiterpenes (38.2%) and monoterpenes (28.8%).Conclusion. The essential oils of P. radiata and P. sabiniana under different climate conditions contained mostly monoterpenes (β-pinene in P. radiata, and α-pinene in P. sabiniana) and their derivatives. The component composition of P. coulteri essential oil was the most variable, with a general tendency towards the predominance of sesquiterpenes and diterpenes; the ratio between those groups and the qualitative composition of sesquiterpenes both varied

Cyclobutyl-Containing Rigid Analogues of Threonine: Synthesis and Physical Chemical Properties

Hitherto unknown <i>cis</i>- and <i>trans</i>-1-amino-3-hydroxy-3-methylcyclobutanecarboxylic acids were synthesized in multigram scale. The obtained compounds can be considered as achiral conformationally restricted analogues of threonine with fixed spatial orientation of functional groups. p<i>K</i>_a values are noticeably different for both amino acids. According to the X-ray data the cyclobutane rings in both compounds are almost planar (the corresponding torsion angles are below 7°)

Charge recombination in excited donor-acceptor complexes with two absorption bands

The dynamics of charge recombination in a photoexcited donor-acceptor complex comprising 1,2,4-trimethoxybenzene (electron donor) and tetracyanoethylene (electron acceptor) in several polar solvents (acetonitrile, valeronitrile, and octanonitrile) was studied in terms of the stochastic approach. The Gibbs energy of charge recombination and the reorganization energies of the medium and quantum and vibrational degrees of freedom were found by fitting the stationary absorption spectrum. The electronic couplings were determined by analyzing the time dependences of the population of the ionic state in acetonitrile. A comparison of the numerical simulation results with the experimental data showed that the nonstationary model under consideration quantitatively described the dynamics of charge recombination and its dependence on the carrier frequency of excitation pulses and the relaxation properties of solvents